Search results for: Massimiliano Nastri
14 Building Envelope Engineering and Typologies for Complex Architectures: Composition and Functional Methodologies
Authors: Massimiliano Nastri
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The study examines the façade systems according to the constitutive and typological characters, as well as the functional and applicative requirements such as the expressive, constructive, and interactive criteria towards the environmental, perceptive, and energy conditions. The envelope systems are understood as instruments of mediation, interchange, and dynamic interaction between environmental conditions. The façades are observed for the sustainable concept of eco-efficient envelopes, selective and multi-purpose filters, adaptable and adjustable according to the environmental performance.Keywords: typologies of façades, environmental and energy sustainability, interaction and perceptive mediation, technical skins
Procedia PDF Downloads 15313 Architectural Engineering and Executive Design: Modelling Procedures, Scientific Tools, Simulation Processing
Authors: Massimiliano Nastri
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The study is part of the scientific references on executive design in engineering and architecture, understood as an interdisciplinary field aimed at anticipating and simulating, planning and managing, guiding and instructing construction operations on site. On this basis, the study intends to provide an analysis of a theoretical, methodological, and guiding character aimed at constituting the disciplinary sphere of the executive design, often in the absence of supporting methodological and procedural guidelines in engineering and architecture. The basic methodologies of the study refer to the investigation of the theories and references that can contribute to constituting the scenario of the executive design as the practice of modelling, visualization, and simulation of the construction phases, through the practices of projection of the pragmatic issues of the building. This by proposing a series of references, interrelations, and openings intended to support (for intellectual, procedural, and applicative purposes) the executive definition of the project, aimed at activating the practices of cognitive acquisition and realization intervention within reality.Keywords: modelling and simulation technology, executive design, discretization of the construction, engineering design for building
Procedia PDF Downloads 7912 Effect of High-Pressure and Thermal Treatments on Quality Markers of Strawberry Nectars
Authors: Karen Louise Lacey, Dario Javier Pavon Vargas, Massimiliano Rinaldi, Luca Cattani, Sara Rainieri
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The effects of high-pressure processing (HPP) and thermal treatments (TT) on quality markers of strawberry nectar (12 °Brix, 3,3 pH) was studied before and after treatments. TT and HPP treatments ensured a 3-log aerobic bacteria inactivation. No significant difference was detected in terms of pH and °Brix. TT samples were less red (a* less positive) than all HPP treated samples, while all samples were less red than the control. Apparent viscosity was significantly increased in all the HPP treatments, at 10 1/s shear rate, control was 79.04±7.94 mPa•s and the 600 MPa-20 min treatment were 327.10±1.64 mPa•s. This work suggests that HPP treatments may maintain the quality markers of strawberry nectar better.Keywords: HPP, strawberry nectar, colour , viscosity
Procedia PDF Downloads 13111 The Shannon Entropy and Multifractional Markets
Authors: Massimiliano Frezza, Sergio Bianchi, Augusto Pianese
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Introduced by Shannon in 1948 in the field of information theory as the average rate at which information is produced by a stochastic set of data, the concept of entropy has gained much attention as a measure of uncertainty and unpredictability associated with a dynamical system, eventually depicted by a stochastic process. In particular, the Shannon entropy measures the degree of order/disorder of a given signal and provides useful information about the underlying dynamical process. It has found widespread application in a variety of fields, such as, for example, cryptography, statistical physics and finance. In this regard, many contributions have employed different measures of entropy in an attempt to characterize the financial time series in terms of market efficiency, market crashes and/or financial crises. The Shannon entropy has also been considered as a measure of the risk of a portfolio or as a tool in asset pricing. This work investigates the theoretical link between the Shannon entropy and the multifractional Brownian motion (mBm), stochastic process which recently is the focus of a renewed interest in finance as a