RNA Interference and cyclooxygenase-2 (COX-2) regulation in colon cancer cells

Despite new methods and combined strategies, conventional cancer chemotherapy still lacks specificity and induces drug resistance. Gene therapy can offer the potential to obtain the success in the clinical treatment of cancer and this can be achieved by replacing mutated tumour suppressor genes, inhibiting gene transcription, introducing new genes encoding for therapeutic products, or specifically silencing any given target gene. Concerning gene silencing, attention has recently shifted onto the RNA interference (RNAi) phenomenon. Gene silencing mediated by RNAi machinery is based on short RNA molecules, small interfering RNAs (siRNAs) and microRNAs (miRNAs), that are fully o partially homologous to the mRNA of the genes being silenced, respectively. On one hand, synthetic siRNAs appear as an important research tool to understand the function of a gene and the prospect of using siRNAs as potent and specific inhibitors of any target gene provides a new therapeutical approach for many untreatable diseases, particularly cancer. On the other hand, the discovery of the gene regulatory pathways mediated by miRNAs, offered to the research community new important perspectives for the comprehension of the physiological and, above all, the pathological mechanisms underlying the gene regulation. Indeed, changes in miRNAs expression have been identified in several types of neoplasia and it has also been proposed that the overexpression of genes in cancer cells may be due to the disruption of a control network in which relevant miRNA are implicated. For these reasons, I focused my research on a possible link between RNAi and the enzyme cyclooxygenase-2 (COX-2) in the field of colorectal cancer (CRC), since it has been established that the transition adenoma-adenocarcinoma and the progression of CRC depend on aberrant constitutive expression of COX-2 gene. In fact, overexpressed COX-2 is involved in the block of apoptosis, the stimulation of tumor-angiogenesis and promotes cell invasion, tumour growth and metastatization. On the basis of data reported in the literature, the first aim of my research was to develop an innovative and effective tool, based on the RNAi mechanism, able to silence strongly and specifically COX-2 expression in human colorectal cancer cell lines. In this study, I firstly show that an siRNA sequence directed against COX-2 mRNA (siCOX-2), potently downregulated COX-2 gene expression in human umbilical vein endothelial cells (HUVEC) and inhibited PMA-induced angiogenesis in vitro in a specific, non-toxic manner. Moreover, I found that the insertion of a specific cassette carrying anti-COX-2 shRNA sequence (shCOX-2, the precursor of siCOX-2 previously tested) into a viral vector (pSUPER.retro) greatly increased silencing potency in a colon cancer cell line (HT-29) without activating any interferon response. Phenotypically, COX-2 deficient HT-29 cells showed a significant impairment of their in vitro malignant behaviour. Thus, results reported here indicate an easy-to-use, powerful and high selective virus-based method to knockdown COX-2 gene in a stable and long-lasting manner, in colon cancer cells. Furthermore, they open up the possibility of an in vivo application of this anti-COX-2 retroviral vector, as therapeutic agent for human cancers overexpressing COX-2. In order to improve the tumour selectivity, pSUPER.retro vector was modified for the shCOX-2 expression cassette. The aim was to obtain a strong, specific transcription of shCOX-2 followed by COX-2 silencing mediated by siCOX-2 only in cancer cells. For this reason, H1 promoter in basic pSUPER.retro vector [pS(H1)] was substituted with the human Cox-2 promoter [pS(COX2)] and with a promoter containing repeated copies of the TCF binding element (TBE) [pS(TBE)]. These promoters were choosen because they are partculary activated in colon cancer cells. COX-2 was effectively silenced in HT-29 and HCA-7 colon cancer cells by using enhanced pS(COX2) and pS(TBE) vectors. In particular, an higher siCOX-2 production followed by a stronger inhibition of Cox-2 gene were achieved by using pS(TBE) vector, that represents not only the most effective, but also the most specific system to downregulate COX-2 in colon cancer cells. Because of the many limits that a retroviral therapy could have in a possible in vivo treatment of CRC, the next goal was to render the enhanced RNAi-mediate COX-2 silencing more suitable for this kind of application. Xiang and et al. (2006) demonstrated that it is possible to induce RNAi in mammalian cells after infection with engineered E. Coli strains expressing Inv and HlyA genes, which encode for two bacterial factors needed for successful transfer of shRNA in mammalian cells. This system, called “trans-kingdom” RNAi (tkRNAi) could represent an optimal approach for the treatment of colorectal cancer, since E. Coli in normally resident in human intestinal flora and could easily vehicled to the tumor tissue. For this reason, I tested the improved COX-2 silencing mediated by pS(COX2) and pS(TBE) vectors by using tkRNAi system. Results obtained in HT-29 and HCA-7 cell lines were in high agreement with data previously collected after the transfection of pS(COX2) and pS(TBE) vectors in the same cell lines. These findings suggest that tkRNAi system for COX-2 silencing, in particular mediated by pS(TBE) vector, could represent a promising tool for the treatment of colorectal cancer. Flanking the studies addressed to the setting-up of a RNAi-mediated therapeutical strategy, I proposed to get ahead with the comprehension of new molecular basis of human colorectal cancer. In particular, it is known that components of the miRNA/RNAi pathway may be altered during the progressive development of colorectal cancer (CRC), and it has been already demonstrated that some miRNAs work as tumor suppressors or oncomiRs in colon cancer. Thus, my hypothesis was that overexpressed COX-2 protein in colon cancer could be the result of decreased levels of one or more tumor suppressor miRNAs. In this thesis, I clearly show an inverse correlation between COX-2 expression and the human miR- 101(1) levels in colon cancer cell lines, tissues and metastases. I also demonstrate that the in vitro modulating of miR-101(1) expression in colon cancer cell lines leads to significant variations in COX-2 expression, and this phenomenon is based on a direct interaction between miR-101(1) and COX-2 mRNA. Moreover, I started to investigate miR-101(1) regulation in the hypoxic environment since adaptation to hypoxia is critical for tumor cell growth and survival and it is known that COX-2 can be induced directly by hypoxia-inducible factor 1 (HIF-1). Surprisingly, I observed that COX-2 overexpression induced by hypoxia is always coupled to a significant decrease of miR-101(1) levels in colon cancer cell lines, suggesting that miR-101(1) regulation could be involved in the adaption of cancer cells to the hypoxic environment that strongly characterize CRC tissues.

