88 results on '"Miani M"'
Search Results
2. Modelling morphodynamic response of a tidal basin to an anthropogenic effect: Ley Bay, East Frisian Wadden Sea – applying tidal forcing only and different sediment fractions
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Dissanayake, D.M.P.K., Wurpts, A., Miani, M., Knaack, H., Niemeyer, H.D., and Roelvink, J.A.
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- 2012
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3. Clinical and pharmacological phase I evaluation of Exherin™ (ADH-1), a selective anti-N-cadherin peptide in patients with N-cadherin-expressing solid tumours
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Perotti, A., Sessa, C., Mancuso, A., Noberasco, C., Cresta, S., Locatelli, A., Carcangiu, M.L., Passera, K., Braghetti, A., Scaramuzza, D., Zanaboni, F., Fasolo, A., Capri, G., Miani, M., Peters, W.P., and Gianni, L.
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- 2009
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4. Signalling danger: endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation
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Eizirik, D. L., Miani, M., and Cardozo, A. K.
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- 2013
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5. CTSH is a type 1 diabetes risk gene that regulates beta cell function and disease progression in newly-diagnosed patients: W20.002
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Fløyel, T., Brorsson, C., Nielsen, L. B., Bang-Berthelsen, C. H., Miani, M., Friedrichsen, M., Wiberg, A., Mortensen, H. B., Størling, J., and Pociot, F.
- Published
- 2012
6. Gel beads from novel ionic polysaccharides
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Miani, M, Gianni, R, Liut, G, Rizzo, R, Toffanin, R, and Delben, F
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- 2004
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7. High-Fiber Diet Supplementation in Patients with Irritable Bowel Syndrome (IBS): A Multicenter, Randomized, Open Trial Comparison Between Wheat Bran Diet and Partially Hydrolyzed Guar Gum (PHGG)
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Parisi, G. C., Zilli, M., Miani, M. P., Carrara, M., Bottona, E., Verdianelli, G., Battaglia, G., Desideri, S., Faedo, A., Marzolino, C., Tonon, A., Ermani, M., and Leandro, G.
- Published
- 2002
8. Altered indirect hemagglutination method for easy serotyping of Haemophilus parasuis
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Lorenson, M.S., Miani, M., Guizzo, J.A., Barasoul, B., Martínez-Martínez, S., Rodríguez-Ferri, E.F., Gutiérrez-Martín, C.B., Kreutz, L.C., and Frandoloso, R.
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sorotipificação ,Haemophilus parasuis ,diagnosis ,indirect hemagglutination ,hemaglutinação indireta ,serotyping ,ácido tânico ,tannic acid ,diagnóstico - Abstract
Glässer's disease is an emergent bacterial disease that affects swine husbandries worldwide causing important economic losses. The aetiological agent, Haemophilus parasuis, is currently divided in fifteen serovars but an increasing number of non-typeable serovars have been reported. Indirect hemagglutination (IHA) is indicated as a serotyping method for H. parasuis. In the present study, we describe an additional step that aims to work around a possible obstacle in the original protocol that may compromise the outcome of this assay. We observed that the choice of anticoagulant for blood collection influences and/or impairs spontaneous adsorption of H. parasuis antigens on sheep red blood cells (SRBCs). However, regardless of the anticoagulant used, chemical treatment of SRBCs with tannic acid induces a stable antigen adsorption (sensitization step). The addition of 1% BSA to SRBCs washing buffer and to antisera dilution augments IHA specificity. Tannic acid treated SRBCs combined with thermo-resistant H. parasuis antigens increases the assay resolution. Thus, our results demonstrate an improvement in the technique of H. parasuis serotyping that will prove valuable to understand Glässer's disease epidemiology and to better characterize serovars involved in outbreaks. RESUMO A Doença de Glässer é uma doença bacteriana emergente que afeta a produção de suínos em todo o mundo e causa importantes perdas econômicas. O agente etiológico, Haemophilus parasuis, é atualmente dividido em quinze sorovares; no entanto, um número crescente de cepas não tipificáveis tem sido relatado. O teste de hemaglutinação indireta (IHA) tem sido utilizado para a sorotipificação de H. parasuis. Neste estudo, descrevemos uma alteração no protocolo original de IHA e que supera uma limitação específica que pode comprometer o uso geral deste ensaio. Descobrimos que o tipo de anticoagulante utilizado para coletar os eritrócitos ovinos (SRBCs) pode comprometer a adsorção espontânea dos antígenos do H. parasuis. Por outro lado, o tratamento químico dos SRBCs com ácido tânico promove uma adsorção antigênica estável (passo de sensibilização) e independente do anticoagulante utilizado. O uso de 1% de BSA durante as lavagens dos SRBCs e na diluição dos antissoros incrementa a especificidade da IHA e, a combinação dos SRBCs tratados quimicamente com antígenos de H. parasuis termo-resistentes aumentam a resolução da IHA. Nossos resultados destacam uma melhoria na principal técnica de sorotipificação de H. parasuis, que auxiliará diretamente no entendimento da epidemiologia da Doença de Glässer e na caracterização dos sorovares envolvidos em surtos da doença.
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- 2017
9. Altered indirect hemagglutination method for easy serotyping of Haemophilus parasuis
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Lorenson, M.S., primary, Miani, M., additional, Guizzo, J.A., additional, Barasoul, B., additional, Martínez-Martínez, S., additional, Rodríguez-Ferri, E.F., additional, Gutiérrez-Martín, C.B., additional, Kreutz, L.C., additional, and Frandoloso, R., additional
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- 2017
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10. The Long March of Chinese Co-operatives: Towards Market Economy, Participation, and Sustainable Development
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Bernardi, A and Miani, M
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- 2015
11. Cathelicidin-derived antimicrobial peptides: in vitro and in vivo activity
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GENNARO, RENATO, SCOCCHI, MARCO, SKERLAVAJ B, RISSO A, MIANI M, ZANETTI M., BENINCASA, MONICA, MARTINEZ J., Gennaro, Renato, Scocchi, Marco, Benincasa, Monica, Skerlavaj, B, Risso, A, Miani, M, and Zanetti, M.
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- 2001
12. Differential usage of NF-κB activating signals by IL-1β and TNF-α in pancreatic beta cells
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Ortis, F., Miani, M., Colli, M.L., Cunha, D.A., Gurzov, E.N., Allagnat, F., Chariot, A., and Eizirik, D.L.
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- 2012
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13. VALUTAZIONE DELLA QUALITA' DI COTTURA DI PASTA FRESCA DI SEMOLA DI GRANO DURO
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Messia, Maria Cristina, Esposito, T, Falasca, Luisa, Greco Miani, M, and Marconi, Emanuele
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- 2011
14. Endoplasmic reticulum stress sensitizes pancreatic beta cells to interleukin-1β-induced apoptosis via Bim/A1 imbalance
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Miani, M, primary, Barthson, J, additional, Colli, M L, additional, Brozzi, F, additional, Cnop, M, additional, and Eizirik, D L, additional
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- 2013
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15. Signalling danger: endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation
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Eizirik, D. L., primary, Miani, M., additional, and Cardozo, A. K., additional
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- 2012
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16. La parotite tubercolare nel bambino descrizione di un caso clinico
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Robiony, Massimo, Demitri, V., Politi, M., Pelizzo, M. T., and Miani, M. P.
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- 1996
17. Phase I dose-finding study of trabectedin (T) in combination with cisplatin (C) in patients (pts) with advanced solid tumors.
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Sessa, C., primary, Gallerani, E., additional, Del Conte, G., additional, Christinat, A., additional, Perotti, A., additional, Lardelli, P., additional, Kahatt, C. M., additional, Florez, A., additional, Fernandez, C., additional, Miani, M., additional, and Gianni, L., additional
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- 2011
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18. O42 Le rôle du système nerveux parasympathique dans la régulation de la régénération des cellules β pancréatiques
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Movassat, J., primary, Pakradouni, J., additional, Bailbe, D., additional, Miani, M., additional, Faro, M., additional, and Portha, B., additional
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- 2009
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19. Phase I study of the oral platinum agent satraplatin (S) in sequential combination with capecitabine (C) in patients with advanced solid tumours
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Sessa, C., primary, Hess, D., additional, Bauer, J., additional, Droege, C., additional, Gallerani, E., additional, Miani, M., additional, Tinazzi, A., additional, Krieter, O., additional, Angst, R., additional, and Nay, C., additional
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- 2008
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20. Monitoring for mefloquine-resistant Plasmodium falciparum in Africa: implications for travelers' health.