driving model of stochastic volatility. In particular, after exploring the current state of research in this area and highlighting some of the key results and open questions that remain, we show a well-defined relationship between the Shannon (log)entropy and the memory function H(t) of the mBm. In details, we allow both the length of time series and time scale to change over analysis to study how the relation modify itself. On the one hand, applications are developed after generating surrogates of mBm trajectories based on different memory functions; on the other hand, an empirical analysis of several international stock indexes, which confirms the previous results, concludes the work.Keywords: Shannon entropy, multifractional Brownian motion, Hurst–Holder exponent, stock indexes
Procedia PDF Downloads 11010 Nanoscale Mapping of the Mechanical Modifications Occurring in the Brain Tumour Microenvironment by Atomic Force Microscopy: The Case of the Highly Aggressive Glioblastoma and the Slowly Growing Meningioma
Authors: Gabriele Ciasca, Tanya E. Sassun, Eleonora Minelli, Manila Antonelli, Massimiliano Papi, Antonio Santoro, Felice Giangaspero, Roberto Delfini, Marco De Spirito
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Glioblastoma multiforme (GBM) is an extremely aggressive brain tumor, characterized by a diffuse infiltration of neoplastic cells into the brain parenchyma. Although rarely considered, mechanical cues play a key role in the infiltration process that is extensively mediated by the tumor microenvironment stiffness and, more in general, by the occurrence of aberrant interactions between neoplastic cells and the extracellular matrix (ECM). Here we provide a nano-mechanical characterization of the viscoelastic response of human GBM tissues by indentation-type atomic force microscopy. High-resolution elasticity maps show a large difference between the biomechanics of GBM tissues and the healthy peritumoral regions, opening possibilities to optimize the tumor resection area. Moreover, we unveil the nanomechanical signature of necrotic regions and anomalous vasculature, that are two major hallmarks useful for glioma staging. Actually, the morphological grading of GBM relies mainly on histopathological findings that make extensive use of qualitative parameters. Our findings have the potential to positively impact on the development of novel quantitative methods to assess the tumor grade, which can be used in combination with conventional histopathological examinations. In order to provide a more in-depth description of the role of mechanical cues in tumor progression, we compared the nano-mechanical fingerprint of GBM tissues with that of grade-I (WHO) meningioma, a benign lesion characterized by a completely different growth pathway with the respect to GBM, that, in turn hints at a completely different role of the biomechanical interactions.Keywords: AFM, nano-mechanics, nanomedicine, brain tumors, glioblastoma
Procedia PDF Downloads 3429 Flotation of Rare Earth Oxides from Iron-Oxide Silicate Rich Tailings Using Fatty Acids
Authors: George B. Abaka-Wood, Massimiliano Zanin, Jonas Addai-Mensah, William Skinner
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The versatility of froth flotation has made it vital in the beneficiation of rare earth elements minerals from either high or low-grade ores. There has been a significant increase in the quantity of iron oxide silicate-rich tailings generated from the extraction of primary commodities such as copper and gold in Australia, which have been identified to contain very low-grade rare earth oxides (≤ 1%). There is a vast knowledge gap in the beneficiation of rare earth oxides from such tailings. The aim of this research is to investigate the feasibility of using fatty acids as collectors for the flotation recovery and upgrade of rare earth oxides from selected iron-oxide silicate-rich tailings. Two forms of fatty acid collectors (oleic acid and sodium oleate) were tested in this investigation. Flotation tests were carried out using a 1.2 L Denver D-12 cell. The effects of pulp pH, fatty acid dosage, particle size distribution (-150 +75 µm, -75 +38 µm and -38 µm) and conventional depressants (sodium silicate and starch) dosage on flotation recovery of rare earth oxides were investigated. A comparison of the flotation results indicated that sodium oleate was the more efficient fatty acid for rare earth oxides flotation at all the pulp pH investigated. The flotation performance was found to be particle size-dependent. Both sodium silicate and starch were unselective in decreasing the recovery of iron oxides and silicate minerals, respectively with the corresponding decrease in rare earth oxides recovery. Generally, iron oxides and silicate minerals formed the substantial fraction of the flotation concentrates obtained, both in the absence and presence of depressants, resulting in a generally low rare earth oxides upgrade, even though rare earth oxides recoveries were high. The flotation tests carried out on the tailings sample suggest the feasibility of rare earth oxides recovery using fatty acids, although particle size distribution and minerals liberation are key limiting factors in achieving selective rare earth oxides upgrade.Keywords: depressants, flotation, oleic acid, sodium oleate
