The firm. Techno-organizational changes, industrial relations and performances. An enquiry on Reggio Emilia local industrial system

It is not unknown that the evolution of firm theories has been developed along a path paved by an increasing awareness of the organizational structure importance. From the early “neoclassical” conceptualizations that intended the firm as a rational actor whose aim is to produce that amount of output, given the inputs at its disposal and in accordance to technological or environmental constraints, which maximizes the revenue (see Boulding, 1942 for a past mid century state of the art discussion) to the knowledge based theory of the firm (Nonaka & Takeuchi, 1995; Nonaka & Toyama, 2005), which recognizes in the firm a knnowledge creating entity, with specific organizational capabilities (Teece, 1996; Teece & Pisano, 1998) that allow to sustaine competitive advantages. Tracing back a map of the theory of the firm evolution, taking into account the several perspectives adopted in the history of thought, would take the length of many books. Because of that a more fruitful strategy is circumscribing the focus of the description of the literature evolution to one flow connected to a crucial question about the nature of firm’s behaviour and about the determinants of competitive advantages. In so doing I adopt a perspective that allows me to consider the organizational structure of the firm as an element according to which the different theories can be discriminated. The approach adopted starts by considering the drawbacks of the standard neoclassical theory of the firm. Discussing the most influential theoretical approaches I end up with a close examination of the knowledge based perspective of the firm. Within this perspective the firm is considered as a knowledge creating entity that produce and mange knowledge (Nonaka, Toyama, & Nagata, 2000; Nonaka & Toyama, 2005). In a knowledge intensive organization, knowledge is clearly embedded for the most part in the human capital of the individuals that compose such an organization. In a knowledge based organization, the management, in order to cope with knowledge intensive productions, ought to develop and accumulate capabilities that shape the organizational forms in a way that relies on “cross-functional processes, extensive delayering and empowerment” (Foss 2005, p.12). This mechanism contributes to determine the absorptive capacity of the firm towards specific technologies and, in so doing, it also shape the technological trajectories along which the firm moves. After having recognized the growing importance of the firm’s organizational structure in the theoretical literature concerning the firm theory, the subsequent point of the analysis is that of providing an overview of the changes that have been occurred at micro level to the firm’s organization of production. The economic actors have to deal with challenges posed by processes of internationalisation and globalization, increased and increasing competitive pressure of less developed countries on low value added production activities, changes in technologies and increased environmental turbulence and volatility. As a consequence, it has been widely recognized that the main organizational models of production that fitted well in the 20th century are now partially inadequate and processes aiming to reorganize production activities have been widespread across several economies in recent years. Recently, the emergence of a “new” form of production organization has been proposed both by scholars, practitioners and institutions: the most prominent characteristic of such a model is its recognition of the importance of employees commitment and involvement. As a consequence it is characterized by a strong accent on the human resource management and on those practices that aim to widen the autonomy and responsibility of the workers as well as increasing their commitment to the organization (Osterman, 1994; 2000; Lynch, 2007). This “model” of production organization is by many defined as High Performance Work System (HPWS). Despite the increasing diffusion of workplace practices that may be inscribed within the concept of HPWS in western countries’ companies, it is an hazard, to some extent, to speak about the emergence of a “new organizational paradigm”. The discussion about organizational changes and the diffusion of HPWP the focus cannot abstract from a discussion about the industrial relations systems, with a particular accent on the employment relationships, because of their relevance, in the same way as production organization, in determining two major outcomes of the firm: innovation and economic performances. The argument is treated starting from the issue of the Social Dialogue at macro level, both in an European perspective and Italian perspective. The model of interaction between the social parties has repercussions, at micro level, on the employment relationships, that is to say on the relations between union delegates and management or workers and management. Finding economic and social policies capable of sustaining growth and employment within a knowledge based scenario is likely to constitute the major challenge for the next generation of social pacts, which are the main social dialogue outcomes. As Acocella and Leoni (2007) put forward the social pacts may constitute an instrument to trade wage moderation for high intensity in ICT, organizational and human capital investments. Empirical evidence, especially focused on the micro level, about the positive relation between economic growth and new organizational designs coupled with ICT adoption and non adversarial industrial relations is growing. Partnership among social parties may become an instrument to enhance firm competitiveness. The outcome of the discussion is the integration of organizational changes and industrial relations elements within a unified framework: the HPWS. Such a choice may help in disentangling the potential existence of complementarities between these two aspects of the firm internal structure on economic and innovative performance. With the third chapter starts the more original part of the thesis. The data utilized in order to disentangle the relations between HPWS practices, innovation and economic performance refer to the manufacturing firms of the Reggio Emilia province with more than 50 employees. The data have been collected through face to face interviews both to management (199 respondents) and to union representatives (181 respondents). Coupled with the cross section datasets a further data source is