A Quantum Yield Map for Synthetic Eumelanin

The quantum yield of synthetic eumelanin is known to be extremely low and it has recently been reported to be dependent on excitation wavelength. In this paper, we present quantum yield as a function of excitation wavelength between 250 and 500 nm, showing it to be a factor of 4 higher at 250 nm than at 500 nm. In addition, we present a definitive map of the steady-state fluorescence as a function of excitation and emission wavelengths, and significantly, a three-dimensional map of the specific quantum yield: the fraction of photons absorbed at each wavelength that are subsequently radiated at each emission wavelength. This map contains clear features, which we attribute to certain structural models, and shows that radiative emission and specific quantum yield are negligible at emission wavelengths outside the range of 585 and 385 nm (2.2 and 3.2 eV), regardless of excitation wavelength. This information is important in the context of understanding melanin biofunctionality, and the quantum molecular biophysics therein.Comment: 10 pages, 6 figure

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

Noninvasive Ultrasound Monitoring of Embryonic and Fetal Development in Chinchilla lanigera to Predict Gestational Age: Preliminary Evaluation of This Species as a Novel Animal Model of Human Pregnancy

Ultrasound is a noninvasive routine method that allows real-time monitoring of fetal development in utero to determine gestational age and to detect congenital anomalies and multiple pregnancies. To date, the developmental biology of Chinchilla lanigera has not yet been characterized. This species has been found to undergo placentation, long gestation, and fetal dimensions similar to those in humans. The aim of this study was to assess the use of high-frequency ultrasound (HFUS) and clinical ultrasound (US) to predict gestational age in chinchillas and evaluate the possibility of this species as a new animal model for the study of human pregnancy. In this study, 35 pregnant females and a total of 74 embryos and fetuses were monitored. Ultrasound examination was feasible in almost all chinchilla subjects. It was possible to monitor the chinchilla embryo with HFUS from embryonic day (E) 15 to 60 and with US from E15 to E115 due to fetus dimensions. The placenta could be visualized and measured with HFUS from E15, but not with US until E30. From E30, the heartbeat became detectable and it was possible to measure fetal biometrics. In the late stages of pregnancy, stomach, eyes, and lenses became visible. Our study demonstrated the importance of employing both techniques while monitoring embryonic and fetal development to obtain an overall and detailed view of all structures and to recognize any malformation at an early stage. Pregnancy in chinchillas can be confirmed as early as the 15th day postmating, and sonographic changes and gestational age are well correlated. The quantitative measurements of fetal and placental growth performed in this study could be useful in setting up a database for comparison with human fetal ultrasounds. We speculate that, in the future, the chinchilla could be used as an animal model for the study of US in human pregnancy

Biochemical sites of gene action for melanogenesis in mammals

International audienc

Effectiveness of dolutegravir-based regimens as either first-line or switch antiretroviral therapy: data from the Icona cohort

Introduction: Concerns about dolutegravir (DTG) tolerability in the real-life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG-based regimens from a large cohort of HIV-infected individuals. Methods: We performed a multicentre, observational study including all antiretroviral therapy (ART)-naïve and virologically suppressed treatment-experienced (TE) patients from the Icona (Italian Cohort Naïve Antiretrovirals) cohort who started, for the first time, a DTG-based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan–Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation. Results: About 1679 individuals (932 ART-naïve, 747 TE) were included. The one- and two-year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART-naïve and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART-naïve and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART-naïve (2.1%) and TE (1.7%) patients. In ART-naïve, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH) = 3.38, p = 0.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of toxicity (aRH = 3.30, p = 0.009). TE patients starting a DTG-based dual therapy compared to a triple therapy had a lower risk of discontinuation for any reason (adjusted hazard ratio (aHR) = 2.50, p = 0.037 for ABC-based triple-therapies, aHR = 3.56, p = 0.012 for tenofovir-based) and for toxicity (aHR = 5.26, p = 0.030 for ABC-based, aHR = 6.60, p = 0.024 for tenofovir-based). The one- and two-year probabilities (95% CI) of virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART naïve group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group. Conclusions: In this large cohort, DTG showed excellent efficacy and optimal tolerability both as first-line and switching ART. The low risk of treatment-limiting toxicities in ART-naïve as well as in treated individuals reassures on the use of DTG in everyday clinical practice

Masonry behaviour and modelling

In this Chapter we present the basic experimental facts on masonry materials and introduce simple and refined models for masonry. The simple models are essentially macroscopic and based on the assumption that the material is incapable of sustaining tensile loads (No-Tension assumption). The refined models account for the microscopic structure of masonry, modeling the interaction between the blocks and the interfaces.(undefined

