Damage assessment in single-nave churches and analysis of the most recurring mechanisms after the 2016–2017 central Italy earthquakes

Assessment of churches based on empirical data at a territorial scale is a suitable tool to have an overview of the seismic behaviour of this peculiar structural typology and to evaluate their current state of vulnerability. Fragility and vulnerability curves are also aimed to perform the analysis of different seismic scenarios. The paper presents a detailed typological analysis of 633 single-nave churches, as a selected subset of the database previously examined by the authors, with the aim of evaluating more in detail the influence of some parameters, such as masonry typology, church dimensions and presence of the bell tower, on the vulnerability of the overall church. Then, specific analyses are carried out to assess the influence played by single mechanisms on the definition of the overall damage index, with the focus of providing qualitative evaluations and explicit vulnerability and fragility curves related to the most recurring and significant collapse mechanisms. This is an original contribution of the paper in the field of the vulnerability assessment of churches, since nowadays little information is available in the literature about the damage levels related to specific mechanisms, while most attention is still focused on global damage

Shake table tests for the seismic fragility evaluation of hospital rooms

© 2014 John Wiley & Sons, Ltd. Health care facilities may undergo severe and widespread damage that impairs the functionality of the system when it is stricken by an earthquake. Such detrimental response is emphasized either for the hospital buildings designed primarily for gravity loads or without employing base isolation/supplemental damping systems. Moreover, these buildings need to warrant operability especially in the aftermath of moderate-to-severe earthquake ground motions. The provisions implemented in the new seismic codes allow obtaining adequate seismic performance for the hospital structural components; nevertheless, they do not provide definite yet reliable rules to design and protect the building contents. To date, very few experimental tests have been carried out on hospital buildings equipped with nonstructural components as well as building contents. The present paper is aimed at establishing the limit states for a typical health care room and deriving empirical fragility curves by considering a systemic approach. Toward this aim, a full scale three-dimensional model of an examination (out patients consultation) room is constructed and tested dynamically by using the shaking table facility of the University of Naples, Italy. The sample room contains a number of typical medical components, which are either directly connected to the panel boards of the perimeter walls or behave as simple freestanding elements. The outcomes of the comprehensive shaking table tests carried out on the examination room have been utilized to derive fragility curves based on a systemic approach

Understanding the mechanisms of lung mechanical stress

Physical forces affect both the function and phenotype of cells in the lung. Bronchial, alveolar, and other parenchymal cells, as well as fibroblasts and macrophages, are normally subjected to a variety of passive and active mechanical forces associated with lung inflation and vascular perfusion as a result of the dynamic nature of lung function. These forces include changes in stress (force per unit area) or strain (any forced change in length in relation to the initial length) and shear stress (the stress component parallel to a given surface). The responses of cells to mechanical forces are the result of the cell's ability to sense and transduce these stimuli into intracellular signaling pathways able to communicate the information to its interior. This review will focus on the modulation of intracellular pathways by lung mechanical forces and the intercellular signaling. A better understanding of the mechanisms by which lung cells transduce physical forces into biochemical and biological signals is of key importance for identifying targets for the treatment and prevention of physical force-related disorders

Reduction in regulatory T cells in preterm newborns is associated with necrotizing enterocolitis

BackgroundDespite multifactorial pathogenesis, dysregulation of inflammatory immune response may play a crucial role in necrotizing enterocolitis (NEC). Regulatory T cells (Tregs) are involved in immune tolerance early in life. We aimed to investigate the predicting role of Tregs in developing NEC in neonates at high risk.MethodsWe studied six newborns with a diagnosis of NEC (cases) in comparison with 52 controls (without NEC). We further classified controls as neonates with feeding intolerance (FI) and neonates without it (FeedTol). The rate of female and male neonates (sex defined as a biological attribute) was similar. We analyzed the blood frequency of Tregs (not overall numbers) at three time points: 0-3 (T0), 7-10 (T1), and 27-30 (T2) days after birth by flow cytometry. Neonates' sex was defined based on the inspection of external genitalia at birth.ResultsWe observed, at T0, a significantly lower frequency of Tregs in NEC cases (p < 0.001) compared with both FI (p < 0.01) and FeedTol controls (p < 0.01). Multivariate analysis reported that the occurrence of NEC was independently influenced by Treg frequency at birth (ss 2.98; p = 0.039).ConclusionTregs frequency and features in the peripheral blood of preterm neonates, early in life, may contribute to identifying neonates at high risk of developing NEC.ImpactRegulatory T cells may play a pivotal role in regulating the immune response in early life. Reduction of Tregs in early life could predispose preterm newborns to necrotizing enterocolitis.Early markers of necrotizing enterocolitis are still lacking. We demonstrated a predicting role of assessment of regulatory T cells in the diagnosis of this gastrointestinal emergency.Early identification of newborns at high risk of necrotizing enterocolitis through measurement of regulatory T cells may guide clinicians in the management of preterm newborns in order to reduce the development of this severe condition

The pigmented life of a redhead.

