Pluripotent embryonic stem cells (ESCs) can differentiate into all somatic cell types, making them a useful platform for studying a variety of cellular phenomenon. Furthermore, ESCs can be induced to form aggregates called embryoid bodies (EBs) which recapitulate the dynamics of development and morphogenesis. However, many different factors such as gradients of soluble morphogens, direct cell-to-cell signaling, and cell-matrix interactions have all been implicated in directing ESC differentiation. Though the effects of individual factors have often been investigated independently, the inherent difficulty in assaying combinatorial effects has made it difficult to ascertain the concerted effects of different environmental parameters, particularly due to the spatial and temporal dynamics associated with such cues. Dynamic computational models of ESC differentiation can provide powerful insight into how different cues function in combination both spatially and temporally. By combining particle based diffusion models, cellular agent based approaches, and physical models of morphogenesis, a multi-scale, rules-based modeling framework can provide insight into how each component contributes to differentiation. I propose to investigate the complex regulatory cues which govern complex morphogenic behavior in 3D ESC systems via a computational rules based modeling approach. The objective of this study is to examine how spatial patterns of differentiation by ESCs arise as a function of the microenvironment. The central hypothesis is that spatial control of soluble morphogens and cell-cell signaling will allow enhanced control over the patterns and efficiency of stem cell differentiation in embryoid bodies.

Synucleinopathies are a family of neurodegenerative diseases, with the distinctive pathological feature of Lewy bodies, which include Parkinson’s disease. Lewy bodies are intracellular inclusions filled with α-synuclein, a small neuronal protein with prion-like properties. The main function of α-synuclein is not fully understood, however, it plays a major role in disease progression. Dopamine interactions with α-synuclein have also been implicated in the progression of Parkinson’s disease. Dopamine crosslinks α-synuclein and causes generation of toxic oligomeric species of the protein. Little is known about dopamine-α-synuclein adducts, and one section of the current dissertation focuses on dopamine, levodopa, and α-synuclein interactions. Studies detailed herein demonstrated that lysine residues on α-synuclein have an essential role in the dopamine-induced oligomer formation. Evidence is also presented showing that removal of one of the reactive sites on dopamine by N-acetylcysteine and/or glutathione inhibits dopamine-induced oligomer formation, although the dopamine thiol-conjugates still bind to α-synuclein. In contrast, thiol-conjugates of the dopamine precursor levodopa, significantly increase α-synuclein oligomer formation. The data demonstrate the importance of the scavenging of dopamine and levodopa quinones by N-acetylcysteine and glutathione, and the subsequent changes in the interaction with α-synuclein and its oligomeric states. Environmental factors are key players in the development of synucleinopathies. Although arsenic pesticide exposure has been linked to elevated risk of Parkinson’s disease, there is a paucity of information on arsenic-induced pathological changes, which may be attributed to the onset of neurodegenerative processes. SH-SY5Y cells exposed to environmentally relevant levels of arsenic for 72 hours, develop α-synuclein oligomers and exhibitaugmented expression of stress markers. Thus, there is an increase in autophagy markers and other stress markers, including the accumulation and co-localization of LC3, major autophagy marker, and α-synuclein. Animals transiently exposed to arsenic through drinking water for 2 or 5 weeks, exhibited pathological features resembling synucleinopathies. Although animals were exposed at two-months of age and remained exposure free up to geriatric age (18 months), they still exhibited accumulation of α-synuclein and elevations in autophagy markers. The results demonstrated how even a short period of exposure to a toxicant can have detrimental neurological effects, which may contribute to the development of neurodegenerative disease years after exposure.