Cooperation and competition in the air transport market: current scenario, possible evolutions and analytical tools

dall'avvento della liberalizzazione, aeroporti e vettori hanno vissuto cambiamenti. Il maggior miglioramneto nella gestione degli aeroporti è una gestione più commerciale ed efficiente. Le forme di regolazione economica e le caratteristiche della gestione manageriale sono state indagate. Dodici paesi sono stati scelti per indagare la situazione del trasporto aereo mondiale, fra questi sia paesi con un sistema maturo sia paesi emergenti. La distribuzione del traffico è stata analizzata con l'indice HHI per evidenziare aeroporti con concentrazione maggiore di 0,25 (in accordo con la normativa statunitense); il sistema aeroportuale è stato analizzato con l'indice di Gini e con l'indice di dominanza. Infine, la teoria dei giochi si è dimostrata un valido supporto per studiare il mercato del trasporto aereo anche con l'uso di giochi di tipo DP

Evaluating non-price effects of regulatory and competition enforcement interventions

This thesis provides an ex-post evaluation of the effects of regulatory and competition policy enforcement interventions on non-price dimensions of competition. Chapter 1 examines the effects of a merger between two large Dutch supermarket chains on the variety and composition of product assortment. Chapter 2 and Chapter 3 investigate, both theoretically and empirically, the effects of access regulation in fixed telecoms markets on incentives to invest in superior infrastructure technologies. Non-price effects, together with price effects, are crucial to shed light on the extent of competition in a market and assess the effectiveness of regulatory and competition authorities' interventions. When evaluating non-price effects, however, it is harder to draw conclusions on the overall impact on consumers' welfare.

The APSEL4D Monolithic Active Pixel Sensor and its Usage in a Single Electron Interference Experiment

We have realized a Data Acquisition chain for the use and characterization of APSEL4D, a 32 x 128 Monolithic Active Pixel Sensor, developed as a prototype for frontier experiments in high energy particle physics. In particular a transition board was realized for the conversion between the chip and the FPGA voltage levels and for the signal quality enhancing. A Xilinx Spartan-3 FPGA was used for real time data processing, for the chip control and the communication with a Personal Computer through a 2.0 USB port. For this purpose a firmware code, developed in VHDL language, was written. Finally a Graphical User Interface for the online system monitoring, hit display and chip control, based on windows and widgets, was realized developing a C++ code and using Qt and Qwt dedicated libraries. APSEL4D and the full acquisition chain were characterized for the first time with the electron beam of the transmission electron microscope and with 55Fe and 90Sr radioactive sources. In addition, a beam test was performed at the T9 station of the CERN PS, where hadrons of momentum of 12 GeV/c are available. The very high time resolution of APSEL4D (up to 2.5 Mfps, but used at 6 kfps) was fundamental in realizing a single electron Young experiment using nanometric double slits obtained by a FIB technique. On high statistical samples, it was possible to observe the interference and diffractions of single isolated electrons traveling inside a transmission electron microscope. For the first time, the information on the distribution of the arrival time of the single electrons has been extracted.

