Novel 4h-chromen-4-one, 2h-chromene and chroman derivatives: design, synthesis and biological evaluation

La progettazione e sintesi di nuovi antivirali strutturalmente correlati a flavanoidi e flavonoidi sia naturali che sintetici e lo studio della relativa attività anti-picornavirus dei 4H-cromen-4-oni e 2H-cromeni ha portato ad identificare l’(E)-3-stiril-2H-cromene come un inibitore potente, selettivo e ad ampio spettro d’azione nei confronti dei rhinovirus umani (HRV). l’(E)-3-stiril-2H-cromene è stato perciò selezionato come hit compound sul quale effettuare uno studio sistematico di ottimizzazione della struttura. Sono stati quindi progettati e sintetizzati un ampio numero di arilalchil cromeni, cromanoni e cromoni che sono stati saggiati in vitro nei confronti dei sierotipi 14 e 1B di HRV, scelti come rappresentati rispettivamente dei gruppi A e B di HRV. L’estensione dello screening ad altri virus ad RNA conferma la bassa citotossicità e la selettività dell’azione anti-HRV. Sono stati così selezionati i composti più potenti, ad ampio spettro d’azione anti-HRV e con alto indice terapeutico per valutarne il meccanismo d’azione. I risultati ottenuti sia sulla particella virale che sulla moltiplicazione virale suggeriscono che tutti i composti selezionati si comportano da capsid-binder, interferendo con le prime fasi dell’infezione virale, ma mentre l’(E)-3-stiril-2H-cromene agisce sull’adsorbimento del virus al recettore cellulare gli altri composti studiati non interferiscono in questa fase ma solo sul processo di uncoating. Il risultato è di notevole interesse dal momento che l’utilizzo di combinazioni di farmaci che agiscono su fasi successive della replicazione virale potrebbe essere utile per superare il problema delle mutazioni virali che rendono rapidamente inefficace la monoterapia

Novel 4h-chromen-4-one, 2h-chromene and chroman derivatives: design, synthesis and biological evaluation

La progettazione e sintesi di nuovi antivirali strutturalmente correlati a flavanoidi e flavonoidi sia naturali che sintetici e lo studio della relativa attività anti-picornavirus dei 4H-cromen-4-oni e 2H-cromeni ha portato ad identificare l’(E)-3-stiril-2H-cromene come un inibitore potente, selettivo e ad ampio spettro d’azione nei confronti dei rhinovirus umani (HRV). l’(E)-3-stiril-2H-cromene è stato perciò selezionato come hit compound sul quale effettuare uno studio sistematico di ottimizzazione della struttura. Sono stati quindi progettati e sintetizzati un ampio numero di arilalchil cromeni, cromanoni e cromoni che sono stati saggiati in vitro nei confronti dei sierotipi 14 e 1B di HRV, scelti come rappresentati rispettivamente dei gruppi A e B di HRV. L’estensione dello screening ad altri virus ad RNA conferma la bassa citotossicità e la selettività dell’azione anti-HRV. Sono stati così selezionati i composti più potenti, ad ampio spettro d’azione anti-HRV e con alto indice terapeutico per valutarne il meccanismo d’azione. I risultati ottenuti sia sulla particella virale che sulla moltiplicazione virale suggeriscono che tutti i composti selezionati si comportano da capsid-binder, interferendo con le prime fasi dell’infezione virale, ma mentre l’(E)-3-stiril-2H-cromene agisce sull’adsorbimento del virus al recettore cellulare gli altri composti studiati non interferiscono in questa fase ma solo sul processo di uncoating. Il risultato è di notevole interesse dal momento che l’utilizzo di combinazioni di farmaci che agiscono su fasi successive della replicazione virale potrebbe essere utile per superare il problema delle mutazioni virali che rendono rapidamente inefficace la monoterapia

