Design and synthesis of molecular hybrids between drugs for psoriasis treatment and H2S donors

Psoriasis is a chronic and relapsing immune-mediated inflammatory skin disease, characterized by uncontrolled keratinocyte proliferation and dysfunctional differentiation, that affects 2-4% of people worldwide. Glucocorticoids and retinoids are commonly used in the treatment of psoriasis. More recently, H2S has been described to exert positive effect on this disease. Bearing in mind that an improved pharmacological activity and a reduced toxicity can be obtained through hybridization of different molecules, the project has been principally focused on design, synthesis and characterization of molecular hybrids containing a portion pharmacologically active in the treatment of psoriasis and an H2S-releasing moiety, with the aim to develop novel compounds able to modulate multiple targets in antipsoriatic therapy. The molecular hybrids have been evaluated in vitro for their H2S releasing properties via amperometric assay, as well as for their cytoprotective activity and anti-inflammatory power. Antipsoriatic activity has been evaluated in vivo by performing skin tests on animal models of imiquimod-induced psoriasis, determining the ability of the compounds to reduce inflammation and itching. Finally, the study has been extended to the evaluation of the antiasthmatic properties for the obtained derivatives, testing the H2S releasing profile in the cytosol of bronchial smooth muscle cells (BSMC), the inhibitory effect on mast cell degranulation and the ability to induce cell membrane hyperpolarization in BSMC. The second unit of the thesis is focused to the experience held at the Department of Biosciences - University of Salzburg and referred to the synthesis and characterization of three types of peptides: phosphopeptides to investigate the effect of serine phosphorylation on the conformation, peptide models to investigate π-cation interactions, and fluorogenic peptides to investigate the activity of proteases by FRET measurements. In the third unit of the thesis the design of potential formulations for the synthesized compounds that have shown more promising results is described, as well as the studies finalized to the evaluation of physicochemical stability for the active substances and formulations, and to the characterization of their in vitro performances. These activities have been performed at the Genetic s.p.a. in Fisciano (Italy)

Modelling and simulation of conducted emissions in the powertrain of electric vehicles

In the general framework of intelligent transportation, the increasing use of information communication technology in full or hybrid electric vehicles requires careful assessment of electromagnetic compatibility, with specific reference to the conducted emissions (CE) generated by the inverter in a broad frequency range (10 kHz-100 MHz). To this aim, this work reports a modelling approach for the prediction of CE in electric powertrains, which is based on circuit representation of each single subsystem, that is, the battery, the inverter, the three-phase synchronous motor, and the power buses composed of shielded cables. The proposed models are able to represent both low-frequency functional aspects and high-frequency parasitic effects of paramount importance for CE analysis, and can be implemented into a Simulation-Programme-with-Integrated-Circuit-Emphasis (SPICE) solver. The proposed modelling approach is exploited to simulate virtual CE measurements according to international standard CISPR 25, and to investigate the impact of setup features, including grounding connections of shields, the propagation of CE in electrically long power buses, the operating point (power, torque, speed) of the motor-drive system

Derivation of fragility curves for URM school buildings in Nepal

In recent years there has been an increasing interest from governmental authorities and Non-Governmental Organizations (NGOs) in the seismic safety enhancement of school buildings in developing countries. Schools represent a reference point for local communities and can be used as primary facilities for emergency and recovery activities after an earthquake. Focusing on the Nepal case, the last 2015 seismic events have shown that Nepalese school buildings are characterized by a high level of vulnerability. According to post-disaster surveys, more than the 20 percent of the countrys classrooms experienced damage or collapse during the earthquake. Nepals building stock is mainly constituted by non-engineered constructions realized without seismic detailing and material quality controls. Particularly, unreinforced masonry (URM) structures, representing the majority of the total building inventory, are characterized by numerous construction deficiencies such as inadequate wall-to-wall or wall-to-floor connections which have led to frequent out-of-plane collapses. Herein, a spectral-based methodology to derive fragility curves for Nepalese unreinforced masonry school buildings subjected to out-of-plane damage is discussed. The technique is applied to the case of typical mud-mortar URM Nepalese structures, by taking into account regional variations in construction practice, material properties and recurrent failure modes detected after the 2015 seismic events.This work was funded by the Engineering and Physical Science Research Council (EPSRC) under the project Seismic Safety and Resilience of Schools in Nepal SAFER (EP/P028926/1)

Modeling of imbalance in differential lines targeted to SPICE simulation

partially_open5siIn this paper, a SPICE model representative for the mode conversion occurring in differential lines affected by imbalance either of the line cross-section and the terminal networks is developed. The model is based on the assumption of weak imbalance and allows approximate prediction of modal quantities, through separate modeling of the contributions due to line and termination imbalance by controlled sources with (possibly) frequency dependent gain. The proposed SPICE model is used to perform worst-case prediction of undesired modal voltages induced at line terminals by mode conversion.openGrassi, Flavia; Wu, Xinglong; Yang, Yuehong; Spadacini, Giordano; Pignari, Sergio A.Grassi, Flavia; Wu, Xinglong; Yang, Yuehong; Spadacini, Giordano; Pignari, SERGIO AMEDE

UMAP: Urban Mobility Analysis Platform to Harvest Car Sharing Data

Car sharing is nowadays a popular transport means in smart cities. In particular, the free-floating paradigm lets the users look for available cars, book one, and then start and stop the rental at their will, within the city area. This is done by using a smartphone app, which in turn contacts a web-based backend to exchange information. In this paper we present UMAP, a platform to harvest data freely made available on the web to extract driving habits in cities. We design UMAP to fetch data from car sharing platforms in real time, and process it to extract more advanced information about driving patterns and user’s habits while augmenting data with mapping and direction information fetched from other web platforms. This information is stored in a data lake where historical series are built, and later analyzed using easy to design and customize analytics modules. We prove the flexibility of UMAP by presenting a case of study for the city of Turin. We collect car sharing usage data over 50 days, and characterize both the temporal and spatial properties of rentals, as well as users’ habits in using the service, which we contrast with public transportation alternatives. Results provide insights about the driving style and needs, that are useful for smart city planners, and prove the feasibility of our approach

Scattering parameters characterization of periodically nonuniform transmission lines with a perturbative technique

In this article, a novel procedure for the frequency-domain solution of nonuniform transmission lines (NUTLs) is presented. The procedure is based on a recently proposed perturbative technique, which is proven to be computationally more efficient than standard solution approaches, which are based on line subdivision into uniform cascaded sections. With respect to the original perturbation technique, the procedure proposed here offers more flexibility, as it provides a representation of the NUTL under analysis in terms of S and/or T parameters at its ports. Moreover, it retains the same prediction accuracy at the price of a slight increase in computational burden, which can be mitigated anyway through parallel computing. Furthermore, even without ad hoc (parallel) implementations, the proposed procedure outperforms other approaches to solve differential lines with partially or fully repetitive geometries. Namely, it assures accurate prediction of output quantities with reduced simulation time. This is proven by three application examples, namely, two differential trapezoidal tabbed lines (one with interdigital tabs and one with facing tabs), and a differential microstrip line with a varying common-mode (CM) impedance (as such reducing CM noise). Comparison with full-wave simulations allows assessing the prediction accuracy of the proposed procedure. Comparison with the aforementioned transmission-line-based solutions allows appreciating the enhanced computational efficiency