constituted by longitudinal balance sheets (1994-2004). Collecting reliable data that in turn provide reliable results needs always a great effort to which are connected uncertain results. Data at micro level are often subjected to a trade off: the wider is the geographical context to which the population surveyed belong the lesser is the amount of information usually collected (low level of resolution); the narrower is the focus on specific geographical context, the higher is the amount of information usually collected (high level of resolution). For the Italian case the evidence about the diffusion of HPWP and their effects on firm performances is still scanty and usually limited to local level studies (Cristini, et al., 2003). The thesis is also devoted to the deepening of an argument of particular interest: the existence of complementarities between the HPWS practices. It has been widely shown by empirical evidence that when HPWP are adopted in bundles they are more likely to impact on firm’s performances than when adopted in isolation (Ichniowski, Prennushi, Shaw, 1997). Is it true also for the local production system of Reggio Emilia? The empirical analysis has the precise aim of providing evidence on the relations between the HPWS dimensions and the innovative and economic performances of the firm. As far as the first line of analysis is concerned it must to be stressed the fundamental role that innovation plays in the economy (Geroski & Machin, 1993; Stoneman & Kwoon 1994, 1996; OECD, 2005; EC, 2002). On this point the evidence goes from the traditional innovations, usually approximated by R&D investment expenditure or number of patents, to the introduction and adoption of ICT, in the recent years (Brynjolfsson & Hitt, 2000). If innovation is important then it is critical to analyse its determinants. In this work it is hypothesised that organizational changes and firm level industrial relations/employment relations aspects that can be put under the heading of HPWS, influence the propensity to innovate in product, process and quality of the firm. The general argument may goes as follow: changes in production management and work organization reconfigure the absorptive capacity of the firm towards specific technologies and, in so doing, they shape the technological trajectories along which the firm moves; cooperative industrial relations may lead to smother adoption of innovations, because not contrasted by unions. From the first empirical chapter emerges that the different types of innovations seem to respond in different ways to the HPWS variables. The underlying processes of product, process and quality innovations are likely to answer to different firm’s strategies and needs. Nevertheless, it is possible to extract some general results in terms of the most influencing HPWS factors on innovative performance. The main three aspects are training coverage, employees involvement and the diffusion of bonuses. These variables show persistent and significant relations with all the three innovation types. The same do the components having such variables at their inside. In sum the aspects of the HPWS influence the propensity to innovate of the firm. At the same time, emerges a quite neat (although not always strong) evidence of complementarities presence between HPWS practices. In terns of the complementarity issue it can be said that some specific complementarities exist. Training activities, when adopted and managed in bundles, are related to the propensity to innovate. Having a sound skill base may be an element that enhances the firm’s capacity to innovate. It may enhance both the capacity to absorbe exogenous innovation and the capacity to endogenously develop innovations. The presence and diffusion of bonuses and the employees involvement also spur innovative propensity. The former because of their incentive nature and the latter because direct workers participation may increase workers commitment to the organizationa and thus their willingness to support and suggest inovations. The other line of analysis provides results on the relation between HPWS and economic performances of the firm. There have been a bulk of international empirical studies on the relation between organizational changes and economic performance (Black & Lynch 2001; Zwick 2004; Janod & Saint-Martin 2004; Huselid 1995; Huselid & Becker 1996; Cappelli & Neumark 2001), while the works aiming to capture the relations between economic performance and unions or industrial relations aspects are quite scant (Addison & Belfield, 2001; Pencavel, 2003; Machin & Stewart, 1990; Addison, 2005). In the empirical analysis the integration of the two main areas of the HPWS represent a scarcely exploited approach in the panorama of both national and international empirical studies. As remarked by Addison “although most analysis of workers representation and employee involvement/high performance work practices have been conducted in isolation – while sometimes including the other as controls – research is beginning to consider their interactions” (Addison, 2005, p.407). The analysis conducted exploiting temporal lags between dependent and covariates, possibility given by the merger of cross section and panel data, provides evidence in favour of the existence of HPWS practices impact on firm’s economic performance, differently measured. Although it does not seem to emerge robust evidence on the existence of complementarities among HPWS aspects on performances there is evidence of a general positive influence of the single practices. The results are quite sensible to the time lags, inducing to hypothesize that time varying heterogeneity is an important factor in determining the impact of organizational changes on economic performance. The implications of the analysis can be of help both to management and local level policy makers. Although the results are not simply extendible to other local production systems it may be argued that for contexts similar to the Reggio Emilia province, characterized by the presence of small and medium enterprises organized in districts and by a deep rooted unionism, with strong supporting institutions, the results and the implications here obtained can also fit well. However, a hope for future researches on the subject treated in the present work is that of collecting good quality information over wider geographical areas, possibly at national level, and repeated in time. Only in this way it is possible to solve the Gordian knot about the linkages between innovation, performance, high performance work practices and industrial relations.