Procedia PDF Downloads 1898 Selective Effect of Occipital Alpha Transcranial Alternating Current Stimulation in Perception and Working Memory
Authors: Andreina Giustiniani, Massimiliano Oliveri
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Rhythmic activity in different frequencies could subserve distinct functional roles during visual perception and visual mental imagery. In particular, alpha band activity is thought to play a role in active inhibition of both task-irrelevant regions and processing of non-relevant information. In the present blind placebo-controlled study we applied alpha transcranial alternating current stimulation (tACS) in the occipital cortex both during a basic visual perception and a visual working memory task. To understand if the role of alpha is more related to a general inhibition of distractors or to an inhibition of task-irrelevant regions, we added a non visual distraction to both the tasks.Sixteen adult volunteers performed both a simple perception and a working memory task during 10 Hz tACS. The electrodes were placed over the left and right occipital cortex, the current intensity was 1 mA peak-to-baseline. Sham stimulation was chosen as control condition and in order to elicit the skin sensation similar to the real stimulation, electrical stimulation was applied for short periods (30 s) at the beginning of the session and then turned off. The tasks were split in two sets, in one set distracters were included and in the other set, there were no distracters. Motor interference was added by changing the answer key after subjects completed the first set of trials.The results show that alpha tACS improves working memory only when no motor distracters are added, suggesting a role of alpha tACS in inhibiting non-relevant regions rather than in a general inhibition of distractors. Additionally, we found that alpha tACS does not affect accuracy and hit rates during the visual perception task. These results suggest that alpha activity in the occipital cortex plays a different role in perception and working memory and it could optimize performance in tasks in which attention is internally directed, as in this working memory paradigm, but only when there is not motor distraction. Moreover, alpha tACS improves working memory performance by means of inhibition of task-irrelevant regions while it does not affect perception.Keywords: alpha activity, interference, perception, working memory
Procedia PDF Downloads 2567 The Volume–Volatility Relationship Conditional to Market Efficiency
Authors: Massimiliano Frezza, Sergio Bianchi, Augusto Pianese
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The relation between stock price volatility and trading volume represents a controversial issue which has received a remarkable attention over the past decades. In fact, an extensive literature shows a positive relation between price volatility and trading volume in the financial markets, but the causal relationship which originates such association is an open question, from both a theoretical and empirical point of view. In this regard, various models, which can be considered as complementary rather than competitive, have been introduced to explain this relationship. They include the long debated Mixture of Distributions Hypothesis (MDH); the Sequential Arrival of Information Hypothesis (SAIH); the Dispersion of Beliefs Hypothesis (DBH); the Noise Trader Hypothesis (NTH). In this work, we analyze whether stock market efficiency can explain the diversity of results achieved during the years. For this purpose, we propose an alternative measure of market efficiency, based on the pointwise regularity of a stochastic process, which is the Hurst–H¨older dynamic exponent. In particular, we model the stock market by means of the multifractional Brownian motion (mBm) that displays the property of a time-changing regularity. Mostly, such models have in common the fact that they locally behave as a fractional Brownian motion, in the sense that their local regularity at time t0 (measured by the local Hurst–H¨older exponent in a neighborhood of t0 equals the exponent of a fractional Brownian motion of parameter H(t0)). Assuming that the stock price follows an mBm, we introduce and theoretically justify the Hurst–H¨older dynamical exponent as a measure of market efficiency. This allows to measure, at any time t, markets’ departures from the martingale property, i.e. from efficiency as stated by the Efficient Market Hypothesis. This approach is applied to financial markets; using data for the SP500 index from 1978 to 2017, on the one hand we find that when efficiency is not accounted for, a positive contemporaneous relationship emerges and is stable over time. Conversely, it disappears as soon as efficiency is taken into account. In particular, this association is more pronounced during time frames of high volatility and tends to disappear when market becomes fully efficient.Keywords: volume–volatility relationship, efficient market hypothesis, martingale model, Hurst–Hölder exponent
