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An experimental investigation about nanosecond Dielectric Barrier Discharge (ns-DBD) plasma actuator is presented in this thesis. This work aimed to answer fundamental questions on the actuation mechanism of this device. In order to do so, parametric studies in a quiescent air as well as laminar bounded of free shear layers were performed. Amplitude and location of the input with respect to the receptivity region as well as frequency of flow actuation were investigated. This work required the implementation of acquisition techniques such as Schlieren, Particle Image Velocimetry (PIV), infrared thermography, back current shunt technique and balancemeasurements. Moreover, tools of analysis were employed such as Linear Stability Theory (LST), Proper Orthogonal Decomposition (POD) and Inverse Heat Transfer Problem(IHTP). Results revealed that the effect of a ns-DBD is that of “enhancing” the development of natural hydrodynamic instabilities of the specific field of motion. Therefore, in case of a laminar boundary layer, the effect of a ns-DBD plasma actuator was to amplify Tollmien–Schlichting waves according to linear stability theory. Such results led to understand the influence of the actuator position on the achievement of a specific flow control task. A ns-DBD is capable of producing several effects: a shock wave, a small body force and a thermal gradient within the discharge volume. Thus, three were the possible causes of flow actuation. The shock wave was found to be too weak to be capable of introducing an appreciable disturbance. As the shock wave, also the momentum injection induced by the body force produced by the pulsed discharge was found to be relatively too small to justify a control authority based on momentum redistribution within the boundary layer, for cases of relatively high freestream velocity. Thus, the thermal gradient induced within the discharge volume by the energy deposition of a high voltage nanosecond discharge is the effect capable of inducing a relatively large disturbance into the field of motion. Nevertheless, a thermal gradient within a gaseous flow induces two effects, it reduces density and increases viscosity. At the moment it is still unclear which of these two effects is more relevant. Once identified the thermal gradient as the main cause of flow control mechanism, a characterization study was performed aimed to identify the properties of a ns-DBD plasma actuator (thermal, electrical and geometrical) important tomaximize the induced thermal gradient within the discharge volume. In general, a higher efficiency is achieved by a strong dielectric material concerning thermal energy deposition. A barrier of a ns-DBD plasma actuator should be as thin as possible. However, the thickness affects also the lifetime of the barrier itself. Nanosecond pulsed DBD plasma actuators have shown to have the capability to delay leading edge separation. However, in the relevant literature, an influence of the actuation frequency on the achieved results is always reported. In order to investigate this frequency effect, a parametric study on a Backward Facing Step was performed. This geometry was selected because it mimics a fixed point laminar separation, the flow sceixnario of interest. Such flow scenario is unstable at high frequencies close to the step and low frequencies downstream the step and it naturally develops a most unstable mode within it. However, when a flow is actuated, its stability changes, so do the most unstable frequencies naturally developed within it. Results showed that the effect of actuation is the redistribution of energy among modes and that the optimal frequency of actuation must be based on the new stability achieved by the flow due to the actuation itself. Moreover, results indicated that the optimal frequency of actuation is not related to the most unstable frequencies naturally present within the base non-actuated flow. A method to quantify the efficiency of ns-DBDs in depositing energy within the discharge volume is proposed. This energy is the one that eventually contributes to the formation of the thermal gradient responsible of the flow control capabilities shown by these devices. Such method is based on simultaneous implementation of infrared thermography and back-current shunt techniques. Results showed that the overall efficiency of a ns-DBD plasma actuator is inversely proportional to the thickness of the dielectric barrier. Last part of this thesis is concerned with a demonstrative application of a ns-DBD plasma actuator on a two element airfoil, at Reynolds numbers ranging between 0.2·106 and 2 ·106. Results demonstrated its capability to delay separation, increase lift and reduce drag in the post stall regime. Moreover, the plasma actuator showed the capability to eliminate both a laminar bubble separation for small angles of attack and the hysteresis behaviour of the selected airfoil. In conclusion, this work shed some light on the flow actuation mechanism of a ns- DBD plasma actuator and deepened its basic knowledge.

