AMS Tesi di Dottorato

    Non-thermal emission in the lobes of radio galaxies.

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    Radio and gamma-ray measurements of radiogalaxy lobes are useful to determine whether emission in these widely separated spectral regions is mainly by non-thermal (NT) electrons. This is of interest as there is yet no proof for a significant emission component from pion decay following NT proton interactions in the ambient lobe gas. An assessment of the hadronic yield needs full accounting of the local (FGL) and background (EBL, CMB) radiation fields in the lobes. Assuming a truncated single-PL electron energy distribution, exact calculation of the emission by NT electrons in the magnetized plasma in the Fornax A lobes leads to the conclusion that its Fermi-LAT emission is mostly IC/GFL: this result weakens earlier conclusions on the hadronic origin of the LAT emission. Similar analyses of the lobe emissions of Cen A, Cen B, and NGC 6251 suggest their measured LAT emissions, too, to be of IC/(EBL, CFGL, CMB) nature. Measured emissions of distant radio-galaxy lobes (3C98, Pictor A, DA240, Cygnus A, 3C326, and 3C236) are currently limited to the radio and X-ray bands: they can give no information on the presence of NT protons, but do trace the properties of NT electrons, and allow calculations of the related IC gamma-ray emission to be performed. The e/B energy density ratios, U_e/U_B, turn out to be in the range ~1-100. The NT proton energy density, U_p, is spectrally constrained to be less than a few tens of eV/cm3. Despite this limit, arguably U_p >> U_e -- as suggested by arguments of lobe internal vs external pressure. Thus the lobes' NT energy budget is likely dominated by particles. Given the low thermal energy densities measured in lobes, NT energy dominance is probably a general feature of lobe energetics

    Investigation of heterogeneous catalysts for the synthesis of fine chemicals

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    In order to match the more stringent environmental regulations, heterogenization of traditional homogeneous processes is one of the main challenges of the modern chemical industry. Great results have been achieved in the fields of petrochemicals and base chemicals, whereas in fine chemical industry most of the synthetic procedures are based on multistep processes catalyzed by homogeneous catalysts mainly used in stoichiometric amounts. In the fine chemicals manufacture not so much efforts have been devoted to the investigation of suitable solid catalysts for the development of greener processes, then this sector represent a very attractive field of research. In this context, the present work deals with the extensive investigation of the possibility to heterogenize existing processes, in particular two different classes of reactions have been studied: alkylation of aromatic and heteroaromatic compounds and selective oxidation of aromatic alcohols. Traditional solid acid catalysts, such as zeolites, clays and alumina have been tested in the gas phase alkylation of 1,2-methylendioxybenzene, core building block of many drugs, pesticides and fragrances. The observed reactivity were clarified through a deep FTIR investigation complemented by ab initio calculation. The same catalysts were tested in the gas phase isopropylation of thiophene with the aim of clearly attribute the role of the reaction parameters in the reaction proceeding and verify the possibility to enhance the selectivity of one of the two possible isomers. Finally various Au/CeO2 catalysts were tested in the synthesis of benzaldehyde and piperonal, two aldehydes largely employed in the manufacture of fine chemical products, through liquid phase oxidation of the corresponding alcohols in very mild conditions

    Bioinformatic methods in applied genomic research

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    Here I will focus on three main topics that best address and include the projects I have been working in during my three year PhD period that I have spent in different research laboratories addressing both computationally and practically important problems all related to modern molecular genomics. The first topic is the use of livestock species (pigs) as a model of obesity, a complex human dysfunction. My efforts here concern the detection and annotation of Single Nucleotide Polymorphisms. I developed a pipeline for mining human and porcine sequences. Starting from a set of human genes related with obesity the platform returns a list of annotated porcine SNPs extracted from a new set of potential obesity-genes. 565 of these SNPs were analyzed on an Illumina chip to test the involvement in obesity on a population composed by more than 500 pigs. Results will be discussed. All the computational analysis and experiments were done in collaboration with the Biocomputing group and Dr.Luca Fontanesi, respectively, under the direction of prof. Rita Casadio at the Bologna University, Italy. The second topic concerns developing a methodology, based on Factor Analysis, to simultaneously mine information from different levels of biological organization. With specific test cases we develop models of the complexity of the mRNA-miRNA molecular interaction in brain tumors measured indirectly by microarray and quantitative PCR. This work was done under the supervision of Prof. Christine Nardini, at the “CAS-MPG Partner Institute for Computational Biology” of Shangai, China (co-founded by the Max Planck Society and the Chinese Academy of Sciences jointly) The third topic concerns the development of a new method to overcome the variety of PCR technologies routinely adopted to characterize unknown flanking DNA regions of a viral integration locus of the human genome after clinical gene therapy. This new method is entirely based on next generation sequencing and it reduces the time required to detect insertion sites, decreasing the complexity of the procedure. This work was done in collaboration with the group of Dr. Manfred Schmidt at the Nationales Centrum für Tumorerkrankungen (Heidelberg, Germany) supervised by Dr. Annette Deichmann and Dr. Ali Nowrouzi. Furthermore I add as an Appendix the description of a R package for gene network reconstruction that I helped to develop for scientific usage (

