Comparison of plane mirror vs retroreflector performance for laser-self-mixing displacement sensors

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Seismic Assessment and Strengthening Interventions of Atop Single-Block Rocking Elements in Monumental Buildings: the Case Study of the San Felice sul Panaro Fortress

The paper describes the seismic assessment of the San Felice sul Panaro Fortress (Italy), focusing the attention on the activation of the out-of-plane response of the North walkway, characterized by the presence of an apparatus of merlons which highlighted a significant damage after the Emilia earthquake (2012). Nonlinear kinematic analyses have been performed, referring to a macro-block model and considering both the original configuration and two different possible strengthened strategies. For the definition of the seismic input in terms of floor spectra, the analyses also benefitted from the results obtained for the global response through a detailed 3D model of the whole fortress. The results were coherent with the observed damage after the seismic event, highlighting in this way the reliability of the adopted modelling strategies and analysis method, and allowed to outline possible strengthening solutions targeted to minimize the impact on the monument and guarantee its preservation

Towards an Ontological Modelling of Preference Relations

Preference relations are intensively studied in Economics, but they are also approached in AI, Knowledge Representation, and Conceptual Modelling, as they provide a key concept in a variety of domains of application. In this paper, we propose an ontological foundation of preference relations to formalise their essential aspects across domains. Firstly, we shall discuss what is the ontological status of the relata of a preference relation. Secondly, we investigate the place of preference relations within a rich taxonomy of relations (e.g. we ask whether they are internal or external, essential or contingent, descriptive or nondescriptive relations). Finally, we provide an ontological modelling of preference relation as a module of a foundational (or upper) ontology (viz. OntoUML). The aim of this paper is to provide a sharable foundational theory of preference relation that foster interoperability across the heterogeneous domains of application of preference relations

Strategies for Improved pDNA Loading and Protection Using Cationic and Neutral LNPs with Industrial Scalability Potential Using Microfluidic Technology

Purpose: In recent years, microfluidic technologies have become mainstream in producing gene therapy nanomedicines (NMeds) following the Covid-19 vaccine; however, extensive optimizations are needed for each NMed type and genetic material. This article strives to improve LNPs for pDNA loading, protection, and delivery, while minimizing toxicity. Methods: The microfluidic technique was optimized to form cationic or neutral LNPs to load pDNA. Classical “post-formulation” DNA addition vs “pre” addition in the aqueous phase were compared. All formulations were characterized (size, homogeneity, zeta potential, morphology, weight yield, and stability), then tested for loading efficiency, nuclease protection, toxicity, and cell uptake. Results: Optimized LNPs formulated with DPPC: Chol:DOTAP 1:1:0.1 molar ratio and 10 μg of DOPE-Rhod, had a size of 160 nm and good homogeneity. The chemico-physical characteristics of cationic LNPs worsened when adding 15 μg/mL of pDNA with the “post” method, while maintaining their characteristics up to 100 μg/mL of pDNA with the “pre” addition remaining stable for 30 days. Interestingly, neutral LNPs formulated with the same method loaded up to 50% of the DNA. Both particles could protect the DNA from nucleases even after one month of storage, and low cell toxicity was found up to 40 μg/mL LNPs. Cell uptake occurred within 2 hours for both formulations with the DNA intact in the cytoplasm, outside of the lysosomes. Conclusion: In this study, the upcoming microfluidic technique was applied to two strategies to generate pDNA-LNPs. Cationic LNPs could load 10x the amount of DNA as the classical approach, while neutral LNPs, which also loaded and protected DNA, showed lower toxicity and good DNA protection. This is a big step forward at minimizing doses and toxicity of LNP-based gene therapy

Damage and vulnerability analysis of URM churches after the Canterbury earthquake sequence 2010-2011

The Canterbury earthquake sequence, in 2010-2011, has highlighted once again the vulnerability ofmonumental structures, in particular churches, and the importance of reducing their risk from an economic, cultural and social point of view. Within this context, detailed analysis is reported of the earthquake-induced damage to a stock of 48 unreinforcedmasonry churches located in the Canterbury Region and the vulnerability analysis of a wider stock of 293 churches located all around New Zealand. New tools were developed forthe assessmentof New Zealand churches. The computation of a new damage grade isproposed, assessed as a proper combination of the damage level to each macroelement, as a step towards the definition of a New Zealand specific damage survey form. Several vulnerability indicators were selected, which are related to easily detectable structural details and geometric dimensions. The collection of such data for the larger set of churches (293) constitutes a useful basis for evaluating the potential impact of future seismic event

Fragility functions for tall URM buildings around early 20th century in Lisbon. Part 1: Methodology and application at building level