Background: Sevelamer hydrochloride, a major phosphate binder for patients on maintenance hemodialysis (MHD) is associated with reduced serum bicarbonate concentration due to hydrochloric acid release in the gut and to the binding of short chain fatty acids in the large intestine. Since metabolic acidosis can be deleterious, a study was devised to compare the time course of serum bicarbonate concentration during treatment with sevelamer hydrochloride or calcium carbonate.Methods: Sixteen well nourished patients on MHD who were in excellent clinical conditions and achieving target levels for blood pressure (BP) and hemoglobin (Hb), while on a protein intake of 1.1g/kg body weight (bw), were enrolled in the study. After a 2-week washout period, the patients were divided into two groups, each consisting of eight patients, and randomized either to 24 weeks of sevelamer followed by 24 weeks of calcium carbonate (group A) or to 24 weeks of calcium carbonate followed by 24 weeks of sevelamer (group B). Protein intake, n-protein catabolic rate (nPCR), serum concentrations of calcium, phosphate, calcium x phosphate (Ca x P) product, bicarbonate, intact parathyroid hormone (iPTH) and albumin were monitored. Time course changes in serum bicarbonate concentrations in relation to short and long dialytic intervals (48 vs. 72 hr) were also investigated.Results: Both sevelamer and calcium carbonate effectively controlled serum phosphate and the Ca x P product. During calcium carbonate treatment plasma phosphate concentrations were significantly below those of patients on sevelamer. Plasma bicarbonate concentration fell within target DOQI values during calcium carbonate administration both in group A and in group B, a goal which was not achieved under sevelamer administration. After a long dialytic interval in patients on sevelamer, serum bicarbonate concentration averaged 17.3 +/- 1.1mEq/L, whereas it averaged 21.1 +/- 0.7mEq/L in patients on calcium carbonate (p < 0.01). Finally, a 24-week sevelamer administration caused a statistically significant (p < 0.05) reduction (0.8 g/dL) in serum albumin concentration, without affecting iPTH. Taken together, these results indicate that sevelamer worsens metabolic acidosis, which needs to be corrected.

We report evidence of an unusual C-H--O interaction between an α-methylene hydrogen of the alkylamine chain of substituted (N,N-dimethylamino)propyl-azetidinones, substituted (N,N-dimethylamino)propyl-thiazolidinones and substituted (N,N-dimethylamino)propyl-thiazinone and the lactam carbonyl oxygen. NMR analysis results, supported by molecular mechanic predictions, were in agreement with ab initio calculations. The observed interaction shorting the nitrogen–nitrogen distance in the H1-histamine antagonist, 2-(4-methylphenyl)-3-[3-(N,N-dimethylamino)propyl]-1,3-thiazolidin-4-one (1) could explain its fitting with the H1-antihistaminic pharmacophoric model and the high antihistaminic activity.

The iminoquinone is an important moiety of a large number of antineoplastic drugs and plays a significant role in the nucleus of actinomycins, powerful, highly toxic, natural antibiotics that target DNA as intercalating agents. A series of polycyclic iminoquinonic compounds, 2-amino-3H-phenoxazin-3-one (1), 2-amino-1,9-diacetyl-3H-phenoxazin-3-one (2), 2-acetylamino-3H-phenoxazin-3-one (3), 3H-phenoxazin-3-one (4), 5H-pyrido[3,2-a]phenoxazin-5-one (5), and 5H-pyrido[3,2-a]phenothiazin-5-one (6), strictly related to the actinomycin chromophore, were synthesized for developing new anticancer intercalating drugs. The antiproliferative activity of these compounds, evaluated against representative human liquid and solid neoplastic cell lines, showed that 5 and its isoster 6 were the most active compounds inhibiting cell proliferation in a submicromolar range. Compound 5 was also evaluated against KB subclones (KBMDR, KB7D, and KBV20C), which overexpress the MDR1/P-glycoprotein drug efflux pump responsible for drug resistance. All the above KB subclones did not show altered sensitivity to the antiproliferative activity of 5. UV-vis and (1)H NMR spectroscopy experiments support the phenoxazinone 5/DNA binding. Molecular mechanics methods were used to build a three-dimensional model of the 5/[d(GAAGCTTC)]2 complex. Electrostatic interactions between the hydrogen of the positively charged pyridine nitrogen of 5 and the negatively charged oxygen atoms (O4' and O5') of the cytosine C5 residue together with stacking forces contribute to the high antiproliferative activity. The metal(II)-assisted synthesis procedure of 5 is described, and the formation mechanism is proposed.