Development of Clinical Decision Support Systems based on Mathematical Models of Physiological Systems

In the last years of research, I focused my studies on different physiological problems. Together with my supervisors, I developed/improved different mathematical models in order to create valid tools useful for a better understanding of important clinical issues. The aim of all this work is to develop tools for learning and understanding cardiac and cerebrovascular physiology as well as pathology, generating research questions and developing clinical decision support systems useful for intensive care unit patients. I. ICP-model Designed for Medical Education We developed a comprehensive cerebral blood flow and intracranial pressure model to simulate and study the complex interactions in cerebrovascular dynamics caused by multiple simultaneous alterations, including normal and abnormal functional states of auto-regulation of the brain. Individual published equations (derived from prior animal and human studies) were implemented into a comprehensive simulation program. Included in the normal physiological modelling was: intracranial pressure, cerebral blood flow, blood pressure, and carbon dioxide (CO2) partial pressure. We also added external and pathological perturbations, such as head up position and intracranial haemorrhage. The model performed clinically realistically given inputs of published traumatized patients, and cases encountered by clinicians. The pulsatile nature of the output graphics was easy for clinicians to interpret. The manoeuvres simulated include changes of basic physiological inputs (e.g. blood pressure, central venous pressure, CO2 tension, head up position, and respiratory effects on vascular pressures) as well as pathological inputs (e.g. acute intracranial bleeding, and obstruction of cerebrospinal outflow). Based on the results, we believe the model would be useful to teach complex relationships of brain haemodynamics and study clinical research questions such as the optimal head-up position, the effects of intracranial haemorrhage on cerebral haemodynamics, as well as the best CO2 concentration to reach the optimal compromise between intracranial pressure and perfusion. We believe this model would be useful for both beginners and advanced learners. It could be used by practicing clinicians to model individual patients (entering the effects of needed clinical manipulations, and then running the model to test for optimal combinations of therapeutic manoeuvres). II. A Heterogeneous Cerebrovascular Mathematical Model Cerebrovascular pathologies are extremely complex, due to the multitude of factors acting simultaneously on cerebral haemodynamics. In this work, the mathematical model of cerebral haemodynamics and intracranial pressure dynamics, described in the point I, is extended to account for heterogeneity in cerebral blood flow. The model includes the Circle of Willis, six regional districts independently regulated by autoregulation and CO2 reactivity, distal cortical anastomoses, venous circulation, the cerebrospinal fluid circulation, and the intracranial pressure-volume relationship. Results agree with data in the literature and highlight the existence of a monotonic relationship between transient hyperemic response and the autoregulation gain. During unilateral internal carotid artery stenosis, local blood flow regulation is progressively lost in the ipsilateral territory with the presence of a steal phenomenon, while the anterior communicating artery plays the major role to redistribute the available blood flow. Conversely, distal collateral circulation plays a major role during unilateral occlusion of the middle cerebral artery. In conclusion, the model is able to reproduce several different pathological conditions