Studio dei metodi di valutazione della pericolosità associata ai "debris flow" in ambiente alpino

The present work concerns with the study of debris flows and, in particular, with the related hazard in the Alpine Environment. During the last years several methodologies have been developed to evaluate hazard associated to such a complex phenomenon, whose velocity, impacting force and inappropriate temporal prediction are responsible of the related high hazard level. This research focuses its attention on the depositional phase of debris flows through the application of a numerical model (DFlowz), and on hazard evaluation related to watersheds morphometric, morphological and geological characterization. The main aims are to test the validity of DFlowz simulations and assess sources of errors in order to understand how the empirical uncertainties influence the predictions; on the other side the research concerns with the possibility of performing hazard analysis starting from the identification of susceptible debris flow catchments and definition of their activity level. 25 well documented debris flow events have been back analyzed with the model DFlowz (Berti and Simoni, 2007): derived form the implementation of the empirical relations between event volume and planimetric and cross section inundated areas, the code allows to delineate areas affected by an event by taking into account information about volume, preferential flow path and digital elevation model (DEM) of fan area. The analysis uses an objective methodology for evaluating the accuracy of the prediction and involve the calibration of the model based on factors describing the uncertainty associated to the semi empirical relationships. The general assumptions on which the model is based have been verified although the predictive capabilities are influenced by the uncertainties of the empirical scaling relationships, which have to be necessarily taken into account and depend mostly on errors concerning deposited volume estimation. In addition, in order to test prediction capabilities of physical-based models, some events have been simulated through the use of RAMMS (RApid Mass MovementS). The model, which has been developed by the Swiss Federal Institute for Forest, Snow and Landscape Research (WSL) in Birmensdorf and the Swiss Federal Institute for Snow and Avalanche Research (SLF) takes into account a one-phase approach based on Voellmy rheology (Voellmy, 1955; Salm et al., 1990). The input file combines the total volume of the debris flow located in a release area with a mean depth. The model predicts the affected area, the maximum depth and the flow velocity in each cell of the input DTM. Relatively to hazard analysis related to watersheds characterization, the database collected by the Alto Adige Province represents an opportunity to examine debris-flow sediment dynamics at the regional scale and analyze lithologic controls. With the aim of advancing current understandings about debris flow, this study focuses on 82 events in order to characterize the topographic conditions associated with their initiation , transportation and deposition, seasonal patterns of occurrence and examine the role played by bedrock geology on sediment transfer.

Development and applications of hollow fiber flow field-flow fractionation in the bioanalytical field. Studies of aggregation phenomena in complex protein samples

Recent advances in the fast growing area of therapeutic/diagnostic proteins and antibodies - novel and highly specific drugs - as well as the progress in the field of functional proteomics regarding the correlation between the aggregation of damaged proteins and (immuno) senescence or aging-related pathologies, underline the need for adequate analytical methods for the detection, separation, characterization and quantification of protein aggregates, regardless of the their origin or formation mechanism. Hollow fiber flow field-flow fractionation (HF5), the miniaturized version of FlowFFF and integral part of the Eclipse DUALTEC FFF separation system, was the focus of this research; this flow-based separation technique proved to be uniquely suited for the hydrodynamic size-based separation of proteins and protein aggregates in a very broad size and molecular weight (MW) range, often present at trace levels. HF5 has shown to be (a) highly selective in terms of protein diffusion coefficients, (b) versatile in terms of bio-compatible carrier solution choice, (c) able to preserve the biophysical properties/molecular conformation of the proteins/protein aggregates and (d) able to discriminate between different types of protein aggregates. Thanks to the miniaturization advantages and the online coupling with highly sensitive detection techniques (UV/Vis, intrinsic fluorescence and multi-angle light scattering), HF5 had very low detection/quantification limits for protein aggregates. Compared to size-exclusion chromatography (SEC), HF5 demonstrated superior selectivity and potential as orthogonal analytical method in the extended characterization assays, often required by therapeutic protein formulations. In addition, the developed HF5 methods have proven to be rapid, highly selective, sensitive and repeatable. HF5 was ideally suitable as first dimension of separation of aging-related protein aggregates from whole cell lysates (proteome pre-fractionation method) and, by HF5-(UV)-MALS online coupling, important biophysical information on the fractionated proteins and protein aggregates was gathered: size (rms radius and hydrodynamic radius), absolute MW and conformation.

