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Funding: We thank Liliana Bento for valuable assistance in formatting the manuscript. This article was supported by the LYSOCIL project. This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 811087. CGA has funding from Maratona da Saúde 2016 and Fundaçao para a Ciência e a Tecnologia ˜ , I.P. (CEECIND/00410/2017). FMP is a Wellcome Investigator in Science and a Royal Society Wilson merit award holder. Since the discovery of lysosomes more than 70 years ago, much has been learned about the functions of these organelles. Lysosomes were regarded as exclusively degradative organelles, but more recent research has revealed that they play essential roles in several other cellular functions, such as nutrient sensing, intracellular signalling, and metabolism. Methodological advances played a key part in generating our current knowledge about the biology of this multifaceted organelle. In this review, we cover current methods used to analyse lysosome morphology, positioning, motility, and function. We highlight the principles behind these methods, the methodological strategies, and their advantages and limitations. To extract accurate information and avoid misinterpretations, we discuss the best strategies to identify lysosomes and assess their characteristics and functions. With this review, we aim to stimulate an increase in the quantity and quality of research on lysosomes and further ground-breaking discoveries on an organelle that continues to surprise and excite cell biologists. publishersversion published

Background:Nonlinear behaviour of beam-column joints might significantly affect seismic performance of typical existing buildings, especially in the case of poor structural detailing, as the lack of an adequate transverse reinforcement in the joint panel or deficiencies in the anchorage details. A very limited number of studies deals with beam-column joints reinforced with plain hook-ended longitudinal bars, widespread in Mediterranean building stock, or with the analysis of local aspects, such as the evaluation of joint shear strain capacity. The almost totality of the models proposed in the literature for simulating the cyclic behaviour of RC joints was calibrated by means of tests performed on elements with deformed bars. Such models may be not suitable for elements with hook-ended plain bars, due to their peculiarities in terms of failure mode and concrete-to-steel interaction mechanisms. Objective:An empirical macro-modeling approach is proposed in this work for exterior unreinforced joints with hook-ended plain bars, suitable for extensive nonlinear analyses. Methods:A dedicated database of experimental tests is first collected. Based on this dataset, a shear strength model is developed. The joint panel constitutive parameters are also defined to reproduce the cyclic experimental joint shear stress-strain behaviour. Results:The whole modeling approach is validated through the comparison with the collected experimental data. It well reproduces the global response, in terms of elastic stiffness, global deformability, softening stiffness, unloading and reloading stiffness degradation and pinching effect for all the investigated tests. Conclusion:The proposed model thus results reliable for the investigated typology of beam-column joints.

The extension of the damages observed after the last major earthquakes shows that the seismic risk mitigation of infilled reinforced concrete structures is a paramount topic in seismic prone regions. In the assessment of existing structures and the design of new ones, the infill walls are considered as nonstructural elements by most of the seismic codes and, generally, comprehensive provisions for practitioners are missing. However, nowadays, it is well recognized by the community the importance of the infills in the seismic behaviour of the reinforced concrete structures. Accurate modelling strategies and appropriate seismic assessment methodologies are crucial to understand the behaviour of existing buildings and to develop efficient and appropriate mitigation measures to prevent high level of damages, casualties, and economic losses. The development of effective strengthening solutions to improve the infill seismic behaviour and proper analytical formulations that could help design engineers are still open issues, among others, on this topic. The main aim of this paper is to provide a state-of-the-art review concerning the typologies of damages observed in the last earthquakes where the causes and possible solutions are discussed. After that, a review of in-plane and out-of-plane testing campaigns from the literature on infilled reinforced concrete frames are presented as well as their relevant findings. The most common strengthening solutions to improve the seismic behaviour are presented, and some examples are discussed. Finally, a brief summary of the modelling strategies available in the literature is presented.