characterized by heterogeneity in cerebrovascular haemodynamics and can not only explain generalized results in terms of physiological mechanisms involved, but also, by individualizing parameters, may represent a valuable tool to help with difficult clinical decisions. III. Effect of Cushing Response on Systemic Arterial Pressure. During cerebral hypoxic conditions, the sympathetic system causes an increase in arterial pressure (Cushing response), creating a link between the cerebral and the systemic circulation. This work investigates the complex relationships among cerebrovascular dynamics, intracranial pressure, Cushing response, and short-term systemic regulation, during plateau waves, by means of an original mathematical model. The model incorporates the pulsating heart, the pulmonary circulation and the systemic circulation, with an accurate description of the cerebral circulation and the intracranial pressure dynamics (same model as in the first paragraph). Various regulatory mechanisms are included: cerebral autoregulation, local blood flow control by oxygen (O2) and/or CO2 changes, sympathetic and vagal regulation of cardiovascular parameters by several reflex mechanisms (chemoreceptors, lung-stretch receptors, baroreceptors). The Cushing response has been described assuming a dramatic increase in sympathetic activity to vessels during a fall in brain O2 delivery. With this assumption, the model is able to simulate the cardiovascular effects experimentally observed when intracranial pressure is artificially elevated and maintained at constant level (arterial pressure increase and bradicardia). According to the model, these effects arise from the interaction between the Cushing response and the baroreflex response (secondary to arterial pressure increase). Then, patients with severe head injury have been simulated by reducing intracranial compliance and cerebrospinal fluid reabsorption. With these changes, oscillations with plateau waves developed. In these conditions, model results indicate that the Cushing response may have both positive effects, reducing the duration of the plateau phase via an increase in cerebral perfusion pressure, and negative effects, increasing the intracranial pressure plateau level, with a risk of greater compression of the cerebral vessels. This model may be of value to assist clinicians in finding the balance between clinical benefits of the Cushing response and its shortcomings. IV. Comprehensive Cardiopulmonary Simulation Model for the Analysis of Hypercapnic Respiratory Failure We developed a new comprehensive cardiopulmonary model that takes into account the mutual interactions between the cardiovascular and the respiratory systems along with their short-term regulatory mechanisms. The model includes the heart, systemic and pulmonary circulations, lung mechanics, gas exchange and transport equations, and cardio-ventilatory control. Results show good agreement with published patient data in case of normoxic and hyperoxic hypercapnia simulations. In particular, simulations predict a moderate increase in mean systemic arterial pressure and heart rate, with almost no change in cardiac output, paralleled by a relevant increase in minute ventilation, tidal volume and respiratory rate. The model can represent a valid tool for clinical practice and medical research, providing an alternative way to experience-based clinical decisions. In conclusion, models are not only capable of summarizing current knowledge, but also identifying missing knowledge. In the former case they can serve as training aids for teaching the operation of complex systems, especially if the model can be used to demonstrate the outcome of experiments. In the latter case they generate experiments to be performed to gather the missing data.