    Magnetic Resonance guided Focused Ultrasound Surgery: study of potential applications in skeletal diseases, example n.1 – osteoid osteoma

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    La chirurgia con ultrasuoni focalizzati guidati da MRI (MR-g-FUS) è un trattamento di minima invasività, guidato dal più sofisticato strumento di imaging a disposizione, che utilizza a scopo diagnostico e terapeutico forme di energia non ionizzante. Le sue caratteristiche portano a pensare un suo possibile e promettente utilizzo in numerose aree della patologia umana, in particolare scheletrica. L'osteoma osteoide affligge frequentemente pazienti di giovane età, è una patologia benigna, con origine ed evoluzione non chiare, e trova nella termoablazione con radiofrequenza continua sotto guida CT (CT-g-RFA) il suo trattamento di elezione. Questo lavoro ha valutato l’efficacia, gli effetti e la sicurezza del trattamento dell’osteoma osteoide con MR-g-FUS. Sono stati presi in considerazione pazienti arruolati per MR-g-FUS e, come gruppo di controllo, pazienti sottoposti a CT-g-RFA, che hanno raggiunto un follow-up minimo di 18 mesi (rispettivamente 6 e 24 pazienti). Due pazienti erano stati esclusi dal trattamento MR-g-FUS per claustrofobia (2/8). Tutti i trattamenti sono stati portati a termine con successo tecnico e clinico. Non sono state registrate complicanze o eventi avversi correlati all’anestesia o alle procedure di trattamento, e tutti i pazienti sono stati dimessi regolarmente dopo 12-24 ore. La durata media dei trattamenti di MR-g-FUS è stata di 40±21 min. Da valori di score VAS pre-trattamento oscillanti tra 6 e 10 (su scala 0-10), i trattamenti hanno condotto tutti i pazienti a VAS 0 (senza integrazioni farmacologiche). Nessun paziente ha manifestato segni di persistenza di malattia o di recidiva al follow-up. Nonostante la neurolisi e la risoluzione dei sintomi, la perfusione del nidus è stata ritrovata ancora presente in oltre il 70% dei casi sottoposti a MR-g-FUS (4/6 pazienti). I risultati derivati da un'analisi estesa a pazienti più recentemente arruolati confermano questi dati. Il trattamento con MR-g-FUS sembra essere efficace e sicuro nel risolvere la sintomatologia dell'osteoma osteoide.Magnetic Resonance guided Focused Ultrasound Surgery (MR-g-FUS) is a minimally invasive treatment guided by the most sophisticated imaging tool available in today clinical practice. Both imaging and therapeutic sides of the equipment are based on non-ionizing energy. This technique is a very promising option as potential treatment of several pathologies, including skeletal disorders. Osteoid osteoma is considered a benign lesion of the bone, and it usually affects young patients. Although the origin and evolution of the disease have not been completely understood, the treatment of choice was found in thermal ablation by continuous radiofrequency under CT guidance (CT-g-RFA). This work aimed at the evaluation of the efficacy, the effects and the safety of MR-g-FUS in the treatment of osteoid osteoma. Patients enrolled for MR-g-FUS treatment of osteoid osteoma were included, as well as a control group made up of patients routinely submitted to CT-g-RFA. Only patients with a minimum follow-up period of 18 months were considered (6 and 24 patients, for MR-g-FUS and CT-g-RFA respectively). Two patients had been previously excluded from MR-g-FUS, because of claustrophobia (2/8 patients). All treatments were concluded with technical and clinical success. No complications or adverse events were registered. The mean duration of an entire MR-g-FUS procedure was 40(±21) min, and all patients were discharged after 12-24 h. The interventional procedures took the patients from pre-treatment VAS ranging 6-10 to post-treatment score 0 (removing drugs). No patient showed persistence or recurrence of the disease during the follow-up. Despite the neurolysis carried out by MR-g-FUS, the nidus presented with still active vascularization at imaging follow-up in over 70% of lesions undergoing MR-g-FUS (4/6 patients). Results achieved by extending the analysis to more recently recruited patients confirm data as preliminarily reported. MR-g-FUS seems to be effective and safe in the treatment of symptoms related to osteoid osteoma