Procedia PDF Downloads 786 Tribological Behavior Of 17-4PH Steel Produced Via Binder Jetting And Low Energy High Current Pulsed Electron Beam Surface Treated
Authors: Lorenza Fabiocchi, Marco Mariani, Andrea Lucchini Huspek, Matteo Pozzi, Massimiliano Bestetti, Serena Graziosi, Nora Lecis
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Additive manufacturing of stainless steels is rapidly developing thanks to the ability to achieve complex designs effortlessly. Stainless steel 17-4PH is valued for its high strength and corrosion resistance, however intricate geometries are challenging to obtain due to rapid tool wear when machined. Binder jetting additive manufacturing was used to produce 17–4PH samples and pulsed electron beam surface treatment was investigated to enhance surface properties of components. The aim is to improve the tribological performance compared to the as-sintered condition and the H900 aging process, which optimizes hardness and wear resistance. Printed samples were sintered in a reducing atmosphere and superficially treated with an electron beam by varying the voltage (20 - 25 - 30 kV) and pulse count (20 – 40 pulses). Then, the surface was characterized from a microstructural and mechanical standpoint. Scratch tests were performed, and a reciprocating linear pin-on-disk wear test was conducted at 2 N and 10 Hz. Results showed that the voltage affects the roughness and thickness of the treated layer, whilst the number of pulses influences the hardening of the microstructure and consequently the wear resistance. Treated samples exhibited lower coefficients of friction compared to as-printed surfaces, though the values approached those of aged samples after the abrasion of the melted layer, indicating a deeper heat-affected zone formation. Different amounts of residual stress in the heat effected zone were individuated through the scratch tests. Still, the friction remained lower than that of as-printed specimens. This study demonstrates that optimizing electron beam parameters is vital for achieving surface performance comparable to bulk aging treatments, with significant implications for long-term wear resistance.Keywords: low energy high current pulsed electron beam, tribology, binder jetting 3D printing, 17-4PH stainless steel
Procedia PDF Downloads 125 Urban Noise and Air Quality: Correlation between Air and Noise Pollution; Sensors, Data Collection, Analysis and Mapping in Urban Planning
Authors: Massimiliano Condotta, Paolo Ruggeri, Chiara Scanagatta, Giovanni Borga
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Architects and urban planners, when designing and renewing cities, have to face a complex set of problems, including the issues of noise and air pollution which are considered as hot topics (i.e., the Clean Air Act of London and the Soundscape definition). It is usually taken for granted that these problems go by together because the noise pollution present in cities is often linked to traffic and industries, and these produce air pollutants as well. Traffic congestion can create both noise pollution and air pollution, because NO₂ is mostly created from the oxidation of NO, and these two are notoriously produced by processes of combustion at high temperatures (i.e., car engines or thermal power stations). We can see the same process for industrial plants as well. What have to be investigated – and is the topic of this paper – is whether or not there really is a correlation between noise pollution and air pollution (taking into account NO₂) in urban areas. To evaluate if there is a correlation, some low-cost methodologies will be used. For noise measurements, the OpeNoise App will be installed on an Android phone. The smartphone will be positioned inside a waterproof box, to stay outdoor, with an external battery to allow it to collect data continuously. The box will have a small hole to install an external microphone, connected to the smartphone, which will be calibrated to collect the most accurate data. For air, pollution measurements will be used the AirMonitor device, an Arduino board to which the sensors, and all the other components, are plugged. After assembling