Umberto Chierici e la Soprintendenza ai Monumenti del Piemonte, 1953-1976. Il contributo alla cultura della tutela e la pratica di cantiere

Nel Piemonte del dopoguerra, tra gli anni 1953 e 1976, la tutela istituzionale è incarnata da una figura di Soprintendente che regge con continuità le politiche di salvaguardia tracciandone decisamente anche le linee teoriche: l’architetto Umberto Chierici (1911-1980). Per estrazione sociale e capacità precipue U. Chierici, impegnato in un’attività vastissima che ha toccato quello che ancora oggi rappresenta il nucleo centrale del patrimonio nel territorio di competenza, interloquisce con i più autorevoli colleghi e studiosi del tempo, governando la transizione del restauro da quegli “esordi scientifici” al perfezionamento metodologico. La sua formazione a Napoli ha come riferimenti Croce e Giovannoni, oltre al padre Gino, e si costituisce pertanto tra estetica e tecnica. Appena arrivato a Torino nel 1937 nel ruolo di “Architetto aggiunto” e prima delle esperienze in Calabria, Abruzzo e Molise (presso la Soprintendenza dell’Aquila organizza un Gabinetto di Restauro per le opere d’arte figurativa) che lo faranno rientrare in Piemonte solo nel 1953, lamenta la mancanza presso l’Ufficio di una biblioteca e di un “gabinetto fotografico”, per l’importanza rivestita dalla fotografia nella documentazione delle consistenze e dei processi di conservazione. Di ritorno come Soprintendente si impegna nella dimensione “urbana” del restauro lavorando sui centri storici, individua sistemi di beni da ricondurre a politiche coordinate (quello delle Residenze Sabaude in occasione delle celebrazioni del centenario dell’Unità d’Italia), promuove il riordino dei musei, tiene conferenze (fra cui quella su “Il falso nell’opera d’arte”, 1964), pubblica saggi critici che si muovono dallo studio storico-filologico ai problemi di degrado dei materiali lapidei e delle patine. I suoi epistolari con Guglielmo De Angeli d’Ossat, l’attività in ICOMOS con Sanpaolesi, Di Stefano, Gazzola e altri, nonché gli scambi con Roberto Pane lo proiettano a pieno titolo in quella compagine culturale che il convegno di Firenze, il cui esito è il numero monografico della rivista, ha inteso esplorare e dettagliare comparativamente. Le sue riflessioni teoretiche ed esperienze applicate vengono altresì trasferite in ambito accademico: è abilitato fin dal 1952 alla libera docenza di “Restauro dei Monumenti” e terrà corsi alla Facoltà di Architettura del Politecnico di Torino nel 1953 e dal 1955 al 1980, contribuendo alla riflessione sulla formazione dell’Architetto e alla pedagogia del Restauro, quello “monumentale” e quello “urbanistico”. Il saggio, guardando all’esperienza dei cantieri seguiti nel corso della sua attività di Soprintendente, tra cui quelli poco noti dell’abbazia di Santa Giustina di Sezzadio - Alessandria, del complesso di San Francesco a Cuneo e della chiesa cimiteriale di San Lorenzo a Montiglio - Asti (che compendiano istanze architettoniche e storico-artistiche di grande complessità), tratteggia i principali impulsi innovativi e scientifici del suo approccio, contribuendo alla costruzione di un quadro critico-conoscitivo finora inedito. / The protection of cultural heritage in Piedmont, during the post-war period between 1953 and 1976, was assigned to Superintendent Umberto Chierici (architect, 1911-1980), who directed conservation policies with continuity, carrying out the restoration project of many monuments and pursuing university teaching experience. During his long commitment in Turin (after services in Calabria, Abruzzo and Molise), he explored urban restoration in historical centres, restored the Residences of the Royal House of Savoy as an organic heritage system, promoted the reorganisation of museums, held conferences, and published critical and historiographical essays. The contribution explores three little-known restoration sites of his work in the Soprintendenza, those of Santa Giustina in Sezzadio abbey, the San Francesco in Cuneo and the San Lorenzo in Montiglio churches in southern Piedmont, using unpublished archive documents. The aim is to verify Chierici’s adherence to the theoretical assumptions of restoration at the time and his contribution to the definition of scientific methodologies for conservation

Exploiting magnetic properties of Fe doping in zirconia

In this study we explore, both from theoretical and experimental side, the effect of Fe doping in ZrO2 (ZrO2:Fe). By means of first principles simulation we study the magnetization density and the magnetic interaction between Fe atoms. We also consider how this is affected by the presence of oxygen vacancies and compare our findings with models based on impurity band and carrier mediated magnetic interaction. Experimentally thin films (~ 20 nm) of ZrO2:Fe at high doping concentration are grown by atomic layer deposition. We provide experimental evidence that Fe is uniformly distributed in the ZrO2 by transmission electron microscopy and energy dispersive X-ray mapping, while X-ray diffraction evidences the presence of the fluorite crystal structure. Alternating gradient force magnetometer measurements show magnetic signal at room temperature, however with low magnetic moment per atom. Results from experimental measures and theoretical simulations are compared.Comment: 8 pages, 9 figures. JEMS 201

