702 research outputs found
Sort by
Synthesis of novel conjugates based on a functionalized cyclo[DKP-isoDGR] integrin ligand and potent cytotoxic agents
Full text linkTargeted drug delivery is a growing-interest field in cancer therapy as a strategy for overcoming the systemic cytotoxicity associated to traditional chemotherapy. One important approach in this research area is represented by the small molecule-drug conjugates (SMDCs), where the drug-targeting is performed by a low molecular weight ligand (peptide, vitamin or peptidomimetic) connected to a potent warhead through a stable linker. This PhD thesis describes the synthesis and biological evaluation of novel SMDCs containing the functionalized cyclo[DKP-isoDGR] integrin ligand developed by our research group and potent cytotoxic drugs (α-amanitin, MMAE and MMAF) combined via different linkers and spacers. The conjugates were evaluated for their binding affinity to the isolated αvβ3 receptor and for their antiproliferative activity on cancer cell lines with different levels of αVβ3 expression in order to study the efficacy of the cyclo[DKP-isoDGR] integrin ligand as a vector for tumor drug-delivery
Equations and systems of nonlinear equations: from high order numerical methods to fast Eigensolvers for structured matrices and applications
Full text linkA parametrized multi-step Newton method is constructed for widening the region of convergence of classical multi-step Newton method. The second improvement is proposed in the context of multistep Newton methods, by introducing preconditioners to enhance their accuracy, without disturbing their original order of convergence and the related computational cost (in most of the cases).
To find roots with unknown multiplicities preconditioners are also effective when they are applied to the Newton method for roots with unknown multiplicities. Frozen Jacobian higher order multistep iterative method for the solution of systems of nonlinear equations are developed and the related results better than those obtained when employing the classical frozen Jacobian multi-step Newton method.
To get benefit from the past information that is produced by the iterative method, we constructed iterative methods with memory for solving systems of nonlinear equations. Iterative methods with memory have a greater rate of convergence, if compared with the iterative method without memory. In terms of computational cost, iterative methods with memory are marginally superior comparatively.
Numerical methods are also introduced for approximating all the eigenvalues of banded symmetric Toeplitz and preconditioned Toeplitz matrices.
Our proposed numerical methods work very efficiently, when the generating symbols of the considered Toeplitz matrices are bijective
Effects of some stable derivatives of butyrate used as feed additives on fish intestinal microbiota, histone modifications and the expression of genes related to epigenetic regulatory mechanisms and immune response.
No full textBacteria that inhabit the epithelium of the animals’ digestive tract provide the essential biochemical pathways for fermenting otherwise indigestible dietary fibers, leading to the production of short-chain fatty acids (SCFAs). Of the major SCFAs, butyrate has received particular attention due to its numerous positive effects on the health of the intestinal tract and peripheral tissues.
Butyrate plays a major role in enhancing epithelial cell proliferation and differentiation and in improving the intestinal absorptive function. It has also potential immunomodulatory and anti-inflammatory properties in the intestine and may prevent colorectal cancer in humans.
The mechanisms of action of butyrate are different; this four-carbon chain organic acid is a histone deacetylase inhibitor that play a predominant role in the epigenetic regulation of gene expression and cell function, therefore many of its mechanisms are related to its potent regulatory effect on gene expression.
During the first year of PhD, my research activity was related to the study of the effects of dietary sodium butyrate on histone modifications and the expression of genes involved in epigenetic regulatory mechanisms and immune response in European sea bass (Dicentrarchus Labrax) fed a plant-based diet.
Accordingly, the effects of butyrate used as a feed additive on fish epigenetics as well as its regulatory role in mucosal protection and immune homeostasis through impact on gene expression, were investigated.
