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Estimating map completeness in robot exploration
We present a novel method that, given a grid map of a partially explored indoor environment, estimates the amount of the explored area in the map and whether it is worth continuing to explore the uncovered part of the environment. Our method is based on the idea that modern deep learning models can successfully solve this task by leveraging visual clues in the map. Thus, we train a deep convolutional neural network on images depicting grid maps from partially explored environments, with annotations derived from the knowledge of the entire map, which is not available when the network is used for inference. We show that our network can be used to define a stopping criterion to successfully terminate the exploration process when this is expected to no longer add relevant details about the environment to the map, saving more than 35% of the total exploration time compared to covering the whole environment area
«UN ARCHIVIO VIVO» PER «UNA STORIA IMMEDIATA». L'ISTITUTO ERNESTO DE MARTINO NELLO SCENARIO INTERNAZIONALE
La tesi ricostruisce la storia dell’Istituto Ernesto de Martino (IEdM) inquadrandola nel più ampio scenario di scoperta delle fonti orali, segnato da pratiche e riflessioni condivise che – in forme spesso
non strutturate ed episodiche – attraversano reti transnazionali di ricercatori, enti, artisti e intellettuali attivi nella loro documentazione e valorizzazione. L’Istituto è analizzato sia come luogo di elaborazione culturale, con un proprio indirizzo di politica culturale, sia come archivio «politico», la cui genesi, impostazione ed evoluzione sono lette alla luce del contesto italiano e internazionale. L’impianto e lo sviluppo della tesi corrono lungo due direttrici principali: da un lato, la messa a fuoco della rete di rapporti che l’IEdM stabilisce con soggetti di affine vocazione in paesi europei ed
extraeuropei; dall’altro, l’indagine sulla nascita e la diffusione della oral history, con particolare attenzione ai possibili legami tra i suoi promotori e l’esperienza dell’Istituto. L’indagine si muove in prospettiva transnazionale e comparata, con un impianto che incrocia storia culturale e degli intellettuali, microstoria in chiave translocale, sound studies e riflessioni sull’archival activism, assumendo la registrazione come processo culturale e il sapere come «in transito» tra contesti e collettivi di pensiero. La tesi si articola in un’introduzione metodologica, un quadro storico sulle
premesse italiane e internazionali dell’uso delle testimonianze sonore, un’analisi in profondità del mandato culturale dell’IEdM con la ricostruzione del suo network di contatti, un capitolo conclusivo
sugli anni Settanta-Ottanta e sui rapporti tra l’Istituto e la cosiddetta «scuola italiana di storia orale». La base documentaria comprende corrispondenza, carte progettuali, materiali a stampa, fondi sonori
dell’IEdM e quindici interviste raccolte tra il 2023 e il 2024. La ricerca d’archivio si estende a istituti con sede in Germania, Ungheria, Regno Unito e Svizzera, seguendo i fili della circolazione di libri, dischi, nastri e bollettini. I risultati mostrano il superamento dell’immagine «autarchica» dell’Istituto. Esso intrattiene scambi con un ampio ventaglio di paesi – in particolare Stati Uniti, Gran Bretagna,
Repubblica Democratica Tedesca, Ungheria, Cuba e Cina – entro le coordinate di una cultura internazionalista antifascista e terzomondista, ed entra in contatto con enti e intellettuali che, in alcuni contesti, le storiografie nazionali riconoscono come casi pionieristici nella diffusione della oral history. Le dinamiche transnazionali non si configurano come importazioni unidirezionali, ma come scambi orizzontali nei quali transitano libri, bollettini, formati discografici, script radiofonici e saggi teorici, contribuendo a generare un orizzonte di riferimenti transnazionali. Per quanto riguarda la politica culturale dell’IEdM, emerge la centralità della nastroteca, fondata su un imperativo dell’archiviazione delle forme di espressività dei soggetti «non egemonici»: un mandato dalla natura
duplice, in cui dimensione politica e dimensione culturale risultano inscindibilmente intrecciate. Analizzare l’attività dell’IEdM significa osservare una pratica che va dalla raccolta alla descrizione,
dalla conservazione alla rielaborazione collettiva e alla circolazione pubblica delle fonti – e che concepisce la registrazione come processo culturale e il sapere come «in transito» tra contesti e gruppi
di intellettuali-militanti. Questo impianto è messo a fuoco attraverso l’analisi delle prime campagne di ricerca, dell’esperimento discografico degli Archivi Sonori e degli interventi in alcuni quartieri
