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.

Innovative analytical methods for Central Nervous System Drug analysis in biological fluids

During recent years a consistent number of central nervous system (CNS) drugs have been approved and introduced on the market for the treatment of many psychiatric and neurological disorders, including psychosis, depression, Parkinson disease and epilepsy. Despite the great advancements obtained in the treatment of CNS diseases/disorders, partial response to therapy or treatment failure are frequent, at least in part due to poor compliance, but also genetic variability in the metabolism of psychotropic agents or polypharmacy, which may lead to sub-therapeutic or toxic plasma levels of the drugs, and finally inefficacy of the treatment or adverse/toxic effects. With the aim of improving the treatment, reducing toxic/side effects and patient hospitalisation, Therapeutic Drug Monitoring (TDM) is certainly useful, allowing for a personalisation of the therapy. Reliable analytical methods are required to determine the plasma levels of psychotropic drugs, which are often present at low concentrations (tens or hundreds of nanograms per millilitre). The present PhD Thesis has focused on the development of analytical methods for the determination of CNS drugs in biological fluids, including antidepressants (sertraline and duloxetine), antipsychotics (aripiprazole), antiepileptics (vigabatrin and topiramate) and antiparkinsons (pramipexole). Innovative methods based on liquid chromatography or capillary electrophoresis coupled to diode-array or laser-induced fluorescence detectors have been developed, together with the suitable sample pre-treatment for interference removal and fluorescent labelling in case of LIF detection. All methods have been validated according to official guidelines and applied to the analysis of real samples obtained from patients, resulting suitable for the TDM of psychotropic drugs.

Molecular interactions: metal ions and protein chaperones in the urease system from Helicobacter pylori

Although nickel is a toxic metal for living organisms in its soluble form, its importance in many biological processes recently emerged. In this view, the investigation of the nickel-dependent enzymes urease and [NiFe]-hydrogenase, especially the mechanism of nickel insertion into their active sites, represent two intriguing case studies to understand other analogous systems and therefore to lead to a comprehension of the nickel trafficking inside the cell. Moreover, these two enzymes have been demonstrated to ensure survival and colonization of the human pathogen H. pylori, the only known microorganism able to proliferate in the gastric niche. The right nickel delivering into the urease active site requires the presence of at least four accessory proteins, UreD, UreE, UreF and UreG. Similarly, analogous process is principally mediated by HypA and HypB proteins in the [NiFe]-hydrogenase system. Indeed, HpHypA and HpHypB also have been proposed to act in the activation of the urease enzyme from H. pylori, probably mobilizing nickel ions from HpHypA to the HpUreE-HpUreG complex. A complete comprehension of the interaction mechanism between the accessory proteins and the crosstalk between urease and hydrogenase accessory systems requires the determination of the role of each protein chaperone that strictly depends on their structural and biochemical properties. The availability of HpUreE, HpUreG and HpHypA proteins in a pure form is a pre-requisite to perform all the subsequent protein characterizations, thus their purification was the first aim of this work. Subsequently, the structural and biochemical properties of HpUreE were investigated using multi-angle and quasi-elastic light scattering, as well as NMR and circular dichroism spectroscopy. The thermodynamic parameters of Ni2+ and Zn2+ binding to HpUreE were principally established using isothermal titration calorimetry and the importance of key histidine residues in the process of binding metal ions was studied using site-directed mutagenesis. The molecular details of the HpUreE-HpUreG and HpUreE-HpHypA protein-protein assemblies were also elucidated. The interaction between HpUreE and HpUreG was investigated using ITC and NMR spectroscopy, and the influence of Ni2+ and Zn2+ metal ions on the stabilization of this association was established using native gel electrophoresis, light scattering and thermal denaturation scanning followed by CD spectroscopy. Preliminary HpUreE-HpHypA interaction studies were conducted using ITC. Finally, the possible structural architectures of the two protein-protein assemblies were rationalized using homology modeling and docking computational approaches. All the obtained data were interpreted in order to achieve a more exhaustive picture of the urease activation process, and the correlation with the accessory system of the hydrogenase enzyme, considering the specific role and activity of the involved protein players. A possible function for Zn2+ in the chaperone network involved in Ni2+ trafficking and urease activation is also envisaged.

