Are Public Private Partnerships that Rigid ? And Why ? : Evidence from Toll Road Concession Contracts

Transport concession contracts are commonly said to be standardized and too rigid. They would not allow public authorities to adapt them to evolving context and circumstances. This paper aims at challenging this view and, more particularly, the view that contractual rigidity for transport concessions is exogenous. Using a transaction cost framework, we disentangle between three main determinants of contractual rigidity: traffic uncertainty; connivance between contracting parties; quality of the institutional environment. Using an original database of toll road concession contracts, we observe a great variety of provisions for toll adjustment. We find that these exogenous determinants significantly influence contractual choices.

Impact of T cell receptor affinity on the molecular mechanisms modulating CD8 T cell signalling and function against NY-ESO-1 tumour antigen

It is well established that cytotoxic T lymphocytes play a pivotal role in the protection against intracellular pathogens and tumour cells. Such protective immune responses rely on the specific T cell receptor (TCR)-mediated recognition by CD8 T cells of small antigenic peptides presented in the context of class-I Major Histocompatibility Complex molecules (pMHCs) on the surface of infected or malignant cells. The strength (affinity/avidity) of this interaction is a major correlate of protection. Although tumour-reactive CD8 T cells can be observed in cancer patients, anti-tumour immune responses are often ineffective in controlling or eradicating the disease due to the relative low TCR affinity of these cells. To overcome this limitation, tumour-specific CD8 T cells can be genetically modified to express TCRs of improved binding strength against a defined tumour antigen before adoptive cell transfer into cancer patients. We previously generated a panel of TCRs specific for the cancer-testis antigen NY-ESO-l,57.165 with progressively increased affinities for the pMHC complex, thus providing us with a unique tool to investigate the causal link between the surface expression of such TCRs and T cell activation and function. We recently demonstrated that anti-tumour CD8 T cell reactivity could only be improved within physiological affinity limits, beyond which drastic functional declines were observed, suggesting the presence of multiple regulatory mechanisms limiting T cell activation and function in a TCR affinity-dependent manner. The overarching goal of this thesis was (i) to assess the precise impact of TCR affinity on T cell activation and signalling at the molecular level and (ii) to gain further insights on the mechanisms that regulate and delimitate maximal/optimized CD8 T cell activation and signalling. Specifically, by combining several technical approaches we characterized the activation status of proximal (i.e. CD3Ç, Lek, and ZAP-70) and distal (i.e. ERK1/2) signalling molecules along the TCR affinity gradient. Moreover, we assessed the extent of TCR downmodulation, a critical step for initial T cell activation. CD8 T cells engineered with the optimal TCR affinity variants showed increased activation levels of both proximal and distal signalling molecules when compared to the wild-type T cells. Our analyses also highlighted the "paradoxical" status of tumour-reactive CD8 T cells bearing very high TCR affinities, which retained strong proximal signalling capacity and TCR downmodulation, but were unable to propagate signalling distally (i.e. pERKl/2), resulting in impaired cell-mediated functions. Importantly, these very high affinity T cells displayed maximal levels of SHP-1 and SHP-2 phosphatases, two negative regulatory molecules, and this correlated with a partial pERKl/2 signalling recovery upon pharmacological SHP-l/SHP-2 inhibition. These findings revealed the putative presence of inhibitory regulators of the TCR signalling cascade acting very rapidly following tumour-specific stimulation. Moreover, the very high affinity T cells were only able to transiently express enhanced proximal signalling molecules, suggesting the presence of an additional level of regulation that operates through the activation of negative feedback loops over time, limiting the duration of the TCR-mediated signalling. Overall, the determination of TCR-pMHC binding parameters eliciting optimal CD8 T cell activation, signalling, and effector function while guaranteeing high antigen specificity, together with the identification of critical regulatory