cittadini. Nel quadro dell’affermazione della storia orale in Italia dalla metà degli anni Settanta, si ricostruisce il ruolo giocato dall’IEdM in un’arena segnata da una tensione costante tra circuito militante e istanze di legittimazione accademica. Adottando una prospettiva non teleologica sullo sviluppo della storia orale – in dialogo con le riflessioni di Graham Smith, Linda Shopes e Daniel Kerr – la tesi mette in luce anticipazioni e permanenze nelle modalità di intendere la fonte sonora, la sua narratività e l’intersoggettività dell’intervista, e propone una rilettura della traiettoria della oral history in Italia, evidenziando continuità, frizioni e processi di scambio e circolazione.This study investigates the history of the Ernesto de Martino Institute (IEdM) within the broader framework of the discovery and use of oral sources, a field shaped by shared practices and reflections that – often in fragmented and episodic forms – cut across transnational networks of researchers, institutions, artists, and intellectuals engaged in their documentation and enhancement. The Institute is examined both as a site of cultural elaboration, with its own orientation in cultural politics, and as a “political” archive, whose origins, structure, and evolution are interpreted considering the Italian and international context. The present PhD thesis develops along two main lines: on the one hand, an examination of the IEdM’s transnational relationships established with like-minded institutions and individuals in Europe and beyond; on the other, the exploration of the emergence and diffusion of oral history, with particular attention to potential intersections between its early promoters and the Institute’s experience. Adopting a transnational and comparative perspective, the research combines approaches from cultural and intellectual history, translocal microhistory, sound studies, and archival activism. It understands sound recording as a cultural process and knowledge as «in transit» between contexts and communities of thought. The dissertation is structured into a methodological introduction; a historical overview of Italian and international precedents in the use of sound testimony; an in-depth analysis of the IEdM’s cultural mandate, including a reconstruction of its network of contacts; and a final chapter on the 1970s–1980s, focusing on the Institute’s relationship with the so-called «Italian school of oral history». The documentary corpus includes correspondence, project files, printed materials, the Institute’s sound holdings, and fifteen interviews conducted between 2023 and 2024. Archival research was also carried out in Germany, Hungary, the United Kingdom, and Switzerland, following the circulation of books, records, tapes, and newsletters. The findings challenge the view of the Institute as an “insular” entity, showing instead its exchanges with a wide range of countries – most notably the United States, Great Britain, the German Democratic Republic, Hungary, Cuba, and China – within an antifascist, Third-Worldist, and internationalist cultural horizon. The IEdM engaged with institutions and intellectuals that, in some contexts, national historiographies identify as pioneers in the development of oral history. These transnational dynamics did not operate as one-way transfers but as horizontal exchanges involving books, recording formats, radio scripts, and theoretical essays, thereby generating a shared transnational framework of reference. The Institute’s cultural politics focused on its sound archive, conceived as an imperative to document the expressive forms of “subaltern” subjects. This dual mandate – at once political and cultural – highlighted the inseparability of the two dimensions. Studying the IEdM thus means tracing a practice that ranged from collection to description, preservation, collective re-elaboration, and public dissemination of sources – always conceiving recording as a cultural process and knowledge as “in transit” between contexts and intellectual-militant groups. This perspective is brought into focus through the analysis of the Institute’s first fieldwork campaigns, the Sound Archives record series, and community-based projects. In the context of the rise of oral history in Italy from the mid1970s, the thesis highlights the IEdM’s role in a field characterized by a persistent tension between militant circuits and the pursuit of academic recognition. Rejecting a teleological approach to the development of oral history – and engaging with the reflections of Graham Smith, Linda Shopes, and Daniel Kerr – the research sheds light on both anticipations and continuities in the ways sound sources were conceived, their narrative dimension, and the intersubjectivity of the interview. In doing so, it offers a new interpretation of the trajectories of oral history in Italy, emphasizing continuities, frictions, and processes of exchange and circulation
Can Hypopressive Abdominal Gymnastics Improve Sleep? Evidence from a Pilot Study
Purpose Postpartum women and individuals with diastasis recti, pelvic floor disorders, or chronic lower back pain are always more and more encouraged to practise Hypopressive Abdominal Gymnastics (HAG). It is a postural method designed to engage core and pelvic floor muscles by combining specific breathing techniques with low-pressure exercises. HAG aims to reduce intra-abdominal pressure and support muscle function. Although its benefits are well explored, its potential impact on sleep quality remains unclear. This study aimed to explore whether HAG might influence subjective and objective sleep parameters in women with rectus abdominis diastasis.