    Mandibular reconstruction using CAD-CAM technology

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    L’obbiettivo di una ricostruzione micro vascolare di mandibola è quello di assicurare al paziente il miglior risultato estetico e funzionale auspicabile. Ciò può essere conseguito utilizzando il lembo microvascolare di perone/cresta iliaca e una placca ricostruttiva in titanio che funga da guida nella fase di modellamento del lembo per ricreare un contorno parabolico il più possibile simile al profilo mandibolare originario del paziente. Il modellamento manuale ed artigianale intraoperatorio di una placca ricostruttiva è operatore dipendente ed anche in mani molto abili o ricorrendo a modelli anatomici stereolitografici non sempre risulta preciso quanto voluto e spesso non porta ai risultati postoperatori attesi e desiderati. Obbiettivo del nostro studio è stato pertanto, sfruttando le moderne tecnologie CAD-CAM, la produzione di placche ricostruttive “custom -made” progettate direttamente al computer ricreanti il profilo osseo originale del paziente.This paper describes a new protocol for mandibular reconstruction. CAD/CAM technology was used to manufacture custom-made cutting guides for tumor ablation and reconstructive plates to support fibula free flaps in five patrients presenting oral tumour involving the mandibular bone. CT scan data from the patients were elaborated to produce a virtual surgical plan of mandibular osteotomy in safe tissue for complete ramus/body resection. The CAD/CAM procedure was used to construct a customized surgical device composed of a cutting guide and a titanium reconstructive bone plate. The cutting guide allowed the surgeon to precisely transfer the virtual planned osteotomy into the surgical environment. The bone plate, including in two cases a custom-made anatomical condylar prosthesis, was designed using the outer surface of the healthy side of the mandible to obtain an ideal contour and avoid the bone deformities present on the side affected by the tumor. Operation time was reduced in the demolition and reconstruction phases. Functional and aesthetic outcomes allowed patients to immediately recover their usual appearance and functionality. This new protocol for mandibular reconstruction using CAD/CAM to construct custom-made guides and plates may represent a viable way to reproduce the patient's anatomical contour, give the surgeon better procedural control, and reduce operation time

    New methods for early diagnosis of ceramic failure in ceramic on ceramic hip prosthesis

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    L’accoppiamento articolare in ceramica è sempre più utilizzato in chirurgia protesica dell’anca per le sue eccellenti proprietà tribologiche. Tuttavia la fragilità della ceramica è causa di fallimenti meccanici. Abbiamo quindi condotto una serie di studi al fine di individuare un metodo efficace di diagnosi precoce del fallimento della ceramica. Abbiamo analizzato delle componenti ceramiche espiantate e abbiamo trovato un pattern di usura pre-frattura che faceva supporre una dispersione di particelle di ceramica nello spazio articolare. Per la diagnosi precoce abbiamo validato una metodica basata sulla microanalisi del liquido sinoviale. Per validare la metodica abbiamo eseguito un agoaspirato in 12 protesi ben funzionanti (bianchi) e confrontato i risultati di 39 protesi con segni di rottura con quelli di 7 senza segni di rottura. Per individuare i pazienti a rischio rottura i dati demografici di 26 pazienti con ceramica rotta sono stati confrontati con 49 controlli comparabili in termini demografici, tipo di ceramica e tipo di protesi. Infine è stata condotta una revisione sistematica della letteratura sulla diagnosi della rottura della ceramica. Nell’aspirato la presenza di almeno 11 particelle ceramiche di dimensioni inferiori a 3 micron o di una maggiore di 3 micron per ogni campo di osservazione sono segno di rottura della ceramica. La metodica con agoaspirato ha 100% di sensibilità e 88 % di specificità nel predire rotture della ceramica. Nel gruppo delle ceramiche rotte è stato trovato un maggior numero di malposizionamenti della protesi rispetto ai controlli (p=0,001). Il rumore in protesi con ceramica dovrebbe sollevare il sospetto di fallimento ed indurre ad eseguire una TC e un agoaspirato. Dal confronto con la letteratura la nostra metodica risulta essere la più efficace.Ceramic is increasingly used in total hip replacement for its excellent tribological properties. However, the brittleness of ceramics is of concern and mechanical failures are reported. We conducted a series of studies in order to identify an effective method of early diagnosis of ceramic failure. We have analyzed 20 ceramic components explanted and found a pattern of wear that would suggest a dispersion of ceramic particles in the joint space. We therefore investigated whether isolation, observation at scanning electron microscopy, and chemical identification with microanalysis of particles from synovial fluid could be predictive of ceramic damage. Firstly, the level of ‘‘physiological wear’’ of well functioning hip prostheses was assessed with this method, then the test was validated as diagnostic method for liner fracture. Twelve asymptomatic patients were enrolled to demonstrate the first aim; 39 cases of noisy hip, and 7 cases of pending failure not related to ceramic were enrolled for the second aim. To detect risk factors for ceramic liner fractures we compared 26 ceramic hips revised because of ceramic liner fracture with 49 well-functioning hips. Finally a systematic review was done to compare our results with those reported in the litterature. In the aspirate the presence of at least 11 ceramic particles of size less than 3 microns or the presence of one greater than 3 microns for each field of observation are a sign of ceramic failure. The method with fine needle aspiration has 100% sensitivity and 88% specificity in predicting breakage of the ceramic. A cup anteversion angle out of the optimal range of 15 ̊+/-10 ̊ was found to be a risk factor for ceramic liner fracture. There are no other diagnostic methodologies described in the literature as specific and sensible as the one we have proposed

