Archivio Istituzionale della Ricerca - Università degli Studi di Pavia
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Advancing the antituberculosis activity of nitropicolinic acids and amides
No full textAmbitious milestones set by the World Health Organisation (WHO) to end the tuberculosis epidemic by 2030 currently appear out of reach, and there remains an urgent need to develop more effective novel therapies. While exploring dipicolinic acid derivatives as putative glutamate racemase inhibitors, we recently discovered 6-nitropicolinamides as promising antituberculosis agents. SAR studies on the non-cytotoxic N-[4-(trifluoromethoxy)benzyl] hit 20 (MIC90 1.4 μM) confirmed the importance of the 6-nitro group and amide NH; side chain extension enhanced potency but reduced aqueous solubility, and some analogues were rapidly metabolised. The best new candidate (77: MIC90 0.30 μM) was well tolerated in mice and provided an adequate pharmacokinetic profile, although a time-kill assay indicated largely bacteriostatic activity. An analysis of its effects on cell wall lipids and mycolic acids revealed changes consistent with inhibiting arabinogalactan biosynthesis, and further testing against mutant or overexpressing mycobacterial strains identified the enzyme target as decaprenylphosphoryl-β-D-ribose 2′-oxidase (DprE1)
Design of a High-Resolution Sigma-Delta Modulator for a Predominantly Digital Class-D Amplifier
No full textThis thesis presents a novel predominantly Digital Class-D Audio Amplifier, fully com- patible with standard BCD technologies, that features in the direct signal path a High- Resolution Sigma-Delta Modulator. The research on high-performance car audio systems has experienced a surge of interest in recent years, thanks to the spreading of new tech- nologies and the growth of the automotive sector. In this framework, the increasingly stringent market demands have led to the definition of specifications for cost efficiency, area, and performance at an ever-higher level. Indeed, by placing a high-performance sigma-delta modulator in the direct path, most of the signal processing functions are pushed towards the digital domain, thus allowing the use of scaled technologies with denser digital circuits to reduce costs and size. Additionally, most audio amplifiers aim to achieve high performance in terms of THD (Total Harmonic Distortion) and SNR (Signal-to-Noise Ratio). Therefore, a high gain to suppress noise and non-linearities is another requirement of primary importance. This work explores the design strategies and methodologies to meet these rigorous requirements, contributing to advancements in cost-effective, high-performance audio amplification. It starts with an overview of the entire architecture, followed by a detailed description of the Sigma-Delta modulator. The test chip has been designed and fabricated in 90-nm CMOS process technology and that are the results of three years of research activities that has been done in collaboration with STMicroelectronics. The conception, design, layout and testing phases are all described in detail and are supported by simulation and measurement results.This thesis presents a novel predominantly Digital Class-D Audio Amplifier, fully com- patible with standard BCD technologies, that features in the direct signal path a High- Resolution Sigma-Delta Modulator. The research on high-performance car audio systems has experienced a surge of interest in recent years, thanks to the spreading of new tech- nologies and the growth of the automotive sector. In this framework, the increasingly stringent market demands have led to the definition of specifications for cost efficiency, area, and performance at an ever-higher level. Indeed, by placing a high-performance sigma-delta modulator in the direct path, most of the signal processing functions are pushed towards the digital domain, thus allowing the use of scaled technologies with denser digital circuits to reduce costs and size. Additionally, most audio amplifiers aim to achieve high performance in terms of THD (Total Harmonic Distortion) and SNR (Signal-to-Noise Ratio). Therefore, a high gain to suppress noise and non-linearities is another requirement of primary importance. This work explores the design strategies and methodologies to meet these rigorous requirements, contributing to advancements in cost-effective, high-performance audio amplification. It starts with an overview of the entire architecture, followed by a detailed description of the Sigma-Delta modulator. The test chip has been designed and fabricated in 90-nm CMOS process technology and that are the results of three years of research activities that has been done in collaboration with STMicroelectronics. The conception, design, layout and testing phases are all described in detail and are supported by simulation and measurement results
Artificial intelligence in human-assisted reproduction: a paradigm shift still in search of clinical impact
No full textPurpose: Artificial intelligence in human-assisted reproduction has attracted intense interest and inflated expectations, with proposed applications ranging from ovarian stimulation to gamete and embryo selection and outcome prediction. Despite the initial enthusiasm, its real-world clinical value remains uncertain. This review critically reassesses the current evidence to clarify where artificial intelligence meaningfully contributes and where expectations exceed demonstrated impact. Recent findings: Most published studies show relevant methodological weaknesses, including limited reproducibility, poor external validation, scarce explainability, and weak comparison with standard clinical practice. Research efforts have disproportionately focused on embryo selection, an area with intrinsically constrained potential to improve treatment efficacy, while other clinically relevant domains remain underexplored. As a result, reported improvements often concern surrogate or intermediate endpoints rather than robust clinical outcomes. Summary: Artificial intelligence holds greater promise in domains such as gamete assessment, automated data extraction, and personalized outcome prediction, where it may enhance treatment management, counselling, and decision-making for both clinicians and patients. Realizing this potential requires a strategic shift in research priorities and rigorous adherence to shared standards, including model transparency, uniformity, external validation, and benchmarking against established clinical workflows. Without such recalibration, artificial intelligence risks becoming a hyped technology with limited clinical relevance in assisted reproduction
Teoria e prassi della delega di funzioni. Contributo allo studio della ripartizione della responsabilità penale nelle organizzazioni complesse.
