A computational model of gene expression in an inducible synthetic circuit

Synthetic biology aims to the rational design of gene circuits with predictable behaviours. Great efforts have been done so far to introduce in the field mathematical models that could facilitate the design of synthetic networks. Here we present a mathematical model of a synthetic gene-circuit with a negative feedback. The closed loop configuration allows the control of transcription by an inducer molecule (IPTG). Escherichia coli bacterial cells were transformed and expression of a fluorescent reporter (GFP) was measured for different inducer levels. Computer model simulations well reproduced the experimental induction data, using a single fitting parameter. Independent genetic components were used to assemble the synthetic circuit. The mathematical model here presented could be useful to predict how changes in these genetic components affect the behaviour of the synthetic circuit

Simplified Seismic Vulnerability Assessment Methods: A Comparative Analysis with Reference to Regional School Building Stock in Italy

The paper compares several simplified methods proposed in the literature for assessing the seismic vulnerability of existing buildings. Type and number of input and output data, limitations of use for different structural typologies, and complexity of use are examined for each methodology to identify the most suitable for assessing the vulnerability of a given class of buildings, based on the available data, the computational effort, and the type of vulnerability judgment. The selected methods were applied to a sample of school buildings located in the province of Naples (Italy). Data were available due to a digital platform and were used to verify the possibility of providing reliable large scale vulnerability judgments based on a reduced set of information, without carrying out additional surveys. The most simplified methods were applied to a sample of about a thousand of buildings, while more detailed methods, needing more information, were applied to a smaller sample. The comparison between the results obtained from different methods allows highlighting advantages and weaknesses of each, so as to identify the convenience in their use according to the specific available information and the objectives of the analysis, finally to evaluate which is more or less safe

In-plane behaviour of masonry walls: Numerical analysis and design formulations

This paper presents the results of several numerical analyses aimed at investigating the in-plane resistance of masonry walls by means of two modelling approaches: a finite element model (FEM) and a discrete macro-element model (DMEM). Non-linear analyses are developed, in both cases, by changing the mechanical properties of masonry (compressive and tensile strengths, fracture energy in compression and tension, shear strength) and the value of the vertical compression stress applied on the walls. The reliability of both numerical models is firstly checked by means of comparisons with experimental tests available in the literature. The analyses show that the numerical results provided by the two modelling approaches are in good agreement, in terms of both failure loads and modes, while some differences are observed in their load-displacement curves, espe-cially in the non-linear field. Finally, the numerical in-plane resistances are compared with the theoretical formulations provided by the Italian building code for both flexural and shear failure modes and an amendment for the shape factor ‘b’ introduced in the code formulation for squat walls is proposed

Literature review of the in-plane behavior of masonry walls: Theoretical vs. experimental results

In-plane strength of masonry walls is affected by the resistant mechanisms activated in the walls, i.e., related to flexural or shear behavior. The latter one can occur in the walls according to different failure modes depending on both mortar and unit strengths and on the type of assembling, i.e., ‘regular’ or ‘irregular’ texture. In this paper, a critical review of the existing design formulations for the in-plane strength of masonry walls is firstly presented, with important information on the achievable failure modes depending on the geometrical and mechanical features of the masonry fabric. Then, experimental tests are collected from the literature and a comparison between theoretical and experimental results is carried out. The presented analyses are aimed to highlight the differences between the existing formulations and to identify the most suitable ones

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

Experimental results of a national technical assessment procedure on commercial FRP for structural strengthening: wet-lay-up systems

n/

Genetics of anophthalmia and microphthalmia. Part 1, Non-syndromic anophthalmia/microphthalmia

Eye formation is the result of coordinated induction and differentiation processes during embryogenesis. Disruption of any one of these events has the potential to cause ocular growth and structural defects, such as anophthalmia and microphthalmia (A/M). A/M can be isolated or occur with systemic anomalies, when they may form part of a recognizable syndrome. Their etiology includes genetic and environmental factors; several hundred genes involved in ocular development have been identified in humans or animal models. In humans, around 30 genes have been repeatedly implicated in A/M families, although many other genes have been described in single cases or families, and some genetic syndromes include eye anomalies occasionally as part of a wider phenotype. As a result of this broad genetic heterogeneity, with one or two notable exceptions, each gene explains only a small percentage of cases. Given the overlapping phenotypes, these genes can be most efficiently tested on panels or by whole exome/genome sequencing for the purposes of molecular diagnosis. However, despite whole exome/genome testing more than half of patients currently remain without a molecular diagnosis. The proportion of undiagnosed cases is even higher in those individuals with unilateral or milder phenotypes. Furthermore, even when a strong gene candidate is available for a patient, issues of incomplete penetrance and germinal mosaicism make diagnosis and genetic counselling challenging. In this review, we present the main genes implicated in nonsyndromic human A/M phenotypes and, for practical purposes, classify them according to the most frequent or predominant phenotype each is associated with. Our intention is that this will allow clinicians to rank and prioritize their molecular analyses and interpretations according to the phenotypes of their patients

Doxorubicin and congo red effectiveness on prion infectivity in golden Syrian hamster

The effect of doxorubicin and Congo Red on prion protein (PrP) infectivity in experimental scrapie was studied to better understand the effect of these compounds in prion diseases and to establish whether a dose-response correlation exists for Congo Red. This was performed in order to test the effectiveness of compounds that may easily be used in human prion diseases. Brain homogenate containing membrane bound PrPSc monomers was used as inoculum and was previously incubated with doxorubicin 10(-3) M and with increasing concentrations of Congo Red ranging from 10(-7) to 10(-2) M. This study shows for the first time that doxorubicin, and confirms that Congo Red, may interact with pathological PrP monomers modifying their infectious properties. Pre-incubation of infected brain homogenate with Congo Red resulted in prolonged incubation time and survival, independently of Congo Red concentration (p<0.05). Doxorubicin and Congo Red effects do not depend upon interaction with PrP amyloid material