The abuse of intellectual property rights and regulations in China: a law and economic analysis

From the institutional point of view, the legal system of IPR (intellectual property right, hereafter, IPR) is one of incentive institutions of innovation and it plays very important role in the development of economy. According to the law, the owner of the IPR enjoy a kind of exclusive right to use his IP(intellectual property, hereafter, IP), in other words, he enjoys a kind of legal monopoly position in the market. How to well protect the IPR and at the same time to regulate the abuse of IPR is very interested topic in this knowledge-orientated market and it is the basic research question in this dissertation. In this paper, by way of comparing study and by way of law and economic analyses, and based on the Austrian Economics School’s theories, the writer claims that there is no any contradiction between the IPR and competition law. However, in this new economy (high-technology industries), there is really probability of the owner of IPR to abuse his dominant position. And with the characteristics of the new economy, such as, the high rates of innovation, “instant scalability”, network externality and lock-in effects, the IPR “will vest the dominant undertakings with the power not just to monopolize the market but to shift such power from one market to another, to create strong barriers to enter and, in so doing, granting the perpetuation of such dominance for quite a long time.”1 Therefore, in order to keep the order of market, to vitalize the competition and innovation, and to benefit the customer, in EU and US, it is common ways to apply the competition law to regulate the IPR abuse. In Austrian Economic School perspective, especially the Schumpeterian theories, the innovation/competition/monopoly and entrepreneurship are inter-correlated, therefore, we should apply the dynamic antitrust model based on the AES theories to analysis the relationship between the IPR and competition law. China is still a developing country with relative not so high ability of innovation. Therefore, at present, to protect the IPR and to make good use of the incentive mechanism of IPR legal system is the first important task for Chinese government to do. However, according to the investigation reports,2 based on their IPR advantage and capital advantage, some multinational companies really obtained the dominant or monopoly market position in some aspects of some industries, and there are some IPR abuses conducted by such multinational companies. And then, the Chinese government should be paying close attention to regulate any IPR abuse. However, how to effectively regulate the IPR abuse by way of competition law in Chinese situation, from the law and economic theories’ perspective, from the legislation perspective, and from the judicial practice perspective, there is a long way for China to go!

