Supply Chain Management e Finanza per la Valorizzazione del Potenziale Sinergico delle Relazioni di Filiera verso la Sostenibilità

L’analisi della solidità finanziaria di un’impresa deve necessariamente includere la gestione della supply chain, considerata un asset strategico capace di generare valore competitivo. L’integrazione tra Supply Chain Management (di seguito anche "SCM") e finanza consente di valutare l’impatto economico-finanziario delle decisioni operative, migliorando la gestione del rischio e delle opportunità lungo la filiera. Tuttavia, gli approcci tradizionali trascurano spesso la correlazione tra performance logistiche e finanziarie, limitando le potenzialità aziendali. In tal senso, la Supply Chain Finance (di seguito anche "SCF") rappresenta una soluzione per ottimizzare il capitale circolante, rafforzando la resilienza e la competitività, in particolare per le PMI, che spesso incontrano ostacoli nell’accesso al credito. Con l’aumento dell’attenzione ai criteri ESG, si afferma la Sustainable Supply Chain Finance (SSCF), che promuove investimenti sostenibili e responsabili. In questo contesto, strumenti digitali innovativi supportano la misurazione delle performance ESG e la valutazione del potenziale di crescita delle imprese nella filiera. Inoltre, normative europee come la CSRD e la CSDDD impongono maggiore trasparenza nella supply chain, coinvolgendo anche le PMI, che devono affrontare i costi di conformità e la transizione ecologica. Un ruolo centrale è svolto dalla funzione approvvigionamenti, evoluta da attività amministrativa a leva strategica. Oggi le imprese riconoscono i fornitori come partner strategici, capaci di migliorare la qualità e le prestazioni del prodotto finale. Tuttavia, molte aziende adottano ancora un approccio tradizionale, focalizzato sulla riduzione dei costi piuttosto che su innovazione e sostenibilità. Per massimizzare il valore della supply chain, è essenziale un modello di gestione dei fornitori basato su tre livelli di integrazione: operativa, prestazionale e strategica. La collaborazione tra settore finanziario e industriale, unita all’adozione di strumenti innovativi, è cruciale per promuovere modelli di crescita sostenibile e rafforzare la competitività delle imprese

Optical applications of Terahertz/Infrared spectroscopy for the detection of biomolecules

Biomedical and biophysical science is one of the most significant research fields in the 21st century. Several techniques are used for studying biomolecules dynamics and biosystems (generally not in their physiological environment), e.g., magnetic resonance, fluorescence imaging techniques, vibrational and acoustics spectroscopy and biochemical assays. Among them, one of the most important technique is the Terahertz Infrared (THz/IR) spectroscopy. This PhD project proposes the design and the development of a TH z/IR spectroscopic platform and a novel methodological approach for the detection and study of biomolecules of biological relevance and biosystems. The project is divided in different tasks, as follows (i) Design and Development of a THz /IR spectroscopy setups , (ii) evaluation of its performances, (iii) conceptualization and comparison of THz/IR spectroscopy for biomolecules and biosystems of interest

EZH2 gene mutations and copy number variation as prognostic markers in advanced follicular lymphoma