La sostenibilità organizzativa dei progetti agricoli di cooperazione internazionale allo sviluppo

The importance of organizational issues to assess the success of international development project has not been fully considered yet. After a brief overview, in 1st chapter, on main actors involved on international cooperation, in the 2nd chapter an analysis of the literature on the project success definition, focused on the success criteria and success factors, was carried out by surveying the contribution of different authors and approaches. Traditionally projects were perceived as successful when they met time, budget and performance goals, assuming a basic similarity among projects (universalistic approach). However, starting from a non-universalistic approach, the importance of organization’s effectiveness, in terms of Relations Sustainability, emerged as a dimension able to define and assess a project success. The identification of the factors influencing the relationship between and inside the organizations becomes consequently a priority. In 3th chapter, starting from a literature survey, the different analytical approaches related to the inter and intra-organization relationships are analysed. They involve two different groups: the first includes studies focused on the type of organizations relationship structure (Supply Chains, Networks, Clusters and Industrial Districts); the second group includes approaches related to the general theories on firms relationship interpretation (Transaction Costs Economics, Resource Based View, Organization Theory). The variables and logical frameworks provided by these different theoretical contributions are compared and classified in order to find out possible connections and/or juxtapositions. Being an exhaustive collection of the literature on the subject is impossible, the main goal is to underline the existence of potentially overlapping and/or integrating approaches examining the contribution provided by different representative authors. The survey showed first of all many variables in common between approaches coming from different disciplines; furthermore the non overlapping variables can be integrated contributing to a broader picture of the variables influencing the organization relations; in particular a theoretical design for the identification of connections between the inter and the intra-organizations relations was made possible. The results obtained in 3th chapter help to defining a general theoretical framework linking the different interpretative variables. Based on extensive research contributions on the factors influencing the relations between organizations, the 4th chapter expands the analysis of the influence of variables like Human Resource Management, Organizational Climate, Psychological Contract and KSA (Knowledge, Skills, Abilities) on the relation sustainability. A detailed analysis of these relations is provided and a research hypothesis are built. According to this new framework in 5th chapter a statistical analysis was performed to qualify and quantify the influence of Organizational Climate on the Relations Sustainability. To this end the Structural Equation Modeling (SEMs) has adopted as method for the definition of the latent variables and the measure of their relations. The results obtained are satisfactory. An effective strategy to motivate the respondents to participate in the survey seems to be at the moment one of the major obstacles to the analysis implementation since the organizational performances are not specifically required by the projects’ evaluation guidelines and they represent an increase in the project related transaction costs. Their explicit introduction in the project presentation guidelines should be explored as an opportunity to increase the chances of success of these projects.

Le strategie di internazionalizzazione delle imprese distrettuali: un'analisi comparata di tre diversi sistemi locali di produzione in Emilia Romagna

Since the Nineties, the process of globalization has caused a sharp increase in the real and financial integration of the worldwide economy, reducing the obstacles to international trade and minimizing the cost of transaction. The entrance of foreign firms in the domestic market has deeply modified the competitive situation of Italian enterprises, which have been forced to change their strategies in order to cope with those of the new competitors. In this scenario, internationalization is no longer one of the different strategic options available for the firm, but it becomes a forced choice to maintain or acquire a competitive advantage sustainable over time. Internationalization strategies of SMEs, however, are hindered by the shortage of financial resources and entrepreneurial skills, therefore this kind of firms tends toward light forms of foreign expansion, like export and subcontracting. Despite this, many studies have demonstrated that the district localisation increases the firms’ productivity and innovative capacity, so their competiveness both at a domestic and international level. The majority of these empirical contributions has focused mainly on the analysis of commercial flows, confirming that district enterprises reach a superior international performance compared to their external competitors. On the contrary, only few works have tried to evaluate the existence of a district effect on the firms’ ability to invest abroad, but the obtained results are not straightforward. One of the reason of these conclusions is that the phenomena has been analysed without taking into account the differences existing between districts in terms of enterprises’ dimension, diffusion of industrial groups and, above all, the sector of productive specialization, because the technological content of production could improve the innovativeness of district firms, allowing them to adopt advanced forms of internationalisation as foreign direct investments (FDI). The aim of the thesis is to further investigate the district effect on internationalisation, trough an econometric analysis of the international strategies carried out by firms localised in three different local system of production characterised by different technological specialization.