Max Bill in Italia . Lo spazio logico dell'architettura

I Max Bill is an intense giornata of a big fresco. An analysis of the main social, artistic and cultural events throughout the twentieth century is needed in order to trace his career through his masterpieces and architectures. Some of the faces of this hypothetical mural painting are, among others, Le Corbusier, Walter Gropius, Ernesto Nathan Rogers, Kandinskij, Klee, Mondrian, Vatongerloo, Ignazio Silone, while the backcloth is given by artistic avant-gardes, Bauhaus, International Exhibitions, CIAM, war events, reconstruction, Milan Triennali, Venice Biennali, the School of Ulm. Architect, even though more known as painter, sculptor, designer and graphic artist, Max Bill attends the Bauhaus as a student in the years 1927-1929, and from this experience derives the main features of a rational, objective, constructive and non figurative art. His research is devoted to give his art a scientific methodology: each work proceeds from the analysis of a problem to the logical and always verifiable solution of the same problem. By means of composition elements (such as rhythm, seriality, theme and its variation, harmony and dissonance), he faces, with consistent results, themes apparently very distant from each other as the project for the H.f.G. or the design for a font. Mathematics are a constant reference frame as field of certainties, order, objectivity: ‘for Bill mathematics are never confined to a simple function: they represent a climate of spiritual certainties, and also the theme of non attempted in its purest state, objectivity of the sign and of the geometrical place, and at the same time restlessness of the infinity: Limited and Unlimited ’. In almost sixty years of activity, experiencing all artistic fields, Max Bill works, projects, designs, holds conferences and exhibitions in Europe, Asia and Americas, confronting himself with the most influencing personalities of the twentieth century. In such a vast scenery, the need to limit the investigation field combined with the necessity to address and analyse the unpublished and original aspect of Bill’s relations with Italy. The original contribution of the present research regards this particular ‘geographic delimitation’; in particular, beyond the deep cultural exchanges between Bill and a series of Milanese architects, most of all with Rogers, two main projects have been addressed: the realtà nuova at Milan Triennale in 1947, and the Contemporary Art Museum in Florence in 1980. It is important to note that these projects have not been previously investigated, and the former never appears in the sources either. These works, together with the most well-known ones, such as the projects for the VI and IX Triennale, and the Swiss pavilion for the Biennale, add important details to the reference frame of the relations which took place between Zurich and Milan. Most of the occasions for exchanges took part in between the Thirties and the Fifties, years during which Bill underwent a significant period of artistic growth. He meets the Swiss progressive architects and the Paris artists from the Abstraction-Création movement, enters the CIAM, collaborates with Le Corbusier to the third volume of his Complete Works, and in Milan he works and gets confronted with the events related to post-war reconstruction. In these years Bill defines his own working methodology, attaining an artistic maturity in his work. The present research investigates the mentioned time period, despite some necessary exceptions. II The official Max Bill bibliography is naturally wide, including spreading works along with ones more devoted to analytical investigation, mainly written in German and often translated into French and English (Max Bill himself published his works in three languages). Few works have been published in Italian and, excluding the catalogue of the Parma exhibition from 1977, they cannot be considered comprehensive. Many publications are exhibition catalogues, some of which include essays written by Max Bill himself, some others bring Bill’s comments in a educational-pedagogical approach, to accompany the observer towards a full understanding of the composition processes of his art works. Bill also left a great amount of theoretical speculations to encourage a critical reading of his works in the form of books edited or written by him, and essays published in ‘Werk’, magazine of the Swiss Werkbund, and other international reviews, among which Domus and Casabella. These three reviews have been important tools of analysis, since they include tracks of some of Max Bill’s architectural works. The architectural aspect is less investigated than the plastic and pictorial ones in all the main reference manuals on the subject: Benevolo, Tafuri and Dal Co, Frampton, Allenspach consider Max Bill as an artist proceeding in his work from Bauhaus in the Ulm experience . A first filing of his works was published in 2004 in the monographic issue of the Spanish magazine 2G, together with critical essays by Karin Gimmi, Stanislaus von Moos, Arthur Rüegg and Hans Frei, and in ‘Konkrete Architektur?’, again by Hans Frei. Moreover, the monographic essay on the Atelier Haus building by Arthur Rüegg from 1997, and the DPA 17 issue of the Catalonia Polytechnic with contributions of Carlos Martì, Bruno Reichlin and Ton Salvadò, the latter publication concentrating on a few Bill’s themes and architectures. An urge to studying and going in depth in Max Bill’s works was marked in 2008 by the centenary of his birth and by a recent rediscovery of Bill as initiator of the ‘minimalist’ tradition in Swiss architecture. Bill’s heirs are both very active in promoting exhibitions, researching and publishing. Jakob Bill, Max Bill’s son and painter himself, recently published a work on Bill’s experience in Bauhaus, and earlier on he had published an in-depth study on ‘Endless Ribbons’ sculptures. Angela Thomas Schmid, Bill’s wife and art historian, published in end 2008 the first volume of a biography on Max Bill and, together with the film maker Eric Schmid, produced a documentary film which was also presented at the last Locarno Film Festival. Both biography and documentary concentrate on Max Bill’s political involvement, from antifascism and 1968 protest movements to Bill experiences as Zurich Municipality councilman and member of the Swiss Confederation Parliament. In the present research, the bibliography includes also direct sources, such as interviews and original materials in the form of letters correspondence and graphic works together with related essays, kept in the max+binia+jakob bill stiftung archive in Zurich. III The results of the present research are organized into four main chapters, each of them subdivided into four parts. The first chapter concentrates on the research field, reasons, tools and methodologies employed, whereas the second one consists of a short biographical note organized by topics, introducing the subject of the research. The third chapter, which includes unpublished events, traces the historical and cultural frame with particular reference to the relations between Max Bill and the Italian scene, especially Milan and the architects Rogers and Baldessari around the Fifties, searching the themes and the keys for interpretation of Bill’s architectures and investigating the critical debate on the reviews and the plastic survey through sculpture. The fourth and last chapter examines four main architectures chosen on a geographical basis, all devoted to exhibition spaces, investigating Max Bill’s composition process related to the pictorial field. Paintings has surely been easier and faster to investigate and verify than the building field. A doctoral thesis discussed in Lausanne in 1977 investigating Max Bill’s plastic and pictorial works, provided a series of devices which were corrected and adapted for the definition of the interpretation grid for the composition structures of Bill’s main architectures. Four different tools are employed in the investigation of each work: a context analysis related to chapter three results; a specific theoretical essay by Max Bill briefly explaining his main theses, even though not directly linked to the very same work of art considered; the interpretation grid for the composition themes derived from a related pictorial work; the architecture drawing and digital three-dimensional model. The double analysis of the architectural and pictorial fields is functional to underlining the relation among the different elements of the composition process; the two fields, however, cannot be compared and they stay, in Max Bill’s works as in the present research, interdependent though self-sufficient. IV An important aspect of Max Bill production is self-referentiality: talking of Max Bill, also through Max Bill, as a need for coherence instead of a method limitation. Ernesto Nathan Rogers describes Bill as the last humanist, and his horizon is the known world but, as the ‘Concrete Art’ of which he is one of the main representatives, his production justifies itself: Max Bill not only found a method, but he autonomously re-wrote the ‘rules of the game’, derived timeless theoretical principles and verified them through a rich and interdisciplinary artistic production. The most recurrent words in the present research work are synthesis, unity, space and logic. These terms are part of Max Bill’s vocabulary and can be referred to his works. Similarly, graphic settings or analytical schemes in this research text referring to or commenting Bill’s architectural projects were drawn up keeping in mind the concise precision of his architectural design. As for Mies van der Rohe, it has been written that Max Bill took art to ‘zero degree’ reaching in this way a high complexity. His works are a synthesis of art: they conceptually encompass all previous and –considered their developments- most of contemporary pictures. Contents and message are generally explicitly declared in the title or in Bill’s essays on his artistic works and architectural projects: the beneficiary is invited to go through and re-build the process of synthesis generating the shape. In the course of the interview with the Milan artist Getulio Alviani, he tells how he would not write more than a page for an essay on Josef Albers: everything was already evident ‘on the surface’ and any additional sentence would be redundant. Two years after that interview, these pages attempt to decompose and single out the elements and processes connected with some of Max Bill’s works which, for their own origin, already contain all possible explanations and interpretations. The formal reduction in favour of contents maximization is, perhaps, Max Bill’s main lesson.