the sensors, they will be coupled (one noise and one air sensor) and placed in different critical locations in the area of Mestre (Venice) to map the existing situation. The sensors will collect data for a fixed period of time to have an input for both week and weekend days, in this way it will be possible to see the changes of the situation during the week. The novelty is that data will be compared to check if there is a correlation between the two pollutants using graphs that should show the percentage of pollution instead of the values obtained with the sensors. To do so, the data will be converted to fit on a scale that goes up to 100% and will be shown thru a mapping of the measurement using GIS methods. Another relevant aspect is that this comparison can help to choose which are the right mitigation solutions to be applied in the area of the analysis because it will make it possible to solve both the noise and the air pollution problem making only one intervention. The mitigation solutions must consider not only the health aspect but also how to create a more livable space for citizens. The paper will describe in detail the methodology and the technical solution adopted for the realization of the sensors, the data collection, noise and pollution mapping and analysis.Keywords: air quality, data analysis, data collection, NO₂, noise mapping, noise pollution, particulate matter
Procedia PDF Downloads 2124 The Learning Loops in the Public Realm Project in South Verona: Air Quality and Noise Pollution Participatory Data Collection towards Co-Design, Planning and Construction of Mitigation Measures in Urban Areas
Authors: Massimiliano Condotta, Giovanni Borga, Chiara Scanagatta
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Urban systems are places where the various actors involved interact and enter in conflict, in particular with reference to topics such as traffic congestion and security. But topics of discussion, and often clash because of their strong complexity, are air and noise pollution. For air pollution, the complexity stems from the fact that atmospheric pollution is due to many factors, but above all, the observation and measurement of the amount of pollution of a transparent, mobile and ethereal element like air is very difficult. Often the perceived condition of the inhabitants does not coincide with the real conditions, because it is conditioned - sometimes in positive ways other in negative ways - from many other factors such as the presence, or absence, of natural elements such as trees or rivers. These problems are seen with noise pollution as well, which is also less considered as an issue even if it’s problematic just as much as air quality. Starting from these opposite positions, it is difficult to identify and implement valid, and at the same time shared, mitigation solutions for the problem of urban pollution (air and noise pollution). The LOOPER (Learning Loops in the Public Realm) project –described in this paper – wants to build and test a methodology and a platform for participatory co-design, planning, and construction process inside a learning loop process. Novelties in this approach are various; the most relevant are three. The first is that citizens participation starts since from the research of problems and air quality analysis through a participatory data collection, and that continues in all process steps (design and construction). The second is that the methodology is characterized by a learning loop process. It means that after the first cycle of (1) problems identification, (2) planning and definition of design solution and (3) construction and implementation of mitigation measures, the effectiveness of implemented solutions is measured and verified through a new participatory data collection campaign. In this way, it is possible to understand if the policies and design solution had a positive impact on the territory. As a result of the learning process produced by the first loop, it will be possible to improve the design of the mitigation measures and start the second loop with new and more effective measures. The third relevant aspect is that the citizens' participation is carried out via Urban Living Labs that involve all stakeholder of the city (citizens, public administrators, associations of all urban stakeholders,…) and that the Urban Living Labs last for all the cycling of the design, planning and construction process. The paper will describe in detail the LOOPER methodology and the technical solution adopted for the participatory data collection and design and construction phases.Keywords: air quality, co-design, learning loops, noise pollution, urban living labs
Procedia PDF Downloads 3653 Investigation of a Single Feedstock Particle during Pyrolysis in Fluidized Bed Reactors via X-Ray Imaging Technique
Authors: Stefano Iannello, Massimiliano Materazzi