Partnership fra terzo Settore e Istituzioni Locali nelle Politiche Family Friendly: Il "Distretto famiglia"

L’idea fondamentale da cui prende avvio la presente tesi di dottorato è che sia possibile parlare di una svolta nel modo di concettualizzare e implementare le politiche sociali, il cui fuoco diviene sempre più la costruzione di reti di partnership fra attori pubblici e privati, in cui una serie di soggetti sociali plurimi (stakeholders) attivano fra loro una riflessività relazionale. L’ipotesi generale della ricerca è che, dopo le politiche improntate a modelli statalisti e mercatisti, o un loro mix, nella politica sociale italiana emerga l’esigenza di una svolta riflessiva e relazionale, verso un modello societario, sussidiario e plurale, e che di fatto – specie a livello locale – stiano sorgendo molte iniziative in tal senso. Una delle idee più promettenti sembra essere la creazione di distretti sociali per far collaborare tra loro attori pubblici, privati e di Terzo settore al fine di creare forme innovative di servizi per la famiglia e la persona. La presente tesi si focalizza sul tentativo della Provincia di Trento di distrettualizzare le politiche per la famiglia. Tramite l’analisi del progetto “Trentino – Territorio Amico della Famiglia” e di una sua verticalizzazione, il Distretto Famiglia, si è studiato l’apporto delle partnership pubblico-privato nella formazione di strumenti innovativi di governance che possano determinare una svolta morfogenetica nell’elaborazione di politiche per la famiglia. Le conclusioni del lavoro, attraverso una comparazione tra esperienze territoriali, presentano la differenziazione delle partnership sociali, in base ad alcuni variabili (pluralità di attori, pluralità di risorse, shared project, capitale sociale, decision making, mutual action, logiche di lavoro relazionale, sussidiarietà). Le diverse modalità di gestione delle partnership (capacitante, professionale e generativa) sintetizzano i portati culturali, strutturali e personali coinvolti nelle singole costruzioni. Solo le partnership che interpretano il loro potenziale regolativo e promozionale secondo la riflessività relazionale tendono a generare beni comuni nel contesto sociale.

Modulazione del differenziamento osteogenico di precursori mesenchimali umani per applicazioni di ingegneria tissutale

Lo scheletro è un tessuto dinamico, capace di adattarsi alle richieste funzionali grazie a fenomeni di rimodellamento ed alla peculiare proprietà rigenerativa. Tali processi avvengono attraverso l’azione coordinata di osteoclasti ed osteoblasti. Queste popolazioni cellulari cooperano allo scopo di mantenere l’ equilibrio indispensabile per garantire l’omeostasi dello scheletro. La perdita di tale equilibrio può portare ad una diminuzione della massa ossea e, ad una maggiore suscettibilità alle fratture, come avviene nel caso dell’osteoporosi. E’ noto che, nella fisiopatologia dell’osso, un ruolo cruciale è svolto da fattori endocrini e paracrini. Dati recenti suggeriscono che il rimodellamento osseo potrebbe essere influenzato dal sistema nervoso. L’ipotesi è supportata dalla presenza, nelle vicinanze dell’osso, di fibre nervose sensoriali responsabili del rilascio di alcuni neuro peptidi, tra i quali ricordiamo la sostanza P. Inoltre in modelli animali è stato dimostrato il diretto coinvolgimento del sistema nervoso nel mantenimento dell’omeostasi ossea, infatti ratti sottoposti a denervazione hanno mostrato una perdita dell’equilibrio esistente tra osteoblasti ed osteoclasti. Per tali ragioni negli ultimi anni si è andata intensificando la ricerca in questo campo cercando di comprendere il ruolo dei neuropeptidi nel processo di differenziamento dei precursori mesenchimali in senso osteogenico. Le cellule stromali mesenchimali adulte sono indifferenziate multipotenti che risiedono in maniera predominante nel midollo osseo, ma che possono anche essere isolate da tessuto adiposo, cordone ombelicale e polpa dentale. In questi distretti le MSC sono in uno stato non proliferativo fino a quando non sono richieste per processi locali di riparo e rigenerazione tessutale. MSC, opportunamente stimolate, possono differenziare in diversi tipi di tessuto connettivo quali, tessuto osseo, cartilagineo ed adiposo. L’attività di ricerca è stata finalizzata all’ottimizzazione di un protocollo di espansione ex vivo ed alla valutazione dell’influenza della sostanza P, neuropeptide presente a livello delle terminazioni sensoriali nelle vicinanze dell’osso, nel processo di commissionamento osteogenico.