Adaptive wireless multimedia communication systems

In recent years, due to the rapid convergence of multimedia services, Internet and wireless communications, there has been a growing trend of heterogeneity (in terms of channel bandwidths, mobility levels of terminals, end-user quality-of-service (QoS) requirements) for emerging integrated wired/wireless networks. Moreover, in nowadays systems, a multitude of users coexists within the same network, each of them with his own QoS requirement and bandwidth availability. In this framework, embedded source coding allowing partial decoding at various resolution is an appealing technique for multimedia transmissions. This dissertation includes my PhD research, mainly devoted to the study of embedded multimedia bitstreams in heterogenous networks, developed at the University of Bologna, advised by Prof. O. Andrisano and Prof. A. Conti, and at the University of California, San Diego (UCSD), where I spent eighteen months as a visiting scholar, advised by Prof. L. B. Milstein and Prof. P. C. Cosman. In order to improve the multimedia transmission quality over wireless channels, joint source and channel coding optimization is investigated in a 2D time-frequency resource block for an OFDM system. We show that knowing the order of diversity in time and/or frequency domain can assist image (video) coding in selecting optimal channel code rates (source and channel code rates). Then, adaptive modulation techniques, aimed at maximizing the spectral efficiency, are investigated as another possible solution for improving multimedia transmissions. For both slow and fast adaptive modulations, the effects of imperfect channel estimation errors are evaluated, showing that the fast technique, optimal in ideal systems, might be outperformed by the slow adaptive modulation, when a real test case is considered. Finally, the effects of co-channel interference and approximated bit error probability (BEP) are evaluated in adaptive modulation techniques, providing new decision regions concepts, and showing how the widely used BEP approximations lead to a substantial loss in the overall performance.