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Fluidized bed reactor technologies are one of the most valuable pathways for thermochemical conversions of biogenic fuels due to their good operating flexibility. Nevertheless, there are still issues related to the mixing and separation of heterogeneous phases during operation with highly volatile feedstocks, including biomass and waste. At high temperatures, the volatile content of the feedstock is released in the form of the so-called endogenous bubbles, which generally exert a “lift” effect on the particle itself by dragging it up to the bed surface. Such phenomenon leads to high release of volatile matter into the freeboard and limited mass and heat transfer with particles of the bed inventory. The aim of this work is to get a better understanding of the behaviour of a single reacting particle in a hot fluidized bed reactor during the devolatilization stage. The analysis has been undertaken at different fluidization regimes and temperatures to closely mirror the operating conditions of waste-to-energy processes. Beechwood and polypropylene particles were used to resemble the biomass and plastic fractions present in waste materials, respectively. The non-invasive X-ray technique was coupled to particle tracking algorithms to characterize the motion of a single feedstock particle during the devolatilization with high resolution. A high-energy X-ray beam passes through the vessel where absorption occurs, depending on the distribution and amount of solids and fluids along the beam path. A high-speed video camera is synchronised to the beam and provides frame-by-frame imaging of the flow patterns of fluids and solids within the fluidized bed up to 72 fps (frames per second). A comprehensive mathematical model has been developed in order to validate the experimental results. Beech wood and polypropylene particles have shown a very different dynamic behaviour during the pyrolysis stage. When the feedstock is fed from the bottom, the plastic material tends to spend more time within the bed than the biomass. This behaviour can be attributed to the presence of the endogenous bubbles, which drag effect is more pronounced during the devolatilization of biomass, resulting in a lower residence time of the particle within the bed. At the typical operating temperatures of thermochemical conversions, the synthetic polymer softens and melts, and the bed particles attach on its outer surface, generating a wet plastic-sand agglomerate. Consequently, this additional layer of sand may hinder the rapid evolution of volatiles in the form of endogenous bubbles, and therefore the establishment of a poor drag effect acting on the feedstock itself. Information about the mixing and segregation of solid feedstock is of prime importance for the design and development of more efficient industrial-scale operations.Keywords: fluidized bed, pyrolysis, waste feedstock, X-ray
Procedia PDF Downloads 1722 Screening of Osteoporosis in Aging Populations
Authors: Massimiliano Panella, Sara Bortoluzzi, Sophia Russotto, Daniele Nicolini, Carmela Rinaldi
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Osteoporosis affects more than 200 million people worldwide. About 75% of osteoporosis cases are undiagnosed or diagnosed only when a bone fracture occurs. Since osteoporosis related fractures are significant determinants of the burden of disease and health and social costs of aging populations, we believe that this is the early identification and treatment of high-risk patients should be a priority in actual healthcare systems. Screening for osteoporosis by dual energy x-ray absorptiometry (DEXA) is not cost-effective for general population. An alternative is pulse-echo ultrasound (PEUS) because of the minor costs. To this end, we developed an early detection program for osteoporosis with PEUS, and we evaluated is possible impact and sustainability. We conducted a cross-sectional study including 1,050 people in Italy. Subjects with >1 major or >2 minor risk factors for osteoporosis were invited to PEUS bone mass density (BMD) measurement at the proximal tibia. Based on BMD values, subjects were classified as healthy subjects (BMD>0.783 g/cm²) and pathological including subjects with suspected osteopenia (0.783≤BMD>0.719 g/cm²) or osteoporosis (BMD ≤ 0.719 g/cm²). The responder rate was 60.4% (634/1050). According to the risk, PEUS scan was recommended to 436 people, of whom 300 (mean age 45.2, 81% women) accepted to participate. We identified 240 (80%) healthy and 60 (20%) pathological subjects (47 osteopenic and 13 osteoporotic). We observed a significant association between high risk people and reduced bone density (p=0.043) with increased risks for female gender, older ages, and menopause (p<0.01). The yearly cost of the screening program was 8,242 