mechanisms acting proximally in the TCR signalling cascade, will directly contribute to optimize and support the development of future TCR-based adoptive T cell strategies for the treatment of malignant diseases. -- Les lymphocytes T CD8 cytotoxiques jouent un rôle prédominant dans la protection contre les pathogènes intracellulaires et les cellules tumorales. Ces réponses immunitaires dépendent de la spécificité avec laquelle les récepteurs T (TCR) des lymphocytes CD8 reconnaissent les peptides antigéniques présentés par les molécules du complexe Majeur de Histocompatibilité de classe I (pCMH) à la surface des cellules infectées ou malignes. La force (ou affinité/avidité) de l'interaction du TCR-pCMH est un corrélat majeur de protection. Les réponses immunitaires sont cependant souvent inefficaces et ne permettent pas de contrôler ou d'éliminer les cellules tumorales chez les patients atteint du cancer, et ce à cause de la relative faible reconnaissance des TCRs exprimés par les lymphocytes T CD8 envers les antigènes tumoraux. Afin de surmonter cette limitation, les cellules T anti-tumorales peuvent être génétiquement modifiées en les dotant de TCRs préalablement optimisés afin d'augmenter leur reconnaissance ou affinité contre les antigènes tumoraux, avant leur ré¬infusion dans le patient. Nous avons récemment généré des cellules T CD8 exprimant un panel de TCRs spécifiques pour l'antigène tumoral NY-ESO-l157.16J avec des affinités croissantes, permettant ainsi d'investiguer la causalité directe entre l'affinité du TCR-pCMH et la fonction des cellules T CD8. Nous avons démontré que la réactivité anti-tumorale pouvait être améliorée en augmentant l'affinité du TCR dans une intervalle physiologique, mais au delà duquel nous observons un important déclin fonctionnel. Ces résultats suggèrent la présence de mécanismes de régulation limitant l'activation des cellules T de manière dépendante de l'affinité du TCR. Le but de cette thèse a été (i) de définir l'impact précis de l'affinité du TCR sur l'activation et la signalisation des cellules T CD8 au niveau moléculaire et (ii) d'acquérir de nouvelles connaissances sur les mécanismes qui régulent et délimitent l'activation et la signalisation maximale des cellules T CD8 optimisées. Spécifiquement, en combinant plusieurs approches technologiques, nous avons caractérisé l'état d'activation de différentes protéines de la voie de signalisation proximale (CD3Ç, Lek et ZAP-70) et distale (ERK1/2) le long du gradient d'affinité du TCR, ainsi que l'internalisation du TCR, une étape clef dans l'activation initiale des cellules T. Les lymphocytes T CD8 exprimant des TCRs d'affinité optimale ont montré des niveaux d'activation augmentés des molécules proximales et distales par rapport aux cellules de type sauvage (wild-type). Nos analyses ont également mis en évidence un paradoxe chez les cellules T CD8 équipées avec des TCRs de très haute affinité. En effet, ces cellules anti-tumorales sont capables d'activer leurs circuits biochimiques au niveau proximal et d'internaliser efficacement leur TCR, mais ne parviennent pas à propager les signaux biochimiques dépendants du TCR jusqu'au niveau distal (via phospho-ERKl/2), avec pour conséquence une limitation de leur capacité fonctionnelle. Finalement, nous avons démontré que SHP-1 et SHP-2, deux phosphatases avec des propriétés régulatrices négatives, étaient majoritairement exprimées dans les cellules T CD8 de très hautes affinités. Une récupération partielle des niveaux d'activation de ERK1/2 a pu être observée après l'inhibition pharmacologique de ces phosphatases. Ces découvertes révèlent la présence de régulateurs moléculaires qui inhibent le complexe de signalisation du TCR très rapidement après la stimulation anti-tumorale. De plus, les cellules T de très hautes affinités ne sont capables d'activer les molécules de la cascade de signalisation proximale que de manière transitoire, suggérant ainsi un second niveau de régulation via l'activation de mécanismes de rétroaction prenant place progressivement au cours du temps et limitant la durée de la signalisation dépendante du TCR. En résumé, la détermination des paramètres impliqués dans l'interaction du TCR-pCMH permettant l'activation de voies de signalisation et des fonctions effectrices optimales ainsi que l'identification des mécanismes de régulation au niveau proximal de la cascade de signalisation du TCR contribuent directement à l'optimisation et au développement de stratégies anti-tumorales basées sur l'ingénierie des TCRs pour le traitement des maladies malignes.