Methods Twenty-eight women (mean age 43.2 ± 7 years) with diastasis recti were assigned to either an intervention group (INT, n = 17) or a control group (CTRL, n = 11). The INT group participated in a supervised HAG program for two months (one session per week), while the CTRL group was advised to perform unsupervised home practice. Subjective sleep was evaluated using the Mini Sleep Questionnaire (MSQ), and objective sleep data were collected via actigraphy. Assessments were conducted one week before and after the intervention. ANCOVA (age AS COVARIATE) was used to analyse differences in pre-post delta values between groups.
Results Although not statistically significant, delta MSQ total scores (INT: -2.67 ± 1.19 a.u.; CTRL: -0.94 ± 0.24 a.u.; p = 0.67) and subcomponents, i.e. sleep (INT: -1.7 ± 0.92 a.u.; CTRL: -0.99 ± 0.74 a.u., p = 0.82) and wake domains (INT: -0.97 ± 0.46 a.u.; CTRL: 0.05 ± 0.03 a.u., p = 0.63) showed slightly greater improvements in the INT group compared to CTRL. Actigraphy data also suggested a positive trend in the INT group for delta sleep time (INT: 0.62 ± 0.35 %; CTRL: -0.38 ± 0.22 %; p = 0.49) and immobility percentages (INT: 0.43 ± 0.14 %; CTRL: 0.32 ± 0.25 %; p = 0.23), while the CTRL group showed slight declines. Sleep efficiency remained stable across both groups (INT: 1.48 ± 1.02 %; CTRL: 2.01 ± 1.49 %).
Conclusion This preliminary study suggests that a two-month HAG program may have a modest, positive effect on sleep quality, particularly in subjective assessments. However, results may not have reached statistical significance due to the small sample size and short duration. Future studies with larger cohorts and longer interventions are warranted better to understand HAG's potential role in sleep improvement
ANALISI EVOLUTIVA E SISTEMATICA DELLA FIGURA DEL SEGNALATORE FISCALE, IN BILICO TRA DIRITTO E DOVERE DI COMUNICAZIONE
L’elaborato articola la propria trattazione attorno alla figura del segnalatore fiscale, nella sua duplice accezione di soggetto che esercita un diritto di segnalazione/comunicazione, eventualmente accordatogli all’interno di una data disciplina normativa, da cui possono (auspicabilmente, ma non necessariamente) discendere tutele, garanzie e potenziali incentivi morali e/o patrimoniali, e di soggetto sul quale incombe uno specifico dovere di segnalazione e che non agisce, pertanto, in maniera libera e volontaria, ma in ottemperanza a una determinata normativa che gli impone di adempiere a specifici obblighi comunicativi.