To meet the aims, seven target genes related to inflammatory response and reinforcement of the epithelial defense barrier [tnfα (tumor necrosis factor alpha) il1β, (interleukin 1beta), il-6, il-8, il-10, and muc2 (mucin 2)] and five target genes related to epigenetic modifications [dicer1(doublestranded RNA-specific endoribonuclease), ehmt2 (euchromatic histone-lysine-N-methyltransferase 2), pcgf2 (polycomb group ring finger 2), hdac11 (histone deacetylase-11), and jarid2a (jumonji)] were analyzed in fish intestine and liver. We also investigated the effect of dietary butyrate supplementation on histone acetylation, by performing an immunoblotting analysis on liver core histone extracts. Results of the eight-week feeding trial showed no significant differences in weight gain or Specific Growth Rate (SGR) in sea bass that received 0.2% sodium butyrate supplementation in the diet in comparison to control fish that received a diet without Na-butyrate. Dietary butyrate led to a two-fold increase in the acetylation level of histone H4 at lysine 8, but showed no effect on the histone H3 at Lys9. Moreover, two different isoforms of histone H3 that might correspond to the H3.1 and H3.2 isoforms previously found in terrestrial animals were separated on the immunoblots. The expression of four (il1 β, il8, irf1, and tnfα) out of seven analyzed genes related to mucosal protection and inflammatory response was significantly different between the two analyzed tissues but only il10 showed differences in expression due to the interaction between tissue and butyrate treatment. In addition, butyrate caused significant changes in vivo in the expression of genes related to epigenetic regulatory mechanisms such as hdac11, ehmt2, and dicer1. Statistical analysis by two-way ANOVA for these genes showed not only significant differences due to the butyrate treatment, but also due to the interaction between tissue and treatment.
In the second year of my studies, I focused on a different fish species - gilthead sea bream (Sparus aurata), to investigate the effects of a specific combination of short- and medium-chain 1-monoglycerides on intestinal microbiome, gene expression, and fish growth performance.
In aquaculture research, one important aim of the gut microbiota studies is to provide a scientific basis for developing effective strategies to manipulate gut microbial communities through the diet, promoting fish health and improving productivity.
Currently, there is an increasing research interest towards the use of organic acids in commercial aqua-feeds, due to several beneficial effects they have on growth performance and intestinal tract’s health of farmed fish. Among organic acids, monoglycerides of short-chain fatty acids (SCFAs) and medium-chain fatty acids (MCFAs) have attracted particular research attention also for their bacteriostatic and bactericidal properties. Accordingly, the present study aimed to evaluate the potential beneficial effects of SCFA and MCFA monoglycerides, used as a feed additive, on fish growth performance, and intestinal microbiota composition. For this purpose, a specific combination of short- and medium-chain 1-monoglycerides (SILOhealth 108Z) was tested in 600 juvenile gilthead sea bream (Sparus aurata) of 60 g mean initial weight that were fed for 90 days with plant-based diets. Two isoproteic and isolipidic diets were formulated. The control fish group received a plantbased diet, whereas the other group received the same control feed, but supplemented with 0.5% of SILOhealth 108Z. The Illumina MiSeq platform for high-throughput amplicon sequencing of 16S rRNA gene and QIIME pipeline were used to analyse and characterize the whole microbiome associated with both thefeeds and S. aurata intestine. The number of reads taxonomically classified according to the Greengenes database was 394,611. We identified 259 OTUs at 97% identity in sea bream fecal samples; 90 OTUs constituted the core gut microbiota. Firmicutes, Proteobacteria and Actinobacteria represented the dominant phyla in both experimental groups. Among them, relative abundances of Firmicutes and Proteobacteria were positively and negatively affected by dietary SCFA monoglycerides supplementation, respectively. In summary, our findings clearly indicated that SILOhealth 108Z positively modulated the fish intestinal microbiota by increasing the number of beneficial lactic acid bacteria, namely, Lactobacillus, and reducing Gammaproteobacteria, which include several potential pathogenic bacteria. The specific composition of 1-monoglycerides of short and medium-chain fatty acids contained in SILOhealth 108Z could thus have a great potential as a feed additive in aquaculture
Application of method of lines in chemical engineering problems
Full text linkIn this work, two problems in chemical engineering are studied and
solved. Estimation of an important parameter of dust explosions, the
deflagration index kST , and a study of unsteady state with axial diffusion Plug Flow Reactors are presented. Both problems are approached by
characterizing the physical phenomena involved with suitable transport
equations. Such equations have been developed with the synergy of both
consolidated theoretical models and ad hoc assumptions and semi-empiric
approaches, according to the specific problem analyzed. The final equation systems result in a system of non-linear Partial Differential Equations.
