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Traditionally, regulations employ semi-probabilistic methods with partial safety factors to control design limits. Calibrating these partial safety factors involves estimating the target reliability level and optimizing the partial safety factor values in order to minimize the deviation of the safety index between the considered design scenarios and the target value. This procedure necessitates performing a demanding amount of reliability analyses and is often carried out for simplified design situations. Therefore, high computational costs must be accepted for design problems formulated with complex computational models. This study implements a meta-modeling approach based on active learning in the partial safety calibration procedure, enabling its application to computationally intensive problems. Subsequently, the approach is applied to the running safety of ballasted high-speed railway bridges. This limit state implicitly accounts for the phenomenon of ballast destabilization, the occurrence of which disturbs the load path from the rail level to the bridge structure. The dramatic increase in train operating speeds in recent decades has increased the possibility of this design limit state being violated due to resonance. Despite the evident safety concerns, the adopted safety factors appear to be solely based on engineering judgments rather than calibration through higher-level reliability analysis. Therefore, the proposed calibration method is employed to determine the corresponding partial safety factors for various maximum allowable operating train speeds. The newly calibrated partial safety factors allow for a permissible maximum vertical acceleration of the bridge deck approximately 25% higher than the conventional design approaches. Therefore, incorporating these factors into the design procedure may lead to the construction of lighter bridges., QC 20240115

The operational safety of high-speed trains traversing ballasted bridges is contingent upon the prevention of the ballast destabilization, which can interrupt load transfer from the rail to the bridge. Current design regulations indirectly address this limit-state by specifying a threshold value for the vertical acceleration of the superstructure. This value represents the condition at which the inertial forces induced by train passage exceed the resistive forces. However, this approach is based on limited experimental data and the influence of numerous parameters remains unexplored. As a result, reliability analyses pertaining to running safety are hampered by a lack of knowledge, leading to greater epistemic uncertainties. In this study, the impact of such uncertainties on this dynamic system is investigated using surrogate-based Imprecise Structural Reliability Analysis (ISRA). For this purpose, parametric probability boxes are used to represent lower and upper bounds of the cumulative distribution function for basic random variables with epistemic uncertainties and surrogate models are adaptively trained to reduce computational costs. The obtained results show that neglecting the influence of epistemic uncertainties can lead to permissible operating train speed higher than the speed corresponding to the desired reliability level. In this study, an overestimation of about 13% was observed on average. Furthermore, the rough analyses carried out show that taking epistemic uncertainties into account can lead to a reduction of the system characteristic safety factor by up to 30%. This significant reduction underlines the importance of expanding the available knowledge on the phenomenon of ballast instability., QC 20240108

In this study, the influence of Soil-Structure Interaction (SSI) on the dynamic behavior of a three-span concrete slab railway bridge with integrated retaining walls is investigated. The bridge is subjected to controlled excitations using a hydraulic actuator with different frequencies and load amplitudes. A 3D model of the railway bridge-soil system is implemented and calibrated using the experimental frequency response functions at each sensor location. A soil-free model is also created to compare with the calibrated model. It is observed that the dynamic behavior of the railway bridge is substantially altered by the presence of the surrounding soils, and neglecting SSI can lead to underestimation and inaccurate results. Additionally, the calibrated model is used for further train-passage analyses. For the studied bridge, neglecting SSI increases the maximum acceleration response of the bridge during high-speed train passages from 5.5 m/s2 up to 14.5 m/s2. It is also shown that the response of the bridge during train passage is predominantly influenced by its first bending mode, with higher modes inducing no discernible effect. Finally, parametric studies are performed in order to study the uncertainties related to the soil properties., QC 20240108