Modellizzazione bioeconomica per la gestione dei piccoli pelagici nel Mar Adriatico

Stocks’ overexploitation and socio-economic sustainability are two major issues currently at stake in European fisheries. In this view the European Commission is considering the implementation of management plans as a means to move towards a longer-term perspective on fisheries management, to consider regional differences and to increase stakeholder involvement. Adriatic small pelagic species (anchovies and sardines) are some of the most studied species in the world from a biologic perspective; several economic analysis have also been realised on Italian pelagic fishery; despite that, no complete bioeconomic modelization has been carried out yet considering all biologic, technical and economic issues. Bioeconomic models cannot be considered foolproof tools but are important implements to help decision makers and can supply a fundamental scientific basis for management plans. This research gathers all available information (from biologic, technologic and economic perspectives) in order to carry out a bioeconomic model of the Adriatic pelagic fishery. Different approaches are analyzed and some of them developed to highlight potential divergences in results, characteristics and implications. Growth, production and demand functions are estimated. A formal analysis about interaction and competition between Italian and Croatian fleet is examined proposing different equilibriums for open access, duopoly and a form of cooperative solution. Anyway normative judgments are limited because of poor knowledge of population dynamics and data related to the Croatian fleet.

Committed to reform? Pragmatic antitrust enforcement in electricity markets

This thesis is a collection of essays about the instrumental use of commitment decisions to facilitate the completion of the European internal electricity market. European policy can shape markets in many ways, two most evident being regulation and competition enforcement. The interplay between these two instruments attracts a lot of scholarly attention. One of the major concerns in the competition vs. regulation debate is the instrumental use of competition rules. It has been observed that competition enforcement is triggered not only as a response to an anticompetitive harm occurring in the market, but that it sometimes becomes a powerful tool in the European Commission’s hands to pursue regulatory goals. This thesis looks for examples of such instrumentalisation in the context of electricity markets and finds that the Commission is very pragmatic in using all the possible instruments it has at hand to push forward its project of creating the internal electricity market. This includes regulation, competition enforcement and all sorts of political pressure. To the extent that commitment decisions accelerate sector-specific regulation and overcome political deadlocks, they contribute to the Commission’s energy policy goals. However, instrumentalisation of competition rules comes at a certain cost to competition policy, energy policy and, most importantly, to electricity markets themselves. Markets might be negatively affected either indirectly, by application of sector-specific regulation or competition policy building on previous commitment decisions, or directly, through the implementation of inadequate commitments in individual cases. Concluding, commitment decisions generally contributed to achieving the policy objectives of the internal electricity market, but their use for that purpose does not come without cost. Given that this cost is ultimately borne by the internal electricity market, the Commission should take a more balanced approach to the instrumental use of commitment decisions so that it does not do more harm than good.

Servizi offerti su spazi demaniali in concessione e diritto dell'Unione Europea

La tesi analizza, sotto vari aspetti del diritto dell’Unione Europea, i servizi che sono offerti su spazi demaniali. Si articola in quattro capitoli: Il primo capitolo ricostruisce, valutandone l’impatto sui servizi che sono oggetto della presente indagine, lo sviluppo giurisprudenziale della Libertà di Stabilimento e della Libera Prestazione di Servizi, analizzando, altresì, i principi generali e l’art.16 della Carta dei Diritti Fondamentali dell’Unione. Il secondo capitolo è, invece, dedicato al diritto secondario, ossia alla Direttiva 2006/123/CE, alle Direttive “Appalti” e alla Direttiva “Concessioni”. La prima, che nulla aggiunge al quadro normativo trattato nel primo capitolo, svolge, pertanto una vera e propria funzione appaltante e concessoria. Le seconde, invece, seppur non applicabili alle fattispecie ivi esaminate, restano utili per comprendere quale declinazione possano avere i principi di eguaglianza, di non discriminazione, di trasparenza, di pubblicità e di concorrenza nella regolazione dei servizi offerti su spazi demaniali. La terza, invece, in quanto a rilevanza, presenta alcuni punti critici che fanno propendere per una sua non applicabilità. Resta comunque utile sempre in materia di principi, i quali, come evidenziato nell’ultima parte del secondo capitolo, sono stati utilizzati dalla Corte di Giustizia, pur nella totale assenza, fino alla recente direttiva, di strumenti di diritto secondario applicabili alle concessioni. Il terzo capitolo, invece, affronta le problematiche emerse all’interno dell’ordinamento italiano e attua una comparazione tra il sistema italiano e quello portoghese, croato, francese, spagnolo. Il quarto capitolo, da ultimo, prende in considerazione il delicato equilibrio, sempre più attuale, tra principi in materia di appalti pubblici e aiuti di Stato, valutando come, sia il permanere dello status quo, sia un riordino non conforme alla Direttiva 2006/123/CE e ai principi da essa richiamati possa costituire un aiuto di Stato incompatibile con il mercato interno.