Human papillomavirus (HPV) and associated diseases: between applied diagnostic and basic research

Human Papillomavirus (HPV) is the cause of cervical cancers (among these, adenocarcinoma, AdCa) and is associated to a subgroup of oropharyngeal carcinomas (OPSCCs). Even if the risk for cancer development is linked to the infection by some viral genotypes, mainly HPV16 and 18, viral DNA alone seems not to be sufficient for diagnosis. Moreover, the role of the virus in OPSCCs has not been totally clarified yet. In the first part of the thesis, the performances concerning viral genotyping in clinical cervical samples of a new pyrosequencing-based test and a well-known hybridization-based assay have been compared. Similar results between the methods have been obtained. However, the former showed advantages in detecting intratype variants, higher specificity and a broader spectrum of detectable HPV types. The second part deals with the evaluation of virological markers (genotyping, viral oncoproteins expression, viral load, physical state and CpG methylation of HPV16 genome) in the diagnosis/prognosis of cervical AdCa and HPV-associated OPSCCs. HPV16 has been confirmed the most prevalent genotype in both the populations. Interestingly, the mean methylation frequency of viral DNA at the early promoter showed the tendency to be associated to invasion for cervical AdCa and to a worse prognosis for OPSCCs, suggesting a promising role as diagnostic/prognostic biomarker. The experiments of the third part were performed at the DKFZ in Heidelberg (Germany) and dealt with the analysis of the response to IFN-k transfection in HPV16-positive cervical cancer and head&neck carcinoma cell lines to evaluate its potential role as new treatment. After 24h, we observed increased IFN-b expression which lead to the up-regulation of genes involved in the antigens presentation pathway (MHC class I and immunoproteasome) and antiviral response as well, in particular in cervical cancer cell lines. This fact suggested also the presence of different HPV-mediated carcinogenic pathways between the two anatomical districts.

Caratteristiche ed efficienza economica del Distretto agroalimentare del Pecorino Romano DOP

Una delle realtà economiche più importanti della Sardegna è la produzione di Pecorino Romano DOP. Il contesto nel quale è nato e si è sviluppato ingloba molte delle precondizioni che favoriscono la nascita di un distretto. Il principale obiettivo di questo studio è verificare se il comparto lattiero caseario della Sardegna, focalizzato nella produzione di Pecorino Romano DOP, può creare un effetto distretto. Ciò potrebbe suggerire l'esistenza dello stesso distretto anche se atipico. Per verificare questa ipotesi, in primo luogo è stata esaminata l'efficienza produttiva delle imprese trasformatrici di Pecorino Romano utilizzando il metodo della Frontiera stocastica di produzione. Successivamente sono state cercate le cause delle differenze. Lo studio mostra che i livelli di efficienza osservati sono quasi interamente attribuibili agli input di produzione utilizzati, in particolare al latte. Risulta chiaro che il sistema delle cooperative funziona e che tali aziende ottengono sistematicamente margini di efficienza migliori rispetto alle non cooperative. Le variabili analizzate non permettono di concludere che esiste un "effetto distretto".

La ricostruzione dell'assetto topografico della VI regio augustea di Roma dal periodo repubblicano all'età tardoantica

