INSERTION (CO)POLYMERIZATION OF OLEFINS CATALYZED BY FIRST ROW TRANSITION METAL COMPLEXES

Since polyolefins are an integral part of everyday life and given the ever-growing global demand for these polymers, the insertion polymerization of olefins is one of the most industrially relevant synthetic reaction, widely investigated also in academia. It is in this context that this PhD project is located. The developed research activity was aimed at synthesizing new catalytic systems capable of stereochemically drive the polymerization of various (di)olefins, in particular cyclic olefins such as norbornene and its derivatives. The investigated catalysts are made up of two components: the organometallic complex (pre-catalyst) and an aluminum alkyl compound (co-catalyst or activator). Among the series of the organometallic complexes, during my PhD, complexes of the first row transition metals, i.e., titanium, vanadium, and chromium, bearing nitrogen and phosphorous based ligands were investigated. They were later applied as catalysts for the homopolymerization of ethylene, cyclic olefins (norbornene, dicyclopentadiene and norbornene derivatives) and 1,3-butadiene, and the copolymerization of ethylene with various cyclic olefins. Depending on the employed catalyst and the polymerization conditions, we obtained oligomers or high-polymers. All the products were carefully characterized with different techniques, in order to get more information on the properties of the obtained (co)polymers as well as on the polymerization mechanism. Norbornene and dicyclopentadiene oligomers were mainly obtained from titanium and chromium catalysts, activated by Et2AlCl and methylalumoxane (MAO), respectively, while cyclic olefin copolymers were obtained from the copolymerization of ethylene with cyclic olefins promoted by vanadium based catalysts. In addition, we demonstrated that some vanadium and chromium complexes, in combination with MAO, were active in the polymerization of 1,3-butadiene, affording poly(1,3-butadiene) with different microstructure (cis-1,4, trans-1,4 or 1,2) and stereospecificity (i.e., iso- or syndiotactic polymers), depending on the type of ligand. This study allowed to understand the correlations between the catalyst\u2019s features and the polymerization outcome in terms of activity, regio- and stereoselectivity. Moreover, particular emphasis has been devoted to the study of the catalyst stability over the polymerization time and temperature. At the same time, particular interest has been developed toward the post\uf02dpolymerization functionalization, as a strategy to modify some polymer properties (e.g., solubility and processability) and thus to obtain polymers hardly obtainable by direct (co)polymerization with polar (co)monomers. This PhD dissertation reports the results achieved during the three-year research activity, together with the main difficulties encountered and the actions put in place trying to overcome them

On the main stages of the history of intra-articular therapy

In this review the main stages in the history of intra-articular therapy of the rheumatic diseases are summarized. The first approach to such a local treatment has been likely performed in 1792 by the French physician Jean Gay, who injected in a swelling knee the "eau du Goulard" (Goulard's water), namely a mixture based on lead compounds. In the XIX century iodine derivatives have been mainly applied as an intra-articular treatment. In the XX century, before the wide use of intra-articular corticosteroids, chiefly due to the Joseph Lee Hollander's experiences, a variety of drugs has been employed, including cytostatics and sclerosing substances. A further important stage has been synoviorthesis, by using specific radionuclides, that would actually represent an anti-synovial treatment. In the last years a spread use of intra-articular hyaluronic acid, particularly in osteoarthritis, has been recorded, with the aim to warrant articular viscosupplementation. Future of intra-articular treatment should be represented by the biological drugs, i.e., anti-TNF, but it is still untimely to define the exact role of such a local treatment of arthritis

Synthesis, structure and 1,3-butadiene polymerization behavior of vanadium(III) phosphine complexes

A series of vanadium(III) complexes bearing monodentate tertiary phosphine ligands of the type VCl3(PRnPh3-n)2 (n = 0 (1a); n = 1 and R = Me (1b), Et (1c), iPr (1d), Cy (1e); n = 2 and R = Me (1f), Et (1g), Cy (1h)), and VCl3(PR3)2 (R = Cyp (2a), Cy (2b),nPr (2c),tBu (2d)) were synthesized and characterized. In the case of 1c, 1g and 2a single crystals were also obtained and their molecular structures were determined. All the complexes were used, in combination with methylaluminoxane (sMAO) or AlMe3\u2013free MAO (dMAO), for the polymerization of 1,3-butadiene, exhibiting rather good activity and giving polymers with different microstructure depending on the nature of the phosphine ligand and the type of co-catalyst employed