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Lobel, H O, primary, Varma, J K, additional, Miani, M, additional, Todd, G D, additional, Green, M, additional, Grady, K, additional, and Barber, A M, additional
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- 1998
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21. Long-term malaria prophylaxis with weekly mefloquine
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Lobel, H.O, primary, Campbell, C.C, additional, Hightower, A.H, additional, Eng, T, additional, Miani, M, additional, and Bernard, K.W, additional
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- 1993
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22. Treatment Expectations in Hypertension: Implications for Patients Enrolled in Disease Management Programs.
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Cohen, D., Townsend, R., Miani, M., and Bernard, D.
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THERAPEUTICS ,HYPERTENSION ,DISEASE management ,HEALTH risk assessment - Abstract
Hypertension, an insidious condition affecting approximately 50 million US adults, remains a central factor contributing to cardiac and other target organ disease. Despite increased detection and numerous therapeutic advances, three out of four people with hypertension in the US have uncontrolled or poorly controlled blood pressure. While hypertension is a leading reason for primary care office visits and antihypertensive medications are widely prescribed, most individuals are not achieving goal systolic/diastolic blood pressure of 140/90mm Hg or less. While the definition of adequate blood pressure control varies in different countries, the problem of inadequate control is universal. Numerous barriers contributing to the suboptimal health outcomes have been recognized, including issues related to healthcare providers as well as patient compliance with medication and lifestyle changes. Recently, healthcare provider systems and health plans have turned to disease management strategies to better address quality and outcomes issues in hypertension management. Disease management, a systematic clinical improvement process, encompasses provider and patient education employing national or locally developed best practice guidelines and behavioral interventions coupled with close monitoring of clinical processes and outcomes of care. Disease management programs seek to define a comprehensive and coordinated approach to care across multiple providers and patient subgroups. Through risk assessment and stratification, patients at higher risk of complications can be identified, and customized intensive care support can be offered. Other types of intervention for lower risk individuals include brief visits with a cardiovascular educator or care manager, group classes, or self-instructional programs. Several successful programs initiated by healthcare systems and health plans are described. Adequate blood pressure control is essential to reduce cardiac, renal, and stroke disease later in life. However, large numbers of individuals must be effectively managed for years or decades to achieve reductions in complications and cost savings. Unlike more acute conditions that frequently result in hospitalization and loss of function, the immediate cost offsets of hypertension disease management efforts are less defined, although the eventual savings to society could be vast. Less costly methods to promote healthy outcomes across large, relatively stable populations are needed. Automated systems employing clinical decision support at the point of care and internet-based patient support strategies offer the hope that comprehensive, individualized disease management for hypertension can be affordable as well as effective. In the meantime, the fact that the National Committee on Quality Assurance has included blood pressure control as a future measure of health plan performance will almost certainly lead to the expanded development of hypertension disease management initiatives. [ABSTRACT FROM AUTHOR]
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- 2001
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23. A machine learning approach to determine airport asphalt concrete layer moduli using heavy weight deflectometer data
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Nicola Baldo, Fabio Rondinella, Clara Celauro, Matteo Miani, Baldo, N., Miani, M., Rondinella, F., Celauro, C., Baldo N., Miani M., Rondinella F., and Celauro C.
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Heavy weight deflectometer ,Computer science ,Maintenance ,Runway ,Geography, Planning and Development ,TJ807-830 ,Management, Monitoring, Policy and Law ,Stiffness modulus ,TD194-195 ,Machine learning ,computer.software_genre ,Renewable energy sources ,Performance prediction ,GE1-350 ,Layer (object-oriented design) ,Environmental effects of industries and plants ,Artificial neural network ,Renewable Energy, Sustainability and the Environment ,business.industry ,Feed forward ,Pavement management ,Building and Construction ,Backpropagation ,Environmental sciences ,Asphalt concrete ,Shallow neural network ,Artificial intelligence ,business ,computer - Abstract
An integrated approach based on machine learning and data augmentation techniques has been developed in order to predict the stiffness modulus of the asphalt concrete layer of an airport runway, from data acquired with a heavy weight deflectometer (HWD). The predictive model relies on a shallow neural network (SNN) trained with the results of a backcalculation, by means of a data augmentation method and can produce estimations of the stiffness modulus even at runway points not yet sampled. The Bayesian regularization algorithm was used for training of the feedforward backpropagation SNN, and a k-fold cross-validation procedure was implemented for a fair performance evaluation. The testing phase result concerning the stiffness modulus prediction was characterized by a coefficient of correlation equal to 0.9864 demonstrating that the proposed neural approach is fully reliable for performance evaluation of airfield pavements or any other paved area. Such a performance prediction model can play a crucial role in airport pavement management systems (APMS), allowing the maintenance budget to be optimized.
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- 2021
24. Stiffness Data of High-Modulus Asphalt Concretes for Road Pavements: Predictive Modeling by Machine-Learning
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Nicola Baldo, Matteo Miani, Fabio Rondinella, Jan Valentin, Pavla Vackcová, Evangelos Manthos, Baldo, N., Miani, M., Rondinella, F., Valentin, J., Vackcova, P., and Manthos, E.
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Data augmentation ,asphalt concretes ,road pavements ,polymer modified bitumen ,recycled asphalt pavement ,stiffness modulus ,Marshall stability ,machine learning modeling ,shallow neural networks ,Bayesian optimization ,data augmentation ,Machine learning modeling ,Surfaces and Interfaces ,Stiffness modulus ,Engineering (General). Civil engineering (General) ,Surfaces, Coatings and Films ,Shallow neural networks ,Road pavement ,Shallow neural network ,Recycled asphalt pavement ,Polymer modified bitumen ,Asphalt concrete ,Materials Chemistry ,TA1-2040 ,Asphalt concretes ,Road pavements - Abstract
This paper presents a study about a Machine Learning approach for modeling the stiffness of different high-modulus asphalt concretes (HMAC) prepared in the laboratory with harder paving grades or polymer-modified bitumen which were designed with or without reclaimed asphalt (RA) content. Notably, the mixtures considered in this study are not part of purposeful experimentation in support of modeling, but practical solutions developed in actual mix design processes. Since Machine Learning models require a careful definition of the network hyperparameters, a Bayesian optimization process was used to identify the neural topology, as well as the transfer function, optimal for the type of modeling needed. By employing different performance metrics, it was possible to compare the optimal models obtained by diversifying the type of inputs. Using variables related to the mix composition, namely bitumen content, air voids, maximum and average bulk density, along with a categorical variable that distinguishes the bitumen type and RAP percentages, successful predictions of the Stiffness have been obtained, with a determination coefficient (R2) value equal to 0.9909. Nevertheless, the use of additional input, namely the Marshall stability or quotient, allows the Stiffness prediction to be further improved, with R2 values equal to 0.9938 or 0.9922, respectively. However, the cost and time involved in the Marshall test may not justify such a slight prediction improvement.
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- 2022
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25. Road Pavement Asphalt Concretes for Thin Wearing Layers: A Machine Learning Approach towards Stiffness Modulus and Volumetric Properties Prediction
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Nicola Baldo, Matteo Miani, Fabio Rondinella, Evangelos Manthos, Jan Valentin, Baldo, N, Miani, M, Rondinella, F, Manthos, E, and Valentin, J
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Bayesian optimization ,machine learning ,mix design ,stiffness modulus ,thin surface layer ,stiffness modulu ,Geotechnical Engineering and Engineering Geology ,Civil and Structural Engineering - Abstract
In this study a novel procedure is presented for an efficient development of predictive models of road pavement asphalt concretes mechanical characteristics and volumetric properties, using shallow artificial neural networks. The problems of properly assessing the actual generalization feature of a model and avoiding the effects induced by a fixed training-test data split are addressed. Since machine learning models require a careful definition of the network hyperparameters, a Bayesian approach is presented to set the optimal model configuration. The case study covered a set of 92 asphalt concrete specimens for thin wearing layers.