Holographic duals of 6d RG flows

A notable class of superconformal theories (SCFTs) in six dimensions is parameterized by an integer $N$, an ADE group $G$, and two nilpotent elements $\mu_\mathrm{L,R}$ in $G$. Nilpotent elements have a natural partial ordering, which has been conjectured to coincide with the hierarchy of renormalization-group flows among the SCFTs. In this paper we test this conjecture for $G=\mathrm{SU}(k)$, where AdS$_7$ duals exist in IIA. We work with a seven-dimensional gauged supergravity, consisting of the gravity multiplet and two $\mathrm{SU}(k)$ non-Abelian vector multiplets. We show that this theory has many supersymmetric AdS$_7$ vacua, determined by two nilpotent elements, which are naturally interpreted as IIA AdS$_7$ solutions. The BPS equations for domain walls connecting two such vacua can be solved analytically, up to a Nahm equation with certain boundary conditions. The latter admit a solution connecting two vacua if and only if the corresponding nilpotent elements are related by the natural partial ordering, in agreement with the field theory conjecture.Comment: 33 pages, 2 figure

Simulating realistic disk galaxies with a novel sub-resolution ISM model

We present results of cosmological simulations of disk galaxies carried out with the GADGET-3 TreePM+SPH code, where star formation and stellar feedback are described using our MUlti Phase Particle Integrator (MUPPI) model. This description is based on simple multi-phase model of the interstellar medium at unresolved scales, where mass and energy flows among the components are explicitly followed by solving a system of ordinary differential equations. Thermal energy from SNe is injected into the local hot phase, so as to avoid that it is promptly radiated away. A kinetic feedback prescription generates the massive outflows needed to avoid the over-production of stars. We use two sets of zoomed-in initial conditions of isolated cosmological halos with masses (2-3) * 10^{12} Msun, both available at several resolution levels. In all cases we obtain spiral galaxies with small bulge-over-total stellar mass ratios (B/T \approx 0.2), extended stellar and gas disks, flat rotation curves and realistic values of stellar masses. Gas profiles are relatively flat, molecular gas is found to dominate at the centre of galaxies, with star formation rates following the observed Schmidt-Kennicutt relation. Stars kinematically belonging to the bulge form early, while disk stars show a clear inside-out formation pattern and mostly form after redshift z=2. However, the baryon conversion efficiencies in our simulations differ from the relation given by Moster et al. (2010) at a 3 sigma level, thus indicating that our stellar disks are still too massive for the Dark Matter halo in which they reside. Results are found to be remarkably stable against resolution. This further demonstrates the feasibility of carrying out simulations producing a realistic population of galaxies within representative cosmological volumes, at a relatively modest resolution.Comment: 19 pages, 21 figures, MNRAS accepte

Investigation of Nonlinear Pupil Dynamics by Recurrence Quantification Analysis

Pupil is controlled by the autonomous nervous system(ANS). It shows complexmovements and changes of size even in conditions of constant stimulation. The possibility of extracting information on ANS by processing data recorded during a short experiment using a low cost system for pupil investigation is studied. Moreover, the significance of nonlinear information contained in the pupillogram is investigated. We examined 13 healthy subjects in different stationary conditions, considering habitual dental occlusion (HDO) as a weak stimulation of the ANS with respect to the maintenance of the rest position (RP) of the jaw. Images of pupil captured by infrared cameras were processed to estimate position and size on each frame. From such time series, we extracted linear indexes (e.g., average size, average displacement, and spectral parameters) and nonlinear information using recurrence quantification analysis (RQA). Data were classified using multilayer perceptrons and support vector machines trained using different sets of input indexes: the best performance in classification was obtained including nonlinear indexes in the input features. These results indicate that RQA nonlinear indexes provide additional information on pupil dynamics with respect to linear descriptors, allowing the discrimination of even a slight stimulation of the ANS. Their use in the investigation of pathology is suggeste

(E)-3-Heteroarylidenechroman-4-ones as potent and selective monoamine oxidase-B inhibitors