The association between in-stent neoatherosclerosis and native coronary artery disease progression: a long-term angiographic and optical coherence tomography cohort study

Aims The purpose of the present study was to investigate the relationship between in-stent neoatherosclerosis (NA) and native atherosclerosis progression of untreated coronary segments. Methods and results In-stent NA was assessed by optical coherence tomography (OCT) among patients included in the SIRTAX-LATE OCT study 5 years after drug-eluting stent (DES) (sirolimus-eluting and paclitaxel-eluting stents) implantation. Neoatherosclerosis was defined as the presence of fibroatheroma or fibrocalcific plaque within the neointima of stented segments with a longitudinal extension >1.0 mm. Atherosclerosis progression in untreated native coronary segments was evaluated by serial quantitative coronary angiography (QCA). The change in minimal lumen diameter (MLD) was serially assessed within matched segments at baseline and 5-year angiographic follow-up. The key clinical endpoint was non-target lesion (non-TL) revascularization throughout 5 years. A total of 88 patients with 88 lesions were available for OCT analysis 5 years after DES implantation. In-stent NA was observed in 16% of lesions with the majority of plaques being fibroatheromas (11.4%) followed by fibrocalcific plaques (5.7%). A total of 704 non-TL segments were serially evaluated by QCA. Between baseline and 5-year follow-up, the reduction in MLD was significantly more pronounced in patients with NA (−0.25 mm, 95% CI −0.36 to −0.17 mm) when compared with patients without NA (−0.13 mm, 95% CI −0.17 to −0.10 mm, P = 0.002). Similarly, non-TL revascularization was more frequent in patients with NA (78.6%) when compared with patients without NA (44.6%, P = 0.028) throughout 5 years. Conclusions In-stent NA is more common among patients with angiographic and clinical evidence of native atherosclerosis progression suggesting similar pathophysiological mechanisms. SIRTAX trial is registered at http://www.clinicaltrials.gov/ct2/show/NCT0061708

The NIP7 protein is required for accurate pre-rRNA processing in human cells

Eukaryotic ribosome biogenesis requires the function of a large number of trans-acting factors which interact transiently with the nascent pre-rRNA and dissociate as the ribosomal subunits proceed to maturation and export to the cytoplasm. Loss-of-function mutations in human trans-acting factors or ribosome components may lead to genetic syndromes. In a previous study, we have shown association between the SBDS (Shwachman–Bodian–Diamond syndrome) and NIP7 proteins and that downregulation of SBDS in HEK293 affects gene expression at the transcriptional and translational levels. In this study, we show that downregulation of NIP7 affects pre-rRNA processing, causing an imbalance of the 40S/60S subunit ratio. We also identified defects at the pre-rRNA processing level with a decrease of the 34S pre-rRNA concentration and an increase of the 26S and 21S pre-rRNA concentrations, indicating that processing at site 2 is particularly slower in NIP7-depleted cells and showing that NIP7 is required for maturation of the 18S rRNA. The NIP7 protein is restricted to the nuclear compartment and co-sediments with complexes with molecular masses in the range of 40S–80S, suggesting an association to nucleolar pre-ribosomal particles. Downregulation of NIP7 affects cell proliferation, consistently with an important role for NIP7 in rRNA biosynthesis in human cells

Frovatriptan versus almotriptan for acute treatment of menstrual migraine: analysis of a double-blind, randomized, cross-over, multicenter, Italian, comparative study

The objective of the study was to compare the efficacy and safety of frovatriptan and almotriptan in women with menstrually related migraine (IHS Classification of Headache disorders) enrolled in a multicenter, randomized, double-blind, cross-over study. Patients received frovatriptan 2.5 mg or almotriptan 12.5 mg in a randomized sequence: after treating 3 episodes of migraine in no more than 3 months with the first treatment, the patient was switched to the other treatment. 67 of the 96 female patients of the intention-to-treat population of the main study had regular menstrual cycles and were thus included in this subgroup analysis. 77 migraine attacks classified as related to menses were treated with frovatriptan and 78 with almotriptan. Rate of pain relief at 2 and 4 h was 36 and 53 % for frovatriptan and 41 and 50 % for almotriptan (p = NS between treatments). Rate of pain free at 2 and 4 h was 19 and 47 % with frovatriptan and 29 and 54 % for almotriptan (p = NS). At 24 h, 62 % of frovatriptan-treated and 67 % of almotriptan-treated patients had pain relief, while 60 versus 67 % were pain free (p = NS). Recurrence at 24 h was significantly (p < 0.05) lower with frovatriptan (8 vs. 21 % almotriptan). This was the case also at 48 h (9 vs. 24 %, p < 0.05). Frovatriptan was as effective as almotriptan in the immediate treatment of menstrually related migraine attacks. However, it showed a more favorable sustained effect, as shown by a lower rate of migraine recurrence