Labor Market Signaling and Self-Confidence: Wage Compression and the Gender Pay Gap

I extend Spence's signaling model by assuming that some workers are overconfident-they underestimate their marginal cost of acquiring education-and some are underconfident. Firms cannot observe workers' productive abilities and beliefs but know the fractions of high-ability, overconfident, and underconfident workers. I find that biased beliefs lower the wage spread and compress the wages of unbiased workers. I show that gender differences in self-confidence can contribute to the gender pay gap. If education raises productivity, men are overconfident, and women underconfident, then women will, on average, earn less than men. Finally, I show that biased beliefs can improve welfare.

Study of linkage between miniature and singed genes in Drosophila melanogaster

We have developed a practical exercise for undergraduate students whose main aim is to identify, using genetic crosses, a pair of D. melanogaster mutations (miniature and singed). Each student receives a vial with the problem strain containing two unknown mutations. The first step is to observe and describe both mutations. Then, the students carry out genetic crosses between mutant and normal strains: (P) ♀ mutant strain × ♂ normal strain (P) ♀ normal strain × ♂ mutant strain A different offspring is expected in these crosses: in the first one we will obtain normal females and m sn males, whereas in the second all individuals will present normal phenotype. It is possible to deduce that both are sex linked mutations. With this information and to simplify the amount of work, only F1 individuals from the first cross will be used (m+sn+ / m sn × m sn / Y chrom.) to obtain the F2 generation. By counting the number of miniature (recombinant type), singed (recombinant type), miniature-singed (parental type) and normal (parental type) flies it is possible to estimate the recombination frequency between both genes. Knowing the phenotype, their chromosomal location (X chromosome) and the genetic distance between both mutations, it is possible to identify them by finding all this information in a Drosophila melanogaster genetic map. Additionally, a statistical analysis can be carried out to compare the number of expected F2 individuals with those observed in the experiment. As the distance between both genes is 15.1 m.u., then the expected percentages for each phenotype would be: normal (42.45%), miniature-signed (42.45%), miniature (7.55%) and singed (7.55%). Multiplying the frequency of each class by the total number of individuals obtained in the F2 it is possible to estimate the expected number of flies for each class. Finally, a χ2 test can be computed to ascertain whether there are significant differences between expected and observed number of individuals.

Nuclear magnetic resonance investigation of structure and dynamics of some electrolyte solutions

Electrolyte solutions are of importance in a wide range of scientific contexts and as such have attracted considerable theoretical and experimental effort over many years. Nuclear Magnetic resonance provides a precise and versatile tool for investigation of electrolyte solutions, both in water and in organic solvents. Many structural and dynamic properties can be obtained through NMR experiments. The solution of aluminum chloride in water was studied. Different concentrations were taken for investigation. Independence of maximum line shift from concentration and acidity was shown. Six-coordinated structure of solvation shell was confirmed by experiments on 'H and 27A1 nuclei. Diffusion coefficients were studied. The solution of nickel chloride in methanol was studied. Lines, corresponding to coordinated and bulk methanol were found. Four-, five- and six-coordinated structures were found in different temperatures. The line for coordinated -OD group of deuterated methanol was observed on 2H spectrum for the first time. Partial deuteration of CH3 group was detected. Inability to observe coordinated -OH group was explained.

Evolution and Stellar Content of AGN Host Galaxies

In this dissertation, Active Galactic Nuclei (AGN) and their host galaxies are discussed. Together with transitional events, such as supernovae and gamma-ray bursts, AGN are the most energetic phenomena in the Universe. The dominant fraction of their luminosity originates from the center of a galaxy, where accreting gas falls into a supermassive black hole, converting gravitational energy to radiation. AGN have a wide range of observed properties: e.g. in their emission lines, radio emission, and variability. Most likely, these properties depend significantly on their orientation to our line-of-sight, and to unify AGN into physical classes it is crucial to observe their orientation-independent properties, such as the host galaxies. Furthermore, host galaxy studies are essential to understand the formation and co-evolution of galactic bulges and supermassive black holes. In this thesis, the main focus is on observationally characterizing AGN host galaxies using optical and near-infrared imaging and spectroscopy. BL Lac objects are a class of AGN characterized by rapidly variable and polarized continuum emission across the electromagnetic spectrum, and coredominated radio emission. The near-infrared properties of intermediate redshift BL Lac host galaxies are studied in Paper I. They are found to be large elliptical galaxies that are more luminous than their low redshift counterparts suggesting a strong luminosity evolution, and a contribution from a recent star formation episode. To analyze the stellar content of galaxies in more detail multicolor data, especially observations at blue wavelengths, are essential. In Paper III, optical - near-infrared colors and color gradients are derived for low redshift BL Lac host galaxies. They show bluer colors and steeper color gradients than inactive ellipticals which, most likely, are caused by a relatively young stellar population indicating a different evolutionary stage between AGN hosts and inactive ellipticals. In Paper II, near-infrared imaging of intermediate redshift radio-quiet quasar hosts is used to study their luminosity evolution. The hosts are large elliptical galaxies, but they are systematically fainter than the hosts of radio-loud quasars at similar redshifts, suggesting a link between the luminosity of the host galaxies and the radio properties of AGN. In Paper IV, the characteristics of near-infrared stellar absorption features of low redshift radio galaxies are compared with those of inactive early-type galaxies. The comparison suggests that early-type galaxies with AGN are in a different evolutionary stage than their inactive counterparts. Moreover, radio galaxies are found to contain stellar populations containing both old and intermediate age components.