Development of human visual system analysis for the implementation of a new instrument for flicker measurement

Flicker is a power quality phenomenon that applies to cycle instability of light intensity resulting from supply voltage fluctuation, which, in turn can be caused by disturbances introduced during power generation, transmission or distribution. The standard EN 61000-4-15 which has been recently adopted also by the IEEE as IEEE Standard 1453 relies on the analysis of the supply voltage which is processed according to a suitable model of the lamp – human eye – brain chain. As for the lamp, an incandescent 60 W, 230 V, 50 Hz source is assumed. As far as the human eye – brain model is concerned, it is represented by the so-called flicker curve. Such a curve was determined several years ago by statistically analyzing the results of tests where people were subjected to flicker with different combinations of magnitude and frequency. The limitations of this standard approach to flicker evaluation are essentially two. First, the provided index of annoyance Pst can be related to an actual tiredness of the human visual system only if such an incandescent lamp is used. Moreover, the implemented response to flicker is “subjective” given that it relies on the people answers about their feelings. In the last 15 years, many scientific contributions have tackled these issues by investigating the possibility to develop a novel model of the eye-brain response to flicker and overcome the strict dependence of the standard on the kind of the light source. In this light of fact, this thesis is aimed at presenting an important contribution for a new Flickermeter. An improved visual system model using a physiological parameter that is the mean value of the pupil diameter, has been presented, thus allowing to get a more “objective” representation of the response to flicker. The system used to both generate flicker and measure the pupil diameter has been illustrated along with all the results of several experiments performed on the volunteers. The intent has been to demonstrate that the measurement of that geometrical parameter can give reliable information about the feeling of the human visual system to light flicker.

Multi-level models and infrastructures for simulating biological system development

The hierarchical organisation of biological systems plays a crucial role in the pattern formation of gene expression resulting from the morphogenetic processes, where autonomous internal dynamics of cells, as well as cell-to-cell interactions through membranes, are responsible for the emergent peculiar structures of the individual phenotype. Being able to reproduce the systems dynamics at different levels of such a hierarchy might be very useful for studying such a complex phenomenon of self-organisation. The idea is to model the phenomenon in terms of a large and dynamic network of compartments, where the interplay between inter-compartment and intra-compartment events determines the emergent behaviour resulting in the formation of spatial patterns. According to these premises the thesis proposes a review of the different approaches already developed in modelling developmental biology problems, as well as the main models and infrastructures available in literature for modelling biological systems, analysing their capabilities in tackling multi-compartment / multi-level models. The thesis then introduces a practical framework, MS-BioNET, for modelling and simulating these scenarios exploiting the potential of multi-level dynamics. This is based on (i) a computational model featuring networks of compartments and an enhanced model of chemical reaction addressing molecule transfer, (ii) a logic-oriented language to flexibly specify complex simulation scenarios, and (iii) a simulation engine based on the many-species/many-channels optimised version of Gillespie’s direct method. The thesis finally proposes the adoption of the agent-based model as an approach capable of capture multi-level dynamics. To overcome the problem of parameter tuning in the model, the simulators are supplied with a module for parameter optimisation. The task is defined as an optimisation problem over the parameter space in which the objective function to be minimised is the distance between the output of the simulator and a target one. The problem is tackled with a metaheuristic algorithm. As an example of application of the MS-BioNET framework and of the agent-based model, a model of the first stages of Drosophila Melanogaster development is realised. The model goal is to generate the early spatial pattern of gap gene expression. The correctness of the models is shown comparing the simulation results with real data of gene expression with spatial and temporal resolution, acquired in free on-line sources.

Use of E. coli OMVs as delivery system to elicit neutralizing antibodies against Chlamydia infectivity: the HtrA protein example

The obligate intracellular pathogen Chlamydia trachomatis is a gram negative bacterium which infects epithelial cells of the reproductive tract. C. trachomatis is the leading cause of bacterial sexually transmitted disease worldwide and a vaccine against this pathogen is highly needed. Many evidences suggest that both antigen specific-Th1 cells and antibodies may be important to provide protection against Chlamydia infection. In a previous study we have identified eight new Chlamydia antigens inducing CD4-Th1 and/or antibody responses that, when combined properly, can protect mice from Chlamydia infection. However, all selected recombinant antigens, upon immunization in mice, elicited antibodies not able to neutralize Chlamydia infectivity in vitro. With the aim to improve the quality of the immune response by inducing effective neutralizing antibodies, we used a novel delivery system based on the unique capacity of E. coli Outer Membrane Vesicles (OMV) to present membrane proteins in their natural composition and conformation. We have expressed Chlamydia antigens, previously identified as vaccine candidates, in the OMV system. Among all OMV preparations, the one expressing HtrA Chlamydia antigen (OMV-HtrA), showed to be the best in terms of yield and quantity of expressed protein, was used to produce mice immune sera to be tested in neutralization assay in vitro. We observed that OMV-HtrA elicited specific antibodies able to neutralize efficiently Chlamydia infection in vitro, indicating that the presentation of the antigens in their natural conformation is crucial to induce an effective immune response. This is one of the first examples in which antibodies directed against a new Chlamydia antigen, other than MOMP (the only so far known antigen inducing neutralizing antibodies), are able to block the Chlamydia infectivity in vitro. Finally, by performing an epitope mapping study, we investigated the specificity of the antibody response induced by the recombinant HtrA and by OMV-HtrA. In particular, we identified some linear epitopes exclusively recognized by antibodies raised with the OMV-HtrA system, detecting in this manner the antigen regions likely responsible of the neutralizing effect.