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- 2022
26. Drivers' Braking Behavior Affected by Cognitive Distractions: An Experimental Investigation with a Virtual Car Simulator
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Nicola Baldo, Matteo Miani, Andrea Marini, Baldo, N., Marini, A., and Miani, M.
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Earphone ,lcsh:BF1-990 ,Car driving simulator ,pedestrian crossing ,Pedestrian ,Development ,Pedestrian crossing ,Article ,Task (project management) ,Behavioral Neuroscience ,cognitive distractions ,Cognitive resource theory ,Distraction ,Human factor ,earphones ,0502 economics and business ,Cognitive distractions ,Driver's behavior ,Earphones ,Human factors ,Speed reduction measures ,Genetics ,0501 psychology and cognitive sciences ,car driving simulator ,050107 human factors ,General Psychology ,Ecology, Evolution, Behavior and Systematics ,Simulation ,Cognitive distraction ,050210 logistics & transportation ,05 social sciences ,Cognition ,driver’s behavior ,Risk compensation ,speed reduction measures ,lcsh:Psychology ,Psychology ,Cognitive load ,human factors - Abstract
In this study, a cohort of 78 university students performed a driving experience in a virtual urban scenario, by means of a car driving simulator, to examine effects of a planned hands-free mobile phone conversation on young drivers&rsquo, braking behaviors. To this aim, a control group was left free to drive without any imposed cognitive task. An experimental group faced the same scenario while engaged in a phone call. The conversation via earphones was arranged to diminish the amount of cognitive resources allocated to the driving task. For both groups, the analyses focused on the moment at which a child entered a pedestrian crossing from a sidewalk. The results of a mixed two-way ANOVA showed the presence of a significant difference for distracted and non-distracted drivers with the absence of gender-related differences across the two groups. Distracted participants assumed lower initial speeds, took the first action to stop at shorter distances from the zebra crossing, and had more difficulty in keeping speed variations under control. These findings suggest that the distraction induced by the use of earphones may induce risk compensation behaviors and delay pedestrian perception. Moreover, the effects on the participants' braking behavior suggest that the procedure adopted to increase cognitive load, based on a story retelling, is an effective method to analyze the impact of hands-free cellphone use on driving skills in a car simulation experiment.
- Published
- 2020
27. Safety performance functions for road intersections in the Friuli Venezia Giulia region
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Baldo, N., MATTEO MIANI, Baldo, N., and Miani, M.
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Artificial neural network ,Safety performance function ,Road safety - Abstract
The aim of this paper was developing Safety Performance Functions (SPFs) of four different types of road intersections: unsignalized three-leg intersection, unsignalized four-leg intersection, signalized threeleg intersections, signalized four-leg intersection. The data on accidents and traffic volume of 28 intersections, which are under the jurisdiction of Friuli Venezia Giulia Strade S.p.A., were collected and analyzed. To model the empirical relation between crash frequency and traffic volume, a feed-forward artificial neural network (ANN), characterized by the hyperbolic tangent transfer function and one hidden layer, was used. SPFs of the analyzed road intersections have shown a slope reduction of the tangent line when annual average daily traffic increased on the main leg, namely, the road capacity is not able to meet the increase in the volume of traffic. As a result, this leads to a saturation that induces slowdowns with a lower probability of running into an accident.
- Published
- 2020
28. Semi-empirical model for shear strength of RC interior beam-column joints subjected to cyclic loads
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Giada Frappa, Gaetano Russo, Marco Miani, Margherita Pauletta, Igino Pitacco, Sreekanta Das, Caterina Di Marco, Giuliana Somma, Pauletta, M, Di Marco, C, Frappa, G, Somma, G, Pitacco, I, Miani, M, Das, S, and Russo, G
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Work (thermodynamics) ,Semi empirical model ,Interior beam-column joint ,Reinforced concrete ,Shear strength ,Strut-and-tie model ,Test data ,Design formula ,0211 other engineering and technologies ,020101 civil engineering ,02 engineering and technology ,0201 civil engineering ,021105 building & construction ,Joint (geology) ,Civil and Structural Engineering ,Mathematics ,Basis (linear algebra) ,business.industry ,Structural engineering ,Beam column ,business ,Beam (structure) - Abstract
This paper proposes an extension to RC interior beam-column joints of a model for the shear strength prediction of exterior joints under seismic actions, already presented in the literature and based, for certain assumptions, on a previous work of Park and Mosalam. The necessary changes, due to the joints’ different physical configurations, only one beam converging in exterior joints and two beams converging in interior ones, are introduced. In the proposed model, on the basis of mechanical considerations, a direct formula for interior joint shear strength accounting for the resisting contributions of three inclined concrete struts and of joint reinforcements, the column horizontal stirrups and intermediate vertical bars, is derived. In comparison to the model for exterior joints, three struts are considered instead of two and the influenced of the upper column axial load on the inclination of the concrete struts is taken into account. The coefficients of the contributions of the struts and reinforcements are calibrated using 69 test data sets available in the literature, selecting only cyclic tests showing joint shear failure. For the validation of the proposed model, the shear strength predictions obtained using the proposed expression are compared with those obtained from Kassem’s model, Wang et al.’s formula and Kim and LaFave’s formula, on a set of 28 specimens. It is also proposed a design formula, whose predictions are compared to those of Eurocode 8 and ACI Code.
- Published
- 2020
29. Numerical characterization of high modulus asphalt concrete containing RAP: A comparison among optimized shallow neural models
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Evangelos Manthos, Matteo Miani, Nicola Baldo, Jan Valentin, Baldo, N., Valentin, J., Manthos, E., and Miani, M.
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Asphalt concrete ,Materials science ,business.industry ,Modulus ,Composite material ,business ,Characterization (materials science) - Abstract
Knowing the relationship between the stiffness modulus and the empirical mechanical characteristics of asphalt concrete, road engineers may predict the expected results of costly laboratory tests and save both time and financial resources in the mix design phase. In fact, such a model would make it possible to assess a priori whether the stiffness of a specific mixture, characterised in the laboratory only by the common Marshall test, is suitable for the level of service required by the road pavement under analysis. In this study, 54 Marshall test specimens of high modulus asphalt concrete were prepared and tested in the laboratory to determine an empirical relationship between the stiffness modulus and Marshall stability by means of shallow artificial neural networks. Part out of these mixtures was characterised by different types of bitumen (20/30 or 50/70 penetration grade) and percentages of used reclaimed asphalt (RAP at 20% or 30%); a polymer modified bitumen was used in the preparation of the remaining Marshall test specimens, which do not contain RAP. For the complex and laborious identification of the neural model hyperparameters, which define its architecture and algorithmic functioning, the Bayesian optimization approach has been adopted. Although the results of this methodology depend on the predefined hyperparameters variability ranges, it allows an unbiased definition of the optimal neural model characteristics to be performed by minimizing (or maximizing) a loss function. In this study, the mean square error on 5 validation folds was used as a loss function, in order to avoid a poor performance evaluation due to the small number of samples. In addition, 3 different neural training algorithms were applied to compare results and convergence times. The procedure presented in this study is a valuable guide for the development of predictive models of asphalt concretes’ behaviour, even for different types of bitumen and aggregates considered here.
- Published
- 2020
30. Stiffness modulus and marshall parameters of hot mix asphalts: Laboratory data modeling by artificial neural networks characterized by cross-validation
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Evangelos Manthos, Nicola Baldo, Matteo Miani, Baldo, N., Manthos, E., and Miani, M.