Naturally Occurring PCSK9 Inhibitors

Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role of PCSK9 in controlling low-density lipoprotein (LDL) cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficial effects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurring PCSK9 inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching their LDL-cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown an inhibitory effect on PCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described

Pharmacological aspects of ANGPTL3 and ANGPTL4 inhibitors: new therapeutic approaches for the treatment of atherogenic dyslipidemia

Among the determinants of atherosclerotic cardiovascular disease (ASCVD), genetic and experimental evidence has provided data on a major role of angiopoietin-like proteins 3 and 4 (ANGPTL3 and ANGPTL4) in regulating the activity of lipoprotein lipase (LPL), antagonizing the hydrolysis of triglycerides (TG). Indeed, beyond low-density lipoprotein cholesterol (LDL-C), ASCVD risk is also dependent on a cluster of metabolic abnormalities characterized by elevated fasting and post-prandial levels of TG-rich lipoproteins and their remnants. In a head-to-head comparison between murine models for ANGPTL3 and ANGPTL4, the former was found to be a better pharmacological target for the treatment of hypertriglyceridemia. In humans, loss-of-function mutations of ANGPTL3 are associated with a marked reduction of plasma levels of VLDL, low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Carriers of loss-of-function mutations of ANGPTL4 show instead lower TG-rich lipoproteins and a modest but significant increase of HDL. The relevance of ANGPTL3 and ANGPTL4 as new therapeutic targets is proven by the development of monoclonal antibodies or antisense oligonucleotides. Studies in animal models, including non-human primates, have demonstrated that short-term treatment with monoclonal antibodies against ANGPTL3 and ANGPTL4 induces activation of LPL and a marked reduction of plasma TG-rich-lipoproteins, apparently without any major side effects. Inhibition of both targets also partially reduces LDL-C, independent of the LDL receptor. Similar evidence has been observed with the antisense oligonucleotide ANGPTL3-LRX. The genetic studies have paved the way for the development of new ANGPTL3 and 4 antagonists for the treatment of atherogenic dyslipidemias. Conclusive data of phase 2 and 3 clinical trials are still needed in order to define their safety and efficacy profile

The shift from normal sibling rivalry to emotional maltreatment and Its impact on later psychological wellbeing

While sibling abuse is a predominant form of family conflict, discussion of severe sibling rivalry representing a form of emotional maltreatment has not received the attention it warrants. This thesis examines the nature of sibling rivalry, severe rivalry as a form of emotional maltreatment, the developmental shift from normal to abusive rivalry, and its consequent psychological effects as perceived by emerging adults (n = 414). The findings suggest age, gender, living in separate homes, parental differential treatment, athletic ability, and academic success, influence perceived sibling rivalry. Statistical analysis reveals that severe sibling rivalry significantly resembles emotional maltreatment and is related to decreased psychological wellbeing. Also, the developmental stage where the shift from normal to abusive rivalry exists was not identified. In conclusion, severe sibling rivalry resembles sibling abuse and should be taken seriously, where if it goes unnoticed it is suggested to negatively affect self-esteem and self-concept

Kidseconomics® 2019/2020

RT 11; “Kidseconomics®" is the educational activity developed by CNR to introduce the basic concepts of economics in primary and lower secondary school education. In the first 5 years of activity it has reached about 6,000 students. Starting from the school year 2019/2020, the didactic proposal also includes laboratories, workshops and school/work alternation projects designed to meet the curiosity and skills of students of higher school grades. The contents therefore present a growing level of in-depth analysis, but the proposed methods and involvement remain those of informal teaching

Kidseconomics® 2015/2018

RT 10; “Kidseconomics®" is the educational activity developed by CNR to introduce the basic concepts of economics in primary and lower secondary school education. Economic science permeates the daily life of children and young people and is essential to the life of informed and aware citizens, however it is not included in didactic programmes of the first school years. "Kidseconomics®" therefore represents the first opportunity of economic literacy for many young people. Since 2015, an educational workshop has been proposed during festivals and science events and in the schools of three pilot cities: Genoa, Naples and Turin

484. Preclinical Proof of Concept of Transcriptional Silencing and Replacement Strategy for Treatment of Retinitis Pigmentosa Due To RHODOPSIN Mutations