Più nello specifico, l’analisi si sviluppa lungo tre differenti direttrici, relative: (i) alla nascita e all’evoluzione della disciplina (nazionale, sovranazionale e internazionale) del “segnalatore fiscale”, anche noto come “tax whistleblower”; (ii) alla soggettività tributaria, con particolare attenzione alle figure dei sostituti e dei responsabili d’imposta e agli eventuali soggetti (passivi) gravati di soli obblighi comunicativi (e non anche di obblighi contributivi), tra i quali possono essere annoverati anche i “segnalatori fiscali coatti”; (iii) alla cooperazione amministrativa in ambito fiscale, dando preminente rilievo alla disciplina dello scambio di informazioni in materia tributaria, la cui fonte di innesco può essere rappresentata proprio dalle informazioni fornite (per scelta o per obbligo) dai segnalatori fiscali.
L’attualità della tematica – che necessiterà di essere attentamente monitorata nei mesi e negli anni a venire – è stata di recente posta all’attenzione della stessa Commissione europea, ove è stata avanzata la proposta di un’Agenzia delle Entrate euro-unitaria, diretta (tra l’altro) alla gestione e al coordinamento dei suddetti meccanismi di scambio di informazioni. A ciò si aggiungano, peraltro, la continua evoluzione delle Direttive sulla cooperazione amministrativa, la riforma dello Statuto dei diritti del contribuente – che ha portato all’introduzione dell’articolo 7-quinquies – e le criticità legate alla tutela e alla protezione dei dati personali, aspetto che, nell’attuale epoca caratterizzata da un incessante progresso tecnologico e digitale, non può essere in alcun modo dato per scontato.The thesis focuses on the figure of tax whistleblower, in his dual meaning of a person who exercises a right of reporting, possibly granted within a regulatory framework, from which guarantees and potential moral and/or financial incentives may (hopefully, but not necessarily) derive, and as a person who has a specific duty to report and who does not act, therefore, voluntarily, but in compliance with some regulations that require to fulfil particular reporting obligations.
More specifically, the analysis is developed along three different lines, relating to: (i) the birth and evolution of the (Italian, European and International) discipline of tax whistleblower; (ii) the tax subjectivity, with particular attention to the figures of withholding agents, tax liable persons, and any other (passive) subjects burdened only with reporting obligations (and not also with contribution obligations), among which “mandatory tax whistleblowers” can also be included; (iii) administrative tax cooperation, with particular emphasis on the regulation of the exchange of information in tax matters, which may be triggered by the information provided (either voluntarily or compulsorily) by tax whistleblowers.
The relevance of the issue – which will be monitored in the coming months and years – has recently been brought to the attention of the European Commission, where a proposal has been put forward for a single European Tax Agency, aimed, in particular, at managing and coordinating the information exchange mechanisms. Moreover, the ongoing evolution of the Directives on Administrative Cooperation, the reform of the Taxpayers’ Statute – with the introduction of article 7-quinquies – and the critical issues related to the protection of personal data – a fundamental topic in the current era characterized by digitalization – cannot be taken for granted
Epistemologie della compliance nel semantic turn. Anomia e conformità nell’informatica giuridica e nella filosofia del diritto
Il contributo affronta il tema della compliance nel contesto normativo europeo, con particolare attenzione alla
necessità di sviluppare nuove epistemologie della conformità nell’ambito della compliance based analysis.
L’analisi muove dalla constatazione che i tradizionali modelli ontologici risultano insufficienti a cogliere la
complessità dei contesti operativi e del cosiddetto diritto vivente, specialmente quando la valutazione della
conformità coinvolge processi cognitivi umani e non umani e l’operato della pubblica amministrazione.
L’obiettivo è comprendere e spiegare le dinamiche conoscitive sottese alle pratiche di valutazione della
conformità, ricostruendo le diverse fasi dell’intelligibilità delle disposizioni normative e dei documenti che ne
derivano. I dati e i modelli esaminati consentono di ipotizzare l’emergere di basi epistemiche plurali, capaci di
integrare dimensioni linguistiche, modellistiche e operative.