Aerobic biodegradation of chlorinated solvents and plastics in batch and continuous-flow bioreactors: process development, and identification of suitable chemical pre-Treatments

The purpose of the first part of the research activity was to develop an aerobic cometabolic process in packed bed reactors (PBR) to treat real groundwater contaminated by trichloroethylene (TCE) and 1,1,2,2-tetrachloroethane (TeCA). In an initial screening conducted in batch bioreactors, different groundwater samples from 5 wells of the contaminated site were fed with 5 growth substrates. The work led to the selection of butane as the best growth substrate, and to the development and characterization from the site’s indigenous biomass of a suspended-cell consortium capable to degrade TCE with a 90 % mineralization of the organic chlorine. A kinetic study conducted in batch and continuous flow PBRs and led to the identification of the best carrier. A kinetic study of butane and TCE biodegradation indicated that the attached-cell consortium is characterized by a lower TCE specific degredation rates and by a lower level of mutual butane-TCE inhibition. A 31 L bioreactor was designed and set up for upscaling the experiment. The second part of the research focused on the biodegradation of 4 polymers, with and with-out chemical pre-treatments: linear low density polyethylene (LLDPE), polyethylene (PP), polystyrene (PS) and polyvinyl chloride (PVC). Initially, the 4 polymers were subjected to different chemical pre-treatments: ozonation and UV/ozonation, in gaseous and aqueous phase. It was found that, for LLDPE and PP, the coupling UV and ozone in gas phase is the most effective way to oxidize the polymers and to generate carbonyl groups on the polymer surface. In further tests, the effect of chemical pretreatment on polyner biodegrability was studied. Gas-phase ozonated and virgin polymers were incubated aerobically with: (a) a pure strain, (b) a mixed culture of bacteria; and (c) a fungal culture, together with saccharose as a co-substrate.

Design and Development of a Research Framework for Prototyping Control Tower Augmented Reality Tools

The purpose of the air traffic management system is to ensure the safe and efficient flow of air traffic. Therefore, while augmenting efficiency, throughput and capacity in airport operations, attention has rightly been placed on doing it in a safe manner. In the control tower, many advances in operational safety have come in the form of visualization tools for tower controllers. However, there is a paradox in developing such systems to increase controllers' situational awareness: by creating additional computer displays, the controller's vision is pulled away from the outside view and the time spent looking down at the monitors is increased. This reduces their situational awareness by forcing them to mentally and physically switch between the head-down equipment and the outside view. This research is based on the idea that augmented reality may be able to address this issue. The augmented reality concept has become increasingly popular over the past decade and is being proficiently used in many fields, such as entertainment, cultural heritage, aviation, military & defense. This know-how could be transferred to air traffic control with a relatively low effort and substantial benefits for controllers’ situation awareness. Research on this topic is consistent with SESAR objectives of increasing air traffic controllers’ situation awareness and enable up to 10 % of additional flights at congested airports while still increasing safety and efficiency. During the Ph.D., a research framework for prototyping augmented reality tools was set up. This framework consists of methodological tools for designing the augmented reality overlays, as well as of hardware and software equipment to test them. Several overlays have been designed and implemented in a simulated tower environment, which is a virtual reconstruction of Bologna airport control tower. The positive impact of such tools was preliminary assessed by means of the proposed methodology.

Research of predictive biomarkers to anti-CD22 antibody-drug conjugate treatment in B-cell acute lymphoblastic leukemia

Background: The treatment of B-cell acute lymphoblastic leukemia (B-ALL) has been enriched by novel agents targeting surface markers CD19 and CD22. Inotuzumab ozogamicin (INO) is a CD22-calicheamicin conjugated monoclonal antibody approved in the setting of relapse/refractory (R/R) B-ALL able to induce a high rate of deep responses, not durable over time. Aims: This study aims to identify predictive biomarkers to INO treatment in B- ALL by flow cytometric analysis of CD22 expression and gene expression profile. Materials and methods: Firstly, the impact on patient outcome in 30 R/R B-ALL patients of baseline CD22 expression in terms of CD22 blast percentage and CD22 fluorescent intensity (CD22-FI) was explored. Secondly, baseline gene expression profile of 18 R/R B-ALL patient samples was analyzed. For statistical analysis of differentially expressed genes (DEGs) patients were divided in non-responders (NR), defined as either INO-refractory or with duration of response (DoR) < 3 months, and responders (R). Gene expression results were analyzed with Ingenuity pathway analysis (IPA). Results: In our patient set higher CD22-FI, defined as higher quartiles (Q2-Q4), correlated with better patient outcome in terms of CR rate, OS and DoR, compared to lower CD22-FI (Q1). CD22 blast percentage was less able to discriminate patients’ outcome, although a trend for better outcome in patients with CD22 ≥ 90% could be appreciated. Concerning gene expression profile, 32 genes with corrected p value <0.05 and absolute FC ≥2 were differentially expressed in NR as compared to R. IPA upstream regulator and regulator effect analysis individuated the inhibition of tumor suppressor HIPK2 as causal upstream condition of the downregulation of 6 DEGs. Conclusions: CD22-FI integrates CD22-percentage on leukemic blasts for a more comprehensive target pre-treatment evaluation. Moreover, a unique pattern of gene expression signature based on HIPK2 downregulation was identified, providing important insights in mechanisms of resistance to INO.