The Kentucky Division of Water indicates that agriculture is responsible for 55% of the Commonwealth’s assessed streams not supporting their designated uses. Riparian buffers reduce nonpoint source pollution in agroecosystems by storing and cycling nutrients, stabilizing streambanks, increasing infiltration, and storing water. Specific information regarding riparian buffer management is needed for land managers to maximize buffer effectiveness at reducing agricultural contaminants impairing water quality. Baseline soil properties (texture, pH, C and nutrients) of the riparian buffer surrounding a tributary of Cane Run Creek in Fayette County, KY were characterized prior to imposing three mowing regimes (intense, moderate, and no mow treatments) and one native grass regime. Measurements were made along parallel transects located 2-m and 8-m distances from the stream. Root biomass, aggregate distribution, and saturated hydraulic conductivity were measured along the 2-m transect in two consecutive years following treatment establishment. The 2-m transect soils had the highest C, pH, Ca, Zn, and sand content. The 8-m transect had the highest P, K, Mg, and clay content. Semivariogram analysis of C content indicated slight to moderate spatial dependency along the 2m transect and moderate to strong spatial dependency along the 8m transect. Root biomass increased with decreased mowing frequency at the surface depth after one year; the native grass treatment had significantly less root biomass in both years compared to mowing treatments. There was no significant treatment effect on aggregate size distribution at the surface depth in either year. Mean weight diameter and large macroaggregates decreased from 2011 to 2012. Vegetation treatment had no statistically significant effect on water stable aggregates or saturated hydraulic conductivity. Experimental semivariograms provided evidence of spatial structure at multiple scales in root biomass, aggregates, and soil C. Spatial variability occurred over a shorter lag distance in 2012 than 2011, suggesting an effect of imposed treatments slowly developing over time. This study provides important insights on riparian buffer soil properties, soil sampling strategies to detect spatial variability in riparian buffers, and length of time needed to assess effects of vegetation management regimes on riparian root biomass, soil aggregates, and hydraulic conductivity.

This thesis addresses three relevant macroeconomic issues: (i) why Central Banks behave so cautiously compared to optimal theoretical benchmarks, (ii) do monetary variables add information about future Euro Area inflation to a large amount of non monetary variables and (iii) why national saving and investment are so correlated in OECD countries in spite of the high degree of integration of international financial markets. The process of innovation in the elaboration of economic theory and statistical analysis of the data witnessed in the last thirty years has greatly enriched the toolbox available to macroeconomists. Two aspects of such a process are particularly noteworthy for addressing the issues in this thesis: the development of macroeconomic dynamic stochastic general equilibrium models (see Woodford, 1999b for an historical perspective) and of techniques that enable to handle large data sets in a parsimonious and flexible manner (see Reichlin, 2002 for an historical perspective). Dynamic stochastic general equilibrium models (DSGE) provide the appropriate tools to evaluate the macroeconomic consequences of policy changes. These models, by exploiting modern intertemporal general equilibrium theory, aggregate the optimal responses of individual as consumers and firms in order to identify the aggregate shocks and their propagation mechanisms by the restrictions imposed by optimizing individual behavior. Such a modelling strategy, uncovering economic relationships invariant to a change in policy regimes, provides a framework to analyze the effects of economic policy that is robust to the Lucas'critique (see Lucas, 1976). The early attempts of explaining business cycles by starting from microeconomic behavior suggested that economic policy should play no role since business cycles reflected the efficient response of economic agents to exogenous sources of fluctuations (see the seminal paper by Kydland and Prescott, 1982} and, more recently, King and Rebelo, 1999). This view was challenged by several empirical studies showing that the adjustment mechanisms of variables at the heart of macroeconomic propagation mechanisms like prices and wages are not well represented by efficient responses of individual agents in frictionless economies (see, for example, Kashyap, 1999; Cecchetti, 1986; Bils and Klenow, 2004 and Dhyne et al., 2004). Hence, macroeconomic models currently incorporate some sources of nominal and real rigidities in the DSGE framework and allow the study of the optimal policy reactions to inefficient fluctuations stemming from frictions in macroeconomic propagation mechanisms. Against this background, the first chapter of this thesis sets up a DSGE model in order to analyze optimal monetary policy in an economy with sectorial heterogeneity in the frequency of price adjustments. Price setters are divided in two groups: those subject to Calvo type nominal rigidities and those able to change their prices at each period. Sectorial heterogeneity in price setting behavior is a relevant feature in real economies (see, for example, Bils and Klenow, 2004 for the US and Dhyne, 2004 for the Euro Area). Hence, neglecting it would lead to an understatement of the heterogeneity in the transmission mechanisms of economy wide shocks. In this framework, Aoki (2001) shows that a Central Bank maximizing social welfare should stabilize only inflation in the sector where prices are sticky (hereafter, core inflation). Since complete stabilization is the only true objective of the policymaker in Aoki (2001) and, hence, is not only desirable but also implementable, the equilibrium real interest rate in the economy