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Artificial neural network ,Artificial neural networks ,Cross-validation ,Diabase aggregates ,Hot mix asphalt ,Limestone aggregates ,Marshall test ,Model selection ,Polymer modified bitumen ,Stiffness modulus ,0211 other engineering and technologies ,02 engineering and technology ,lcsh:Technology ,Transfer function ,Stability (probability) ,Data modeling ,lcsh:Chemistry ,0203 mechanical engineering ,021105 building & construction ,Range (statistics) ,General Materials Science ,Diabase aggregate ,lcsh:QH301-705.5 ,Instrumentation ,Mathematics ,Fluid Flow and Transfer Processes ,Aggregate (composite) ,lcsh:T ,business.industry ,Process Chemistry and Technology ,General Engineering ,Structural engineering ,lcsh:QC1-999 ,Computer Science Applications ,TheoryofComputation_MATHEMATICALLOGICANDFORMALLANGUAGES ,020303 mechanical engineering & transports ,lcsh:Biology (General) ,lcsh:QD1-999 ,lcsh:TA1-2040 ,Asphalt ,lcsh:Engineering (General). Civil engineering (General) ,business ,lcsh:Physics ,Limestone aggregate - Abstract
The present paper discusses the analysis and modeling of laboratory data regarding the mechanical characterization of hot mix asphalt (HMA) mixtures for road pavements, by means of artificial neural networks (ANNs). The HMAs investigated were produced using aggregate and bitumen of different types. Stiffness modulus (ITSM) and Marshall stability (MS) and quotient (MQ) were assumed as mechanical parameters to analyze and predict. The ANN modeling approach was characterized by multiple layers, the k-fold cross validation (CV) method, and the positive linear transfer function. The effectiveness of such an approach was verified in terms of the coefficients of correlation ( R ) and mean square errors, in particular, R values were within the range 0.965 &ndash, 0.919 in the training phase and 0.881 &ndash, 0.834 in the CV testing phase, depending on the predicted parameters.
- Published
- 2019
31. Effects of Cognitive Distraction on Driver’s Stopping Behaviour: A Virtual Car Driving Simulator Study
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Matteo Miani, Nicola Baldo, Andrea Marini, Baldo, N., Marini, A., and Miani, M.
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Cognitive distraction ,Car driving ,Psychology ,Simulation - Abstract
Drivers are prone to distractions while driving, due to conversations they have with passengers on board, processing their thoughts or using their mobile phones. These distractions result in a mental workload that compromises driving safety and requires the implementation of risk compensatory behaviours. This study examines the effects of hands-free mobile phone conversations on young drivers’ stopping manoeuvres when a pedestrian enters a zebra crossing. A cohort of seventy-eight university students, aged 20-30 years old, performed a driving task in a virtual urban environment, by means of a virtual car driving simulator. They formed a control and an experimental group, balanced on age and IQ level. The control group was left free to drive without any imposed cognitive task. The experimental group was asked to drive while making a phone call that was planned to diminish the amount of cognitive resources allocated to the driving experience. For both groups, the analyses focused on a specific moment, i.e., while a child suddenly entered a zebra crossing from a sidewalk. Throughout the simulation, the intensity of the participants’ actions on the brake pedal, accelerator, and steering wheel were recorded with a time step of 250 ms. Before the virtual driving experiment, each participant completed a questionnaire on his/her daily driving style, involvement in road accidents, and general mobile phone usage even while driving. A mixed two-way ANOVA with Group as a between-subject factor (1. Control Group; 2. Experimental Group) and Gender (1. Male drivers; 2. Female drivers) as a within-subject factor was performed on the driving parameters as dependent variables. The results showed the presence of a significant difference for distracted and non-distracted drivers with the absence of gender-related differences across the two groups. Participants engaged in a hands-free phone-call while driving assumed lower initial speeds as an element of risk compensation and took the first action to stop at shorter distances from the pedestrian crossing. This suggests a delayed perception of the presence of the pedestrian. In addition, the fluctuation in speed after the distracted driver had released the accelerator pedal reached a statistical significance compared to the control group. These findings suggest that the distraction induced by the use of the mobile phone through the earphones may adversely affect driving behaviour and raise significant safety concerns.
- Published
- 2020
32. Boulder transport by tsunamis: A laboratory experiment on incipient motion
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BRESSAN, LIDIA, ANTONINI, ALESSANDRO, GAETA, MARIA GABRIELLA, GUERRERO, MASSIMO, MIANI, MARCO, PETRUZZELLI, VALENTINA, SAMARAS, ACHILLEAS, Bressan, L., Antonini, A., Gaeta, M.G., Guerrero, M., Miani, M., Petruzzelli, V., and Samaras, A.
- Published
- 2015
33. Gel beads from novel ionic polysaccharides
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Roberto Rizzo, Gianfranco Liut, M Miani, Franco Delben, Renato Toffanin, R. Gianni, Miani, M, Gianni, R, Liut, Gianfranco, Rizzo, Roberto, Toffanin, R, and Delben, Franco
- Subjects
chemistry.chemical_classification ,carboxymethyl cellulose ,Morphology (linguistics) ,Polymers and Plastics ,Molecular mass ,Scanning electron microscope ,Organic Chemistry ,technology, industry, and agriculture ,Ionic bonding ,Pullulan ,Polysaccharide ,Polyelectrolyte ,Carboxymethyl cellulose ,NMR microscopy ,chemistry.chemical_compound ,gel beads ,chemistry ,Polymer chemistry ,Materials Chemistry ,medicine ,aminopropyl pullulan ,gel bead ,medicine.drug - Abstract
Stable gelling systems were obtained by mixing polyanion solutions with solutions containing suitable polycations. Carboxymethyl cellulose was chosen as the polyanion, whilst a number of polycations, with different molecular weights and charge densities, were tested. In particular, both low molecular weight polyamines and new synthetically aminated polysaccharides, derived from pullulan and scleroglucan, were used. Stable gels, in the absence of phase separation, were obtained only with flexible polycationic species. The morphological characterisation of the gel beads obtained were studied by scanning electron microscopy and NMR microscopy.
- Published
- 2004
34. Pro-rich antimicrobial peptides from animals: structure, biological functions and mechanism of action
- Author
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Renato Gennaro, Monica Benincasa, Margherita Zanetti, Elena Podda, Monica Miani, Gennaro, Renato, Zanetti, M., Benincasa, Monica, Podda, E., and Miani, M.
- Subjects
Pharmacology ,chemistry.chemical_classification ,Innate immune system ,Proline ,Neutrophils ,Antimicrobial peptides ,Biological activity ,Peptide ,Biology ,Gram-Positive Bacteria ,Immunity, Innate ,Syndecan 1 ,Anti-Bacterial Agents ,Structure-Activity Relationship ,Mechanism of action ,chemistry ,Biochemistry ,Drug Discovery ,Gram-Negative Bacteria ,medicine ,Animals ,medicine.symptom ,Mode of action ,Antibacterial agent ,Antimicrobial Cationic Peptides - Abstract
Pro-rich antimicrobial peptides are a group of linear peptides of innate immunity isolated from mammals and invertebrates, and characterised by a high content of proline residues (up to 50%). Members of this group are predominantly active against Gram-negative bacterial species which they kill by a non-lytic mechanism, at variance with the majority of the known antimicrobial peptides. Evidence is accumulating that the Pro-rich peptides enter the cells without membrane lysis and, once in the cytoplasm, bind to, and inhibit the activity of specific molecular targets essential to bacterial growth, thereby causing cell death. This mode of action makes these peptides suitable for drug development efforts. In addition to antibacterial action, PR-39, one of the better characterised Pro-rich peptides from mammals, exerts other potentially exploitable biological activities, such as induction of syndecan expression in mesenchymal cells and inhibition of the NADPH oxidase activity of neutrophils, suggesting a role of this peptide in wound repair and inflammation. PR-39 also exerts a protective effect in various animal models of ischemia-reperfusion injury, preventing the post-ischemic oxidant production, and is a potent inducer of angiogenesis both in vitro and in vivo. Although the physiological relevance of all these effects has not yet been established, the above observations underscore the therapeutic potential of this peptide in a number of complex processes such as inflammation, wound repair, ischemia-reperfusion injury, and angiogenesis.