Privatization and Regulation of Toll Motorways in Europe

The private sector plays an increasing and relevant role in highway funding and management. For that reason, the regulation designed and enforced by public authorities becomes even more important for the social welfare results generated by this process. In this study, we analyze the current trends in highway funding and management paying special attention on the recent process of privatization and its motivations. Since public ownership and regulation are substitutes for government intervention, we check the hypothesis that highways privatization induces more strict regulation. Indeed, we observe that as the private sector increases its size, toll regulation becomes more detailed.

Ex-Dividend Day Returns when Dividend and Capital Gains are Taxed at the Same Rate

Due to the overwhelming international evidence that stock prices drop by less than the dividend paid on ex-dividend days, the ex-dividend day anomaly is considered a stylized fact. Two main approaches have emerged to explain this empirical regularity: the tax-clientele hypothesis and the microstructure of financial markets. Although the most widely accepted explanation for this fact relies on taxes, the ex-dividend day anomaly has been reported even in countries where neither dividends nor capital gains are taxed. The 2006 tax reform in Spain established the same tax rate for dividends and capital gains. This paper investigates stock returns on ex-dividend days in the Spanish stock market after the 2006 tax reform using a random coefficient model. Contrary to previous research, we do not observe an ex-dividend day anomaly. Unlike previous investigations, which are mostly concerned with suggesting explanations as to why this anomaly has occurred, we are in the somewhat strange position of discussing why this anomaly has not occurred. Our findings are robust across companies and stock dividend yields, thus supporting a tax--based explanation for the ex-dividend day anomaly.

Some Notes and Comments on the Efficient use of Information in Repeated Games with Poisson Signals

In the present paper we characterize the optimal use of Poisson signals to establish incentives in the "bad" and "good" news models of Abreu et al. [1]. In the former, for small time intervals the signals' quality is high and we observe a "selective" use of information; otherwise there is a "mass" use. In the latter, for small time intervals the signals' quality is low and we observe a "fine" use of information; otherwise there is a "non-selective" use. JEL: C73, D82, D86. KEYWORDS: Repeated Games, Frequent Monitoring, Public Monitoring, Infor- mation Characteristics.

Photometric and Halpha observations of LSI+61·303: detection of a 26 day V and JHK band modulation

We present new optical and infrared photometric observations and high resolution H α spectra of the periodic radio star LSI+61◦303. The optical photometric data set covers the time interval 1985-1993 and amounts to about a hundred nights. A period of ∼26 days is found in the V band. The infrared data also present evidence for a similar periodicity, but with higher amplitude of variation ((0.m 2). The spectroscopic observations include 16 intermediate and high dispersion spectra of LSI+61◦303 collected between January 1989 and February 1993. The H α emission line profile and its variations are analyzed. Several emission line parameters -- among them the H α EW and the width of the H α red hump -- change strongly at or close to radio maximum, and may exhibit periodic variability. We also observe a significant change in the peak separation. The H α profile of LSI+61◦303 does not seem peculiar for a Be star. However, several of the observed variations of the H α profile can probably be associated with the presence of the compact, secondary star.

