188 research outputs found
Comparison of plane mirror vs retroreflector performance for laser-self-mixing displacement sensors
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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 âpost-formulationâ DNA addition vs âpreâ 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 Îźg of DOPE-Rhod, had a size of 160 nm and good homogeneity. The chemico-physical characteristics of cationic LNPs worsened when adding 15 Îźg/mL of pDNA with the âpostâ method, while maintaining their characteristics up to 100 Îźg/mL of pDNA with the âpreâ 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 Îźg/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
Microfluidic technology for the production of hybrid nanomedicines
Microfluidic technologies have recently been applied as innovative methods for the production of a variety of nanomedicines (NMeds), demonstrating their potential on a global scale. The capacity to precisely control variables, such as the flow rate ratio, temperature, total flow rate, etc., allows for greater tunability of the NMed systems that are more standardized and automated than the ones obtained by well-known benchtop protocols. However, it is a crucial aspect to be able to obtain NMeds with the same characteristics of the previously optimized ones. In this study, we focused on the transfer of a production protocol for hybrid NMeds (H-NMeds) consisting of PLGA, Cholesterol, and PluronicÂŽ F68 from a benchtop nanoprecipitation method to a microfluidic device. For this aim, we modified parameters such as the flow rate ratio, the concentration of core materials in the organic phase, and the ratio between PLGA and Cholesterol in the feeding organic phase. Outputs analysed were the chemicoâphysical properties, such as size, PDI, and surface charge, the composition in terms of %Cholesterol and residual %PluronicÂŽ F68, their stability to lyophilization, and the morphology via atomic force and electron microscopy. On the basis of the results, even if microfluidic technology is one of the unique procedures to obtain industrial production of NMeds, we demonstrated that the translation from a benchtop method to a microfluidic one is not a simple transfer of already established parameters, with several variables to be taken into account and to be optimized
Optimization of an Injectable Hydrogel Depot System for the Controlled Release of Retinal-Targeted Hybrid Nanoparticles
A drawback in the development of treatments that can reach the retina is the presence of barriers in the eye that restrain compounds from reaching the target. Intravitreal injections hold promise for retinal delivery, but the natural defenses in the vitreous can rapidly degrade or eliminate therapeutic molecules. Injectable hydrogel implants, which act as a reservoir, can allow for long-term drug delivery with a single injection into the eye, but still suffer due to the fast clearance of the released drugs when traversing the vitreous and random diffusion that leads to lower pharmaceutic efficacy. A combination with HA-covered nanoparticles, which can be released from the gel and more readily pass through the vitreous to increase the delivery of therapeutic agents to the retina, represents an advanced and elegant way to overcome some of the limitations in eye drug delivery. In this article, we developed hybrid PLGA-Dotap NPs that, due to their hyaluronic acid coating, can improve in vivo distribution throughout the vitreous and delivery to retinal cells. Moreover, a hydrogel implant was developed to act as a depot for the hybrid NPs to better control and slow their release. These results are a first step to improve the treatment of retinal diseases by protecting and transporting the therapeutic treatment across the vitreous and to improve treatment options by creating a depot system for long-term treatments
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
TweenÂŽ preserves enzyme activity and stability in PLGA nanoparticles
Enzymes, as natural and potentially long-term treatment options, have become one of the most sought-after pharmaceutical molecules to be delivered with nanoparticles (NPs); however, their instability during formulation often leads to underwhelming results. Various molecules, including the TweenŽ polysorbate series, have demonstrated enzyme activity protection but are often used uncontrolled without optimization. Here, poly(lactic-co-glycolic) acid (PLGA) NPs loaded with β-glucosidase (β-Glu) solutions containing TweenŽ 20, 60, or 80 were compared. Mixing the enzyme with TweenŽ pre-formulation had no effect on particle size or physical characteristics, but increased the amount of enzyme loaded. More importantly, NPs made with TweenŽ 20:enzyme solutions maintained significantly higher enzyme activity. Therefore, TweenŽ 20:enzyme solutions ranging from 60:1 to 2419:1 mol:mol were further analyzed. Isothermal titration calorimetry analysis demonstrated low affinity and unquantifiable binding between TweenŽ 20 and β-Glu. Incorporating these solutions in NPs showed no effect on size, zeta potential, or morphology. The amount of enzyme and TweenŽ 20 in the NPs was constant for all samples, but a trend towards higher activity with higher molar rapports of TweenŽ 20:β-Glu was observed. Finally, a burst release from NPs in the first hour with TweenŽ:β-Glu solutions was the same as free enzyme, but the enzyme remained active longer in solution. These results highlight the importance of stabilizers during NP formulation and how optimizing their use to stabilize an enzyme can help researchers design more efficient and effective enzyme loaded NPs
Three-dimensional simultaneous strainâvolume analysis describes left ventricular remodelling and its progression: a pilot study
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
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