The numerical solution of such equations has been performed by implementing the Method of Lines, a numerical method based on the discretization of spatial derivative operators, transforming a system of PDEs into a
system of ODEs or DAEs. The resulting ODEs/DAEs systems have been
implemented and solved inside MAT LABTMenvironment. The Method
of Lines is presented for uniform and non-uniform grids, generalized with
the use of spatial derivatives discretization stencils of several orders of
accuracy.
For the estimation of kST , we validated the model with 8 organic dust:
Aspirin, Cork, Corn starch, Niacin, Polyethylene, Polystyrene, Sugar and
Wheat flour. Results showed an interesting match between experimental
and simulated data: predictions for the deflagration index were good,
while the evolution of process variables (such as the temperature of the
gas phase), still leaves room for improvements.
For the PFR study, we propose 1-D models, taking in account the
reactor start-up, thermal and material axial diffusion, and the presence
of a heating/cooling system. In order to judge the quality of the results,
we took as case study a reaction well studied in the literature over the
years: the oxidation of Naphthalene. We developed the so-called Runaway Boundaries for the reaction considered. Our results found good
matches with the available literature data and analysis. We also noticed
a shifting of the Runaway Boundaries when considering a more realistic
heating/cooling system
Fine vita e decisioni etiche nelle emergenze anestesiologiche intraospedaliere.
Full text linkBiomedical and biotechnological progress nowadays allowed doctors to prolong life through new and best therapies for many, once deathly, illnesses, and through new machine which can maintain vital functions in an artificial way; the therapeutic limit is always moved forward. Anesthesiologist usually manage emergency and urgencies in all hospitals’ ward where the patients, especially during night and festive shift, can’t always refer to their daily practitioner, who is not present in those context. If a CPR is necessary without the presence of the daily practitioner, bioethical problems, most of all due to the lack of medical deliveries regarding end of life decisions and clinical problems, grow exponentially.
These conditions often lead to a wrong management with a start or a prosecution of treatments even when there shouldn’t have been a proper indication; with a good communication and time to study the case, no one would have probably started CPR in many of those patients.
Our goal was the evaluation of the management of these special cases, in a bioethical field, by visualizing retrospectively one year of intrahospital emergencies with an anaesthesiologist call, looking for basal datas regarding number and typology of emergencies and what is normally reported in medical records, then following results of these patients.
Surely we can conclude that, if we want an improvement regarding ethical approach to CPR to patients with clinical history unknown by anesthesiologist, there should be a more codified decisional flowchart or medical delivery system in order to write and tell clearly ethical and clinical consideration
Considerazioni bioetiche applicate alla medicina dei disastri. Studio osservazionale inerente la conoscenza e la percezione riguardo i dilemmi etici da parte di studenti partecipanti a corsi post-laurea di medicina dei disastri.
Full text linkDisasters, like earthquakes, epidemics and wide and complex emergencies raise many ethical issues for the people involved, who include responders, health specialists, educators and policy-makers. A disaster is defined by the United Nations Office for Disaster Risk Reduction as a “serious disruption of the functioning of a community or a society involving widespread human, material, economic or environmental losses and impacts, which exceeds the ability of the affected community or society to cope using its own resources”. A Disaster is a result of interactions between hazards and manifold community elements, with differing vulnerability and capacity to cope with such situations. The disaster dynamics depict the various phases like a circle: disaster preparedness, response, rehabilitation, reconstruction, development, disaster prevention, mitigation. The requirements of the community for patient care and for research and surveillance vary case by case and are influenced by how risks are managed before, during and after events and by the type and magnitude of the consequences of emergencies when they occur.
Disaster Medicine is concerned with the comprehensive response management and application of various health disciplines, from military and emergency to public health medicines, dealing with human-made and natural catastrophes by the “disaster pillars” of prevention, planning response recovery and mitigation. Such events often result in a large number of victims, who have undergone both physical and mental insults, that temporarily disrupts the ability of the local health response system invalidating the ordinariness socio-economic and public health of the affected resulting in an imbalance between the relief response and the resources immediately available in the area. In these scenarios rescuers have to cope with an imbalance between the relief response and the resources, operate with different standards and specific recommendations out of the ordinary clinical practice.
The wide range of potential types of disasters is also reflected in the field of bioethics that underlie the decisions of planners and those involved in a disaster. The lack of time and the complexity of the operational performance of disaster operations require an ethical reflection process to enable the health operators to take advantage of clear behavioral recommendations to recalibrate on spot their ethical decisions because medical professionals have to face with uncommon and dramatic ethical dilemmas.