- Published
- 2002
35. Perspective: Leveraging the Gut Microbiota to Predict Personalized Responses to Dietary, Prebiotic, and Probiotic Interventions.
- Author
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Gibbons SM, Gurry T, Lampe JW, Chakrabarti A, Dam V, Everard A, Goas A, Gross G, Kleerebezem M, Lane J, Maukonen J, Penna ALB, Pot B, Valdes AM, Walton G, Weiss A, Zanzer YC, Venlet NV, and Miani M
- Subjects
- Animals, Artificial Intelligence, Diet, Humans, Prebiotics, Gastrointestinal Microbiome, Probiotics
- Abstract
Humans often show variable responses to dietary, prebiotic, and probiotic interventions. Emerging evidence indicates that the gut microbiota is a key determinant for this population heterogeneity. Here, we provide an overview of some of the major computational and experimental tools being applied to critical questions of microbiota-mediated personalized nutrition and health. First, we discuss the latest advances in in silico modeling of the microbiota-nutrition-health axis, including the application of statistical, mechanistic, and hybrid artificial intelligence models. Second, we address high-throughput in vitro techniques for assessing interindividual heterogeneity, from ex vivo batch culturing of stool and continuous culturing in anaerobic bioreactors, to more sophisticated organ-on-a-chip models that integrate both host and microbial compartments. Third, we explore in vivo approaches for better understanding of personalized, microbiota-mediated responses to diet, prebiotics, and probiotics, from nonhuman animal models and human observational studies, to human feeding trials and crossover interventions. We highlight examples of existing, consumer-facing precision nutrition platforms that are currently leveraging the gut microbiota. Furthermore, we discuss how the integration of a broader set of the tools and techniques described in this piece can generate the data necessary to support a greater diversity of precision nutrition strategies. Finally, we present a vision of a precision nutrition and healthcare future, which leverages the gut microbiota to design effective, individual-specific interventions., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)
- Published
- 2022
- Full Text
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36. Effect of Durum Wheat Oil on the Physico-Chemical and Sensory Features of Biscuits.
- Author
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Vurro F, Greco Miani M, Summo C, Caponio F, and Pasqualone A
- Abstract
Lipids play an important role in defining the overall quality of biscuits, particularly in terms of resistance to oxidation, as well as for their influence on textural and sensorial properties. The aim of this work was to investigate the effects of durum wheat oil on the physico-chemical and sensory features of biscuits. Control biscuits (C) prepared with the commonly used sunflower oil were compared with samples prepared with durum wheat oil at 50% (D50) and 100% replacement levels (D100). The reformulated biscuits were very rich in tocols, especially tocotrienols (982.9, 635.2, and 64.1 mg/kg on lipid fraction weight in D100, D50, and C, respectively). The higher content of antioxidants extended the resistance to the oxidation of biscuits (induction time = 53.61, 70.87, and 79.92 h in C, D50, and D100, respectively). D100 showed the lowest amounts of triacylglycerol oligopolymers and oxidized triacylglycerols, and the lowest amounts of the volatile markers of lipid oxidation (hexanal and nonanal). The use of durum wheat oil did not affect the sensorial and textural properties, compared to C. This study suggests that durum wheat oil could be effectively used in biscuit-making to decrease the oxidative phenomena and increase the bioactives of the end-products.
- Published
- 2022
- Full Text
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37. Wheat Germ and Lipid Oxidation: An Open Issue.
- Author
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Marzocchi S, Caboni MF, Greco Miani M, and Pasini F
- Abstract
Wheat germ (WG)'s shelf life after the milling process is incredibly short because of the presence of enzymes that aggravate the oxidation process; thus, stabilization is required in order to exploit the nutrients and bioactive compounds within WG. The critical point for the oxidation process is the mechanical treatment used to separate WG from the kernel, which exposes the lipid fraction to the air. Showing the connection between the quality of durum wheat, considering its storage management, and wheat germ oil (WGO), extracted with a cold press, solvent and supercritical CO
2 , is the aim of the study. The acidity and peroxide values were analyzed to evaluate lipid oxidation, while fatty acids, tocols, sterols and policosanols were evaluated for WGO characterization. The first fundamental step to control lipid oxidation is raw material management. Subsequently, the tempering phase of durum wheat, which is applied before the degermination process, is the most critical point for oxidation to develop because of the increase in moisture in the caryopsis and the activation of lipase and lipoxygenase. This represents a paradox: in order to stabilize the germ with degermination, first it seems inevitable to carry out a process that destabilizes it. To retains its highest quality, this will lead to a better use of the whole grain by reducing WG and by-product waste.- Published
- 2022
- Full Text
- View/download PDF
38. Characterization and Effect of Refining on the Oil Extracted from Durum Wheat By-Products.
- Author
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Squeo G, Silletti R, Napoletano G, Greco Miani M, Difonzo G, Pasqualone A, and Caponio F
- Abstract
Durum wheat is one of the most important cereal grains worldwide, used mostly for pasta making and bakery products. The by-products derived for the milling process, although very abundant, have only limited use. The aim of this work was to characterize the oils extracted from the by-products of debranning (DP) and milling processes (MP) of durum wheat and to follow the changes due to the refining process on the minor components. The results showed that DP had significantly higher oil content than MP, but it was characterized by a significantly lower amount of tocols. Polyunsaturated fatty acids content was similar (around 62% of total fatty acids). Consequently, a mixture of DP/MP (60/40 w / w ) was chosen as a basis for further studies concerning the refining process. During refining, carotenoids almost disappeared while tocols were reduced by 24% on average. Free fatty acids, peroxide value, and oxidized triacylglycerols were significantly reduced by refining, while triacylglycerol oligopolymers were significantly higher than the crude oil. Durum wheat oil had an outstanding content of phytosterols and policosanols. Overall, the edible oil obtained from durum wheat after refining could be considered a good source of phytochemicals and could represent a valuable strategy to valorize the by-products from durum wheat mills.
- Published
- 2022
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39. The microbiota-gut-brain axis: pathways to better brain health. Perspectives on what we know, what we need to investigate and how to put knowledge into practice.
- Author
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Chakrabarti A, Geurts L, Hoyles L, Iozzo P, Kraneveld AD, La Fata G, Miani M, Patterson E, Pot B, Shortt C, and Vauzour D
- Subjects
- Animals, Brain physiopathology, Cognition, Humans, Metabolic Networks and Pathways, Signal Transduction, Brain physiology, Brain-Gut Axis, Gastrointestinal Microbiome
- Abstract
The gut and brain link via various metabolic and signalling pathways, each with the potential to influence mental, brain and cognitive health. Over the past decade, the involvement of the gut microbiota in gut-brain communication has become the focus of increased scientific interest, establishing the microbiota-gut-brain axis as a field of research. There is a growing number of association studies exploring the gut microbiota's possible role in memory, learning, anxiety, stress, neurodevelopmental and neurodegenerative disorders. Consequently, attention is now turning to how the microbiota can become the target of nutritional and therapeutic strategies for improved brain health and well-being. However, while such strategies that target the gut microbiota to influence brain health and function are currently under development with varying levels of success, still very little is yet known about the triggers and mechanisms underlying the gut microbiota's apparent influence on cognitive or brain function and most evidence comes from pre-clinical studies rather than well controlled clinical trials/investigations. Filling the knowledge gaps requires establishing a standardised methodology for human studies, including strong guidance for specific focus areas of the microbiota-gut-brain axis, the need for more extensive biological sample analyses, and identification of relevant biomarkers. Other urgent requirements are new advanced models for in vitro and in vivo studies of relevant mechanisms, and a greater focus on omics technologies with supporting bioinformatics resources (training, tools) to efficiently translate study findings, as well as the identification of relevant targets in study populations. The key to building a validated evidence base rely on increasing knowledge sharing and multi-disciplinary collaborations, along with continued public-private funding support. This will allow microbiota-gut-brain axis research to move to its next phase so we can identify realistic opportunities to modulate the microbiota for better brain health., (© 2022. The Author(s).)