is equal to the natural interest rate irrespective of the degree of heterogeneity that is assumed. This would lead to conclude that stabilizing core inflation rather than overall inflation does not imply any observable difference in the aggressiveness of the policy behavior. While maintaining the assumption of sectorial heterogeneity in the frequency of price adjustments, this chapter adds non negligible transaction frictions to the model economy in Aoki (2001). As a consequence, the social welfare maximizing monetary policymaker faces a trade-off among the stabilization of core inflation, economy wide output gap and the nominal interest rate. This feature reflects the trade-offs between conflicting objectives faced by actual policymakers. The chapter shows that the existence of this trade-off makes the aggressiveness of the monetary policy reaction dependent on the degree of sectorial heterogeneity in the economy. In particular, in presence of sectorial heterogeneity in price adjustments, Central Banks are much more likely to behave less aggressively than in an economy where all firms face nominal rigidities. Hence, the chapter concludes that the excessive caution in the conduct of monetary policy shown by actual Central Banks (see, for example, Rudebusch and Svennsson, 1999 and Sack, 2000) might not represent a sub-optimal behavior but, on the contrary, might be the optimal monetary policy response in presence of a relevant sectorial dispersion in the frequency of price adjustments. DSGE models are proving useful also in empirical applications and recently efforts have been made to incorporate large amounts of information in their framework (see Boivin and Giannoni, 2006). However, the typical DSGE model still relies on a handful of variables. Partly, this reflects the fact that, increasing the number of variables, the specification of a plausible set of theoretical restrictions identifying aggregate shocks and their propagation mechanisms becomes cumbersome. On the other hand, several questions in macroeconomics require the study of a large amount of variables. Among others, two examples related to the second and third chapter of this thesis can help to understand why. First, policymakers analyze a large quantity of information to assess the current and future stance of their economies and, because of model uncertainty, do not rely on a single modelling framework. Consequently, macroeconomic policy can be better understood if the econometrician relies on large set of variables without imposing too much a priori structure on the relationships governing their evolution (see, for example, Giannone et al., 2004 and Bernanke et al., 2005). Moreover, the process of integration of good and financial markets implies that the source of aggregate shocks is increasingly global requiring, in turn, the study of their propagation through cross country links (see, among others, Forni and Reichlin, 2001 and Kose et al., 2003). A priori, country specific behavior cannot be ruled out and many of the homogeneity assumptions that are typically embodied in open macroeconomic models for keeping them tractable are rejected by the data. Summing up, in order to deal with such issues, we need modelling frameworks able to treat a large amount of variables in a flexible manner, i.e. without pre-committing on too many a-priori restrictions more likely to be rejected by the data. The large extent of comovement among wide cross sections of economic variables suggests the existence of few common sources of fluctuations (Forni et al., 2000 and Stock and Watson, 2002) around which individual variables may display specific features: a shock to the world price of oil, for example, hits oil exporters and importers with different sign and intensity or global technological advances can affect some countries before others (Giannone and Reichlin, 2004). Factor models mainly rely on the identification assumption that the dynamics of each variable can be decomposed into two orthogonal components - common and idiosyncratic - and provide a parsimonious tool allowing the analysis of the aggregate shocks and their propagation mechanisms in a large cross section of variables. In fact, while the idiosyncratic components are poorly cross-sectionally correlated, driven by shocks specific of a variable or a group of variables or measurement error, the common components capture the bulk of cross-sectional correlation, and are driven by few shocks that affect, through variable specific factor loadings, all items in a panel of economic time series. Focusing on the latter components allows useful insights on the identity and propagation mechanisms of aggregate shocks underlying a large amount of variables. The second and third chapter of this thesis exploit this idea. The second chapter deals with the issue whether monetary variables help to forecast inflation in the Euro Area harmonized index of consumer prices (HICP). Policymakers form their views on the economic outlook by drawing on large amounts of potentially relevant information. Indeed, the monetary policy strategy of the European Central Bank acknowledges that many variables and models can be informative about future Euro Area inflation. A peculiarity of such strategy is that it assigns to monetary information the role of providing insights for the medium - long term evolution of prices while a wide range of alternative non monetary variables and models are employed in order to form a view on the short term and to cross-check the inference based on monetary information. However, both the academic literature and the practice of the leading Central Banks other than the ECB do not assign such a special role to monetary variables (see Gali et al., 2004 and references therein). Hence, the debate whether money really provides relevant information for the inflation outlook in the Euro Area is still open. Specifically, this chapter addresses the issue whether money provides useful information about future inflation beyond what contained in a large amount of non monetary variables. It shows that