In this paper, the dynamic behavior of four railway bridges with integrated retaining walls, considering the effect of soil-structure interaction (SSI), is investigated both numerically and experimentally. Among these bridges, two are single-span, and the remaining two are three-span. Each bridge is equipped with numerous accelerometers and is excited by a hydraulic actuator across various frequencies. Full 3D solid Finite Element (FE) models incorporating the railway bridges and surrounding soils are developed and calibrated using the Frequency Response Functions (FRFs) from each accelerometer. Furthermore, simplified 3D solid and 2D beam models are created for each railway bridge, incorporating springs and dashpots to account for the effect of surrounding soils. The values for these springs and dashpots are obtained from simple equations, except for the impact of the backfill soil in the simplified 2D beam models, which are derived from the impedance functions of the soil medium. The performance of these simplified models is then compared to the calibrated 3D models in terms of modal properties of the first bending mode and the maximum acceleration response during highspeed train passages. The results indicate that the simplified models closely align with the calibrated models in terms of modal properties and high-speed train passage response and can be used as simple and efficient alternatives for practical usage in bridge design., QC 20240912

The assessment of running safety of railway bridges is conditioned by the Eurocode EN 1990 A2 by limiting vertical deck acceleration. On ballastless track bridges, this value is 5 m/s2. The background for this value is not clear, and it is believed that it originates in the application of an arbitrary safety factor of 2 on accelerations around 1 g to avoid loss of wheel–rail contact. However, studies show that the level of acceleration may not be directly related to the occurrence of derailment. In this work, this idea is expanded by assessing both vertical and lateral dynamics, comparing acceleration values with the Unloading and Nadal derailment criteria. The parametric study is comprised of a set of five representative single-track slab bridges with spans between 10 m and 30 m with two levels of track irregularities, corresponding to a well-maintained track and an Alert limit situation. A three-dimensional articulated FE model based on the load properties of the EN 1991-2 High-Speed Load Model A is presented, crossing the bridges at running speeds from 150 km/h to 400 km/h. Despite the complexity of the models, a large amount (1461) of full 3D train–track–bridge interaction dynamic analyses are performed, to produce a data set representative of the phenomenon. Results show a weak correlation between the criteria and deck acceleration (maximum r2 of 0.47 for Unloading and 0.15 for Nadal). Additionally, track quality is shown to be a more conditioning factor for derailment when compared to resonance. This work contributes to discussing the thesis of using deck acceleration as an indicator of running safety, considering lateral dynamics., QC 20240703

This paper studies analytically the steady state response of the generalised coupled modulated pedestrian-beam system. Pedestrians are considered as modulated spring–mass–damper systems with and without a partially attached mass to the structural system. The governing non-dimensional parameters that defined the system's behaviour are found in an analytical framework. An application of the expression is developed, and a parametric analysis is presented considering a reference pedestrian. The frequency shift effect and the dynamic amplification factor, DAFHSI, of the coupled pedestrian-beam system are characterised. The main contribution of this paper is to provide a closed-form solution of the generalised coupled modulated pedestrian-beam system. This solution can consider any distribution of pedestrians and any definition of the pedestrian SDOF properties. A simple and representative example is presented to demonstrate the utility of the found expression in the context of footbridge dynamics., QC 20231006

Operating high-speed trains imposes excessive vibrations to bridges raising concerns about their safety. In this context, it was shown that some conventional design methods such as those related to the running safety suffer from a vague scientific background questioning their reliability or optimality. Therefore, the current article is devoted to updating the conventional design methodology, using Reliability-Based Design Optimization (RBDO) to propose the minimum allowable mass and stiffness which assures satisfying the target reliability. These proposed minimum design values can conceptually replace the conventional partial safety factor-based design method for running safety without the need for dynamic analysis. If the mass and stiffness resulting from the control of other limit states meet the proposed minimum values, the desired target reliability for running safety will be assured. This is achieved by adaptively training Kriging meta-models as a surrogate for the computational models decoupling the RBDO problem. In this regard, a new stopping criteria is proposed using mis-classification ratio of the cross-validated model; which reduces the generalization error of the trained meta-model and consequently the estimated failure probability. Moreover, due to the dependence of the design variables, the Copula concept is used to refine the augmented space and reformulate the RBDO problem., QC 20230710

