An Interdisciplinary Approach for the Experimental Assessments of the Seismic Safety of Artworks

Recent seismic events occurred in areas rich of ancient remains and full of cultural and artistic heritage in terms of artworks. Earthquakes may damage buildings, but the vibrations may also induce the uplift and overturning of their content, implying irreparable loss of cultural values. The seismic assessment of objects is usually tackled modelling them as rigid blocks. This paper focuses on statues, which generally present a very complicated geometry, and proposes a general methodology involving different disciplines, for their experimental seismic assessment. The methodology is here applied to the masterpiece of “Paolo Orsi” museum in Syracuse (Italy), that is the “Venere Landolina”. Due to the complexity of statues, traditional techniques cannot be considered reliable for a proper geometry reconstruction; therefore, Terrestrial Laser Scanner (TLS) and Unmanned Aerial System (UAS) technologies are here employed to obtain a highly detailed and complete digital model. Aiming at providing a low-cost scaled physical model of the statue, a wooden specimen has been arranged employing a Computer Numerical Control (CNC) milling machine, cutting off disks from flat panels which are then superimposed and glued, progressively reconstructing the actual geometry of the statue. The specimen, able to approximately reproduce the scaled actual geometry, was then tested on a shaking table with ground motions compatible with those expected for the site where the statue is located. The obtained results are finally correlated with those expected for the real scale statue

A potent and selective Sirtuin 1 inhibitor alleviates pathology in multiple animal and cell models of Huntington's disease

Protein acetylation, which is central to transcriptional control as well as other cellular processes, is disrupted in Huntington's disease (HD). Treatments that restore global acetylation levels, such as inhibiting histone deacetylases (HDACs), are effective in suppressing HD pathology in model organisms. However, agents that selectively target the disease-relevant HDACs have not been available. SirT1 (Sir2 in Drosophila melanogaster) deacetylates histones and other proteins including transcription factors. Genetically reducing, but not eliminating, Sir2 has been shown to suppress HD pathology in model organisms. To date, small molecule inhibitors of sirtuins have exhibited low potency and unattractive pharmacological and biopharmaceutical properties. Here, we show that highly selective pharmacological inhibition of Drosophila Sir2 and mammalian SirT1 using the novel inhibitor selisistat (selisistat; 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide) can suppress HD pathology caused by mutant huntingtin exon 1 fragments in Drosophila, mammalian cells and mice. We have validated Sir2 as the in vivo target of selisistat by showing that genetic elimination of Sir2 eradicates the effect of this inhibitor in Drosophila. The specificity of selisistat is shown by its effect on recombinant sirtuins in mammalian cells. Reduction of HD pathology by selisistat in Drosophila, mammalian cells and mouse models of HD suggests that this inhibitor has potential as an effective therapeutic treatment for human disease and may also serve as a tool to better understand the downstream pathways of SirT1/Sir2 that may be critical for H

A potent and selective Sirtuin 1 inhibitor alleviates pathology in multiple animal and cell models of Huntington's disease

Protein acetylation, which is central to transcriptional control as well as other cellular processes, is disrupted in Huntington's disease (HD). Treatments that restore global acetylation levels, such as inhibiting histone deacetylases (HDACs), are effective in suppressing HD pathology in model organisms. However, agents that selectively target the disease-relevant HDACs have not been available. SirT1 (Sir2 in Drosophila melanogaster) deacetylates histones and other proteins including transcription factors. Genetically reducing, but not eliminating, Sir2 has been shown to suppress HD pathology in model organisms. To date, small molecule inhibitors of sirtuins have exhibited low potency and unattractive pharmacological and biopharmaceutical properties. Here, we show that highly selective pharmacological inhibition of Drosophila Sir2 and mammalian SirT1 using the novel inhibitor selisistat (selisistat; 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide) can suppress HD pathology caused by mutant huntingtin exon 1 fragments in Drosophila, mammalian cells and mice. We have validated Sir2 as the in vivo target of selisistat by showing that genetic elimination of Sir2 eradicates the effect of this inhibitor in Drosophila. The specificity of selisistat is shown by its effect on recombinant sirtuins in mammalian cells. Reduction of HD pathology by selisistat in Drosophila, mammalian cells and mouse models of HD suggests that this inhibitor has potential as an effective therapeutic treatment for human disease and may also serve as a tool to better understand the downstream pathways of SirT1/Sir2 that may be critical for HD

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Adenosine is a neuromodulator that operates via the most abundant inhibitory adenosine A1 receptors (A1Rs) and the less abundant, but widespread, facilitatory A2ARs. It is commonly assumed that A1Rs play a key role in neuroprotection since they decrease glutamate release and hyperpolarize neurons. In fact, A1R activation at the onset of neuronal injury attenuates brain damage, whereas its blockade exacerbates damage in adult animals. However, there is a down-regulation of central A1Rs in chronic noxious situations. In contrast, A2ARs are up-regulated in noxious brain conditions and their blockade confers robust brain neuroprotection in adult animals. The brain neuroprotective effect of A2AR antagonists is maintained in chronic noxious brain conditions without observable peripheral effects, thus justifying the interest of A2AR antagonists as novel protective agents in neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, ischemic brain damage and epilepsy. The greater interest of A2AR blockade compared to A1R activation does not mean that A1R activation is irrelevant for a neuroprotective strategy. In fact, it is proposed that coupling A2AR antagonists with strategies aimed at bursting the levels of extracellular adenosine (by inhibiting adenosine kinase) to activate A1Rs might constitute the more robust brain neuroprotective strategy based on the adenosine neuromodulatory system. This strategy should be useful in adult animals and especially in the elderly (where brain pathologies are prevalent) but is not valid for fetus or newborns where the impact of adenosine receptors on brain damage is different

Buccheri, cúspide de los Ibleos

La ciudad de Buccheri es un caso singular del altiplano ibleo. Se trata de un gran tablero calcáreo blanco en el que varios cursos de agua han cavado valles profundos

Ateliermap. Oratorio della parrocchia della Sacra Famiglia, Manfredonia, Foggia

Le pagine presentano il progetto per l’oratorio della parrocchia della Sacra Famiglia a Manfredonia, in Provincia di Foggia. Affogato tra le palazzine speculative degli anni Settanta e Ottanta, il recinto del sagrato, la chiesa triangolare e la casa canonica, l’oratorio occupa l’intero lotto residuo, addensando al margine la volumetria di programma e liberando quanto più spazio possibile al suo interno. Un edificio fatto di tre soli materiali: il muro perimetrale in calcestruzzo a doghe orizzontali, gli infissi a correre sui quattro lati del chiostro, il pavimento in cemento levigato. Una costellazione di fori in plexiglas, infine, decora di luce la grande sala interna

Ateliermap. Oratorio della parrocchia della Sacra Famiglia, Manfredonia, Foggia

Le pagine presentano il progetto per l\u2019oratorio della parrocchia della Sacra Famiglia a Manfredonia, in Provincia di Foggia. Affogato tra le palazzine speculative degli anni Settanta e Ottanta, il recinto del sagrato, la chiesa triangolare e la casa canonica, l\u2019oratorio occupa l\u2019intero lotto residuo, addensando al margine la volumetria di programma e liberando quanto pi\uf9 spazio possibile al suo interno. Un edificio fatto di tre soli materiali: il muro perimetrale in calcestruzzo a doghe orizzontali, gli infissi a correre sui quattro lati del chiostro, il pavimento in cemento levigato. Una costellazione di fori in plexiglas, infine, decora di luce la grande sala interna