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!

Molecular approach to Neurodegenerative Disorders: Role of Nociceptin/Orphanin FQ - NOP System in Parkinson and Epigenetic Mechanism in Alzheimer's Disease

With life expectancies increasing around the world, populations are getting age and neurodegenerative diseases have become a global issue. For this reason we have focused our attention on the two most important neurodegenerative diseases: Parkinson’s and Alzheimer’s. Parkinson’s disease is a chronic progressive neurodegenerative movement disorder of multi-factorial origin. Environmental toxins as well as agricultural chemicals have been associated with PD. Has been observed that N/OFQ contributes to both neurotoxicity and symptoms associated with PD and that pronociceptin gene expression is up-regulated in rat SN of 6-OHDA and MPP induced experimental parkinsonism. First, we investigated the role of N/OFQ-NOP system in the pathogenesis of PD in an animal model developed using PQ and/or MB. Then we studied Alzheimer's disease. This disorder is defined as a progressive neurologic disease of the brain leading to the irreversible loss of neurons and the loss of intellectual abilities, including memory and reasoning, which become severe enough to impede social or occupational functioning. Effective biomarker tests could prevent such devastating damage occurring. We utilized the peripheral blood cells of AD discordant monozygotic twin in the search of peripheral markers which could reflect the pathology within the brain, and also support the hypothesis that PBMC might be a useful model of epigenetic gene regulation in the brain. We investigated the mRNA levels in several genes involve in AD pathogenesis, as well DNA methylation by MSP Real-Time PCR. Finally by Western Blotting we assess the immunoreactivity levels for histone modifications. Our results support the idea that epigenetic changes assessed in PBMCs can also be useful in neurodegenerative disorders, like AD and PD, enabling identification of new biomarkers in order to develop early diagnostic programs.

Multifunctional nanocarriers encapsulating anti-Alzheimer drug for nasal delivery to central nervous system

Alzheimer's disease (AD) is a fatal neurodegenerative condition characterized clinically by progressive memory loss and irreversible cognitive deterioration. It has been shown that there is a progressive degeneration of the brain cholinergic neurons which leads to the appearance of cognitive symptoms of the disease. The aim of this work was the formulation of multifunctional nanocarriers for nasal administration of tacrine-HCl (THA). This route has many advantages; in particular is possible to convey the drug directly to the Central Nervous System, through the olfactory bulb. In particular, were prepared Albumin nanoparticles carrying beta cyclodextrin and two different beta cyclodextrin derivatives (hydroxypropyl beta cyclodextrin and sulphobutylether beta cyclodextrin), and Multifunctional liposomes, prepared using traditional excipients (cholesterol and phosphatidylcholine), partly enriched with α-tocopherol (Toc) and/or polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid) (Ω3). Both nanosystems were characterized in terms of size, Zeta potential and encapsulation efficiency. Were also evaluated their functional properties such as mucoadhesion and permeability, using an ex-vivo assay based on nasal sheep mucosa. On Liposomes were also assessed drug neuronal uptake, cell toxicity, antioxidant and, cytoprotective activity in the human neuronal cell line SH-SY5Y and finally tocopherol trans-membrane diffusion. Both the nanocarriers produced presented excellent properties and a high potential as new systems for CNS-delivery of anti-Alzheimer drugs via the nasal route.