    Complete Androgen Insensitivity Syndrome and bone mass. Basal evaluation and after long term estrogen treatment

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    L’osso è un tessuto target per estrogeni ed androgeni ma l’azione singola e la sinergia tra i due non sono compresi interamente. Le donne affette da Sindrome da Insensititvità Completa agli Androgeni (CAIS) hanno un cariotipo 46XY ma presentano una completa inattività del recettore degli androgeni. Nello studio abbiamo valutato la densità minerale ossea (BMD) in un gruppo di donne adulte CAIS sottoposte a gonadectomia al momento della prima visita e dopo almeno 12 mesi di terapia estrogenica. Il principale obiettivo è stato di valutare se, nelle donne CAIS, una ottimale estrogenizzazione fosse sufficiente a mantenere/ripristinare una adeguata BMD. 24 donne CAIS sono state sottoposte a DXA lombare e femorale all'arruolamento nello studio (t1), dopo terapia estrogenica di 12mesi(t2) e oltre (t>2). Sono state valutate: BMD(g/cm2) e Zscore lombare e femorale (a t1,t2 e t>2) E’ stato considerato se fossero rilevanti l’essere (gruppo1) o meno (gruppo 2) in terapia ormonale al t1 e l’età della gonadectomia. Risultati: Al t1 BMD e Zscore lombari e femorale erano significativamente ridotti rispetto alla popolazione controllo nel campione totale (lombare 0,900+0,12; -1,976+0,07, femorale 0,831 + 0,14; -1,385+0,98), nel gruppo 1 (lombare 0,918+0,116;-1,924+0,79, femorale 0,824+0,13;-1,40+1,00) e nel gruppo 2 (lombare 0.845+0,11 -2,13+1,15, femorale 0,857+0,17;-1,348+1,05) Al t2 e t>2 la BMD lombare è risultata significativamente aumentata (p=0,05 e p=0,02). Zscore lombare, BMD e Zscore femorale non hanno dimostrato variazioni significative. L’aver effettuato la gonadectomia in età post puberale è associato a Zscore lombare e femorale più elevati al t1. Nelle donne CAIS la terapia estrogenica è indispensabile per prevenire un'ulteriore perdita di BMD ma, da sola, non sembra in grado di ripristinare normali valori di BMD.I risultati del nostro studio supportano la tesi che gli androgeni, mediante l’azione recettoriale, abbiano un' azione diretta nel raggiungere e mantenere la BMD.Bone is a target tissue for both estrogens and androgens. Women with Complete Androgen Insensitivity Syndrome (CAIS)present with a 46XY cariotype but absence of receptorial androgen action. In our study we evaluated bone mineral density (BMD)among adult CAIS women who previously underwent bilateral gonadectomy at recruitment and after at least 12 month estrogen treatment. The main goal was to evaluate if full dosage estrogen only therapy was enough to preserve/improve BMD. 24 CAIS women underwent lumbar spine and hip DXA scan at recruitment (t1), after estrogen treatment of 12 months (t1) and more (t>2). BMD(g/cm2),lumbar spine (L2-L4) and hip Zscore at t1,t2 e t>2 were evaluated. It was considered wether (group1) or not (group2) women were on hormonal treatment at recruitment and age at gonadectomy. Results:at t1 BMD and Z score at spine and hip were significantly reduced when compared to control population in all groups: all population (spine 0,900+0,12; -1,976+0,07, hip 0,831 + 0,14; -1,385+0,98) , group 1 (spine 0,918+0,116;-1,924+0,79, hip 0,824+0,13;-1,40+1,00) and group 2 (spine 0.845+0,11-2,13+1,15, hip 0,857+0,17;-1,348+1,05).At t2 and t>2 spine BMD and Zscore were significantly increased (p=0,05 e p=0,02). Spine Zscore, hip BMD and Zscore did not show significant changes. Postpubertal age at gonadectomy was related to higher lumbar spine and hip Zscore at t1 In CAIS women estrogen therapy is essential to prevent further bone loss but it doesn't seem to restore normal BMD values. Our study support the hypothesis that androgen, thorough receptorial action, have a direct role in reaching and preserving BMD