In the last decades the scientific community began to wonder about the issues posed by this recent branch of medicine through an embryonic production of both clinical and organizational recommendations for bioethical debates applied to research, training and management of such topics. Triage, Allocation of resources, vulnerability of those involved, risks and benefits of participation in research, informed consent, training represent only some of this thematic. Health professional preparedness is one of the imperative key element of disaster response focused on clinical and organizational conducts. Worldwide training programs in disaster medicine are usually structured to create emergency preparedness core competencies in this matter. But if we focus on bioethics declined to this discipline, create ethical competencies in the field of disaster medicine represent one of the new challenges.
The ability to analyze the boundaries between public health practice, including surveillance, and research and their ethical implications in emergencies, to define adequate processes for ethics review or to define ethically relevant criteria for standards of care in emergency response and the expertise to discuss the professional duties of health care workers during clinical performances, public health surveillance, research and management in disasters and complex humanitarian emergencies, as reported by the WHO “Ethics in epidemics, emergencies and disasters: research, surveillance and patient care” training manual, represent the core competences sum of relief workers, researchers and ethical consultants involved in each phases of disaster events.
According to the third world conference on disaster risk reduction recommendations is fundamental to promote and enhance the training capacities to cope disasters and create resilience. If clinical and managerial educational topics in disaster medicine are strongly depicted, this discipline still reveals a complexity of concerns about several ethical topics. Most of the latest international core curriculum education proposals in disaster medicine embody ethics competency. The purposes of the present pilot study, co-realized by the Center for Clinical Ethics of the University of Insubria (Italy) were to investigate the interest and cognition on ethical issues by a cohort of health operators, mostly medical doctors, attending two disaster medicine international programs delivered by the Research Center in Emergency and Disaster Medicine (CRIMEDIM) of the University of Eastern Piedmont (Italy). An anonymous questionnaire was proposed to the students attending the European Master Degree in Disaster Medicine and the Humanitarian Medic Program in three academic sessions (2015-2017). 128 questionnaires were received. The interest about ethical issues is robust for the 96% of the respondents. As assumed disasters ethical dilemmas are perceived dissimilar to the ordinary medicine practice (χ2 0,916, p=0,011). About the importance of sixteen main topics proposed, like disaster triage, allocation of resources, informed consent, palliative care for non-salvageables or disaster research the range of acceptance was demonstrated (χ2 0,984, p=0,031). A significant portion of attendees consider useful the contribution of an ethical consultant to draft a mass casualty protocol (84%) or in case of debriefing (81%), less into operational phases (59%). The results have depicted a strong involvement in disaster ethics by the participants and various learning needs too that educators has to take in account to frame ethical contents into disaster medical educational programs
Population properties, dissipation and radiative processes in GRBs.
Full text linkGamma Ray Bursts (GRBs) are short and intense flashes of γ–rays with typical energies between keV and a few MeV. They reach luminosities (assuming isotropy) of 1054 erg/s. The γ–ray emission, called “prompt”, is highly variable (with timescales as short as few milliseconds) and can last a fraction of a second (short GRBs, T90 2 s). The prompt is followed by the “afterglow” emission, at lower frequencies (in the X–ray, Optical and Radio band) which has been detected also up to several months after the trigger and is typically smooth and decaying as a function of time. GRBs are cosmological sources having average redshift ∼ 2.5. The progenitors of long GRBs are thought to be very massive stars that collapse at the end of their life, while the progenitors of short GRBs are thought to be the merging of two neutron stars.
Two of the key properties characterizing the population of GRBs are their cosmic formation rate ψ(z) (GRBFR) and their luminosity function φ(L) (LF). Recovering ψ (z) and φ(L) of GRBs allows us to test the nature of their progenitor (e.g. through the comparison with the cosmic star formation rate), to study the possible presence of sub–classes of GRBs and to infer intrinsic properties such as the structure of their jetted outflows. The knowledge of the intrinsic population properties is becoming even more compelling with the recent association of short GRBs with gravitational wave signals produced by the merger of two neutron stars. I also concentrated my work on the prompt emission dissipation and radiation mechanism operating in GRBs
Il diritto di proprietà nella circolazione delle opere d'arte. I confini fra diritti “privati” e interesse pubblico nella teoria dei beni comuni.