- Published
- 2022
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40. A phase II trial of bendamustine in combination with ofatumumab in patients with relapsed or refractory marginal zone B-cell lymphomas.
- Author
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Vannata B, Vanazzi A, Negri M, Liptrott SJ, Bartosek AA, Miani M, Di Sanzo A, Cavalli F, Zucca E, and Stathis A
- Subjects
- Aged, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bendamustine Hydrochloride administration & dosage, Bendamustine Hydrochloride adverse effects, Disease-Free Survival, Female, Humans, Male, Middle Aged, Recurrence, Survival Rate, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Lymphoma, B-Cell, Marginal Zone drug therapy, Lymphoma, B-Cell, Marginal Zone mortality
- Abstract
Marginal zone lymphomas (MZLs) are indolent yet incurable lymphomas with frequent relapses following therapy. For patients with relapsed/refractory disease, no standard therapies exist. Here we report results of an exploratory phase II study aimed at assessing the efficacy and safety of the alkylator agent bendamustine in combination with the second-generation anti-CD20 monoclonal antibody, ofatumumab, in patients with relapsed or refractory MZL. Patients with MZL and previously treated with at least one line of systemic therapy were eligible. Treatment consisted in bendamustine (90 mg/m
2 on days 1 and 2) and ofatumumab (1000 mg on day 1) in 28-day cycles for up to six cycles. Sixteen patients were included in the trial. In one patient, the diagnosis was revised after two cycles of treatment and was excluded from the efficacy analysis. Among 15 patients with MZL, 14 were evaluable for response: the overall and complete response rates were 92.9% and 57.1%, respectively. The median duration of response was 30.4 months (95% confidence interval [CI], 15.5 -not estimable) and 2-years progression-free survival 77% (95% CI, 43%-92%). Fifteen patients (94%) experienced grade 3-4 adverse events. Toxicity was mostly hematological. Neutropenia grade ≥3 was recorded in 27% of patients, lymphocytopenia in 93%, and infections and febrile neutropenia each in 13%. One patient discontinued treatment due to myocardial infarction; no treatment-related deaths occurred. The combination of bendamustine with ofatumumab was active with an acceptable toxicity profile in this small phase II trial and can be considered for further investigation in relapsed/refractory MZL patients., (© 2020 John Wiley & Sons Ltd.)- Published
- 2021
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41. Are current analytical methods suitable to verify VITAL® 2.0/3.0 allergen reference doses for EU allergens in foods?
- Author
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Holzhauser T, Johnson P, Hindley JP, O'Connor G, Chan CH, Costa J, Fæste CK, Hirst BJ, Lambertini F, Miani M, Robert MC, Röder M, Ronsmans S, Bugyi Z, Tömösközi S, and Flanagan SD
- Subjects
- Animals, Enzyme-Linked Immunosorbent Assay, Europe, Food Analysis methods, Humans, Mass Spectrometry, Allergens analysis, Food adverse effects, Food Analysis standards, Food Hypersensitivity immunology
- Abstract
Food allergy affects up to 6% of Europeans. Allergen identification is important for the risk assessment and management of the inadvertent presence of allergens in foods. The VITAL® initiative for voluntary incidental trace allergen labeling suggests protein reference doses, based on clinical reactivity in food challenge studies, at or below which voluntary labelling is unnecessary. Here, we investigated if current analytical methodology could verify the published VITAL® 2.0 doses, that were available during this analysis, in serving sizes between 5 and 500 g. Available data on published and commercial ELISA, PCR and mass spectrometry methods, especially for the detection of peanuts, soy, hazelnut, wheat, cow's milk and hen's egg were reviewed in detail. Limit of detection, quantitative capability, matrix compatibility, and specificity were assessed. Implications by the recently published VITAL® 3.0 doses were also considered. We conclude that available analytical methods are capable of reasonably robust detection of peanut, soy, hazelnut and wheat allergens for levels at or below the VITAL® 2.0 and also 3.0 doses, with some methods even capable of achieving this in a large 500 g serving size. Cow's milk and hen's egg are more problematic, largely due to matrix/processing incompatibility. An unmet need remains for harmonized reporting units, available reference materials, and method ring-trials to enable validation and the provision of comparable measurement results., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
42. Drivers' Braking Behavior Affected by Cognitive Distractions: An Experimental Investigation with a Virtual Car Simulator.
- Author
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Baldo N, Marini A, and Miani M
- Abstract
In this study, a cohort of 78 university students performed a driving experience in a virtual urban scenario, by means of a car driving simulator, to examine effects of a planned hands-free mobile phone conversation on young drivers' braking behaviors. To this aim, a control group was left free to drive without any imposed cognitive task. An experimental group faced the same scenario while engaged in a phone call. The conversation via earphones was arranged to diminish the amount of cognitive resources allocated to the driving task. For both groups, the analyses focused on the moment at which a child entered a pedestrian crossing from a sidewalk. The results of a mixed two-way ANOVA showed the presence of a significant difference for distracted and non-distracted drivers with the absence of gender-related differences across the two groups. Distracted participants assumed lower initial speeds, took the first action to stop at shorter distances from the zebra crossing, and had more difficulty in keeping speed variations under control. These findings suggest that the distraction induced by the use of earphones may induce risk compensation behaviors and delay pedestrian perception. Moreover, the effects on the participants' braking behavior suggest that the procedure adopted to increase cognitive load, based on a story retelling, is an effective method to analyze the impact of hands-free cellphone use on driving skills in a car simulation experiment.
- Published
- 2020
- Full Text
- View/download PDF
43. Gut Microbiota-Stimulated Innate Lymphoid Cells Support β-Defensin 14 Expression in Pancreatic Endocrine Cells, Preventing Autoimmune Diabetes.
- Author
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Miani M, Le Naour J, Waeckel-Enée E, Verma SC, Straube M, Emond P, Ryffel B, van Endert P, Sokol H, and Diana J
- Subjects
- Animals, B-Lymphocytes, Regulatory metabolism, Female, Humans, Immunity, Innate, Interleukins metabolism, Islets of Langerhans metabolism, Kaplan-Meier Estimate, Macrophages metabolism, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred NOD, Statistics, Nonparametric, T-Lymphocytes, Regulatory metabolism, Toll-Like Receptor 2 metabolism, Interleukin-22, Diabetes Mellitus, Type 1 immunology, Diabetes Mellitus, Type 1 prevention & control, Gastrointestinal Microbiome immunology, Insulin-Secreting Cells metabolism, Lymphocytes metabolism, Pancreatic Polypeptide-Secreting Cells metabolism, beta-Defensins metabolism
- Abstract
The gut microbiota is essential for the normal function of the gut immune system, and microbiota alterations are associated with autoimmune disorders. However, how the gut microbiota prevents autoimmunity in distant organs remains poorly defined. Here we reveal that gut microbiota conditioned innate lymphoid cells (ILCs) induce the expression of mouse β-defensin 14 (mBD14) by pancreatic endocrine cells, preventing autoimmune diabetes in the non-obese diabetic (NOD) mice. MBD14 stimulates, via Toll-like receptor 2, interleukin-4 (IL-4)-secreting B cells that induce regulatory macrophages, which in turn induce protective regulatory T cells. The gut microbiota-derived molecules, aryl hydrocarbon receptor (AHR) ligands and butyrate, promote IL-22 secretion by pancreatic ILCs, which induce expression of mBD14 by endocrine cells. Dysbiotic microbiota and low-affinity AHR allele explain the defective pancreatic expression of mBD14 observed in NOD mice. Our study reveals a yet unidentified crosstalk between ILCs and endocrine cells in the pancreas that is essential for the prevention of autoimmune diabetes development., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