Model for interevent times with long tails and multifractality in human communications: An application to financial trading

Social, technological, and economic time series are divided by events which are usually assumed to be random, albeit with some hierarchical structure. It is well known that the interevent statistics observed in these contexts differs from the Poissonian profile by being long-tailed distributed with resting and active periods interwoven. Understanding mechanisms generating consistent statistics has therefore become a central issue. The approach we present is taken from the continuous-time random-walk formalism and represents an analytical alternative to models of nontrivial priority that have been recently proposed. Our analysis also goes one step further by looking at the multifractal structure of the interevent times of human decisions. We here analyze the intertransaction time intervals of several financial markets. We observe that empirical data describe a subtle multifractal behavior. Our model explains this structure by taking the pausing-time density in the form of a superstatistics where the integral kernel quantifies the heterogeneous nature of the executed tasks. A stretched exponential kernel provides a multifractal profile valid for a certain limited range. A suggested heuristic analytical profile is capable of covering a broader region.

Propagation through fractal media: The Sierpinski gasket and the Koch curve

We present new analytical tools able to predict the averaged behavior of fronts spreading through self-similar spatial systems starting from reaction-diffusion equations. The averaged speed for these fronts is predicted and compared with the predictions from a more general equation (proposed in a previous work of ours) and simulations. We focus here on two fractals, the Sierpinski gasket (SG) and the Koch curve (KC), for two reasons, i.e. i) they are widely known structures and ii) they are deterministic fractals, so the analytical study of them turns out to be more intuitive. These structures, despite their simplicity, let us observe several characteristics of fractal fronts. Finally, we discuss the usefulness and limitations of our approa

Imperfectly informed voters and strategic extremism

We analyze a unidimensional model of two-candidate electoral competition where voters have im- perfect information about the candidates' policy proposals, that is, voters cannot observe the exact policy proposals of the candidates but only which candidate offers the most leftist/rightist platform. We assume that candidates are purely office motivated and that one candidate enjoys a valence advan- tage over the other. We characterize the unique Sequential Equilibrium in very-weakly undominated strategies of the game. In this equilibrium the behavior of the two candidates tends to maximum extremism, due to the voters' lack of information. But it may converge or diverge depending on the size of the advantage. For small values of the advantage candidates converge to the extreme policy most preferred by the median and for large values of the advantage candidates strategies diverge: each candidate specializes in a different extreme policy. These results are robust to the introduction of a proportion of well informed voters. In this case the degree of extremism decreases when the voters become more informed.

Evaluation of chitosan microparticles containing curcumin and crosslinked with sodium tripolyphosphate produced by spray drying

The aim of this study was to encapsulate curcumin into chitosan, using sodium tripolyphosphate (TPP) as an ionic crosslinker by the spray drying method. The influence of TPP on the properties of the final product, such as solubility, morphology, loading efficiency, thermal behavior, swelling degree and release profiles, was evaluated. The microparticles had a spherical morphology (0.5-20 µm) with no apparent porosity or cracks. Results indicated the formation of a polymeric network, which ensures effective protection for curcumin. Controlled-release studies were carried out at pH 1.2 and 6.8, to observe the influence of pH on curcumin release while the mechanism was analyzed using the Korsmeyer-Peppas equation.

Characteristics of pyridine adsorption on Au(111) and Au(210) by EIS parameters fitting procedure

Some aspects of the application of electrochemical impedance spectroscopy to studies of solid electrode / solution interface, in the absence of faradaic processes, are analysed. In order to perform this analysis, gold electrodes with (111) and (210) crystallographic orientations in an aqueous solution containing 10 mmol dm-3 KF, as supporting electrolyte, and a pyridine concentration varying from 0.01 to 4.6 mmol dm-3, were used. The experimental data was analysed by using EQUIVCRT software, which utilises non-linear least squares routines, attributing to the solid electrode / solution interface behaviour described by an equivalent circuit with a resistance in series with a constant phase element. The results of this fitting procedure were analysed by the dependence on the electrode potential on two parameters: the pre-exponential factor, Y0, and the exponent n f, related with the phase angle shift. By this analysis it was possible to observe that the pyridine adsorption is strongly affected by the crystallographic orientation of the electrode surface and that the extent of deviation from ideal capacitive behaviour is mainly of interfacial origin.