Definition of display/control requirements for assault transport night/adverse weather capability

A Helicopter Night Vision System was developed to improve low-altitude night and/or adverse weather assult transport capabilities. Man-in-the-loop simulation experiments were performed to define the minimum display and control requirements for the assult transport mission and investigate forward looking infrared sensor requirements, along with alternative displays such as panel mounted displays (PMD) helmet mounted displays (HMD), and integrated control display units. Also explored were navigation requirements, pilot/copilot interaction, and overall cockpit arrangement. Pilot use of an HMD and copilot use of a PMD appear as both the preferred and most effective night navigation combination

From Monoamine Oxidase Inhibition to Antiproliferative Activity: New Biological Perspectives for Polyamine Analogs

Monoamine oxidases (MAOs) are well-known pharmacological targets in neurological and neurodegenerative diseases. However, recent studies have revealed a new role for MAOs in certain types of cancer such as glioblastoma and prostate cancer, in which they have been found overexpressed. This finding is opening new frontiers for MAO inhibitors as potential antiproliferative agents. In light of our previous studies demonstrating how a polyamine scaffold can act as MAO inhibitor, our aim was to search for novel analogs with greater inhibitory potency for human MAOs and possibly with antiproliferative activity. A small in-house library of polyamine analogs (2-7) was selected to investigate the effect of constrained linkers between the inner amine functions of a polyamine backbone on the inhibitory potency. Compounds 4 and 5, characterized by a dianiline (4) or dianilide (5) moiety, emerged as the most potent, reversible, and mainly competitive MAO inhibitors (Ki < 1 μM). Additionally, they exhibited a high antiproliferative activity in the LN-229 human glioblastoma cell line (GI50 < 1 μM). The scaffold of compound 5 could represent a potential starting point for future development of anticancer agents endowed with MAO inhibitory activity

A Complete Meteo/Hydro/Hydraulic Chain Application to Support Early Warning and Monitoring Systems: The Apollo Medicane Use Case

Because of the ongoing changing climate, extreme rainfall events’ frequency at the global scale is expected to increase, thus resulting in high social and economic impacts. A Meteo/Hydro/Hydraulic forecasting chain combining heterogeneous observational data sources is a crucial component for an Early Warning System and is a fundamental asset for Civil Protection Authorities to correctly predict these events, their effects, and put in place anticipatory actions. During the last week of October 2021 an intense Mediterranean hurricane (Apollo) affected many Mediterranean countries (Tunisia, Algeria, Malta, and Italy) with a death toll of seven people. The CIMA Meteo/Hydro/Hydraulic forecasting chain, including the WRF model, the hydrological model Continuum, the automatic system for water detection (AUTOWADE), and the hydraulic model TELEMAC-2D, was operated in real-time to predict the Apollo weather evolution as well as its hydrological and hydraulic impacts, in support of the early warning activities of the Italian Civil Protection Department. The WRF model assimilating radar data and in situ weather stations showed very good predictive capability for rainfall timing and location over eastern Sicily, thus supporting accurate river flow peak forecasting with the hydrological model Continuum. Based on WRF predictions, the daily automatic system for water detection (AUTOWADE) run using Sentinel 1 data was anticipated with respect to the scheduled timing to quickly produce a flood monitoring map. Ad hoc tasking of the COSMO-SkyMed satellite constellation was also performed to overcome the S1 data latency in eastern Sicily. The resulting automated operational mapping of floods and inland waters was integrated with the subsequent execution of the hydraulic model TELEMAC-2D to have a complete representation of the flooded area with water depth and water velocity

Pierluigi Nervi, una scienza per l'architettura

Catalogo della Mostra (Roma 1982

A kinetic study of new polyamine analogs oxidized by bovine serum amine oxidase

The low efficacy of drugs currently used in anticancer therapeutic applications and the development of multidrug-resistance prompted us to study the polyamine pathway as a possible target for the development of new anti-proliferative pharmacological agents. In order to develop new amino oxidase (AO) spermine-based ligands, several spermine analogs were synthesized with the aim to improve their enzymatic oxidative deamination. The insertion of thiophene on one of terminal amines and substitution of the inner nitrogen atoms of spermine with oxygens, led to improved kinetic parameters. (Table 1). In fact, a kinetic study showed that Km and kcat (kc) were better than those of the physiological polyamines spermine and spermidine. Kinetic observations were carried out in buffer phosphate 0.01M, at pH 7.4-7.6, in order to perform cytotoxic studies using BSAO enzyme (Bovine Serum Amine Oxidase) in the presence of polyamine analogs on cancer cells. The kinetic assays were performed using the new synthesized compounds in the range between 0.05-1 mM in the presence of BSAO. BSAO catalyzes, in the presence of O2, the oxidative deamination of spermine, spermidine and their analogs, providing the formation of H2O2, aldehyde(s) and NH3. The improvement of the kinetic parameters obtained at pH 7.6, in comparison with that observed at pH 7.4, is probably due to a better interaction between amine-oxidase with the substrates, constituted by polyamine analogs, that leads to the formation of the Schiff base (1,2,3). As future perspective, these molecules will be assayed alone or in combination with BSAO on several cancer cells, with the aim to evaluate their cytotoxic effect, that could be taken into consideration as new approach in anti-cancer therapy

Novel polyamine analogues: from substrates towards potential inhibitors of monoamine oxidases.