euros. With actual Italian fracture incidence rates in osteoporotic patients, we can reasonably expect in 20 years that at least 6 fractures will occur in our sample. If we consider that the mean costs per fracture in Italy is today 16,785 euros, we can estimate a theoretical cost of 100,710 euros. According to literature, we can assume that the early treatment of osteoporosis could avoid 24,170 euros of such costs. If we add the actual yearly cost of the treatments to the cost of our program and we compare this final amount of 11,682 euros to the avoidable costs of fractures (24,170 euros) we can measure a possible positive benefits/costs ratio of 2.07. As a major outcome, our study let us to early identify 60 people with a significant bone loss that were not aware of their condition. This diagnostic anticipation constitutes an important element of value for the project, both for the patients, for the preventable negative outcomes caused by the fractures, and for the society in general, because of the related avoidable costs. Therefore, based on our finding, we believe that the PEUS based screening performed could be a cost-effective approach to early identify osteoporosis. However, our study has some major limitations. In fact, in our study the economic analysis is based on theoretical scenarios, thus specific studies are needed for a better estimation of the possible benefits and costs of our program.Keywords: osteoporosis, prevention, public health, screening
Procedia PDF Downloads 1221 Absolute Quantification of the Bexsero Vaccine Component Factor H Binding Protein (fHbp) by Selected Reaction Monitoring: The Contribution of Mass Spectrometry in Vaccinology
Authors: Massimiliano Biagini, Marco Spinsanti, Gabriella De Angelis, Sara Tomei, Ilaria Ferlenghi, Maria Scarselli, Alessia Biolchi, Alessandro Muzzi, Brunella Brunelli, Silvana Savino, Marzia M. Giuliani, Isabel Delany, Paolo Costantino, Rino Rappuoli, Vega Masignani, Nathalie Norais
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The gram-negative bacterium Neisseria meningitidis serogroup B (MenB) is an exclusively human pathogen representing the major cause of meningitides and severe sepsis in infants and children but also in young adults. This pathogen is usually present in the 30% of healthy population that act as a reservoir, spreading it through saliva and respiratory fluids during coughing, sneezing, kissing. Among surface-exposed protein components of this diplococcus, factor H binding protein is a lipoprotein proved to be a protective antigen used as a component of the recently licensed Bexsero vaccine. fHbp is a highly variable meningococcal protein: to reflect its remarkable sequence variability, it has been classified in three variants (or two subfamilies), and with poor cross-protection among the different variants. Furthermore, the level of fHbp expression varies significantly among strains, and this has also been considered an important factor for predicting MenB strain susceptibility to anti-fHbp antisera. Different methods have been used to assess fHbp expression on meningococcal strains, however, all these methods use anti-fHbp antibodies, and for this reason, the results are affected by the different affinity that antibodies can have to different antigenic variants. To overcome the limitations of an antibody-based quantification, we developed a quantitative Mass Spectrometry (MS) approach. Selected Reaction Monitoring (SRM) recently emerged as a powerful MS tool for detecting and quantifying proteins in complex mixtures. SRM is based on the targeted detection of ProteoTypicPeptides (PTPs), which are unique signatures of a protein that can be easily detected and quantified by MS. This approach, proven to be highly sensitive, quantitatively accurate and highly reproducible, was used to quantify the absolute amount of fHbp antigen in total extracts derived from 105 clinical isolates, evenly distributed among the three main variant groups and selected to be representative of the fHbp circulating subvariants around the world. We extended the study at the genetic level investigating the correlation between the differential level of expression and polymorphisms present within the genes and their promoter sequences. The implications of fHbp expression on the susceptibility of the strain to killing by anti-fHbp antisera are also presented. To date this is the first comprehensive fHbp expression profiling in a large panel of Neisseria meningitidis clinical isolates driven by an antibody-independent MS-based methodology, opening the door to new applications in vaccine coverage prediction and reinforcing the molecular understanding of released vaccines.Keywords: quantitative mass spectrometry, Neisseria meningitidis, vaccines, bexsero, molecular epidemiology
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