44. Sweet Killing in Obesity and Diabetes: The Metabolic Role of the BH3-only Protein BIM.
- Author
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Miani M, Elvira B, and Gurzov EN
- Subjects
- Animals, Apoptosis, Autoimmunity, Bcl-2-Like Protein 11 antagonists & inhibitors, Bcl-2-Like Protein 11 chemistry, Diabetes Mellitus diagnosis, Diabetes Mellitus drug therapy, Hepatocytes metabolism, Humans, Insulin metabolism, Insulin Resistance, Insulin-Secreting Cells immunology, Insulin-Secreting Cells metabolism, Insulin-Secreting Cells pathology, Mitochondria metabolism, Molecular Targeted Therapy, Obesity drug therapy, Signal Transduction, Bcl-2-Like Protein 11 metabolism, Diabetes Mellitus etiology, Diabetes Mellitus metabolism, Obesity etiology, Obesity metabolism, Peptide Fragments chemistry, Protein Interaction Domains and Motifs, Proto-Oncogene Proteins chemistry
- Abstract
Diabetes is a metabolic disorder affecting more than 400 million individuals and their families worldwide. The major forms of diabetes (types 1 and 2) are characterized by pancreatic β-cell dysfunction and, in some cases, loss of β-cell mass causing hyperglycemia due to absolute or relative insulin deficiency. The BCL-2 homology 3 (BH3)-only protein BIM has a wide role in apoptosis induction in cells. In this review, we describe the apoptotic mechanisms mediated by BIM activation in β cells in obesity and both forms of diabetes. We focus on molecular pathways triggered by inflammation, saturated fats, and high levels of glucose. Besides its role in cell death, BIM has been implicated in the regulation of mitochondrial oxidative phosphorylation and cellular metabolism in hepatocytes. BIM is both a key mediator of pancreatic β-cell death and hepatic insulin resistance and is thus a potential therapeutic target for novel anti-diabetogenic drugs. We consider the implications and challenges of targeting BIM in the treatment of the disease., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
- Full Text
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45. Pannexin-2-deficiency sensitizes pancreatic β-cells to cytokine-induced apoptosis in vitro and impairs glucose tolerance in vivo.
- Author
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Berchtold LA, Miani M, Diep TA, Madsen AN, Cigliola V, Colli M, Krivokapic JM, Pociot F, Eizirik DL, Meda P, Holst B, Billestrup N, and Størling J
- Subjects
- Animals, Connexins metabolism, Gene Knockdown Techniques, Glucose Intolerance pathology, Humans, Hyperglycemia pathology, Inflammation pathology, Mice, Inbred C57BL, Nitric Oxide Synthase Type II metabolism, Phosphorylation drug effects, Rats, STAT3 Transcription Factor metabolism, Streptozocin, Apoptosis drug effects, Connexins deficiency, Cytokines pharmacology, Glucose Intolerance metabolism, Insulin-Secreting Cells metabolism
- Abstract
Pannexins (Panx's) are membrane proteins involved in a variety of biological processes, including cell death signaling and immune functions. The role and functions of Panx's in pancreatic β-cells remain to be clarified. Here, we show Panx1 and Panx2 expression in isolated islets, primary β-cells, and β-cell lines. The expression of Panx2, but not Panx1, was downregulated by interleukin-1β (IL-1β) plus interferon-γ (IFNγ), two pro-inflammatory cytokines suggested to contribute to β-cell demise in type 1 diabetes (T1D). siRNA-mediated knockdown (KD) of Panx2 aggravated cytokine-induced apoptosis in rat INS-1E cells and primary rat β-cells, suggesting anti-apoptotic properties of Panx2. An anti-apoptotic function of Panx2 was confirmed in isolated islets from Panx2
-/- mice and in human EndoC-βH1 cells. Panx2 KD was associated with increased cytokine-induced activation of STAT3 and higher expression of inducible nitric oxide synthase (iNOS). Glucose-stimulated insulin release was impaired in Panx2-/- islets, and Panx2-/- mice subjected to multiple low-dose Streptozotocin (MLDS) treatment, a model of T1D, developed more severe diabetes compared to wild type mice. These data suggest that Panx2 is an important regulator of the insulin secretory capacity and apoptosis in pancreatic β-cells., (Copyright © 2017 Elsevier B.V. All rights reserved.)- Published
- 2017
- Full Text
- View/download PDF
46. Production and characterization of a Brazilian candidate antigen for Hepatitis E Virus genotype 3 diagnosis.
- Author
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de Almeida Ramos D, Miani M, Pandolfi R, Tondo L, Colli ML, Rosado Spilki F, Rovaris Gardinali N, Alves Pinto M, Kreutz LC, and Frandoloso R
- Subjects
- Amino Acid Sequence, Animals, Base Sequence, Brazil, Cloning, Molecular, Escherichia coli genetics, Escherichia coli metabolism, Hepatitis E virus classification, Hepatitis E virus genetics, Humans, Molecular Sequence Data, Polymerase Chain Reaction, RNA, Viral genetics, RNA, Viral isolation & purification, Rats, Rats, Wistar, Sequence Alignment, Sequence Analysis, RNA, Swine, Swine Diseases, Antigens, Viral immunology, Feces virology, Hepatitis E diagnosis, Hepatitis E virus immunology, Open Reading Frames genetics
- Abstract
Hepatitis E, caused by hepatitis E virus (HEV), is a viral infectious pathology of great importance in the public health. Hepatitis E outbreaks were registered in developing countries with poor or no sanitation, where drinking water was contaminated with fecal material, but also in many industrialized countries probably due to consumption of HEV-positive swine meat. In this study, we present the development and characterization of a recombinant antigen from ORF2 HEV genotype 3. Viral RNA was extracted from swine feces infected with the native virus. A total of 267 residues from the C-terminal ORF2((394-661)) coding sequence were cloned into the pET20a vector and expressed in Escherichia coli ER2566. Recombinant protein was purified by liquid chromatography and the fragment obtained a 98% homology against other human or swine HEV genotype 3 ORF2 sequences. Wistar rats were inoculated with ORF2p, developing antibodies able to recognize both the homologous antigen and the native HEV genotype 3 ORF2 present in infected stool. In parallel, HEV-negative swine were experimentally challenged with HEV genotype 3. ORF2 was detected by PCR 14 days post-inoculation in three-fourth piglets' feces and one week later by dot blot. In conclusion, this study proved the immunogenic and antigenic properties of the recombinant protein ORF2p., (© FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2016
- Full Text
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47. CTSH regulates β-cell function and disease progression in newly diagnosed type 1 diabetes patients.
- Author
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Fløyel T, Brorsson C, Nielsen LB, Miani M, Bang-Berthelsen CH, Friedrichsen M, Overgaard AJ, Berchtold LA, Wiberg A, Poulsen P, Hansen L, Rosinger S, Boehm BO, Ram R, Nguyen Q, Mehta M, Morahan G, Concannon P, Bergholdt R, Nielsen JH, Reinheckel T, von Herrath M, Vaag A, Eizirik DL, Mortensen HB, Størling J, and Pociot F
- Subjects
- Adolescent, Alleles, Animals, Apoptosis genetics, Cathepsin H genetics, Cell Line, Child, Child, Preschool, Diabetes Mellitus, Experimental genetics, Diabetes Mellitus, Experimental pathology, Diabetes Mellitus, Experimental therapy, Diabetes Mellitus, Type 1 genetics, Diabetes Mellitus, Type 1 pathology, Diabetes Mellitus, Type 1 therapy, Gene Expression Regulation genetics, Genotype, Humans, Insulin-Secreting Cells pathology, Mice, Mice, Knockout, Rats, Cathepsin H metabolism, Diabetes Mellitus, Experimental metabolism, Diabetes Mellitus, Type 1 metabolism, Insulin-Secreting Cells metabolism
- Abstract
Over 40 susceptibility loci have been identified for type 1 diabetes (T1D). Little is known about how these variants modify disease risk and progression. Here, we combined in vitro and in vivo experiments with clinical studies to determine how genetic variation of the candidate gene cathepsin H (CTSH) affects disease mechanisms and progression in T1D. The T allele of rs3825932 was associated with lower CTSH expression in human lymphoblastoid cell lines and pancreatic tissue. Proinflammatory cytokines decreased the expression of CTSH in human islets and primary rat β-cells, and overexpression of CTSH protected insulin-secreting cells against cytokine-induced apoptosis. Mechanistic studies indicated that CTSH exerts its antiapoptotic effects through decreased JNK and p38 signaling and reduced expression of the proapoptotic factors Bim, DP5, and c-Myc. CTSH overexpression also up-regulated Ins2 expression and increased insulin secretion. Additionally, islets from Ctsh(-/-) mice contained less insulin than islets from WT mice. Importantly, the TT genotype was associated with higher daily insulin dose and faster disease progression in newly diagnosed T1D patients, indicating agreement between the experimental and clinical data. In line with these observations, healthy human subjects carrying the T allele have lower β-cell function, which was evaluated by glucose tolerance testing. The data provide strong evidence that CTSH is an important regulator of β-cell function during progression of T1D and reinforce the concept that candidate genes for T1D may affect disease progression by modulating survival and function of pancreatic β-cells, the target cells of the autoimmune assault.