PRADER-WILLI SYNDROME: ORAL FINDINGS

Aim: Prader-Willi syndrome is a rare multisystemic genetic disorder caused by lack of expression of certain paternal genes located on chromosome 15. The syndrome, associated to hypothalamic and pituitary disfunction, is characterized by severe neonatal hypotonia and feeding problems. Neonatal hypotonia is followed, during childhood by hyperphagia and obesity. In addition, hypothalamic alterations can cause intellectual disability, behavioral problems, a high pain threshold, respiratory sleep disorders. The aim of this work is to evaluate the main dental aspects and the therapeutic implications. Methods: an analysis of the literature was performed using databases. Results: common clinical findings: gingivitis and periodontitis, dental and skeletal malocclusions, enamel hypoplasia, tooth wear and dental erosion, bruxism, xerostomia, candidiasis and angular cheilitis, high risk of caries and increased DMFT score.The typical poor oral hygiene in PWS patients is related to qualitative-quantitative changes in saliva and incoordination in tooth brushing. Conclusion: it is necessary to motivate family and patient to maintain oral hygiene. Due to the various systemic and dental problems, a six-monthly follow-up is required since early childhood. Dental treatment purposes require a multidisciplinary approach which includes periodontal and conservative cares. In prosthetics, we suggest the use of removable dentures because of the difficulty in maintaining oral hygiene

Behavior of Full-Scale Porous GFRP Barrier under Blast Loads

This research paper is part of the SAS (Security of Airport Structures) Project funded by the European Programme for Critical Infrastructure Protection, whose objective was to develop and deploy a fiber reinforced polymer (FRP) fencing system intended to protect airport infrastructures against terrorist acts. In the paper, the efficacy of the proposed glass FRP discontinuous (porous) barrier under blast loads is presented by showing the results of the blast test campaign conducted on full-size specimens with a focus on the reduction of the blast shock wave induced by the barrier. A simplified model predicting the reduction of the shock wave beyond the barrier is proposed and validated via the experimental data obtained in the project

Earthquake induced floor accelerations on a high-rise building: Scale model tests on a shaking table

The paper discusses results of shaking table tests on an in-scale high-rise building model. The purpose was to calibrate a dynamic numerical model for multi-hazard analyses to investigate the effects of floor acceleration. Accelerations, because of vibration of non-structural elements, affect both the comfort and safety of people. The research investigates the acceleration effects of both seismic and wind forces on an aeroelastic in-scale model of a multi-story building. The paper discusses the first phase of experiments and gives results of floor accelerations induced by several different base seismic impulses. Structural analyses were first performed on the full-scale prototype to take soil-structure interaction into account. Subsequently the scale model was designed through aeroelastic scale laws. Shaking table experiments were then carried out under different base accelerations. The response of the model and, in particular, amplification of effects from base to top are discussed

Tetrahydroisoquinoline sulfamates as potent microtubule disruptors: synthesis, anti-proliferative and anti-tubulin activity of dichlorobenzyl-based derivatives and a tubulin co-crystal structure

Tetrahydroisoquinoline (THIQ) 6-O-sulfamate-based anticancer agents, inspired by the endogenous steroid 2-methoxyestradiol and its sulfamate derivatives, are further explored for antiproliferative and microtubule disruptor activity. Based on recently designed C3-methyl C7-methoxy-substituted THIQ derivatives, compounds with mono- and dichloro-substitutions on the pendant N-benzyl ring were synthesized and evaluated. Although improved antiproliferative activity was observed, for example, 4a versus 4b and 4b versus 8c, it was relatively modest. Compound 8c, a 2′,5′-dichlorobenzyl derivative was, however, identified as a promising antiproliferative agent with in vitro activities exceeding that of the parent steroid (e.g., GI50 90 nM in DU-145 cells) and was highly potent against a range of tumor cell lines (e.g., GI50 26 nM for OVCAR-3). 8c inhibited the polymerization of tubulin in vitro with an IC50 only twofold less potent than combretastatin A-4 and inhibited colchicine binding to tubulin. Tubulin polymerization assays showed the parent THIQ 4a to be only a very weak inhibitor, but a striking potency difference was seen between compounds with C2′ methoxy and chloro substituents, whereas this was much smaller when these substituents were positioned at C5′. To confirm the target in atomic detail and because 8c is a racemic mixture, an achiral parent THIQ 6-O-sulfamate derivative 10 was successfully cocrystallized with the αβ-tubulin heterodimer. The derivative 10 binds at the colchicine site on tubulin, the first example of this compound class investigated in such detail, with its sulfamate group interacting with residues beyond the reach of colchicine itself, similar to a recently reported quinazolinone sulfamate derivative, 6a. The structure also suggests that for racemic C3-methyl-substituted THIQ derivatives, such as 8c, the (S)-enantiomer is likely to be preferentially accommodated within the colchicine site for steric reasons. The results further confirm the potential of nonsteroidal THIQ sulfamate derivatives for oncology and suggest that the mechanism of microtubule destabilization for the THIQ compound class is to prevent the curved-to-straight conformational transition of tubulin required for polymerization