Full text linkThe object of this research is twofold: on the one hand the property right, with particular reference to the public property; on the other hand, the issue of national and international circulation of works of art.
The two topics, certainly interrelated and interconnected, are analyzed through the deepening of the theory of commons, from its origins in the sixties of the last century to the recent doctrinal and social debates that have involved, in recent years, the Italian academy and politics.
Can the property be only public or private, or can a third category exist?
Can works of art, and more generally cultural assets, be included among the so-called commons?
Can theories concerning commons influence the adoption by the sovereign States of laws that are more or less favorable to the circulation of works of art?
The answer to these questions can be both normative and philosophical and derives from a value choice that every legal system must necessarily adopt: the answers will certainly be different, in the same way that, all around the world, there are sovereign States "exporters" and sovereign States "importers" of works of art
La gestione dell’attività estrattiva nel Veneto del Settecento come problema storiografico. Il viaggio mineralogico e il progetto minerario di Marco Carburi.
No full textQuesto lavoro è nato nell’interesse per un problema storiografico da tempo individuato, ma solo parzialmente affrontato nel contesto italiano, che riguarda lo studio delle tecniche nella storia delle attività estrattive in età moderna. In particolare, sono stati inizialmente individuati quali oggetti della ricerca, all’interno di un caso di studio significativo ma sostanzialmente inesplorato, gli aspetti legati alla tecnica di escavazione di pietra ornamentale nell’ambito del Veneto del Settecento. A tal proposito si è dato avvio alla ricerca di fonti primarie presso l’Archivio di Stato di Venezia, dove è stato consultato il Fondo Deputati delle Miniere, un ricco ed articolato complesso archivistico che comprende le carte prodotte e ricevute nell’arco temporale 1488-1799, dall’organo chiamato ad amministrare, presso la Repubblica Serenissima, il settore dell’escavazione di cave e miniere.
In considerazione dell’ampia presenza di cave rilevate nel territorio del Veneto nord-orientale, il lavoro di ricerca è poi proseguito presso l’Archivio di Stato di Verona presso cui, vista l’assenza di fondi specifici sul settore oggetto di indagine è stata effettuata una ricognizione del materiale presente elle cartelle Delegazione provinciale, Prefettura e Antico Archivio del Comune.
Gli esiti delle ricerche presso i due archivi veneti hanno portato ai risultati ipotizzati e quindi al possibile emergere di nuove fonti in grado di consentire un’analisi e una ricostruzione storica approfondita delle attività estrattive in cava: considerato tuttavia l’accumulo di una ingente quantità di materiale inedito, di cui si darà conto in seguito e in particolare nel secondo capitolo, si è giunti alla possibilità di ricalibrare su nuove linee di indagine il progetto di ricerca, che si è incentrato di conseguenza sullo studio di diverse figure professionali impiegate in miniera.
E’ stata individuata la figura del sovrintendente di miniera, di cui si è proceduto ad individuare, interpretare e ricostruire responsabilità e competenze. Nel medesimo ambito lavorativo è quindi emersa una figura professionale che solo occasionalmente prestò la sua opera e il suo sapere alla gestione del sito estrattivo, ma che si inserì contestualmente, sia pure in modo controverso, nella pratica del viaggio mineralogico e minerario di istruzione che coinvolse soprattutto a partire dalla seconda metà del Settecento diversi studiosi europei, tra cui alcuni italiani. Si tratta del chimico Marco Carburi (1730-1808), docente presso l’Università di Padova, chiamato dalla Repubblica Serenissima a visitare le miniere di Agordo nel Bellunese e a stendere una relazione particolareggiata su diversi aspetti utili all’aumento della produttività e a un conseguente incremento della rendita non solo attraverso modifiche tecniche, ma anche attraverso espedienti economico finanziari.
Nel primo capitolo viene presentato un inquadramento storiografico che prende in considerazione le differenti fonti disponibili su cave, miniere e terre coloranti nella Serenissima durante il Settecento: a tal proposito è infatti importante evidenziare quanto sia profondamente differente la nature del materiale disponibile, da un lato per le cave di pietra e dall’altro per quelle di miniera.