As a redhead I have had a personal interest in red hair, freckles and sunburns since childhood. An observation of a formaldehyde-induced fluorescence in human epidermal melanocytes initiated my scientific interest in these cells. Prota and Nicolaus demonstrated that oxidation products of cysteinyldopas are the main components of pheomelanin. Our identification of 5-S-cysteinyldopa as the source of formaldehyde-induced fluorescence of normal and pathological melanocytes started a series of investigations into this amino acid, enzymatic and non-enzymatic oxidation of catecholic compounds and the metabolism of thiols. All melanocytes with functioning tyrosinase produce cysteinyldopas and the levels of 5-S-cysteinyldopa in serum and urine are related to the size and pigment forming activity of the melanocyte population. The determination of 5-S-cysteinyldopa in serum or urine is a sensitive diagnostic method in the detection of melanoma metastasis. Some non-specific formation of cysteinyldopa is present in the body, as demonstrated by 5-S-cysteinyldopa in individuals with tyrosinase-negative albinism

Shaking table tests for the experimental verification of the effectiveness of an automated modal parameter monitoring system for existing bridges in seismic areas

Reinforced concrete bridges represent a majority of the Italian stock and they play a primary role to ensure the efficiency of the transportation network and prompt rescue in the case of an emergency. However, most of them have been designed and built according to outdated codes, or even without any seismic detailing. The significant impact of strong motions on the road network as well as the human life and economy emphasizes the need for effective strategies for post-earthquake emergency management and to support rescue operations. The present paper aims at evaluating, against real data, the effectiveness of automated modal parameter monitoring for vibration-based Structural Health Monitoring (SHM) of existing bridges in earthquake prone areas. This objective has been pursued in the context of shaking table tests on a 1:3 scale single span bridge representative of existing highway bridges built in the 60's in Italy. The dynamic response of the structure before and after the application of asynchronous seismic input has been analyzed for damage detection and performance assessment. Results show that partially hidden damage can be remotely detected, thus validating the interesting applicative perspectives of automated output-only modal identification and modal-based damage detection for fast assessment of existing bridges in the early earthquake aftershock. The robustness of the SHM system to sensor overload due to earthquake shaking has been also assessed, demonstrating the applicability of modal-based SHM in seismic regions even in the absence of a measurement chain specifically designed to resolve the large amplitude vibrations induced by earthquakes. Finally, the possibility of complementing modal-based SHM with drift-based estimates is explored

Structural Determinants of the Dictyostatin Chemotype for Tubulin Binding Affinity and Antitumor Activity Against Taxane- and Epothilone-Resistant Cancer Cells

A combined biochemical, structural, and cell biology characterization of dictyostatin is described, which enables an improved understanding of the structural determinants responsible for the high-affinity binding of this anticancer agent to the taxane site in microtubules (MTs). The study reveals that this macrolide is highly optimized for MT binding and that only a few of the structural modifications featured in a library of synthetic analogues resulted in small gains in binding affinity. The high efficiency of the dictyostatin chemotype in overcoming various kinds of clinically relevant resistance mechanisms highlights its potential for therapeutic development for the treatment of drug-resistant tumors. A structural explanation is advanced to account for the synergy observed between dictyostatin and taxanes on the basis of their differential effects on the MT lattice. The X-ray crystal structure of a tubulin−dictyostatin complex and additional molecular modeling have allowed the rationalization of the structure−activity relationships for a set of synthetic dictyostatin analogues, including the highly active hybrid 12 with discodermolide. Altogether, the work reported here is anticipated to facilitate the improved design and synthesis of more efficacious dictyostatin analogues and hybrids with other MT-stabilizing agents.We thank Peter T. Northcote for peloruside A, W.-S. Fang for Flutax-2, K. H. Altmann for epothilone D, Dr. Paraskevi Giannakakou (Weill Cornell Medical Center, New York) for the 1A9, PTX10, PTX22, and A8 cell lines, and Prof. Richard Ludueñ a (University of Texas) for the HeLa βIII-transfected cells. We thank Matadero INCOVA (Segovia) for the calf brains for tubulin purification. This work was supported in part by grants BIO2013-42984-R (J.F.D.) and SAF2012-39760-C02-02 (F.G.) from Ministerio de Economia y Competitividad, grant S2010/ ́ BMD-2457 BIPEDD2 from Comunidad Autonoma de Madrid ́ (F.G. and J.F.D.), and the Swiss National Science Foundation grants 310030B_138659 and 31003A_166608 (M.O.S.). The authors acknowledge networking contribution by the COST Action CM1407 “Challenging organic syntheses inspired by naturefrom natural products chemistry to drug discovery” and the COST action CM1470. I.P. thanks the EPSRC and AstraZeneca for funding, Dr. John Leonard (AstraZeneca) for useful discussions, Dr. Stuart Mickel (Novartis) for the provision of chemicals, and the EPSRC UK National Mass Spectrometry Facility at Swansea University for mass spectra