In tale prospettiva, si sostiene la necessità di una transizione dalle “ontologie” alle “epistemologie”,
particolarmente rilevante quando la conformità è chiamata a misurarsi con standard normativi vincolanti e con
sistemi tecnologici avanzati. Il contributo propone una (ri)lettura di queste dinamiche.This article addresses compliance within the European regulatory framework, arguing for the need to move beyond traditional ontological models toward epistemological approaches to compliance-based analysis: what has been termed as a sematic turn. Static representations of legal norms are increasingly inadequate to capture the complexity of technologically mediated regulatory environments and the dynamics of living law, particularly where compliance assessment involves human and non-human cognitive processes and public administrative action. The contribution conceptualizes compliance not as a binary condition of conformity, but as a dynamic process of knowledge production, interpretation, and justification, closely linked to conditions of structural anomie and regulatory uncertainty. Drawing on legal philosophy and legal informatics, and engaging with phenomenological perspectives, the analysis reconstructs the epistemic dynamics underlying compliance practices, focusing on the intelligibility of legal provisions, risk-based governance, and explainability requirements. The examination of European regulatory regimes such as the GDPR, the NIS II Directive, and the Artificial Intelligence Act highlights the emergence of plural epistemic foundations capable of integrating legal, linguistic, technological, and organizational dimensions. From this perspective, the article argues that a transition to epistemologies of compliance is both theoretically necessary and practically relevant for governing complex regulatory systems shaped by advanced technologies
Art Therapy in Japan: Promoting Resilience and Wellbeing through Community-Based and Culturally Rooted Practices
In contemporary Japan, mental health has become one of the most pressing social concerns. Anxiety, depression, and various forms of psychosocial distress affect a growing number of people within a cultural environment that often silences suffering and places strong emphasis on self-control. Although the healthcare and social welfare system is highly developed, it continues to struggle with complex forms of distress deeply embedded in everyday social relations. Against this backdrop, non-pharmacological approaches capable of restoring a more human, holistic, and community-oriented dimension to care are attracting increasing interest.
Among these approaches, the arts therapies stand out for their capacity to integrate the aesthetic, bodily, and relational dimensions of health. Artistic practices – including music, movement, visual arts, and collaborative creation – play a central role in supporting emotional control, identity reconstruction, social cohesion, and active participation, fostering forms of well-being that are both sustainable and culturally sensitive. Nevertheless, dedicated arts therapy centres offering high-quality and coherent programmes remain limited and unevenly distributed across Japan, reflecting a field that is still in the process of consolidation, while seeking broader institutional recognition.
Within this landscape, the experience of the centre known as momo (Music, Outsider Art, Movement, Open Studio) in Kyoto, alongside other emerging initiatives across the country, offers a significant example of innovation. By integrating multiple arts-therapeutic disciplines, momo provides accessible, non-clinical spaces in which artistic practice becomes a means of expression, self-construction, and the reweaving of community bonds. The centre has also contributed to the development of the Integrated Arts Therapy Evaluation Framework (IATEF), an interdisciplinary methodological tool designed to document engagement, creativity, and psychosomatic well-being without reducing these processes to overly clinical parameters.