Introduction. Among the most common genetic alterations in follicular lymphoma (FL) there are the gain-of-function mutations in the Enhancer of Zeste Homolog 2 (EZH2) gene, encoding for a histone methyltransferase, which can also be over-expressed by copy number variations (CNV). The clinical impact of EZH2 aberrations in FL is debated, with some studies suggesting a favourable outcome, especially when patients received R-CHOP/CVP. Aims. In the “FOLL-EZ” study we aimed to explore the role of EZH2 aberrations in modifying the treatment effect of R- CHOP vs bendamustine-rituximab (BR) in the prospective trial “FOLL12” of the Fondazione Italiana Linfomi (FIL, EudraCT 2012-003170-60), enrolling advanced FL patients treated with frontline R-CHOP or BR, according to physician’s choice. Methods. Leftover DNA samples from unsorted bone marrow (BM) aspirates at baseline, centralized at the FIL MRD Network labs, were tested by a multiplex droplet digital PCR (ddPCR) for the detection of the recurrent EZH2 mutations and by a ddPCR CNV assay for the EZH2 region (chr 7q36.1). Results. Overall, 409 BM samples were tested for mutations and 359 for CNV (337 for both). An EZH2 mutation was found in 137 cases (33%), concordantly with literature, being more frequent in patients with a documented histological infiltration at the BM biopsy (BM+ n=124/309, 40%) than in BM- (n=13/100, 13%). In detail 68 cases were mutated in Y646 (50%), 41 in A682G (30%) and 73 in A692V (53%). 102 cases (74%) showed one single mutation: 52 in Y646, 13 in A682G, 37 in A692V. 6 cases showed all 3 mutations, 21 cases showed mutation in both 682 and 692 and 9 samples in 646 and 682 or 692. The most common mutation in Y646 was the Y646N 38/68 (56%) with a variant allele frequency (VAF) of 0.25% (0.03-32%), the less frequent the Y646S 8/68 (12%), VAF 0.59% (0.03- 21%). Notably 8/68 Y646 cases (12%) carried 2 distinct mutations and only one sample showed 3 distinct mutations. Interestingly, the 137 EZH2 mutated patients showed less favourable clinical features than the WT, in terms of higher B2M (>ULN 72% vs 53%, p<0.001), lower Hb values (Hb<12, 26% vs 15%, p=0.015), more frequent BM+ (91% vs 68%, p<0.001) and higher FLIPI-2 (61% HR vs 40%, p<0.001); also baseline PET parameters were more unfavorable among EZH2 mutated cases, namely metabolic tumor volume (MTV) >200 ml (71% vs 57%, p=0.011) and maximum tumor dissemination (Dmax) >400 mm (34% vs 21%, p=0.013): nonetheless, this did not translate into a statistically significant worse outcome (5-year PFS 59% vs 64%, p=0.324). Overall, no difference in PFS was observed between R-CHOP (n=239) and BR-treated (n=170) patients (5-y PFS 60% vs 67%, p=0.652): EZH2 mutations had no statistically significant impact in modifying the treatment effect of either therapeutic schedule (HR R-CHOP vs BR: 1.77 (95CI 0.96-3.29) p=0.067 for mutated and 0.89 (95CI 0.60-1.32), p=0.564 for WT patients, Figure 1A). In a subgroup analysis, the 30 EZH2 mutated patients who received R-CHOP not followed by R maintenance experienced the worst outcome (5-y PFS 24%, p=0.007). Regarding EZH2 CNV, a CN gain was found in 50 cases (14%) and a CN loss in 9 (3%): among the 337 patients analysed for both mutations and CNV, 13 carried both EZH2 mutation and gain (4%), 106 had mutations only (31%) and 31 had CN gain only (9%). The 50 patients with CN gain had overall less BM involvement (62% vs 79%, p=0.018) but no significant differences in other baseline clinical features nor in outcome; interestingly, among the 199 patients treated with R-CHOP those with CN gain only (n=20) showed a more favorable outcome than the others (5-y PFS: 75% vs 59%, p=0.053, Figure 1B). Conclusions. EZH2 mutations and CNV were tested by ddPCR in 409 BM samples from the largest, prospective series of FL: they had no clear impact in modifying the treatment effect (R-CHOP/BR), so a modulation of the first line treatment choice in FL based on EZH2 does not seem appropriate, so far. To better address this issue, mutational and CNV testing ofdiagnostic lymph node samples is currently ongoing

Hortus inclusus e chiostri urbani. Un approccio per il recupero microclimatico

The topic of functional recovery and the valorization of urban open spaces centers on an oftenoverlooked building type: urban cloisters, which were historically surrounded by convents. In this contribution, the author discusses the restoration of two large monasteries in Parma that are set to be transformed into student residences. The restoration project is further enhanced by the integration of microclimatic analysis and related design considerations

Nanosatellite autonomous navigation via extreme learning machine using magnetometer measurements

This work presents an algorithm to perform autonomous navigation in spacecraft using onboard magnetometer data during GPS outages. An Extended Kalman Filter (EKF) exploiting magnetic field measurements is combined with a Single-Hidden-Layer Feedforward Neural Network (SLFN) trained via the Extreme Learning Machine to improve the accuracy of the state estimate. The SLFN is trained using GPS data when available and predicts the state correction to be applied to the EKF estimates. The CHAOS-7 magnetic field model is used to generate the magnetometer measurements, while a 13th-order IGRF model is exploited by the EKF. Tests on simulated data showed that the algorithm improved the state estimate provided by the EKF by a factor of 2.4 for a total of 51 days when trained on 5 days of GPS data

Numerical analysis and prediction of the effect of debris initial configurations on their dispersion during extreme-hydrodynamic events