Structural Determinants of the Dictyostatin Chemotype for Tubulin Binding Affinity and Antitumor Activity Against Taxane- and Epothilone-Resistant Cancer Cells

A combined biochemical, structural, and cell biology characterization of dictyostatin is described, which enables an improved understanding of the structural determinants responsible for the high-affinity binding of this anticancer agent to the taxane site in microtubules (MTs). The study reveals that this macrolide is highly optimized for MT binding and that only a few of the structural modifications featured in a library of synthetic analogues resulted in small gains in binding affinity. The high efficiency of the dictyostatin chemotype in overcoming various kinds of clinically relevant resistance mechanisms highlights its potential for therapeutic development for the treatment of drug-resistant tumors. A structural explanation is advanced to account for the synergy observed between dictyostatin and taxanes on the basis of their differential effects on the MT lattice. The X-ray crystal structure of a tubulin−dictyostatin complex and additional molecular modeling have allowed the rationalization of the structure−activity relationships for a set of synthetic dictyostatin analogues, including the highly active hybrid 12 with discodermolide. Altogether, the work reported here is anticipated to facilitate the improved design and synthesis of more efficacious dictyostatin analogues and hybrids with other MT-stabilizing agents.We thank Peter T. Northcote for peloruside A, W.-S. Fang for Flutax-2, K. H. Altmann for epothilone D, Dr. Paraskevi Giannakakou (Weill Cornell Medical Center, New York) for the 1A9, PTX10, PTX22, and A8 cell lines, and Prof. Richard Ludueñ a (University of Texas) for the HeLa βIII-transfected cells. We thank Matadero INCOVA (Segovia) for the calf brains for tubulin purification. This work was supported in part by grants BIO2013-42984-R (J.F.D.) and SAF2012-39760-C02-02 (F.G.) from Ministerio de Economia y Competitividad, grant S2010/ ́ BMD-2457 BIPEDD2 from Comunidad Autonoma de Madrid ́ (F.G. and J.F.D.), and the Swiss National Science Foundation grants 310030B_138659 and 31003A_166608 (M.O.S.). The authors acknowledge networking contribution by the COST Action CM1407 “Challenging organic syntheses inspired by naturefrom natural products chemistry to drug discovery” and the COST action CM1470. I.P. thanks the EPSRC and AstraZeneca for funding, Dr. John Leonard (AstraZeneca) for useful discussions, Dr. Stuart Mickel (Novartis) for the provision of chemicals, and the EPSRC UK National Mass Spectrometry Facility at Swansea University for mass spectra

The 2017 Regional Election in Catalonia: An attempt to understand the pro-independence vote

This paper tries to unveil the main factors behind the triumph of the proindependence vote in the 2017 Regional Election in Catalonia. The empirical analysis, which is carried out at the county level and by using a spatial econometric model, reveals that geographical location matters. The estimation results also suggest that the pro-independence vote is mainly linked to the birthplace of individuals. More specifically, it shows that the independence feeling is weaker the higher the share of citizens born outside Catalonia. On the other side, young and highly educated people are more prone to independence. Additionally, it is shown that people working in the public sector are more likely to vote for a political party in favor of Catalonia remaining in Spain, while the opposite happens for those voters working in construction. Finally, the results seem to dispel some myths associated with the role played by the county’s size and level of income on the proindependence vote