a few aggregates of the data explain a large amount of the fluctuations in a large cross section of Euro Area variables. This allows to postulate a factor structure for the large panel of variables at hand and to aggregate it in few synthetic indexes that still retain the salient features of the large cross section. The database is split in two big blocks of variables: non monetary (baseline) and monetary variables. Results show that baseline variables provide a satisfactory predictive performance improving on the best univariate benchmarks in the period 1997 - 2005 at all horizons between 6 and 36 months. Remarkably, monetary variables provide a sensible improvement on the performance of baseline variables at horizons above two years. However, the analysis of the evolution of the forecast errors reveals that most of the gains obtained relative to univariate benchmarks of non forecastability with baseline and monetary variables are realized in the first part of the prediction sample up to the end of 2002, which casts doubts on the current forecastability of inflation in the Euro Area. The third chapter is based on a joint work with Domenico Giannone and gives empirical foundation to the general equilibrium explanation of the Feldstein - Horioka puzzle. Feldstein and Horioka (1980) found that domestic saving and investment in OECD countries strongly comove, contrary to the idea that high capital mobility should allow countries to seek the highest returns in global financial markets and, hence, imply a correlation among national saving and investment closer to zero than one. Moreover, capital mobility has strongly increased since the publication of Feldstein - Horioka's seminal paper while the association between saving and investment does not seem to comparably decrease. Through general equilibrium mechanisms, the presence of global shocks might rationalize the correlation between saving and investment. In fact, global shocks, affecting all countries, tend to create imbalance on global capital markets causing offsetting movements in the global interest rate and can generate the observed correlation across national saving and investment rates. However, previous empirical studies (see Ventura, 2003) that have controlled for the effects of global shocks in the context of saving-investment regressions failed to give empirical foundation to this explanation. We show that previous studies have neglected the fact that global shocks may propagate heterogeneously across countries, failing to properly isolate components of saving and investment that are affected by non pervasive shocks. We propose a novel factor augmented panel regression methodology that allows to isolate idiosyncratic sources of fluctuations under the assumption of heterogenous transmission mechanisms of global shocks. Remarkably, by applying our methodology, the association between domestic saving and investment decreases considerably over time, consistently with the observed increase in international capital mobility. In particular, in the last 25 years the correlation between saving and investment disappears.

<p>Myocardial infarction (MI) is often caused by a disruption of an atherosclerotic plaque with activation of coagulation, platelets and inflammation. The aims were; to investigate whether the oral direct thrombin inhibitor, ximelagatran affected markers for coagulation, platelet and inflammation in a patient cohort with recent MI and if the coagulation markers could identify patients with increased risk of new ischemic events; to evaluate some of the mechanisms involved in formation of platelet-monocyte aggregates (PMAs). </p><p>In a biomarker substudy patients with recent MI were randomized to 24-60 mg of ximelagatran or placebo for six months. There was a persistent dose-independent reduction of coagulation markers (F1+2, D-dimer) by ximelagatran treatment. 60 % reduced their D-dimer levels after one week and that group had less ischemic events during treatment. There was an early increase of the platelet activation marker and ximelagatran in higher doses attenuated these increased levels. Both in vivo and in vitro the direct thrombin inhibitor diminished procoagulant activity and tissue factor (TF) presenting microparticles. In contrast, the inflammatory markers increased after six months of ximelagatran treatment. The PMA-levels were elevated for long-term after MI. In vitro thrombin inhibition diminished formation of PMAs. Formation of PMAs in stimulated whole blood was P-selectin dependent and induced TF expression through phosphorylation of the Src-family member Lyn in monocytes.</p><p>Addition of an oral direct thrombin inhibitor reduces coagulation and platelet activation markers for long-term after a MI together with reduced procoagulant activity which may contribute to the clinical benefit of the drug. Early reduction of D-dimer levels seems to be suitable to identify patients with reduced risk of new ischemic events independent of antithrombotic treatment. Circulating PMAs persist after a MI connecting coagulation to inflammation. Within these aggregates P-selectin induces TF, the main initiator of coagulation, partly through phosphorylation of Lyn.</p>

A 1H, 13C, and 6Li NMR study of 2-ethyl-1-butyllithium indicated that 2-ethyl-1-butyllithium exists only as a hexameric aggregate over the entire temperature range of 25 to - 92.1 ° C in cyclopentane. Reacting 2-ethyl-1-butyllithium with 2-ethyl-1-butanol resulted in alkyllithium/lithium alkoxide mixed aggregates, apparently of the form Ra(RO)bLia+b. A multinuclear, variable temperature NMR study of samples with O:Li ratios of 0.2 and 0.4 showed, in addition to the alkyllithium, the formation of four mixed aggregates, one of them probably an octamer. Higher O:Li ratio samples showed the formation of several other mixed aggregates. Mixing 2-ethyl-1-butyllithium with independently prepared lithium 2-ethyl-1-butoxide formed the same mixed aggregates formed by in situ synthesis of lithium alkoxide. Lithium 2-ethyl-1-butoxide also exists as aggregates in cyclopentane.

