Design, preparazione e caratterizzazione di nanostrutture di DNA come candidati farmaci per terapia a RNA

Le terapie a RNA stanno attraendo interesse crescente vista la loro capacità di colpire target che venivano dapprima considerati undruggable. Uno degli ambiti di applicazione suggeriti della terapia a RNA è la neuroinfiammazione, una condizione patologica che accompagna e agisce da concausa nelle malattie neurodegenerative. In particolare, si è verificato che nei processi neuroinfiammatori, alcuni microRNA risultano sovra-regolati e tra questi miR-34a. Si è quindi proposto di sviluppare metodi atti a ridurre il contenuto cellulare di miR-34a soprattutto nelle cellule la cui attivazione causa maggiormente la neuroinfiammazione: la microglia. L’obiettivo del lavoro di tesi è stato di sviluppare una nanostruttura di DNA in grado di veicolare una sequenza catalitica (DNAzima) che porti al taglio del miR-34a, una volta internalizzata nelle cellule. Durante il lavoro di tesi si sono sviluppati 2 diversi dendrimeri di DNA pensati per ridurre il contenuto di miR-34a. I sistemi sono stati progettati con l’ausilio di strumenti bioinformatici e poi realizzati in laboratorio e caratterizzati con tecniche biochimiche. Il sistema più promettente è stato caratterizzato per quanto riguarda la sua attività enzimatica di taglio di miR-34a e l’efficienza di internalizzazione da parte di cellule vive di microglia. I risultati ottenuti confermano la solidità del metodo utilizzato per il design del sistema progettato. Le prove condotte sul dendrimero finale, contenente la sequenza attiva, dimostrano il mantenimento dell’attività catalitica del DNAzima e l’internalizzazione della nanostruttura nelle cellule bersaglio

Implementazione in Matlab di un modello di calcolo di giunzioni bullonate secondo norma VDI 2230

E' stato implementato un modello di calcolo nel software MATLAB per le giunzioni bullonate, seguendo la norma VDI 2230

StopUP. Development of a combined filtration and ion exchange process for the treatment of combined sewage overflow

Combined sewer overflow (CSO), discharged by sewers during rain events, is a major cause of pollution in surface water bodies. The main goal of this work was to develop a compact CSO treatment process by filtration and cation/anion exchange and to validate it with actual CSO in a real WWTP environment. Preliminary screening of several cation and anion exchange materials led to the selection of a molecular sieve (MS13X) that retained ammonium with an 11.6 mgN g-1 capacity, and a layered double hydroxide (calcined Sorbacid 911) that removed phosphate with a 2.2 mgP g-1 capacity. For both materials, the development of a regeneration procedure allowed to perform several adsorption/regeneration continuous-flow cycles with actual CSO without losses in adsorption performance. The packed bed heights were scale-up to 40 cm (Sorbacid 911) and 60 cm (MS13X) without variations in performance. The combined filtration/cation exchange/anion exchange process was tested at pilot scale in a real WWTP environment, with results detailed in Table 7. The pilot plant testing demonstrated removal rates of 68% for COD, 78% for BOD5, 85% for TSS, 88% for total P, 57% for total N, and 67% for faecal coliforms. Significant removals were also observed for heavy metals (Zn 83%, Cu 89%, Ni 81%) and pesticides (desethyl-atrazine 100%), whereas the process was largely ineffective towards PFAS (12%). While 1-µm microfiltration contributed significantly to overall removals, the cation/anion exchange process was crucial for achieving high removals of specific pollutants, including ammonium (57%), phosphate (95%), and total N (57%). This work represents a relevant step towards the development of a compact CSO treatment process featuring a limited land requirement and the possibility to withstand prolonged periods of dry weather

Pancreatic Metastasis 25 Years after Nephrectomy for Renal Cancer

The authors report a case of renal cell carcinoma metastasis to the pancreas occurring 25 years after nephrectomy. The need for prolonged follow-up of patients is emphasized. The surgical approach Is considered the best way to deal with such late metastases. </jats:p

Interindividual variabiity of the human hepatic sulphotransferases

The variability among subjects of the hepatic activities of O-sulphotransferase towards dopamine, p-nitrophenol, testosterone and ethinyloestradiol and of N-sulphotransferase with 1,2,3,4-tetrahydroisoquinoline (TIQ) as substrate is described. The rates of testosterone and TIQ sulphation were higher in men than women whereas those of ethinyloestradiol, dopamine and p-nitrophenol were similar in both sexes. The sulphotransferase activities towards p-nitrophenol and dopamine were positively skewed whereas those towards ethinyloestradiol approached normality. The coefficients of variations for the sulphotransferase activities ranged between 34% and 62% indicating a considerable variability among subjects. The rates of dopamine-, TIQ- and p-nitrophenol-sulphation were measured in the mucosa of the human intestine, and the duodenum/liver ratios were 10, 0.9 and 0.1, respectively. Thus the contribution of the intestine in the sulphation of xenobiotics is substrate dependent

Space-time mesh adaptation for the VMS-Smagorinsky modeling of high Reynolds number flows

Traditional methods, such as Reynolds-Averaged Navier-Stokes (RANS) equations and Large Eddy Simulations (LES), provide consolidated tools for the numerical approximation of high Reynolds number flows in a wide range of applications - from green energy to industrial design. In general, RANS modeling is practical when the main interest is the time-averaged flow behavior. LES equations offer detailed insights into flow dynamics and a more accurate solution, but the high computational demand necessitates innovative strategies to reduce costs while maintaining precision. In this study, we enhance the Variational MultiScale (VMS)-Smagorinsky LES model by relying on an adaptive discretization strategy in both space and time, driven by a recovery-based a posteriori error analysis. We assess the effectiveness of the approach in capturing flow characteristics across a wide range of Reynolds numbers through benchmark tests