Studio della formazione di complessi tra alluminio e molecole di interesse ambientale, biologico e farmaceutico

In this thesis work, the coordination properties of several ligands with pharmaceutical, biological and toxicological properties towards Al3+ have been studied. The investigated molecules are 3-hydroxy-2-(1H)-pyridinone (HPyr), 2-hydroxyphenylethanone (HPE), 2-hydroxybenzeneacetic acid (HBA), 2-hydroxynicotinic acid (HNic), 3-hydroxypicolinic acid (HPic), and glutamic acid (Glu). The reliability of the speciation data has been considered as one of the primary goals. For this reason, each metal-ligand system has been studied by means of a combination of more analytical techniques, so that independent results have been obtained regarding the stoichiometry of the existing complexes and their stability constants. The techniques employed have been potentiometry, UV-Vis spectrophotometry, and 1H-NMR spectroscopy. For HPyr it was also possible to obtain a crystal, so that the structure of an Al-HPyr complex has been evaluated by means of a X-ray diffractometric analysis. The complexation strength of the studied ligands has been compared each other and with the complexation strength of other ligands previously studied in the literature. The comparison results indicate that Al3+ complexes can be very stable only if the chelating oxygens bear a significant partial negative charge and they can form a 5 or 6-membered chelation ring. HBA forms very weak complexes, as a 7-membered chelation ring is formed by this ligand. In the case of Glu, the complexes are weak because the metal centre is coordinated also by nitrogen, which has a lower affinity towards Al3+ than negatively charged oxygens. HPE bears two oxygens and forms a six-membered chelation ring. However, this ligand forms much weaker complexes than HPyr, HNic, and HPic, because the net negative charge on the HPE oxygens is 0.5, and not (practically) –1 as it is in the other three ligands. Another aim of this work was the set-up of a new computer programme, PITMAP, which can be used for the elaboration of potentiometric titrations. PITMAP input files are the titration data, and the output results are the stability constants of the species which form in solution at equilibrium, through fitting of experimental parameters

SOFTWARE FOR WEATHER DATABASES MANAGEMENT AND CONSTRUCTION OF REFERENCE YEARS

The purpose of this paper is to illustrate a procedure that permits, starting from a sufficiently long database of time series, the construction of a Reference Year (RY) of hourly weather data according to the rules of ISO 15927-4 standard. In order to facilitate the management of the weather database and to allow the users to easily generate the file, an algorithm has been implemented in Microsoft Visual Basic for Application (VBA). By this way, the application of the ISO 15927-4 is possible even using a popular software tool such as Microsoft Excel or Access without any other expensive specialized software. Such tool allows to fulfil all the procedures mentioned in ISO 15927- 4 giving as result a time series of 8760 values of several weather variables, ready to be used in any software for energy simulation of buildings

Two hydroxy pyridinecarboxylic acid derivatives as a possible chelating agents in neurodegenerative disease; equilibrium complexation studies with Cu(II), Zn(II).

The metal ion chelators 4-hydroxy-5-methyl-3-pyridinecarboxylic acid (DQ5) and 1,5-dimethyl-4-hydroxy-3-pyridinecarboxylic acid (DQ715) and Cu(II) and Zn(II) were investigated with the aim to restore the homeostasis of the brain Cu(II) and Zn(II) in neurodegenerative diseases. The proton dissociation constants of the ligands, the stability constants, and the coordination modes of the metal complexes formed were determined by pH-potentiometric, and spectral (UV–Vis and EPR or 1H NMR) methods. The results show that in slightly acidic and neutral pH range mono and bis complexes are formed through bidentate coordination of the ligands. The biological MTT-test reveals that the DQ715 ligand is able to lower the cytotoxic effect of Cu(II) in human embryonic kidney HEK-293 cells. Our studies revealed, however, that none of the chelators were efficient enough to withdraw these metal ions from the amyloid aggregates

Rank-one flavor violation and B-meson anomalies

We assume that the quark-flavor coefficients matrix of the semileptonic operators addressing the neutral-current B-meson anomalies has rank-one, i.e. it can be described by a single vector in quark-flavor space. By correlating the observed anomalies to other flavor and high-pT observables, we constrain its possible directions and we show that a large region of the parameter space of this framework will be explored by flavor data from the NA62, KOTO, LHCb and Belle II experiments

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

Contemporary lipid-lowering management and risk of cardiovascular events in homozygous familial hypercholesterolaemia: insights from the Italian LIPIGEN Registry

Aims: The availability of novel lipid-lowering therapies (LLTs) has remarkably changed the clinical management of homozygous familial hypercholesterolaemia (HoFH). The impact of these advances was evaluated in a cohort of 139 HoFH patients followed in a real-world clinical setting. Methods and results: The clinical characteristics of 139 HoFH patients, along with information about LLTs and low-density lipoprotein cholesterol (LDL-C) levels at baseline and after a median follow-up of 5 years, were retrospectively retrieved from the records of patients enrolled in the LIPid transport disorders Italian GEnetic Network-Familial Hypercholesterolaemia (LIPIGEN-FH) Registry. The annual rates of major atherosclerotic cardiovascular events (MACE-plus) during follow-up were compared before and after baseline. Additionally, the lifelong survival free from MACE-plus was compared with that of the historical LIPIGEN HoFH cohort. At baseline, LDL-C level was 332 ± 138 mg/dL. During follow-up, the potency of LLTs was enhanced and, at the last visit, 15.8% of patients were taking quadruple therapy. Consistently, LDL-C decreased to an average value of 124 mg/dL corresponding to a 58.3% reduction (Pt < 0.001), with the lowest value (∼90 mg/dL) reached in patients receiving proprotein convertase subtilisin/kexin type 9 inhibitors and lomitapide and/or evinacumab as add-on therapies. The average annual MACE-plus rate in the 5-year follow-up was significantly lower than that observed during the 5 years before baseline visit (21.7 vs. 56.5 per 1000 patients/year; P = 0.0016). Conclusion: Our findings indicate that the combination of novel and conventional LLTs significantly improved LDL-C control with a signal of better cardiovascular prognosis in HoFH patients. Overall, these results advocate the use of intensive, multidrug LLTs to effectively manage HoFH