No description available.

Afin de caractériser la physico-chimie des matières en suspension de la Moselle et de ses affluents, ce travail s’est appuyé sur une approche géochimique et minéralogique. Notre étude s’est concentrée sur l’analyse des polluants dans les compartiments dissous et particulaire. Ces études ont notamment permis de déterminer (i) la composition des constituants inorganiques dans les particules et colloïdes du milieu aquatique de la Moselle et d’un de ses affluents : la Fensch, (ii) l’évolution des contributions inorganiques le long de la Moselle et de la Fensch ainsi que leur transfert à la confluence Fensch-Moselle, tout en déterminant les sources principales de contamination, (iii) les associations organo-minérales et l’organisation des agrégats présents et (iv) d’étudier la spéciation de certains éléments par des microanalyses. Ce travail a ainsi permis de mettre en évidence l’importance des matières en suspension, souvent négligées par rapport aux autres compartiments Eau et Sédiments / This work uses geochemical and mineralogical approaches to characterize physical and chemical properties of suspended solids in the Moselle and its tributaries. The study focused on analyzing the pollutants in dissolved and particulate compartments. This allowed (i) the identification of inorganic components composition in particles and colloids in the aquatic environment of the Moselle and one of its tributaries: the Fensch, (ii) the determination of the evolution of inorganic contributions along Moselle and the Fensch and their transfer to the confluence Fensch-Moselle in addition to the determination of main contamination sources, (iii) the identification of organo-mineral associations and the determination of the organization of aggregates, (iv) the analysis of the speciation of some elements by microanalysis. This work highlighted the importance of studying suspended solids that are often neglected compared to water and sediments compartments

Les agrégats multi-échelles (sulfure de zinc: ZnS, ...) ont des propriétés physiques et physicochimiques présentant un grand intérêt industriel (industrie pharmaceutique, matériau, environnement...). L'objectif général de cette thèse est de caractériser ces agrégats multi-échelles par une méthode optique d'une part, et par une étude géométrique d'autre part. Le but est de trouver des relations simples entre propriétés optiques et géométriques. Les résultats présentés sont valables pour tout matériau à haut indice de réfraction.Ce travail comporte une première étape de modélisation en étudiant tout d'abord des modèles simples d'agrégats multi-échelles (agencement ordonné de particules élémentaires sphériques). Différents agrégats sont alors géométriquement modélisés suivant des paramètres de construction prédéfinis (volume global des agrégats, rayon des particules primaires...). Une analyse préliminaire optique puis une analyse géométrique sont alors effectuées afin de déterminer les paramètres respectifs à étudier: la section efficace moyenne de diffusion (...), calculée au moyen d'une extension de la théorie de Mie (GMM pour Generalized Multiparticle Mie) d'Y-L Xu, et des caractéristiques géométriques spécifiques (volume de matière, compacité...).Une seconde étape consiste à étudier les variations de la valeur de ... en fonction de celles des paramètres géométriques des agrégats. Des relations caractérisant ces variations sont établies. Enfin, une expression approchées pour la valeur de ... est recherchée sous la forme d'une loi de puissance, reposant sur des méthodes optiques approchées existantes et sur la sélection de caractéristiques géométriques pertinentes. Le modèle mis en place est robuste et présente un compromis entre précision et complexité. Le travail réalisé ouvre diverses perspectives comme la confrontation du modèle mathématique théorique obtenu, avec l'expérience. / Multiscale aggregates (zinc sulfide: ZnS, ...) havephysical and physicochemical properties of great industrial interest (e.g. pharmaceutical industriy, material, environment). The overall objective of this thesis is to characterize these multiscale aggregates by an optical method on the one hand, and a geometric study of the other. The goal is to find simple relations between optical and geometrical properties. The results presented are valid for any material with high refractive index.The first step of this work is to build in a simple way the multiscale aggregate (like ordered arrangement of spherical elementary particles). Different aggregates are then geometrically modeled thanks to predefined design parameters (e.g. particles radius, aggregates overall volume). A preleminary analysis of optical and geometrical analysis is then performed to determine the relevant parameters: the average scattering cross section (...), calculed using a generalization of the Mie theory (GMM for Generalized Multiparticle Mie) developped by Y.L. Xu, and specific geometric values features. An analysis of the behavior of the optical parameter and the geometrical characteristic (e.g. compactness, volume of matter...), with respect to the construction parameters of the aggregates, is then performed.A second step is to study variations of ... value versus the variation of the geometrical parameter of aggregates. Mathematical relations characterizing these variations are established. Finally, a study on the approximation of the ... value is carried out. A power law is proposed which is basedon previous optical approximate methods and on the selection of geometrical characteristics of the aggregates. The optical properties and geometrical characteristics of the clusters are fairly extensive and contrasted to give a general groundwork to this study. The work done opens various perspectives such as the confrontation of the theorical mathematical model obtained, with experiment.