Beyond methodological advancement, this work invites a broader understanding of care as a social and cultural practice. In a Japan marked by widespread psychological fragility, the arts therapies are increasingly recognised as a crucial resource for regenerating social bonds, promoting creativity and community cohesion, and articulating shared forms of resilience. More than therapeutic techniques, they constitute cultural processes capable of mitigating social fragmentation and strengthening collective well-being in contemporary Japan
Long-term outcomes of stapled haemorrhoidopexy versus conventional haemorrhoidectomy: An updated systematic review, meta-analysis and trial-sequential analysis of randomized controlled trials
Purpose Stapled haemorrhoidopexy (SH) offers well-established short-term advantages over conventional haemorrhoidectomy (CH), but its long-term effectiveness remains controversial. This systematic review and meta-analysis aimed to compare long-term outcomes of SH versus CH in adult patients with grade II–IV haemorrhoids, incorporating Trial Sequential Analysis (TSA). Methods MEDLINE, EMBASE and CENTRAL were searched from January 2001 to October 2025 for randomized controlled trials (RCTs) comparing SH and CH with a minimum follow-up of 12 months. Two reviewers independently performed study selection, data extraction and risk-of-bias assessment (RoB-2). Primary outcomes included recurrence, reintervention, anal function, and quality of life (QoL). Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models. TSA was applied to overall recurrence. Results Seventeen RCTs including 1,041 SH and 1,031 CH patients were analysed. SH was associated with a higher risk of overall recurrence compared with CH (RR = 1.56,95%CI = 1.00–2.44;I2 = 48%). TSA showed that the accrued information size (1,913 patients) did not reach the required information size (2,608 patients), indicating that current evidence remains underpowered. Prolapse-related recurrence was significantly more frequent after SH (RR = 3.28,95%CI = 1.49–7.25;I2 = 12%), whereas bleeding-related recurrence did not differ between groups (RR = 1.20,95%CI = 0.63–2.26;I2 = 23%). No significant differences were found for reintervention, persistent anal pain, functional impairment or QoL. Conclusion SH is associated with a higher risk of long-term recurrence, particularly prolapse-related recurrence, compared with CH, while long-term pain, functional outcomes and QoL appear broadly comparable. These findings suggest that, although SH may remain an option for selected patients, CH provides more durable anatomical correction, and procedural choice should balance early recovery against long-term durability
Detection of kiwifruit low-force early bruise by combining surface textural parameters and near-infrared hyperspectral imaging
This study evaluates the feasibility of detecting and monitoring occurrence and progression of low-force mechanical damage in kiwifruit (Actinidia deliciosa) using Near-Infrared Hyperspectral Imaging combined with surface texture analysis and multivariate classification. Previous studies have applied HSI for bruise detection but often used unrealistically high impact forces, limiting relevance to real-world handling conditions. ‘Hayward’ kiwifruit were subjected to controlled impact forces of very low intensity (23.4 N and 46.8 N) to simulate realistic damage and stored at 25 ± 1 °C for five days. Hyperspectral data were acquired using a short-wave infrared camera (960–2500 nm) at different sampling times. Principal Component Analysis (PCA) was applied to reduce data dimensionality, and surface texture features extracted from PCA score images accounted for fruit shape and surface characteristics. A Partial Least Squares – Discriminant Analysis (PLS-DA) model classified damaged versus healthy tissue, achieving an overall accuracy of 94.7 % across hyperspectral images. Changes in damaged pixels allowed an indirect evaluation of progressive tissue degradation. Results showed a high detection of damaged (invisible to naked eye) and healthy tissue, demonstrating the efficiency of the methodology in preventing fruits affected by realistic damage from entering the fresh market while facilitating their use in alternative applications
DEVELOPMENT OF BIOACTIVE NATURAL PRODUCTS:TOTAL SYNTHESIS AND STRUCTURE MODIFICATION TOWARD ANTIMICROBIAL AND ANTITUMOR AGENTS
Nowadays several challenges are threatening human’s quality of life. Global population is
growing fast, and with that, the demand for food. Daily, 2.4 billion people struggle with food
insecurity, facing either moderate or severe shortages that impact their lives and safety. [1]
This date will probably keep worsening, as a 30% increase in population is expected to be
reached by 2050. [2] In 2015, the United Nations established a plan of action made of 17
goals that must be fulfilled if we want to end poverty and hunger while improving health,
education and equality by 2030.
Agriculture has always been the primary source of food for humanity, and thus it is expected
to play a pivotal role in this sustainable development program. However nowadays it is far
from represent the excellent food system we are dreaming of. In this scenario a factor that
could make a difference is working for decreasing food waste. As a matter of fact, huge crop
losses are recorded in both pre-and post-harvest handling processes mainly because of the
heavy impact of plant diseases. [3] Fungicides represent agriculture’s main weapon in this
emergency, therefore improvements and innovations in this field are fundamental. A strategy
to develop new environmentally friendly fungicides could be to switch from chemicals to
biopesticides inspired by natural compounds (European Commission. Encouraging
Innovation in Biopesticide Development. https://wayback.archive-it.org/12090/). The goal
is to develop new highly efficient agrochemicals, with innovative modes of action, efficient
to counteract development of resistant strains, and with milder impact on the soil as on the
non-target organisms.