La VI regio augustea di Roma rappresenta uno dei settori urbani maggiormente investiti dalle modifiche radicali compiute dall’uomo nel processo di urbanizzazione della città che ne hanno modificato profondamente la situazione altimetrica e la conformazione originaria. Questi notevoli cambiamenti ebbero origine sin dall’età antica, ma si intensificarono profondamente soprattutto nel periodo rinascimentale quando a partire da Pio IV e soprattutto con Sisto V, attivo in tante altre zone della città, si svilupparono numerose opere di rinnovamento urbanistico che incisero notevolmente sul volto e sulle caratteristiche della zona in esame. A partire dal Rinascimento fino ad arrivare ai grandi scavi della fine del 1800 tutto il quartiere incominciò a “popolarsi” di numerosi edifici di grande mole che andarono ad intaccare completamente le vestigia del periodo antico: la costruzione del Palazzo del Quirinale e dei vari palazzi nobiliari ma soprattutto la costruzione dei numerosi ministeri e della prima stazione Termini alla fine dell’800 comportarono numerosi sventramenti senza la produzione di una adeguata documentazione delle indagini di scavo. Questa ricerca intende ricostruire, in un’ottica diacronica, la topografia di uno dei quartieri centrali della Roma antica attraverso l’analisi dei principali fenomeni che contraddistinguono l’evoluzione del tessuto urbano sia per quanto riguarda le strutture pubbliche che in particolar modo quelle private. Infatti, il dato principale che emerge da questa ricerca è che questa regio si configura, a partire già dal periodo tardo-repubblicano, come un quartiere a vocazione prevalentemente residenziale, abitato soprattutto dall’alta aristocrazia appartenente alle più alte cariche dello Stato romano; oltre a domus ed insulae, sul Quirinale, vennero costruiti lungo il corso di tutta l’età repubblicana alcuni tra i più antichi templi della città che con la loro mole occuparono parte dello spazio collinare fino all’età tardoantica, rappresentando così una macroscopica e costante presenza nell’ingombro dello spazio edificato.

Le variazioni anatomiche: La vera immagine dell'anatomia dell'uomo

La studio dell’Anatomia umana presenta una varietà di sfaccettature, che sono alla base della reale comprensione del corpo umano; ovvero la vera anatomia non è quella rappresentata nei testi ma quella che appare durante la dissezione o nelle più sofisticate analisi di immagine. Lo scopo di questa tesi è stato quello di rivisitare alcune situazioni vascolari che possono andare incontro a variazioni e cercare di comprendere, anche con l’aiuto della bibliografia, se tali variazioni possono essere causa o epifenomeni di patologie a carico delle arterie affette dalle variazioni stesse o di territori da esse dipendenti per l’afflusso sanguigno. E’ stata condotta una analisi su preparati cadaverici in particolare in tre distretti: a) addome e tripode celiaco/mesenterica superiore; b) circolo cerebrale; d) orco aortico.

Evolutionary epigenetics of modern human populations

Epigenetic variability is a new mechanism for the study of human microevolution, because it creates both phenotypic diversity within an individual and within population. This mechanism constitutes an important reservoir for adaptation in response to new stimuli and recent studies have demonstrated that selective pressures shape not only the genetic code but also DNA methylation profiles. The aim of this thesis is the study of the role of DNA methylation changes in human adaptive processes, considering the Italian peninsula and macro-geographical areas. A whole-genome analysis of DNA methylation profile across the Italian penisula identified some genes whose methylation levels differ between individuals of different Italian districts (South, Centre and North of Italy). These genes are involved in nitrogen compound metabolism and genes involved in pathogens response. Considering individuals with different macro-geographical origins (individuals of Asians, European and African ancestry) more significant DMRs (differentially methylated regions) were identified and are located in genes involved in glucoronidation, in immune response as well as in cell comunication processes. A "profile" of each ancestry (African, Asian and European) was described. Moreover a deepen analysis of three candidate genes (KRTCAP3, MAD1L and BRSK2) in a cohort of individuals of different countries (Morocco, Nigeria, China and Philippines) living in Bologna, was performed in order to explore genetic and epigenetic diversity. Moreover this thesis have paved the way for the application of DNA methylation for the study of hystorical remains and in particular for the age-estimation of individuals starting from biological samples (such as teeth or blood). Noteworthy, a mathematical model that considered methylation values of DNA extracted from cementum and pulp of living individuals can estimate chronological age with high accuracy (median absolute difference between age estimated from DNA methylation and chronological age was 1.2 years).