A series of (E)-3-heteroarylidenechroman-4-ones (1a-r) was designed, synthesized and investigated in vitro for their ability to inhibit the enzymatic activity of both human monoamine oxidase (hMAO) isoforms, hMAO-A and hMAO-B. All the compounds were found to be selective hMAO-B inhibitors showing IC50 values in the nanomolar or micromolar range. (E)-5,7-Dichloro-3-{[(2-(dimethylamino) pyrimidin-5-yl]methylene}chroman-4-one (1c) was the most interesting compound identified in this study, endowed with higher hMAO-B potency (IC50 ¼ 10.58 nM) and selectivity (SI > 9452) with respect to the reference selective inhibitor selegiline (IC50 ¼ 19.60 nM, IC50 > 3431). Molecular modelling studies were performed for rationalizing at molecular level the target selective inhibition of our compounds, revealing a remarkable contribution of hydrogen bond network and water solvent

GrGadget: an N-body TreePM relativistic code for cosmological simulations

We present the merging of the Particle-Mesh (PM) relativistic Gevolution code with the TreePM Gadget-4 code, with the aim of studying general relativity effects in cosmology. Our code, called GrGadget, is able to track the evolution of metric perturbations in the weak field limit by using Gevolution's implementation of a relativistic PM in the Poisson gauge. To achieve this, starting from Gevolution we have written a C++ library called libgevolution, that allows a code to access and use the same abstractions and resources that Gevolution uses for its PM-only N-body simulations. The code works under the assumption that particle interactions at short distances can be approximated as Newtonian, so that we can combine the forces computed with a Newtonian Tree with those computed with a relativistic PM. The result is a TreePM simulation code that represents metric perturbations at the scales where they are relevant, while resolving non-linear structures. We validate our code by closely matching Gadget-4 forces, computed with the Tree switched off, with those computed with libgevolution in the Newtonian limit. With GrGadget we obtain a matter power spectrum that is compatible with Newtonian Gadget at small scales and contains GR features at large scales that are consistent with results obtained with Gevolution. We demonstrate that, due to the better resolution of the highly non-linear regime, the representation of the relativistic fields sampled on the mesh improves with respect to the PM-only simulations.Comment: 15 pages, 14 figure

Introduzione al determinismo

In questo lavoro di tesi ci si concentra sul problema del determinismo nel mondo della fisica. Il primo capitolo è dedicato a vari tentativi di definire il determinismo; si parte da definizioni puramente empiriche fino ad arrivare, in un graduale processo costitutivo, a quella coinvolgente il concetto di mondi possibili che risulta soddisfacente. Nel secondo capitolo si analizza il problema del determinismo nella fisica classica, introducendo brevemente lo spazio-temo classico e trattando poi diversi casi fisici di interesse. Nel terzo capitolo si discutono le implicazioni che la struttura dello spazio-tempo di Minkowski ha sul determinismo nel caso della relatività ristretta e si accennano alcune considerazioni sulla relatività generale. Nel quarto ed ultimo capitolo, infine, è trattato il problema del determinismo nel caso della meccanica quantistica, analizzando in particolare il significato di una misurazione e le implicazioni del collasso della funzione d’onda

Use of nano zero-valent iron to reduce inorganic species electrogenerated during anodic oxidation on boron doped diamond anodes

In this paper, the solution coming from an anodic oxidation on boron doped diamond of chloride-containing solution is treated with addition of nano zero-valent iron (nZVI) to reduce the amount of chlorinated byproducts into chloride ions. The electrolyzed solutions have been obtained under galvanostatic conditions in an undivided reactor. The evolution and depletion of all the chlorinated species have been monitored by spectrophotometry and ion chromatography. The nanoscale iron particles have been synthesized in our laboratory by a fast and facile method through reaction of FeSO4 and NaBH4 solutions without addition of dispersants. The effect on the conversion yield of several operative parameters has been investigated and discussed. The preliminary results indicate that a nZVI postreatment can be considered a viable technology for the treatment of solutions containing active chlorine and chlorate. However, the reduction of perchlorate, either in mixed solutions or alone, requires too drastic conditions to be completed