New antiproliferative compounds, 5H-pyrido[3,2-a]phenoxazin-5-ones (1-10), 5H-benzophenoxazin-5-one (11), 5H-pyrido[2,3-a]phenoxazin-5-one (12), 5H-pyrido[3,4-a]phenoxazin-5-one (13), and 5H-pyrido[4,3-a]phenoxazin-5-one (14), were synthesized and evaluated against representative human neoplastic cell lines. The excellent cytotoxic activity of these polycyclic phenoxazinones, structurally related to the actinomycin chromophore, is discussed in terms of structural changes made to rings A and D (Chart 1). Electron-withdrawing or electron-donating substituents were introduced at different positions of ring A to probe the electronic and positional effects of the substitution. A nitro group in R(2) or in R(1) increases the cytotoxic activity, whereas electron-donating methyl groups in any position lead to 10- to 100-fold decreasing of the activity. The low antiproliferative activity of benzophenoxazinone 11 and pyridophenoxazinones 13 and 14 confirms the crucial role of pyridine nitrogen in the W position of ring D in DNA binding. The unexpected high activity exhibited by 12, which has the nitrogen in the X position, could be ascribed to a different mechanism of action, which needs further investigation.

Si ripercorre l'attività scientifica della compianta Collega Fabiola Ardizzone, dai suoi esordi come allieva della Cattedra di Archeologia Cristiana dell'Università di Palermo, all'attività di insegnamento e di ricerca sul campo in qualità di Professore Associato. Il contributo dato da Fabiola Ardizzone agli studi sulla Tarda Antichità e sul Medioevo siciliani hanno riguardato molteplici direttrici di ricerca: dall'identificazione di nuove classi ceramiche alle modalità di organizzazione delle aree funerarie, dai problemi di topografia urbana all'archeologia dei cimiteri e ai problemi della produzione e circolazione delle produzioni ceramiche. The paper traces the scientific activity of Fabiola Ardizzone, from her beginnings as a student of the Chair of Christian Archeology at the University of Palermo, to the teaching and field research as Associate Professor. The contribution given by Fabiola Ardizzone to the studies on the Late Antiquity and Medieval Sicily concerns multiple research lines: identification of new ceramic productions, problems of urban topography, funerary archeology, production and circulation of fine and coarse wares in Medieval Mediterranean.

New antiproliferative compounds, dimethyl-5H-pyrido[3,2-a]phenoxazin-5-ones (1-6), tetrahydro-5H-benzopyrido[2,3-j]phenoxazin-5-ones (7-9), and 5H-benzopyrido[3,2-a]phenoxazin-5-ones (10-12) were synthesized and evaluated against representative human neoplastic cell lines. Dimethyl derivatives 1-6 were more active against carcinoma than leukemia cell lines. The tetrahydrobenzo derivatives 7-9 were scarcely active, whereas the corresponding benzo derivatives 10-12 showed notable cytotoxicity against a majority of the tested cell lines. Molecular modeling studies indicated that the high potency of 10 and 11, the most cytotoxic compounds of the whole series, could be due to the position of the condensed benzene ring, which favors pi-pi stacking interactions with purine and pyrimidine bases in the DNA active site. Biological studies suggested that 10-12 have no effect on human topoisomerases I and II and that they induce arrest at the G2/M phase.