The article proposes a procedure for the derivation of fragility functions for unreinforced masonry buildings considering the in-plane and out-of-plane response. Different approaches are considered for the generation of the corresponding fragility functions and for the evaluation of the propagation of uncertainties. The contributions for the dispersion of the fragility functions account for the variability in the definition of the capacity, the aleatory uncertainty in the definition of the seismic demand and the aleatory uncertainty in the definition of the modified/floor response spectrum, when the local mechanisms are located in the upper level of the building. In the end, the individual fragility curves are properly combined in order to define a single fragility curve for the class of buildings. As a case study, the procedure is applied to the assessment of one of the most vulnerable unreinforced masonry buildings constructed in the early 20th century in Lisbon, considering a typical prototype building with five storeys high. Results for a seismic event, as defined in the earthquake-resistant code for Lisbon, indicate that the typical building has about 50% probability of having heavy damage and about 30% probability of collapse.The first author would like to acknowledge the financial support of Fundação para a Ciência e a Tecnologia (FCT, Ministério da Educação e Ciência, Portugal) through the scholarship PD/BD/106076/2015 through the FCT Doctoral Program: Analysis and Mitigation of Risks in Infrastructures, INFRARISK- (http://infrarisk.tecnico.ulisboa.pt)

Strategies for Improved pDNA Loading and Protection Using Cationic and Neutral LNPs with Industrial Scalability Potential Using Microfluidic Technology

Ilaria Ottonelli,1,* Elisa Adani,2,* Andrea Bighinati,2 Sabrina Cuoghi,1 Giovanni Tosi,1,3 Maria Angela Vandelli,1 Barbara Ruozi,1 Valeria Marigo,2,3 Jason Thomas Duskey1 1Nanotech Lab, Te.Far.T.I., Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy; 2Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy; 3Center for Neuroscience and Neurotechnology, Modena, Italy*These authors contributed equally to this workCorrespondence: Jason Thomas Duskey, Nanotech Lab, Te.Far.T.I., Department of Life Sciences, University of Modena and Reggio Emilia, Via Giuseppe Campi 103, Modena, MO, Italy, 41125, Tel +390592058573, Email [email protected] Valeria Marigo, Department of Life Sciences, University of Modena and Reggio Emilia, Via Giuseppe Campi 287, Modena, MO, 41125, Italy, Tel +390592055392, Email [email protected]: In recent years, microfluidic technologies have become mainstream in producing gene therapy nanomedicines (NMeds) following the Covid-19 vaccine; however, extensive optimizations are needed for each NMed type and genetic material. This article strives to improve LNPs for pDNA loading, protection, and delivery, while minimizing toxicity.Methods: The microfluidic technique was optimized to form cationic or neutral LNPs to load pDNA. Classical “post-formulation” DNA addition vs “pre” addition in the aqueous phase were compared. All formulations were characterized (size, homogeneity, zeta potential, morphology, weight yield, and stability), then tested for loading efficiency, nuclease protection, toxicity, and cell uptake.Results: Optimized LNPs formulated with DPPC: Chol:DOTAP 1:1:0.1 molar ratio and 10 μg of DOPE-Rhod, had a size of 160 nm and good homogeneity. The chemico-physical characteristics of cationic LNPs worsened when adding 15 μg/mL of pDNA with the “post” method, while maintaining their characteristics up to 100 μg/mL of pDNA with the “pre” addition remaining stable for 30 days. Interestingly, neutral LNPs formulated with the same method loaded up to 50% of the DNA. Both particles could protect the DNA from nucleases even after one month of storage, and low cell toxicity was found up to 40 μg/mL LNPs. Cell uptake occurred within 2 hours for both formulations with the DNA intact in the cytoplasm, outside of the lysosomes.Conclusion: In this study, the upcoming microfluidic technique was applied to two strategies to generate pDNA-LNPs. Cationic LNPs could load 10x the amount of DNA as the classical approach, while neutral LNPs, which also loaded and protected DNA, showed lower toxicity and good DNA protection. This is a big step forward at minimizing doses and toxicity of LNP-based gene therapy.Keywords: gene therapy, lipid nanoparticles, microfluidics, lipoplexes, DNA deliver

The effectiveness of the Liverpool care pathway in improving end of life care for dying cancer patients in hospital. A cluster randomised trial

<p>Abstract</p> <p>Background</p> <p>Most cancer patients still die in hospital, mainly in medical wards. Many studies in different countries have shown the poor quality of end-of-life care delivery in hospitals. The Program "Liverpool Care Pathway for the dying patient" (LCP), developed in the UK to transfer the hospice model of care into hospitals and other care settings, is a complex intervention to improve the quality of end-of-life care. The results from qualitative and quantitative studies suggest that the LCP Program can improve significantly the quality of end-of-life care delivery in hospitals, but no randomised trial has been conducted till now.</p> <p>Methods and design</p> <p>This is a randomized cluster trial, stratified by regions and matched for assessment period. Pairs of eligible medical wards from different hospitals will be randomized to receive the LCP-I Program or no intervention until the end of the trial. The LCP-I Program will be implemented by a Palliative Care Unit.</p> <p>The assessment of the end-points will be performed for all cancer deaths occurred in the six months after the end of the LCP-I implementation in the experimental wards and, in the same period of time, in the matched control wards. The primary end-point is the overall quality of end-of-life care provided on the ward to dying cancer patients and their families, assessed using the Global Scale of the Italian version of the Toolkit <it>"After-death Bereaved Family Member Interview</it>".</p> <p>Discussion</p> <p>This study can be interpreted as a Phase III trial according to the Medical Research Council Framework. In this study, the effectiveness of a fully defined intervention is assessed by comparing the distribution of the endpoints in the experimental and in the control arm.</p> <p>Research ID</p> <p>RFPS-2006-6-341619</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01081899">NCT01081899</a></p