Le partecipazioni azionarie degli enti locali tra dismissione ed esigenze di governo dei servizi pubblici

La ricerca indaga le relazioni che si sono instaurate nel corso degli anni tra il principio di legalità, inteso nella sua declinazione di principio di funzionalizzazione, e principio di concorrenza nell’ambito delle società per la gestione dei servizi pubblici locali. Più precisamente, lo scopo del lavoro è valutare le evoluzioni di tale rapporto, dal momento in cui gli enti locali sono stati ufficialmente autorizzati a costituire società per la gestione dei servizi pubblici locali nel 1990. Lo stimolo a sviluppare queste considerazioni trova la sua ragione nelle pressioni provenienti dalle istituzioni europee, che hanno gradualmente imposto una qualificazione prettamente economica ai servizi a favore della collettività, ritenuti un ambito in cui possa naturalmente imporsi una competizione economica tra operatori economici, indipendentemente dalla loro natura giuridica. Il problema del vincolo funzionale nella partecipazione in società degli enti locali è certamente l’oggetto principale del lavoro. Tuttavia, la questione non può essere analizzata separatamente dalle politiche di dismissione promosse dal legislatore nell’ultimo decennio. L’obiettivo principale delle riforme avviate è stato quello di frenare la proliferazione di società costituite dagli enti locali, così da garantire sia un risparmio di risorse pubbliche sia una maggiore facilità per gli imprenditori privati ad affacciarsi su mercati tradizionalmente appannaggio delle amministrazioni. Stona però con le intenzioni il fatto che gli obblighi ex lege di cessione delle partecipazioni azionarie detenute dagli enti locali non siano stati generalmente imposti per le società di gestione dei servizi pubblici (resi in favore della collettività), bensì per quelle che svolgono servizi strumentali (in favore dell’amministrazione stessa). La scelta appare contraddittoria, in quanto il distacco tra vincolo funzionale e partecipazione degli enti locali nella compagine societaria si ravvisa in particolar modo nel primo dei due moduli menzionati. Si assiste dunque ad una frammentazione del principio di legalità.

Consecuencias negociales de las prácticas desleales contra los consumidores: relaciones entre el Derecho de contratos y el Derecho de la competencia desleal

En los últimos tiempos hemos asistido a diversas situaciones en las que la contratación de productos y servicios por los consumidores se encuentra fuertemente influenciada por distintas actuaciones empresariales que pueden calificarse como prácticas desleales por engañosas o agresivas. Esta realidad pone de manifiesto la intensa interrelación que existe entre contrato y mercado, y consecuentemente la necesidad de articular puentes de conexión entre el Derecho contratos y de la competencia desleal. Este trabajo aborda las conexiones entre estos sectores normativos con el fin de analizar las posibles soluciones a los problemas derivados de la contratación de consumo afectada por prácticas desleales. Tras una breve introducción donde se da debida cuenta del propósito y justificación de la investigación, el trabajo inicia con la exposición de la tradicional situación de desconexión entre las disciplinas contractual y concurrencial. Posteriormente, se analizan las conexiones intersectoriales en los planos axiológico y funcional, así como los distintos materiales normativos de los que se infieren esas aun incipientes conexiones. Sobre la base de lo anterior, se examinan las medidas correctoras individuales que el Derecho de la competencia desleal pone a disposición de los consumidores para hacer frente a las prácticas desleales, las propuestas de lege ferenda proporcionadas por la doctrina patria para remover los efectos contractuales de estas prácticas, así como las diversas soluciones ofrecidas por distintos Estados miembros de la UE. A continuación, se analizan los nuevos materiales normativos provenientes de la UE que ahondan en el proceso de permeabilización entre el Derecho de contratos y de la competencia desleal, así como las iniciativas legislativas tendentes a su incorporación a nuestro ordenamiento. El trabajo concluye con un conjunto de conclusiones reasuntivas entresacadas del estudio realizado, que se clausuran con la propuesta de algunas directrices para lo que entendemos sería una correcta incorporación de la normativa comunitaria.