Le travail rapporté dans ce manuscrit s’inscrit dans la perspective de mieux comprendre les propriétés électriques des tissus biologiques dans la gamme de fréquence allant de 10 kHz à 100 MHz. La connaissance de ces propriétés est essentielle pour évaluer les effets du champ électromagnétique sur le corps humain en cas d’exposition involontaire mais aussi pour diagnostiquer un changement physiologique quand le tissu est exposé volontairement. De nombreux travaux ont été effectués pour mesurer les propriétés électriques des différents tissus mais le comportement électrique relevé n’est pas toujours bien compris en raison de la complexité de la structure du tissu. De plus, on constate une grande variabilité dans les données rapportées dans la littérature. Pour mieux appréhender le comportement électrique du tissu, la démarche originale proposée dans ce manuscrit consiste à partir de l’échelle de la cellule. Ainsi la première partie du manuscrit est consacrée à la caractérisation électrique de cellule humaines de type HEK (Human Embryonic Kidney) par électrorotation. La mise en oeuvre de cette technique a permis d’extraire les propriétés électrique de la membrane et du cytoplasme des cellules HEK. La deuxième partie du manuscrit se focalise sur la création d’agrégats de cellules à partir de cellules HEK isolées. Deux techniques ont été essayées. La première s’appuie sur la nature des jonctions intercellulaires. Même si elle donne des résultats, cette approche n’est pas satisfaisante dans la mesure où on ne peut contrôler ni la forme ni la taille des agrégats. L’autre technique consiste à utiliser un champ électrique pour manipuler les cellules par diélectrophorèse. Un microsystème a été conçu à cet effet avec un réseau d’électrodes quadripolaires. On a ainsi pu obtenir des agrégats permanents de cellules HEK ayant une taille et une forme contrôlée. La dernière partie du manuscrit porte sur l’étude du comportement électrique des agrégats de cellules par le biais de simulations numériques de spectres d’électrorotation. La comparaison du comportement électrique d’une cellule isolée et celui d’un agrégat de cellules montre que le milieu extra cellulaire influe fortement sur la réponse électrique de l’agrégat ; la différence de taille entre les cellules de même que la présence de jonctions intercellulaires ne semblent pas avoir un impact significatif. Ces résultats de simulation devront être appuyés par des études expérimentales. / The work reported in this manuscript aims at understanding the electrical properties of biological tissues in the frequency range between 10 kHz and 100 MHz. Knowing these properties is essential to assess the effects of involuntary exposure of human body to electromagnetic fields, but also to diagnose a physiological change when the tissue is exposed voluntarily. Many studies have been conducted to measure the electrical properties of different tissues but existing data are not well understood because of the complexity of tissues structure. Moreover, there is considerable variability of data among studies evaluating these properties. To better understand the electrical behavior of tissues, the original approach proposed in this manuscript consists in investigating their properties starting from the cell scale. The first part of the manuscript is dedicated to the electrical characterization of HEK 293 (HumanEmbryonic Kidney) cells by electrorotation. This technique has been used to extract the electrical properties of the membrane and the cytoplasm of HEK cells. The second part of the manuscript focuses on creating cell aggregates from isolated HEKcells. Two approaches have been proposed. The first one was based on the nature of intercellular junctions. This approach led to the formation of aggregates of irregularsize and shape. The other technique consisted in using an electric field to perform dielectrophoresis-assisted cell assembly. A microsystem comprising quadrupole electrodes was designed for this purpose. Permanent aggregates of HEK cells having a controlled size and shape could be obtained using this approach. The last part of the manuscript focuses on study of the electrical behavior of the cell aggregates through numerical simulations of electrorotation spectra. The confrontation between results obtained for a single cell and those obtained for an aggregate tend to show that the extracellular medium influences strongly the electrical response of the aggregate ; Conversely, the difference in size between the cells as well as the presence of intercellular junctions does not seem to have had a notable impact. These simulation results will have to be supported by experimental studies.