Spinal cord injury: assessment of autonomic state-dependent control of cardiovascular system and body core temperature

Spinal cord injury (SCI) results not only in paralysis; but it is also associated with a range of autonomic dysregulation that can interfere with cardiovascular, bladder, bowel, temperature, and sexual function. The entity of the autonomic dysfunction is related to the level and severity of injury to descending autonomic (sympathetic) pathways. For many years there was limited awareness of these issues and the attention given to them by the scientific and medical community was scarce. Yet, even if a new system to document the impact of SCI on autonomic function has recently been proposed, the current standard of assessment of SCI (American Spinal Injury Association (ASIA) examination) evaluates motor and sensory pathways, but not severity of injury to autonomic pathways. Beside the severe impact on quality of life, autonomic dysfunction in persons with SCI is associated with increased risk of cardiovascular disease and mortality. Therefore, obtaining information regarding autonomic function in persons with SCI is pivotal and clinical examinations and laboratory evaluations to detect the presence of autonomic dysfunction and quantitate its severity are mandatory. Furthermore, previous studies demonstrated that there is an intimate relationship between the autonomic nervous system and sleep from anatomical, physiological, and neurochemical points of view. Although, even if previous epidemiological studies demonstrated that sleep problems are common in spinal cord injury (SCI), so far only limited polysomnographic (PSG) data are available. Finally, until now, circadian and state dependent autonomic regulation of blood pressure (BP), heart rate (HR) and body core temperature (BcT) were never assessed in SCI patients. Aim of the current study was to establish the association between the autonomic control of the cardiovascular function and thermoregulation, sleep parameters and increased cardiovascular risk in SCI patients.

Antipodal random sequences with prescribed second-order statistics: application to Compressive Sensing and UWB system based on DS-CDMA

It is usual to hear a strange short sentence: «Random is better than...». Why is randomness a good solution to a certain engineering problem? There are many possible answers, and all of them are related to the considered topic. In this thesis I will discuss about two crucial topics that take advantage by randomizing some waveforms involved in signals manipulations. In particular, advantages are guaranteed by shaping the second order statistic of antipodal sequences involved in an intermediate signal processing stages. The first topic is in the area of analog-to-digital conversion, and it is named Compressive Sensing (CS). CS is a novel paradigm in signal processing that tries to merge signal acquisition and compression at the same time. Consequently it allows to direct acquire a signal in a compressed form. In this thesis, after an ample description of the CS methodology and its related architectures, I will present a new approach that tries to achieve high compression by design the second order statistics of a set of additional waveforms involved in the signal acquisition/compression stage. The second topic addressed in this thesis is in the area of communication system, in particular I focused the attention on ultra-wideband (UWB) systems. An option to produce and decode UWB signals is direct-sequence spreading with multiple access based on code division (DS-CDMA). Focusing on this methodology, I will address the coexistence of a DS-CDMA system with a narrowband interferer. To do so, I minimize the joint effect of both multiple access (MAI) and narrowband (NBI) interference on a simple matched filter receiver. I will show that, when spreading sequence statistical properties are suitably designed, performance improvements are possible with respect to a system exploiting chaos-based sequences minimizing MAI only.

Monitoring Complex Processes to Verify System Conformance: A Declarative Rule-Based Framework

Over the last 60 years, computers and software have favoured incredible advancements in every field. Nowadays, however, these systems are so complicated that it is difficult – if not challenging – to understand whether they meet some requirement or are able to show some desired behaviour or property. This dissertation introduces a Just-In-Time (JIT) a posteriori approach to perform the conformance check to identify any deviation from the desired behaviour as soon as possible, and possibly apply some corrections. The declarative framework that implements our approach – entirely developed on the promising open source forward-chaining Production Rule System (PRS) named Drools – consists of three components: 1. a monitoring module based on a novel, efficient implementation of Event Calculus (EC), 2. a general purpose hybrid reasoning module (the first of its genre) merging temporal, semantic, fuzzy and rule-based reasoning, 3. a logic formalism based on the concept of expectations introducing Event-Condition-Expectation rules (ECE-rules) to assess the global conformance of a system. The framework is also accompanied by an optional module that provides Probabilistic Inductive Logic Programming (PILP). By shifting the conformance check from after execution to just in time, this approach combines the advantages of many a posteriori and a priori methods proposed in literature. Quite remarkably, if the corrective actions are explicitly given, the reactive nature of this methodology allows to reconcile any deviations from the desired behaviour as soon as it is detected. In conclusion, the proposed methodology brings some advancements to solve the problem of the conformance checking, helping to fill the gap between humans and the increasingly complex technology.