Nel secondo capitolo viene evidenziato, sotto il punto di vista di un duplice problema, lo studio storico delle cave: in particolare si considerano gli aspetti desumibili per ciò che riguarda, da un lato, la tecnica e dall’altro, la contribuzione fiscale derivante dall’estrazione lapìdea. Un analogo percorso di ricerca viene dedicato alla coltivazione delle miniere, per quanto concerne in particolare gli aspetti amministrativi e il ruolo delle tecniche: nello specifico viene utilizzata una tipologia di fonte primaria finora scarsamente utilizzata e costituita dalle relazioni dei tecnici.
Le relazioni prese in considerazione sono in particolare quelle datate tra il 1710 3 il 1745, a firma di Iseppo Zanchi, nonché alcune carte inserite nel Fondo Scritture del Magistrato sopra le Miniere.
Attraverso le relazioni dio Iseppo Zanchi viene ricostruita una breve storia della famiglia di questo tecnico, che per molti anni fu impiegato presso le pubbliche miniere di Agordo. Il caso degli Zanchi si rivela estremamente interessante poiché evidenzia l’attività di diverse generazioni di questa famiglia presso le miniere dell’Agordino: sono state contate almeno cinque generazioni e sarà quindi proposta una prima ricostruzione dell’albero genealogico e delle diverse competenze professionali dei vari membri impiegati nelle attività di miniera in Agordo.
Il terzo capitolo è dedicato ad inquadrare la figura del professore di chimica sperimentale dell’ateneo di Padova Marco Carburi, il quale, oltre alla coltivazione delle miniere di rame nella valle d’Agordo in provincia di Belluno, coltivò nel corso della sua lunga carriera universitaria molteplici interessi di studio. Una volta terminate le sue visite agli stabilimenti di Agordo e dopo aver compiuto un viaggio nelle regioni minerarie del Nord Europa, Carburi propose alla Serenissima alcune misure da adottare anche in Veneto per migliorare le tecniche estrattive di miniera e riorganizzare la produttività dell’azienda statale: questi suggerimenti sono contenuti in un manoscritto finora inedito che è stato analizzato, trascritto integralmente e dotato di un apparato critico.
Il capitolo finale della tesi è dedicato all’approfondimento del ruolo che l’impresa estrattiva di miniera ha avuto nell’ambito del Settecento veneto, soprattutto nell’ottica di una possibile appartenenza dell’eredità culturale e materiale delle tecniche e delle conoscenze minerarie storiche all’ambito dei beni comuni contemporanei. In particolare, le conoscenze tecniche sono considerate nei loro molteplici aspetti: gestione, competenza, responsabilità e diffusione.
Negli allegati sono proposte le trascrizioni e le edizioni critiche di alcune fonti inedite, opportunamente selezionate
Iron oxide nanoparticles: a platform for biomolecule conjugation
Full text linkAmong the nanomaterials, of great interest are iron oxide nanoparticles (IONPs), which possess unique magnetic properties, low toxicity and high biocompatibility. For these reason, IONPs are widely used in industrial and biomedical field. Here, IONPs were synthetized via co-precipitation method, obtaining NPs reproducible in shape and size distribution. First, IONPs were used as a platform for the conjugation of two thermophilic enzymes, L-aspartate oxidase and amylase to obtain an effective biocatalyst. Different binding strategies were studied leading to different enzymatic activity due to the different orientations and stretching of the proteins. Next, the NP-enzyme systems were nanoactuated by an alternate magnetic field (AMF) without increasing the overall temperature of the solution. Remarkably, the nano-systems were successfully reused for at three consecutive cycles of AMF with the loss of the 40% of the initial activity. IONPs were also used developed a nano-antibiotic system, using teicoplanin. The antimicrobial efficacy of NP-TEICO was assessed through classical microbiological methods and morphological studies. Results indicate that teicoplanin conjugation confers high and prolonged antimicrobial activity to IONPs toward Gram-positive bacteria, inhibiting also S. aureus biofilm formation, while no antimicrobial activity was detectable towards Gramnegative. Additionally, conjugation of teicoplanin improved the cytocompatibility of IONPs towards two human cell lines. To conclude, IONPs were successfully synthetized, functionalized and employed as a platform for biomolecules conjugation. Indeed two effective different nano-biocatalysts and a nano-antibiotic were obtained