- Published
- 2014
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48. Temporal profiling of cytokine-induced genes in pancreatic β-cells by meta-analysis and network inference.
- Author
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Lopes M, Kutlu B, Miani M, Bang-Berthelsen CH, Størling J, Pociot F, Goodman N, Hood L, Welsh N, Bontempi G, and Eizirik DL
- Subjects
- Animals, Cytokines pharmacology, DNA-Binding Proteins genetics, Diabetes Mellitus, Type 1, Humans, Insulin-Secreting Cells drug effects, Interferon-gamma metabolism, Interferon-gamma pharmacology, Islets of Langerhans physiology, Proto-Oncogene Proteins c-ets genetics, Rats, Receptor-Interacting Protein Serine-Threonine Kinase 2 genetics, Reproducibility of Results, Transcription Factors genetics, Cytokines metabolism, Gene Expression Profiling methods, Gene Regulatory Networks, Insulin-Secreting Cells physiology
- Abstract
Type 1 Diabetes (T1D) is an autoimmune disease where local release of cytokines such as IL-1β and IFN-γ contributes to β-cell apoptosis. To identify relevant genes regulating this process we performed a meta-analysis of 8 datasets of β-cell gene expression after exposure to IL-1β and IFN-γ. Two of these datasets are novel and contain time-series expressions in human islet cells and rat INS-1E cells. Genes were ranked according to their differential expression within and after 24 h from exposure, and characterized by function and prior knowledge in the literature. A regulatory network was then inferred from the human time expression datasets, using a time-series extension of a network inference method. The two most differentially expressed genes previously unknown in T1D literature (RIPK2 and ELF3) were found to modulate cytokine-induced apoptosis. The inferred regulatory network is thus supported by the experimental validation, providing a proof-of-concept for the proposed statistical inference approach., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
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49. 1,25-Dihydroxyvitamin D3 curtails the inflammatory and T cell stimulatory capacity of macrophages through an IL-10-dependent mechanism.
- Author
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Korf H, Wenes M, Stijlemans B, Takiishi T, Robert S, Miani M, Eizirik DL, Gysemans C, and Mathieu C
- Subjects
- Animals, Calcitriol metabolism, Cells, Cultured, Chemokines, CXC immunology, Chemokines, CXC metabolism, Diabetes Mellitus, Type 1 immunology, Diabetes Mellitus, Type 1 metabolism, Disease Models, Animal, Female, Inflammation metabolism, Interleukin-10 metabolism, Interleukin-12 Subunit p40 immunology, Interleukin-12 Subunit p40 metabolism, Lymphocyte Activation immunology, Macrophages metabolism, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Nitric Oxide Synthase Type II immunology, Nitric Oxide Synthase Type II metabolism, Receptors, Calcitriol immunology, Receptors, Calcitriol metabolism, T-Lymphocytes metabolism, Tumor Necrosis Factor-alpha immunology, Tumor Necrosis Factor-alpha metabolism, Calcitriol immunology, Inflammation immunology, Interleukin-10 immunology, Macrophages immunology, T-Lymphocytes immunology
- Abstract
The vitamin D receptor (VDR) is a hormone nuclear receptor regulating bone and calcium homeostasis. Studies revealing the expression of VDR on immune cells point toward a role for VDR-dependent signaling pathways in immunity. Here we verified the ability of the natural VDR ligand, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) to interfere in inflammatory and T cell stimulatory capacity of macrophages, in particular within a chronic inflammatory disease features of experimental type 1 diabetes (T1D). We demonstrated that VDR is constitutively expressed in macrophages and both the levels of VDR and its downstream targets, are clearly induced by 1,25(OH)(2)D(3). In control mice, macrophage programming with 1,25(OH)(2)D(3) partially abrogated the activation-provoked expression of IL-12p40, TNFα and iNOS as well as the effector T cell-recruiting chemokines, CXCL9, CXCL10 and CXCL11. Targeting VDR signaling in macrophages counteracted their T-cell stimulatory ability despite essentially unaltered expression of antigen-presenting and costimulatory molecules. Furthermore, even in non-obese diabetic (NOD) mice, where macrophages/monocytes featured a heightened responsiveness toward danger signals and a superior T cell stimulatory capacity, 1,25(OH)(2)D(3) successfully curtailed these basic macrophage-mediated functions. Interestingly, the inhibitory action of the active compound was associated with an IL-10-dependent mechanism since 1,25(OH)(2)D(3)-treatment of IL-10-deficient macrophages failed to reproduce the characteristic repression on inflammatory mediators or T cell proliferation. Combined, these results highlight the possible therapeutic applicability of this natural immunomodulator, due to its ability to counteract macrophage inflammatory and T cell-activating pathways., (Copyright © 2012 Elsevier GmbH. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
50. Mild endoplasmic reticulum stress augments the proinflammatory effect of IL-1β in pancreatic rat β-cells via the IRE1α/XBP1s pathway.
- Author
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Miani M, Colli ML, Ladrière L, Cnop M, and Eizirik DL
- Subjects
- Animals, Apoptosis, Genes, Reporter, Inflammation, Insulinoma metabolism, Male, Microscopy, Fluorescence methods, Models, Biological, NF-kappa B metabolism, RNA Interference, Rats, Rats, Wistar, Regulatory Factor X Transcription Factors, X-Box Binding Protein 1, DNA-Binding Proteins metabolism, Endoplasmic Reticulum metabolism, Endoribonucleases metabolism, Insulin-Secreting Cells cytology, Interleukin-1beta metabolism, Multienzyme Complexes metabolism, Protein Serine-Threonine Kinases metabolism, Transcription Factors metabolism
- Abstract
The prevalence of obesity and type 1 diabetes in children is increasing worldwide. Insulin resistance and augmented circulating free fatty acids associated with obesity may cause pancreatic β-cell endoplasmic reticulum (ER) stress. We tested the hypothesis that mild ER stress predisposes β-cells to an exacerbated inflammatory response when exposed to IL-1β or TNF-α, cytokines that contribute to the pathogenesis of type 1 diabetes. INS-1E cells or primary rat β-cells were exposed to a low dose of the ER stressor cyclopiazonic acid (CPA) or free fatty acids, followed by low-dose IL-1β or TNF-α. ER stress signaling was inhibited by small interfering RNA. Cells were evaluated for proinflammatory gene expression by RT-PCR and ELISA, gene reporter activity, p65 activation by immunofluorescence, and apoptosis. CPA pretreatment enhanced IL-1β- induced, but not TNF-α-induced, expression of chemokine (C-C motif) ligand 2, chemokine (C-X-C motif) ligand 1, inducible nitric oxide synthase, and Fas via augmented nuclear factor κB (NF-κB) activation. X-box binding protein 1 (XBP1) and inositol-requiring enzyme 1, but not CCAAT/enhancer binding protein homologous protein, knockdown prevented the CPA-induced exacerbation of NF-κB-dependent genes and decreased IL-1β-induced NF-κB promoter activity. XBP1 modulated NF-κB activity via forkhead box O1 inhibition. In conclusion, rat β-cells facing mild ER stress are sensitized to IL-1β, generating a more intense and protracted inflammatory response through inositol-requiring enzyme 1/XBP1 activation. These observations link β-cell ER stress to the triggering of exacerbated local inflammation.
- Published
- 2012
- Full Text
- View/download PDF
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