No full textLa presente ricerca intende offrire un contributo aggiornato all’elaborazione dottrinale in materia di responsabilità penale derivante dalla delega di funzioni nell’ambito di strutture organizzative complesse. Tale istituto, attualmente disciplinato dagli articoli 16 e 17 del d. lgs. 9 aprile 2008, n. 81, trova oggi applicazione in un ambito sempre più esteso e trasversale rispetto al settore originario della salute e sicurezza sul lavoro.
L’indagine si articola in cinque capitoli.
Il primo capitolo è dedicato all’analisi dei profili di teoria generale del diritto penale che interagiscono con l’istituto della delega di funzioni, con specifico riferimento ai reati propri, alla responsabilità omissiva, alla partecipazione criminosa e alla colpa.
Il secondo capitolo ricostruisce il percorso storico-evolutivo che ha condotto alla vigente configurazione normativa degli articoli 16 e 17 del D.Lgs. n. 81/2008, evidenziando le principali direttrici di sviluppo giurisprudenziale e legislativo.
Il terzo capitolo esamina i presupposti applicativi e le implicazioni della delega di funzioni nel contesto lavorativo, con particolare attenzione alla posizione giuridica del datore di lavoro delegante e alla sua eventuale responsabilità residuale.
Il quarto capitolo offre una ricognizione sistematica dei settori dell’ordinamento, ulteriori rispetto a quello prevenzionistico, nei quali la delega di funzioni trova oggi riconoscimento sia a livello normativo sia nella prassi giurisprudenziale. Tra tali ambiti si annoverano, in particolare, i settori ambientale, agroalimentare, economico-societario, tributario, dell’informazione e sanitario.
Il quinto e ultimo capitolo propone una sintesi complessiva degli esiti della ricerca e formula le considerazioni conclusive. Esse si sviluppano lungo due direttrici: da un lato, in una prospettiva de jure condendo, si avanza una proposta di ricostruzione della responsabilità penale del delegante secondo i criteri dogmatici propri della partecipazione criminosa, discostandosi dall’impostazione dominante che la riconduce nell’ambito della responsabilità omissiva; dall’altro lato, in una prospettiva de jure condito, a seguito dell’analisi delle principali proposte di riforma susseguitesi nel tempo, si individua un possibile intervento legislativo volto a introdurre, all’interno della parte generale del Codice penale, una disciplina espressa dell’istituto della delega di funzioni.The PhD thesis seeks to offer an updated contribution to the doctrinal analysis of criminal liability arising from the delegation of functions within complex organizational structures. This legal construct, currently governed exclusively by Articles 16 and 17 of Legislative Decree No. 81 of 9 April 2008, is now applied across a broader range of regulatory sectors.
The research is articulated in five chapters.
The first chapter addresses the general theoretical constructs of criminal law that intersect with the delegation of functions, with particular regard to offences requiring specific personal qualifications, omission-based liability, participation in crime, and negligence.
The second chapter reconstructs the historical and evolutionary trajectory that led to the current normative configuration of Articles 16 and 17 of Legislative Decree 81/2008.
The third chapter examines the operational prerequisites and legal implications of the delegation of functions pursuant to the aforementioned provisions, with a focus on the position and residual liability of the delegating employer.