    Metal ion levels in patients with metal-on-metal hip resurfacing: a long-term comparison with metal-on-metal total hip arthroplasty

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    Lo scopo di questo studio è stato quello di determinare se a lungo termine le concentrazioni sieriche di ioni nei pazienti con protesi di rivestimento d’anca metallo-metallo (MOM-HR, metal-on-metal hip resurfacing) fossero differenti da quelle valutate nei pazienti con protesi totale d’anca metallo-metallo e testa del diametro di 28 mm (MOM-THA, metal-on-metal total hip arthroplasty); inoltre è stato valutato se le concentrazioni ioniche fossero al di sopra dei valori di riferimento e se fosse possibile stabilire l’esistenza di una relazione tra sesso e concentrazioni di ioni con riferimento al tipo di impianto. Il gruppo MOM-HR era costituito da 25 pazienti mentre il gruppo MOM-THA era di 16 pazienti. Per poter ricavare i valori di riferimento sono stati reclutati 48 donatori sani. La misurazione delle concentrazioni degli ioni cobalto (Co), cromo (Cr), nickel (Ni) e molibdeno (Mo) è stata effettuata utilizzando la spettrofotometria ad assorbimento atomico su fornace di grafite. A parte il Ni, le concentrazioni di ioni nei pazienti con MOM-HR erano più elevate rispetto ai controlli. Il rilascio di ioni Cr e Co nei pazienti con MOM-HR è risultato superiore rispetto ai soggetti con MOM-THA. Da un’analisi basata sul sesso, è emerso che nelle femmine con MOM-HR i livelli di ioni Cr e Co sono risultati significativamente aumentati rispetto alle femmine con MOM-THA. Indipendentemente dal tipo di impianto, gli accoppiamenti metallo-metallo (MOM) producono concentrazioni di ioni metallici significativamente più alte a follow-up a lungo termine rispetto a quelle osservate nei soggetti sani. Un fattore che deve essere attentamente considerato nella scelta dell’impianto, e in particolar modo nei soggetti giovani, è il cospicuo rilascio di ioni Cr e Co nella popolazione femminile con MOM-HR.The purpose of this study was to determine if long-term serum ion concentrations in patients with metal-on-metal hip resurfacing were different from those assessed in patients with metal-on-metal total hip arthroplasty; moreover we evaluated whether these concentrations would be above the reference values and whether a relation between gender and ion concentrations with regards to implant type was present. Twenty-five and sixteen patients constituted MOM-HR and MOM-THA groups, respectively. Forty-eight healthy donors were recruited for reference values. Cobalt, chromium, nickel and molybdenum were measured by furnace graphite atomic absorption spectrofotometry. Except nickel, ion concentrations in MOM-HR patients, were higher than in controls. Chromium and cobalt release in MOM-HR were higher than in MOM-THA subjects. A gender-based analysis, showed that in MOM-HR females chromium and cobalt were significantly increased compared to MOM-THA ones. Regardless of implant type MOM couplings produce significantly higher metal ion concentrations at the long-term follow-up than those observed in healthy subjects. The conspicuous release of chromium and cobalt in the female MOM-HR population should be carefully considered during implant selection, particularly in young subjects
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