Polyamine analogues are extensively researched investigated for their potential pharmacological applications as anticancer (Casero et al. 2009) and antimalarial agents (Verlinden et al., 2011), as well as in the development of multitarget-directed ligands (MTDLs) for novel therapies in neurodegenerative and other multi-factorial diseases (Melchiorre et al. 2010). In the MTLDs field, the polyamine backbone behaves as a \u201cuniversal template\u201d, able to bind different biological targets with an affinity and selectivity that may be fine-tuned by inserting appropriate substituents on nitrogen atoms and by varying the polymethylene chain lengths (Minarini et al. 2010). In the search of new MTDLs to combat neurodegenerative diseases, we designed new polyamines with the aim to inhibit additional target involved in these pathologies. Among these, human monoamine oxidases (MAOs) are emerging potential targets (Bortolato et al., 2008, Boomsma et al., 2003), since may contribute to the oxidative damage involved not only in neurodegenerative diseases but also in other ones and other pathologies, such as diabetes, cardiovascular and inflammatory disorders (Cohen and Tong 2010). Monoamine oxidases (MAO A and MAO B) and Semicarbazide-Sensitive Amine Oxidase/Vascular Adhesion Protein-1 (SSAO/VAP-1) catalyze the oxidative deamination of biogenic amines to produce aldehyde, hydrogen peroxide and ammonia. The starting points of our study were the negligible enzyme activities of MAOs and SSAO/VAP-1 on spermine and our previous results on Bis-BZA-DIADO, which we found able to inhibit both MAO B and SSAO/VAP-1 (Bonaiuto et al., 2012). Eight novel synthetic polyamines were tested as substrates and inhibitors on SSAO/VAP-1 and MAOs. From the kinetic studies carried out so far, we found novel substrates of SSAO/VAP-1 and two novel types of specific MAOs inhibitors: BD28, more selective for MAO B (Ki= 32 \uf06dM) and NT27 (Ki = 15 \uf06dM). Interestingly, NT 27 acts as an irreversible inhibitor of MAO A while, on MAO B, it behaves as a mixed and reversible inhibitor. Further studies are in progress to understand elucidate the binding mode of these compounds to MAOs, in such a way, to modify their structure in order to improve their affinity and selectivity for future application as MTLDs in neurodegenerative diseases

A kinetic study of new polyamine analogs oxidized by bovine serum amine oxidase .

The low efficacy of drugs currently used in anticancer therapeutic applications and the development of multidrug-resistance prompted us to study the polyamine pathway as a possible target for the development of new anti-proliferative pharmacological agents. In order to develop new amino oxidase (AO) spermine-based ligands, several spermine analogs were synthesized with the aim to improve their enzymatic oxidative deamination. The insertion of thiophene on one of terminal amines and substitution of the inner nitrogen atoms of spermine with oxygens, led to improved kinetic parameters. (Table 1). In fact, a kinetic study showed that Km and kcat (kc) were better than those of the physiological polyamines spermine and spermidine. Kinetic observations were carried out in buffer phosphate 0.01M, at pH 7.4-7.6, in order to perform cytotoxic studies using BSAO enzyme (Bovine Serum Amine Oxidase) in the presence of polyamine analogs on cancer cells. The kinetic assays were performed using the new synthesized compounds in the range between 0.05-1 mM in the presence of BSAO. BSAO catalyzes, in the presence of O2, the oxidative deamination of spermine, spermidine and their analogs, providing the formation of H2O2, aldehyde(s) and NH3. The improvement of the kinetic parameters obtained at pH 7.6, in comparison with that observed at pH 7.4, is probably due to a better interaction between amine-oxidase with the substrates, constituted by polyamine analogs, that leads to the formation of the Schiff base (1,2,3). As future perspective, these molecules will be assayed alone or in combination with BSAO on several cancer cells, with the aim to evaluate their cytotoxic effect, that could be taken into consideration as new approach in anti-cancer therapy

Oxidative deamination of new polyamine analogs by bovine serum amine oxidase: a kinetic study

none8noneS. Saccoccio; A. Minarini; A. Milelli; V. Tumiatti; G. tempera; N. Viceconte; R. Stevanato; E. AgostinelliS. Saccoccio; A. Minarini; A. Milelli; V. Tumiatti; G. tempera; N. Viceconte; R. Stevanato; E. Agostinell