The NIP7 protein is required for accurate pre-rRNA processing in human cells

Eukaryotic ribosome biogenesis requires the function of a large number of trans-acting factors which interact transiently with the nascent pre-rRNA and dissociate as the ribosomal subunits proceed to maturation and export to the cytoplasm. Loss-of-function mutations in human trans-acting factors or ribosome components may lead to genetic syndromes. In a previous study, we have shown association between the SBDS (Shwachman–Bodian–Diamond syndrome) and NIP7 proteins and that downregulation of SBDS in HEK293 affects gene expression at the transcriptional and translational levels. In this study, we show that downregulation of NIP7 affects pre-rRNA processing, causing an imbalance of the 40S/60S subunit ratio. We also identified defects at the pre-rRNA processing level with a decrease of the 34S pre-rRNA concentration and an increase of the 26S and 21S pre-rRNA concentrations, indicating that processing at site 2 is particularly slower in NIP7-depleted cells and showing that NIP7 is required for maturation of the 18S rRNA. The NIP7 protein is restricted to the nuclear compartment and co-sediments with complexes with molecular masses in the range of 40S–80S, suggesting an association to nucleolar pre-ribosomal particles. Downregulation of NIP7 affects cell proliferation, consistently with an important role for NIP7 in rRNA biosynthesis in human cells

Gravitational quasinormal modes of AdS black branes in d spacetime dimensions

The AdS/CFT duality has established a mapping between quantities in the bulk AdS black-hole physics and observables in a boundary finite-temperature field theory. Such a relationship appears to be valid for an arbitrary number of spacetime dimensions, extrapolating the original formulations of Maldacena's correspondence. In the same sense properties like the hydrodynamic behavior of AdS black-hole fluctuations have been proved to be universal. We investigate in this work the complete quasinormal spectra of gravitational perturbations of $d$-dimensional plane-symmetric AdS black holes (black branes). Holographically the frequencies of the quasinormal modes correspond to the poles of two-point correlation functions of the field-theory stress-energy tensor. The important issue of the correct boundary condition to be imposed on the gauge-invariant perturbation fields at the AdS boundary is studied and elucidated in a fully $d$-dimensional context. We obtain the dispersion relations of the first few modes in the low-, intermediate- and high-wavenumber regimes. The sound-wave (shear-mode) behavior of scalar (vector)-type low-frequency quasinormal mode is analytically and numerically confirmed. These results are found employing both a power series method and a direct numerical integration scheme.Comment: added references, typos corrected, minor changes, final version for JHE

Spherical and planar three-dimensional anti-de Sitter black holes

The technique of dimensional reduction was used in a recent paper (Zanchin et al, Phys. Rev. D66, 064022,(2002)) where a three-dimensional (3D) Einstein-Maxwell-Dilaton theory was built from the usual four-dimensional (4D) Einstein-Maxwell-Hilbert action for general relativity. Starting from a class of 4D toroidal black holes in asymptotically anti-de Sitter (AdS) spacetimes several 3D black holes were obtained and studied in such a context. In the present work we choose a particular case of the 3D action which presents Maxwell field, dilaton field and an extra scalar field, besides gravity field and a negative cosmological constant, and obtain new 3D static black hole solutions whose horizons may have spherical or planar topology. We show that there is a 3D static spherically symmetric solution analogous to the 4D Reissner-Nordstr\"om-AdS black hole, and obtain other new 3D black holes with planar topology. From the static spherical solutions, new rotating 3D black holes are also obtained and analyzed in some detail.Comment: 27 pages, uses "iopclass" files (Latex2e