Tsunamis and other extreme hydrodynamic events have the potential to transport large debris that, along with the flow, are capable of causing severe damage to coastal structures and infrastructures. Therefore, modelling such processes is essential when assessing the multiple hazards associated to this type of events. In harbour areas, transport inland of shipping containers and subsequent impacts are relevant examples of waterborne debris hazards. The present work addresses two gaps in the scientific research of this problem using numerical methods; the understanding of the effect of containers initial layouts and that of the flow impact angle on the transport and diffusion. To fill these gaps a numerical study was carried out using idealised flow conditions. To this end a Smoothed Particles Hydrodynamics solver (DualSPHysics), coupled with a Discrete Element Method model (Project CHRONO), was used and initially validated with experiments published in the literature. Subsequently, four layouts commonly used in shipping containers yards were simulated, including incident flow depth and impact angle variability, resulting in 76 total simulations. The results were analysed in terms of normalised standard deviation and normalised range differences with respect to the initial values of both parameters. These parameters were related to the flow impact angle, water depth to containers height ratio DhR, and normalised displacement of the container clusters centroids. Standard deviation and range are shown to reach, for almost all results, a quasi-steady state by the end of the simulations. It is shown that the standard deviation and range are more sensitive to the impact angle for DhR ≤ 1.7. In this case, the configurations with flow impacting orthogonally to one of the containers axes show larger values of the two parameters than for intermediate angles. For larger values, DhR drives the standard deviation and range, independently from the impact angle. DhR is shown to be a physical parameter that well describes the relative importance of dispersion and advection of containers transported in extreme hydrodynamic events. Finally, existing relationships, that assume an infinite growth of the range, are shown to overestimate numerical results at the stage in which dispersion does not grow further. Two new regression formulae are numerically derived to predict the dispersion parameters at this stage. They include the effects of the cluster layout, impact angle α and DhR making them a valid alternative to existing relationship

The Tight Relationship Between the Tumoral Microenvironment and Radium-223

Radium-223 (223Ra) was the first radioactive isotope approved for treating castration-resistant prostate cancer (CRPC) with symptomatic bone metastases without visceral metastatic disease. To better understand the action of 223Ra, its role in the tumor microenvironment represents a crucial aspect. A literature search was conducted using the PubMed/MEDLINE database and studies regarding the relationship between 223Ra and the tumoral microenvironment were considered. The tumoral microenvironment is a complex setting in which complex interactions between cells and molecules occur. Radium223, as an alpha-emitter, induces double-stranded DNA breaks; to potentiate this effect, it could be used in patients with genetic instability but also in combination with therapies which inhibit DNA repair, modulate the immune response, or control tumor growth. In conclusion, a few studies have taken into consideration the tumoral microenvironment in association with 223Ra. However, its understanding is a priority to better comprehend how to effectively exploit 223Ra and its action mechanism

Architettura euclidea. Un abaco per l'azione adattiva

Il testo analizza la fragilità in architettura come valore creativo: un’opportunità per adottare un approccio adattivo e formalista per l’intervento sul costruito. Un esempio pratico è il progetto di una fabbrica a Casoria, dove interventi minimi e soluzioni geometriche hanno enfatizzato luce e chiaroscuro. La metodologia utilizzata si basa su un approccio euclideo che appiattisce la complessità spaziale su un piano bidimensionale ed esplora la relazione tra composizione e progettazione: non per creare bellezza assoluta, ma per articolare spazi nuovi e significativi attraverso una consonanza con le condizioni pregresse. La fragilità emerge così come valore estetico, funzionale e progettuale, capace di ispirare un’architettura mutevole e che non teme di testare il suo statuto figurale.The text analyzes fragility in architecture as a creative value: an opportunity to adopt an adaptive and formalist approach to interventions on existing structures. A practical example is the project for a factory in Casoria, where minimal interventions and geometric solutions emphasized light and chiaroscuro. The methodology is based on a Euclidean approach that flattens spatial complexity onto a two-dimensional plane and explore the relationship between composition and design, not to create absolute beauty, but to articulate new and meaningful spaces in harmony with pre-existing conditions. Fragility thus emerges as an aesthetic, functional, and design value, capable of inspiring architecture that evolves and dares to test its figurative nature

I modelli di partecipazione civica per la tutela e valorizzazione delle aree verdi urbane

L’articolo analizza i modelli di partecipazione civica per la tutela e valorizzazione delle aree verdi nel contesto della rigenerazione urbana. In effetti, i cittadini intervengono non soltanto nell’ambito del procedimento amministrativo relativo all’adozione dei piani o programmi ma anche al di fuori con iniziative spontanee non guidate dall’amministrazione contribuendo alla realizzazione di una città verde c.d. informale

AdaLightLog: Enhancing Application Logs Anomaly Detection via Adaptive Federating Learning

The role of anomaly detection systems in Critical Infrastructures (CIs) is critical due to the complexity of CIs and their control systems, which are usually implemented by computer-based controllers that constantly produce logs of their activities. Moreover, many CIs, located in different locations or even belonging to different companies, may share similar application software for controlling the CIs themselves. The goal of this work is to use such logs to perform automatic anomaly detection in a federated learning (FL) paradigm, which ensures that no data is exchanged between sites to train the anomaly detection models, but each learning agent learns on its own data, leveraging the knowledge acquired by the other agents. Our proposed approach - AdaLightLog - which implements a modified FL paradigm with adaptive loss functions at local servers side and weighted averaging of local server models, so to differentiate the quality of the different local servers’ models in the global averaging, is tested against state-of-the-art methods and shows an improvement in performance in terms of accuracy, precision and recall with respect to the standard FL implementation (FedAvg). Furthermore, a comparison between different metrics for the adaptive loss functions and the dynamic weights is presented