The fourth chapter presents a systematic survey of regulatory domains beyond occupational health and safety in which the delegation of functions is currently acknowledged in legal practice and case law — specifically, the environmental, agri-food, corporate-economic, tax, press, and medical sectors.
The fifth and final chapter offers a synthesis of the research outcomes and sets forth the concluding arguments. These are developed along two axes: from a de jure condendo perspective, the thesis advocates for a reconstruction of the delegator’s criminal liability within the dogmatic framework of participation in crime, thereby departing from the prevailing view that subsumes such liability under the rubric of omissive offences. From a de jure condito standpoint, and following an examination of the various reform proposals advanced over time, the work identifies a possible normative intervention aimed at introducing, within the General Part of the Italian Penal Code, an explicit statutory discipline of the delegation of functions
Assessing the context‐dependence of invasiveness in the Italian wall lizard (Podarcis siculus) )
No full textThe number of alien species has increased significantly in recent decades, but only a few become invasive, posing threats to biodiversity and human activities. However, the invasive potential of alien species might depend on environmental compatibility and local conditions. The Italian wall lizard (Podarcis siculus) has been introduced across Europe, North Africa, and North America, and its actual invasiveness varies by location. Detrimental impacts have been observed mainly on congeneric species, often due to competition or habitat overlap. Nevertheless, in some regions, including the United States, no evidence for spread and impact has been reported. On Gorgona Island, Italy, the Italian wall lizard was likely introduced accidentally around 2000 and has rapidly expanded. This study examined the colonization of the Italian wall lizard on Gorgona Island and its interaction with the native common wall lizard (P. muralis). Findings indicate the Italian wall lizard thrives in human-altered habitats, while the common wall lizard persists in natural areas. The spread of the Italian wall lizard appears to be driven by environmental conditions rather than inherent aggressiveness, aligning with patterns observed on other Mediterranean islands. Its expansion stalled between 2021 and 2024, suggesting habitat saturation, not competition, limits spread. The study warns against labeling the Italian wall lizard as uniformly invasive, advocating context-specific assessments to avoid misdirecting conservation resources
Virtual Reality and Artificial Intelligence-Assisted Visual Inspections for Cultural Heritage Structures: A Review
No full textVisual inspections are essential for the preservation of cultural heritage (CH) structures and oftenserve as the first line of defense in assessing structural integrity before events of serious deteriora-tion. These inspections are conducted either through direct eye observation by professionals orwith the assistance of artificial intelligence (AI)–based object detection algorithms that identifyanomalies in the image/video data. The combination of information and communication technol-ogy (ICT), virtual reality (VR), and AI-assisted inspections enables automation processes andimmersive quality is provided by VR systems. This paper presents a review of immersive technol-ogies for building and infrastructure inspections with a more focused discussion on the integrationof AI–VR for cultural heritage inspection and diagnosis. A case study of the Vistarino Palace in Pavia,Italy, presents a VR-based and expert-driven visual inspection, which is used to clarify methodo-logical and procedural aspects that could, in the future, be developed in line with the main trendsemerging from the previous review and case-oriented literature studies. The paper also outlinesthe respective advantages along with their limitations of manual, smart AI-based sensing, and VR-assisted visual inspections, and discusses future research directions for their development andintegratio
Data-driven Nonlinear Model Predictive Control: Stability, Robustness and Offset-free Tracking
No full textThe use of data-driven and learning-based models in model predictive control (MPC) has gained an increasing popularity in recent years thanks to the growing availability of data collected in industrial plants and on the development of powerful deep learning techniques. In this framework, the aim of this thesis is to design nonlinear MPC algorithms with guaranteed stability and robustness properties based on data-driven models of the system under control. A particular attention is devoted to the development of strategies that take into account modeling errors and uncertainties, and that guarantee offset-free tracking.
The first part of the thesis explores the design of MPC algorithms for incrementally input-to-state stable (δISS) nonlinear systems modeled by recurrent neural networks (RNN). This class of models can be trained using input-output data, and stability properties of the model can be enforced during the training procedure. Considering different RNN architectures, the thesis develops output-feedback MPC algorithms that ensure closed-loop stability, satisfaction of input and incremental input constraints, robust satisfaction of output constraints in presence of uncertainties and offset-free tracking. Moreover, considering a general δISS system, it is presented how it is possible to guarantee stability considering a positive semi-definite stage cost in the MPC optimization problem (e.g. for output weighting), and how it is possible to enlarge the feasibility region employing an artificial reference.