Silencing and replacement strategy is a promising approach to overcome mutational heterogeneity of genetic defects. In autosomal dominant retinitis pigmentosa (adRP) due to rhodopsin gene (RHO) approximately 200 different mutations have been described, posing a challenge for the design of effective therapeutics.We designed a silencing and replacement strategy based on transcriptional silencing through an artificial zinc finger DNA-binding protein lacking effector domains (ZF6DBD), and tested both efficacy and safety in two animal models.In a murine model of adRP, we show that AAV-mediate retinal delivery (AAV2/8-CMV-ZF6-DBD) is associated with selective transcriptional silencing of the human mutated allele resulting in morphological and functional (Electroretinography, ERG a-wave and b-wave responses) rescue. We then tested the effect of transcriptional silencing in the porcine large pre-clinical model. Delivery of a low dose (AAV2/8-CMV-ZF6-DBD, 1×10e10 vector genomes, vg) of the ZF6 transcriptional silencer to the porcine retina resulted in robust transcriptional silencing of the endogenous porcine RHO transcript. Cell sorting of transduced photoreceptors showed an almost complete RHO transcriptional silencing effect (90% RHO transcriptional repression), underscoring the potency of the system. To determine the safety of the zinc-finger silencer we performed extensive RNA-seq analysis on treated and control retinae. The data sets generated demonstrate selective RHO gene transcriptional repression and a remarkably low number of differential expressed genes (DEGs), supporting specificity and thus, safety. The co-administration to the porcine retina of the AAV-ZF6 silencer (AAV2/8-CMV-ZF6-DBD) and the AAV-RHO replacement (5×10e11 vg, AAV2/8-GNAT1-HumanRHO) constructs resulted in a balanced silencing and replacement effect. This data support the use of zinc-finger based RHO transcriptional silencing for the development of a clinical trial for adRP patients

320 transcriptional silencing via synthetic dna binding protein lacking canonical repressor domains as a potent tool to generate therapeutics

Transcription factors (TFs) function by the combined activity of their DNA-binding domains (DBDs) and effector domains (EDs). Here we show that in vivo delivery of an engineered DNA-binding protein uncoupled from the repressor domain entails complete and gene-specific transcriptional silencing. To silence RHODOPSIN (RHO) gain-of-function mutations, we engineered a synthetic DNA-binding protein lacking canonical repressor domains and targeted to the regulatory region of the RHO gene. AAV-mediate retinal delivery at a low dose (AAV2/8-CMV-ZF6-DBD, 1×10e10 vector genomes, vg) in the porcine retina resulted in selective transcriptional silencing of RHO expression. The rod photoreceptors (the RHO expressing cells) transduced cells when isolated by FACS-sorting showed the remarkable 90% RHO transcriptional repression. To evaluate genome-wide transcriptional specificity, we analyzed the porcine retina transcriptome by RNA sequencing (RNA-Seq). The differentially expressed genes (DEGs) analysis showed that only 19 genes were perturbed. In this study, we describe a system based on a synthetic DNA binding protein enabling targeted transcriptional silencing of the RHO gene by in vivo gene transfer. The high rate of transcriptional silencing occurring in transduced cells supports applications of this regulatory genomic interference with a synthetic trans-acting factor for diseases requiring gene silencing in a large number of affected cells, including for instance a number of neurodegeneration disorders. The result support a novel mode of gene targeted silencing with a DNA-binding protein lacking intrinsic activity

Clinical Impact of Pretransplant Multidrug-Resistant Gram-Negative Colonization in Autologous and Allogeneic Hematopoietic Stem Cell Transplantation

Abstract Multidrug-resistant Gram-negative bacteria (MDR-GNB) are an emerging cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Three-hundred forty-eight consecutive patients transplanted at our hospital from July 2012 to January 2016 were screened for a pretransplant MDR-GNB colonization and evaluated for clinical outcomes. A pretransplant MDR-GNB colonization was found in 16.9% of allo-HSCT and in 9.6% of auto-HSCT recipients. Both in auto- and in allo-HSCT, carriers of a MDR-GNB showed no significant differences in overall survival (OS), transplant-related mortality (TRM), or infection-related mortality (IRM) compared with noncarriers. OS at 2 years for carriers compared with noncarriers was 85% versus 81% ( P  = .262) in auto-HSCT and 50% versus 43% ( P  = .091) in allo-HSCT. TRM at 2 years was 14% versus 5% ( P  = .405) in auto-HSCT and 31% versus 25% ( P  = .301) in allo-HSCT. IRM at 2 years was 14% versus 2% ( P  = .142) in auto-HSCT and 23% versus 14% ( P  = .304) in allo-HSCT. In multivariate analysis, only grade III to IV acute graft-versus-host disease was an independent factor for reduced OS ( P P P P  = .207). We conclude that in this extended single-center experience, a pretransplant MDR-GNB colonization did not significantly influence OS, TRM, and IRM both in auto- and allo-HSCT settings and that MDR-GNB attributed mortality can be controlled in carriers when an early pre-emptive antimicrobial therapy is started in case of neutropenic fever