Parallel Architectures for Many-Core Systems-On-Chip in Deep Sub-Micron Technology

Despite the several issues faced in the past, the evolutionary trend of silicon has kept its constant pace. Today an ever increasing number of cores is integrated onto the same die. Unfortunately, the extraordinary performance achievable by the many-core paradigm is limited by several factors. Memory bandwidth limitation, combined with inefficient synchronization mechanisms, can severely overcome the potential computation capabilities. Moreover, the huge HW/SW design space requires accurate and flexible tools to perform architectural explorations and validation of design choices. In this thesis we focus on the aforementioned aspects: a flexible and accurate Virtual Platform has been developed, targeting a reference many-core architecture. Such tool has been used to perform architectural explorations, focusing on instruction caching architecture and hybrid HW/SW synchronization mechanism. Beside architectural implications, another issue of embedded systems is considered: energy efficiency. Near Threshold Computing is a key research area in the Ultra-Low-Power domain, as it promises a tenfold improvement in energy efficiency compared to super-threshold operation and it mitigates thermal bottlenecks. The physical implications of modern deep sub-micron technology are severely limiting performance and reliability of modern designs. Reliability becomes a major obstacle when operating in NTC, especially memory operation becomes unreliable and can compromise system correctness. In the present work a novel hybrid memory architecture is devised to overcome reliability issues and at the same time improve energy efficiency by means of aggressive voltage scaling when allowed by workload requirements. Variability is another great drawback of near-threshold operation. The greatly increased sensitivity to threshold voltage variations in today a major concern for electronic devices. We introduce a variation-tolerant extension of the baseline many-core architecture. By means of micro-architectural knobs and a lightweight runtime control unit, the baseline architecture becomes dynamically tolerant to variations.

Il discorso politico culturale del Deutscher Geist in Gefahr di Ernst Robert Curtius

Nel 1932 Ernst Robert Curtius pubblica il pamphlet politico culturale Deutscher Geist in Gefahr nel quale chiarisce il suo pensiero di fronte alla grave crisi in cui versa la Germania. Egli si schiera contro le posizioni di destra del suo tempo, delle quali critica apertamente la boria nazionalista, il rozzo antisemitismo e la creazione di un mito nazionale elaborato come strumento di manipolazione dell’opinione pubblica. Ritiene inoltre inaccettabili le posizioni rivoluzionarie, tanto di destra quanto di sinistra, che vogliono liberarsi della tradizione umanistica europea e disprezzano la Zivilisation francese; allo stesso modo rifiuta l’ideale di un germanesimo eroico avulso dalla storia europea e respinge infine tutte le forme di nichilismo che si risolvono in un atteggiamento di indifferenza nei confronti della realtà, dei valori e della storia. Curtius accetta il sistema democratico come unica soluzione e ritiene che le decisioni politiche debbano mirare al bene di tutti i ceti sociali indipendentemente dagli interessi di partiti e di singoli gruppi. Rifiuta qualunque forma, anche culturale, di supremazia della Germania, aspira a un’Europa cosmopolita, le cui nazioni siano valorizzate nelle loro caratteristiche specifiche, ed è convinto che per la costruzione della pace gli europei debbano vivere, studiare e lavorare insieme imparando gli uni le lingue degli altri. Per Curtius l’Umanesimo della tradizione classica e la letteratura del Medioevo sono parte integrante della vita di ogni europeo e fonte di energie spirituali per affrontare in modo creativo il presente e il futuro.

Cannabinoid system combined to classic targets for a new MTDL strategy: design and synthesis of natural inspired molecules for Alzheimer's disease

In this thesis is described the design and synthesis of potential agents for the treatment of the multifactorial Alzheimer’s disease (AD). Our multi-target approach was to consider cannabinoid system involved in AD, together with classic targets. In the first project, designed modifications were performed on lead molecule in order to increase potency and obtain balanced activities on fatty acid amide hydrolase and cholinesterases. A small library of compounds was synthesized and biological results showed increased inhibitory activity (nanomolar range) related to selected target. The second project was focused on the benzofuran framework, a privileged structure being a common moiety found in many biologically active natural products and therapeutics. Hybrid molecules were designed and synthesized, focusing on the inhibition of cholinesterases, Aβ aggregation, FAAH and on the interaction with CB receptors. Preliminary results showed that several compounds are potent CB ligands, in particular the high affinity for CB2 receptors, could open new opportunities to modulate neuroinflammation. The third and the fourth project were carried out at the IMS, Aberdeen, under the supervision of Prof. Matteo Zanda. The role of the cannabinoid system in the brain is still largely unexplored and the relationship between the CB1 receptors functional modification, density and distribution and the onset of a pathological state is not well understood. For this reasons, Rimonabant analogues suitable as radioligands were synthesized. The latter, through PET, could provide reliable measurements of density and distribution of CB1 receptors in the brain. In the fifth project, in collaboration with CHyM of York, the goal was to develop arginine analogues that are target specific due to their exclusively location into NOS enzymes and could work as MRI contrasting agents. Synthesized analogues could be suitable substrate for the transfer of polarization by p-H2 molecules through SABRE technique transforming MRI a more sensitive and faster technique.