The second part of the thesis considers data-driven models in the Koopman framework, and studies how convergence to the origin can be guaranteed in presence of modeling errors. First, an offset-free MPC algorithm is designed for systems modeled using extended dynamic mode decomposition (EDMD). Then, considering kernel based EDMD models, it is shown how asymptotic stability of MPC without terminal ingredients can be achieved provided that there exist suitable bounds on the modeling error.
The last part of the thesis presents the application of MPC to the current control in synchronous reluctance motors, showing performance improvement in presence of model uncertainties compared to the baseline control approaches.
All the control algorithms developed in the thesis have been theoretically analyzed, and their validity is assessed in simulation examples.The use of data-driven and learning-based models in model predictive control (MPC) has gained an increasing popularity in recent years thanks to the growing availability of data collected in industrial plants and on the development of powerful deep learning techniques. In this framework, the aim of this thesis is to design nonlinear MPC algorithms with guaranteed stability and robustness properties based on data-driven models of the system under control. A particular attention is devoted to the development of strategies that take into account modeling errors and uncertainties, and that guarantee offset-free tracking.
The first part of the thesis explores the design of MPC algorithms for incrementally input-to-state stable (δISS) nonlinear systems modeled by recurrent neural networks (RNN). This class of models can be trained using input-output data, and stability properties of the model can be enforced during the training procedure. Considering different RNN architectures, the thesis develops output-feedback MPC algorithms that ensure closed-loop stability, satisfaction of input and incremental input constraints, robust satisfaction of output constraints in presence of uncertainties and offset-free tracking. Moreover, considering a general δISS system, it is presented how it is possible to guarantee stability considering a positive semi-definite stage cost in the MPC optimization problem (e.g. for output weighting), and how it is possible to enlarge the feasibility region employing an artificial reference.
The second part of the thesis considers data-driven models in the Koopman framework, and studies how convergence to the origin can be guaranteed in presence of modeling errors. First, an offset-free MPC algorithm is designed for systems modeled using extended dynamic mode decomposition (EDMD). Then, considering kernel based EDMD models, it is shown how asymptotic stability of MPC without terminal ingredients can be achieved provided that there exist suitable bounds on the modeling error.
The last part of the thesis presents the application of MPC to the current control in synchronous reluctance motors, showing performance improvement in presence of model uncertainties compared to the baseline control approaches.
All the control algorithms developed in the thesis have been theoretically analyzed, and their validity is assessed in simulation examples
Effect of Collar Diameter and Simulated Aging on the Orthogonal Load Resistance of Orthodontic Miniscrews
No full textThe use of miniscrews as Temporary Skeletal Anchorage Devices (TSAD) in orthodontics has allowed clinicians to perform challenging tooth movements by dissipating undesired forces into the bone structure; thus, avoiding unwanted movement of the adjacent teeth. It is essential for miniscrews to be highly resistant to fracture during clinical use. While many studies have analysed torsional loads, none have measured the changes in flexural and bending strength of miniscrews before and after an ageing process. This study aims to analyse the resistance to orthogonal forces of miniscrews with different diameters, focusing on both new and aged materials, the latter subjected to thermocycling and autoclaving laboratory processes to simulate a 3- and a 6-month exposure to the oral environment. A total of 105 pristine miniscrews have been tested; specimens were divided into seven groups based on the different endosseous body diameters. Each group was further subdivided into three subgroups, according to the simulated ageing of the miniscrews (intact, 3 months of ageing and 6 months of ageing, respectively). An Instron Universal Testing Machine has been used to measure deflection at 0.1 mm and 0.2 mm, as well as maximum load at fracture. The results evidenced that miniscrews respond differently to cutting forces; in particular, the resistance to orthogonal loads increases as the diameter of the miniscrews increases. Linear regression analysis revealed a significant influence between all the dependent variables—maximum load, 0.1 mm deflection load, and 0.2 mm deflection load—and the independent variables, such as diameter and thermocycling (p < 0.05). Both new and aged miniscrews are suitable for orthodontic and orthopaedic loads; moreover, ageing up to 6 months does not seem to significantly decrease the resistance to shear forces for the same diameter. Linear regression analysis of the miniscrews subjected to experimental ageing showed a slight but significant decrease in resistance to orthogonal loading