Luis Sousa

Human umbilical cord tissue-derived mesenchymal stromal cells attenuate remodeling after myocardial infarction by proangiogenic, antiapoptotic, and endogenous cell-activation mechanisms.

IntroductionAmong the plethora of cells under investigation to restore a functional myocardium, mesenchymal stromal cells (MSCs) have been granted considerable interest. However, whereas the beneficial effects of bone marrow MSCs (BM-MSCs) in the context of the diseased heart are widely reported, data are still scarce on MSCs from the umbilical cord matrix (UCM-MSCs). Herein we report on the effect of UCM-MSC transplantation to the infarcted murine heart, seconded by the dissection of the molecular mechanisms at play.MethodsHuman umbilical cord tissue-derived MSCs (UCX®), obtained by using a proprietary technology developed by ECBio, were delivered via intramyocardial injection to C57BL/6 females subjected to permanent ligation of the left descending coronary artery. Moreover, medium produced by cultured UCX® preconditioned under normoxia (CM) or hypoxia (CMH) was collected for subsequent in vitro assays.ResultsEvaluation of the effects upon intramyocardial transplantation shows that UCX® preserved cardiac function and attenuated cardiac remodeling subsequent to myocardial infarction (MI). UCX® further led to increased capillary density and decreased apoptosis in the injured tissue. In vitro, UCX®-conditioned medium displayed (a) proangiogenic activity by promoting the formation of capillary-like structures by human umbilical vein endothelial cells (HUVECs), and (b) antiapoptotic activity in HL-1 cardiomyocytes subjected to hypoxia. Moreover, in adult murine cardiac Sca-1+ progenitor cells (CPCs), conditioned medium enhanced mitogenic activity while activating a gene program characteristic of cardiomyogenic differentiation.ConclusionsUCX® preserve cardiac function after intramyocardial transplantation in a MI murine model. The cardioprotective effects of UCX® were attributed to paracrine mechanisms that appear to enhance angiogenesis, limit the extent of the apoptosis, augment proliferation, and activate a pool of resident CPCs. Overall, these results suggest that UCX® should be considered an alternative cell source when designing new therapeutic approaches to treat MI.

Including Multiple IMTs in the Development of Fragility Functions for Earthquake Loss Estimation

This article presents a proposal for an innovative approach for including multiple intensity measure types (IMTs) in the representation of building fragility. Thousands of nonlinear dynamic analyses are performed in a 2D environment in which reinforced concrete frames are simulated using a Monte Carlo approach, according to geometrical and material variability of typical pre-code reinforced concrete buildings in Portugal. Seismic action variability is foreseen through the selection and scaling of appropriate Spectrum compatible record sets, following the most recent proposals for linking nonlinear dynamic analysis back to probabilistic seismic hazard. A literature review of seismic Intensity Measures is performed, in order to select a number of IMTs capable of representing a comprehensive set of earthquake shaking characteristics. A proposal for multiple IMT based fragility is outlined, whereby variability in structural damage effects along the considered seismic intensity range is accounted for by including the explicative power of an additional set of IMTs.

Energy Efficiency and Seismic Resilience: A Common Approach

To the present date, building retrofit and enhancement interventions tend to focus on either energy efficiency or seismic resilience techniques, highlighting the lack of consistent language and understanding across both fields, as well as the disconnection among stakeholders that arises from the development of seismic risk mitigation independently of sustainable development goals. Although extensive know-how can be identified in both areas, efforts for its joint consideration presented in the literature are based on the evaluation of environmental impacts of expected repairs due to seismic action over a period of time, neglecting the potential of energy efficiency enhancements and, more importantly, the possible benefits of an integrated investment strategy. This chapter presents a proposal for the integrated assessment of energy efficiency and earthquake resilience, according to which environmental and seismic impact metrics are translated into common financial decision-making variables. In this context, similarly to what is a common practice when evaluating the energy and environmental performance of buildings, discrete classes of both earthquake resilience and energy efficiency are proposed, providing a consistent proxy for building classification—green and resilient indicator (GRI)—as a function of mutual performance parameters. The findings of this chapter highlight the fact that it is possible to directly compare energy efficiency and seismic resilience from a common point of view, as it is plausible to assume the green and resilient counterparts of the GRI classes as a proxy for investment return potential. In addition, it is verified that the benefit of a given intervention can only be maximized up to the point in which an additional investment does not result in increased performance. Thus, an integrated approach shall always be advantageous with respect to the investment in only earthquake resiliency or energy efficiency, devising an investment strategy in a way that simultaneously maximizes “individual” benefits and its integrated result.

Using Resilience Indicators in the Prediction of Earthquake Recovery

This paper presents a probabilistic methodology for the prediction of post-earthquake community recovery over time, based on a set of socioeconomic resilience parameters and a post-earthquake damage indicator. Pre-existing socioeconomic conditions are widely associated with the ability of a community to recover following an earthquake and, therefore, should be considered in a recovery prediction model. The city of Napa, California and the monitored recovery from the 2014 South Napa earthquake were used as a case study for the development and validation of the proposed methodology. The documentation of the recovery, which is herein associated with the recovery of the building stock, was accomplished via field surveys over a period of 18 months following the event. In addition to community-level recovery predictions in different areas over time, the methodology allows for the identification of the pre-existing socioeconomic parameters that most significantly affect the recovery trajectory. Thus, emergency managers can identify critical areas that take longer to recover, as well as identify strengths and weaknesses of their communities and respectively promote or address issues that facilitate recovery.

Hazard Disaggregation and Record Selection for Fragility Analysis and Earthquake Loss Estimation

Economic losses and collapse probability are critical measures for evaluating the earthquake risk of existing buildings. In this context, this study sheds light on several problems and limitations in current practice of hazard-consistent ground-motion selection and fragility analysis, focusing on the impact that (commonly assumed) approximations in disaggregation outputs have on the aforementioned risk metrics, as opposed to an exact solution. These issues are investigated for several building classes, seismicity models and ground motion prediction equations (GMPE), for a site in the city of Lisbon (Portugal). It is observed that only an exact (i.e., rupture-by-rupture) disaggregation can lead to satisfactory results in terms of accuracy, when limit state criteria are not structure-specific. On the other hand, an approximate method is proposed, which still leads to statistically valid results regardless of the chosen structural class, seismicity model or GMPE.

Development of a Fragility Model for Moment-frame RC buildings in Portugal

This study presents the development of a set of fragility functions for six reinforced concrete building typologies, categorized based on the date of construction (which has a direct relation with the design code level) and number of storeys (height of the building). The structural fragility of the Portuguese building stock has been the target of only limited investigation in recent years and moreover, the existing studies relied mainly in simplified methodologies which might not be sufficient to represent the structural characteristics of the RC building typologies in Portugal. An analytical methodology was adopted, in which thousands of nonlinear dynamic analyses were performed on 2D moment resisting frames with masonry infills, using one hundred ground motion records as much as possible compatible with the Portuguese tectonic environment. The generation of the structural models was carried out using the probabilistic distribution of a set of geometric and material properties, compiled based on information gathered from a large sample of drawings and technical specifications of typical Portuguese reinforced concrete buildings, located in various regions in the country. Various key aspects in the development of the fragility model are investigated herein, such as the selection of the ground motion records, the definition of the damage criterion and the evaluation of dynamic (i.e. period of vibration) parameters of the frames. The resulting fragility model can be applied directly in earthquake loss assessment, which is a fundamental tool for the development of risk mitigation actions.