Since the very early manned missions in space, a state of anemia associated with reduced erythropoietin levels and reduced plasma volume was disclosed. The reduction in red blood cell mass is driven by a process of selective hemolysis, which has been named neocytolysis. This phenomenon also occurs in people living at a high altitude who descend rapidly to sea level. The origin of the signal leading to destruction of newly produced red blood cells probably is located in central circulation, but the operating mechanism is unknown. The importance of plasma cell volume reduction in the genesis of a lower red cell mass also is supported by the inverse correlation seen at moderate altitude. People arriving at moderate altitude have increased erythropoietin concentration that decreases after a few days and is in inverse correlation with central venous pressure. Studies under simulated microgravity conditions in human beings (bed rest, head-down tilt at -6°, water immersion) and in rats provide further insight in unraveling the mechanism of astronauts' anemia, a problem difficult to study in space because of the limited availability of spaceflights. © 2005 Elsevier Inc. All rights reserved.

Carbon and proton NMR spectra of several substituted 5H-pyrido[3,2-a]-, 5H-pyrido[2,3-a]phenoxazin-5-ones and 3H-phenoxazin-3-one derivatives have been assigned, and the experimental chemical shifts have been compared with the results of density functional calculations employing large basis sets. Solvent effects were explored by means of the polarizable continuum method (PCM), while the ( limited) side-chain flexibility of the compounds has been addressed by Boltzmann averaging of the computed spectral parameters over different conformational minima. Overall, the calculated shifts reproduce well the experiment results; thus, the computational procedure represents a feasible and useful complement to multidimensional NMR experiments in the assignment process.

New antiproliferative compounds, the 1-aryl-3-ethoxycarbonyl-pyrido[2,3-g]isoquinolin-5,10-diones (PIQDs, 1-7), were designed on the basis of a molecular model obtained by aligning the common quinolinquinone substructure of 5H-pyrido[3,2-a]phenoxazin-5-one (PPH) and some known anticancer agents. A Diels-Alder reaction between quinolin-5,8-dione (QD) and a 2-azadiene, formed by demolition of 2-aryl-1,3-thiazolidine ethyl esters (T compounds), was used to produce 1-7 and the isomeric 1-aryl-3-ethoxycarbonylpyrido[3,2-g]isoquinolin-5,10-diones (8-14). Two other compounds, the 3-amino-3-ethoxycarbonyldihydrothieno[2,3-g]quinolin-4,9-dione (15) and the 3-amino-3-ethoxycarbonyldihydrothieno[3,2-g]quinolin-4,9-dione (16), arising from a 1,4 Michael reaction of QD with a thiolate species formed by opening of T compounds, were recovered from the reaction mixture. The antiproliferative activity of 1-16 was evaluated against representative human liquid and solid neoplastic cell lines. The IC(50) of these compounds had median values in the range 2.00-0.01 microM, with 2-4 and 15 exhibiting significantly higher in vitro cytotoxic activity. Compound 2, also evaluated against KB subclones (KB(MDR), KB(7D), and KB(V20C)), was shown to be scarcely subject to the MDR1/P-glycoprotein drug efflux pump responsible for drug resistance. The noncovalent DNA-binding properties of PIQDs were examined using UV-vis and (1)H NMR spectroscopy experiments. Accordingly, these compounds were confirmed to have an ability to intercalate into double-stranded DNA by topoisomerase I superhelix unwinding assay. Interesting structure-activity relationships were found. Three important features seem to contribute to the cytotoxic activity of these anticancer ligands: (i) the DNA intercalating capability of the three-cyclic quinonic system, typical of this class of compounds, (ii) the position of the pendant phenyl ring that, according to the superimposition model, must occupy the same area of the corresponding benzo-fused ring A of PPH, and (iii) the effect of electron-withdrawing substituents on the phenyl ring, which can contribute improving the pi-pi stacking interactions between ligand and DNA base pairs. Besides, a mechanism of action suspected to involve topoisomerases could be hypothesized to interpret the antiproliferative activity of the thienoquinolindione 15, which can be regarded as a cyclic cysteine derivative.