Another burden impacting in the quality of life is the improper treatments used to counteract
the highest fatality-related illnesses. First, there is the devastating threat of cancers, among
the first cause of death worldwide. [4] Second, the challenges in counteracting the spreading
of infections caused by multi-drug-resistant bacteria. [5] Even in this case chemicals are
expected to play a central role and to be optimized to efficiently counteract the insurgence
of resistant malignities. Moreover, diminishing the devastating drug related side-effects is
urgent in the case of chemotherapy, while increasing the willingness and efficacy is
fundamental in the development of antibiotics.
The aim of my project was to explore the limitless source of bioactive molecules represent
by nature, to develop new antimicrobial and antitumor compounds. NPs unique scaffolds,
innovative mode of action, high bioactivity, and mild impact on the environment are just few
of the intrinsic characteristics that make these scaffolds suitable to be considered in the
development of leads compounds. As NPs are mostly secondary metabolites, produced by
organism under well-defined conditions, their recovery from the natural matrix could be troublesome, low yielding and challenging for complex purification steps. [6] Therefore, the
employment of natural compounds obtained directly from extracts is often impractical and
tedious. In this context, the development of chemical and chemoenzymatic approaches to
make natural molecules more accessible in high amount could open the possibility to
improve the understanding and knowledge of NPs related biological activities. Moreover,
structure modifications could be applied on identified natural leads compounds to try and
expand the collection of compounds with nature-inspired analogues. These SAR studies
could enable to find the best combination of chemical features, to obtain optimized new
scaffolds with improved biological activity.
In this project five classes of phytoalexins were considered: phenolamides,
dehydrodiferulates, stilbenoids, iron-chelating hydroxamates, and thioamidates. These
molecules are organisms’ secondary metabolites accumulated under biotic or abiotic stress
conditions, which role in organisms’ self-defence mechanisms has already been reported in
literature. Briefly, for NPs phenolamides and dehydrodiferulates a chemoenzymatic strategy
was successfully applied to obtain high amounts of the natural molecules. Moreover,
biological screening led to identification of some active compounds. As for
dehydrodiferulates, structure modifications were applied resulting in the synthesis of some
new scaffolds that, also in this case, turned out to be endowed with broad activity as both
antimicrobials and cytotoxic compounds. The stilbenoids project was focused on the
synthesis of multi-target antifungals, as strategy to enhance strobirulins effect on P. oryzae
resistant strains. Finally, in this thesis the approach to the total synthesis of two NPs has been
described. In the case of rhodotorulic acid our strategy was to obtain a short and scalable
procedure, while for thioholgamide A its total synthesis has never been approached before This PhD project offered me the opportunity to collaborate with several research groups. The
antifungal biological evaluation tests were performed in collaboration with the group of Prof.
Andrea Kunova (Department of Food, Environmental and Nutritional Sciences, DeFENS,
University of Milan), while the antibacterial tests in collaboration with the group of Prof.
Piera Anna Martino (Department of Biomedical, Surgical, and Dental Sciences, DSBCO,
One Health Unit, University of Milan) and Prof. Federico Baruzzi (Institute of Sciences of
Food Production, CNR-ISPA, Bari). In the dehydrodiferulates project two international
research groups were involved, the one of Prof. Jean-Paul Vincken (Laboratory of Food
Chemistry, University of Wageningen, Netherlands) and that of Prof. Elke Richling
(Department of Chemistry, Division of Food Chemistry and Toxicology, Technische
Universität Kaiserslautern, Germany). Finally, I had the opportunity to take part on the total
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synthesis of thioholgamide A project while hosted by Prof. Philipp Heretsch (Institut für
Organische Chemie, University of Hannover, Germany) during my Erasmus stint.
In the following chapters the identification and the design of new nature-derived
antimicrobial and antitumoral agents will be described, starting from their synthesis to the
investigation of their biological properties