In this paper, a closed-form solution of the moving harmonic load problem for continuous Euler- Bernoulli beam systems is presented. The generality of the boundary conditions is taken into account by solving the characteristic equation of the system, obtaining its natural frequencies and mode shapes. The undetermined coefficient method is applied to solve the governing differential equation of motion, determining the base functions of the solution space of the problem. For vertical vibrations, three numerical examples of footbridges are presented. The main contribution of this paper is to provide the closed-form solution of the moving harmonic load problem applied to continuous footbridges including the phase angle in the load definition. In this way, it is possible to find the solution in the time domain of the harmonic component of any load spectra., QC 20220216

Railway bridges may experience large vibrations from passing trains if the load frequency of the train coincides with the natural frequency of the bridge. For long and slender bridges on high-speed lines, this may occur within the range of the operational speed. In combination with low inherent damping of the bridge, excessive vibrations during train passage may pose both safety risks and riding comfort issues. One approach to mitigate the response of railway bridges and ensure resilience is to install external damping devices. In this chapter, a generalized theoretical model of a bridge-viscous damper system is derived based on the rotation of the bridge deck around the neutral axis. The dampers are installed horizontally in the vicinity of the roller bearing. A setup for a real-time hybrid simulation is described, in which a numerical model of a bridge is connected to a large-scale magnetorheological damper. From both cases, it is found that the vertical bridge deck acceleration could be significantly reduced, indicating that the proposed installation of the damping devices is applicable., QC 20230523

The transition from preclinical biological drug development into clinical trials requires an efficient upscaling process. In this context, bispecific antibody drugs are particularly challenging due to their propensity to form aggregates and generally produce low titers. Here, the upscaling process for a tetravalent bispecific antibody expressed by a piggyBac transposon-mediated stable HEK293 cell pool has been evaluated. The project was performed as a case study at Testa Center, a non-GMP facility for scale-up testing of biologics in Sweden, and encompassed media adaptation strategies, fed-batch optimization and a novel antibody purification technology. The cell pool was adapted to different culture media for evaluation in terms of cell viability and titers compared to its original Expi293 Expression Medium. These parameters were assessed in both sequential stepwise adaption and direct media exchanges. By this, a more affordable medium was identified that did not require stepwise adaptation and with similar titers and viability as in the Expi293 Expression Medium. Fed-batch optimizations resulted in culture densities reaching up to 20 x 106 viable cells/mL with over 90 % viability 12 days postinoculum, and antibody titers three times higher than corresponding batch cultures. By implementing a novel high-speed protein A fiber technology (Fibro PrismA) with a capture residence time of only 7.5 s, 8 L of supernatant could be purified in 4.5 h without compromising the purity, structural integrity and function of the bispecific antibody. Results from this study related to medium adaptation and design of fed-batch protocols will be highly beneficial during the forthcoming scale-up of this therapeutic antibody., QC 20210916

The objective of this study is to evaluate the vibratory response of two-span continuous beams subjected tomoving loads and, in particular, to investigate the maximum resonance and cancellation of resonance phenomena.The main practical interest is the evaluation of the maximum acceleration response in railway bridges,which is one of the most demanding Serviceability Limit States for traffic safety according to current regulations.Two-span continuous bridges, in their simplest version (i.e. uniform identical spans), present antisymmetric andsymmetric modes with closely spaced natural frequencies, leading to a more involved dynamic behaviour thanthat of simply-supported bridges. First, the free vibration response of a Bernoulli-Euler two-span beam after thepassage of a single load at constant speed is formulated analytically, and non-dimensional speeds leading tocancellation or maximum response in free vibration are obtained for each mode. Then, these conditions areequated to resonant speeds induced by equidistant load series, and span length-to-characteristic distance ratioscausing cancelled out resonances, or remarkably prominent ones, are obtained. Based on the previous derivations,a methodology for detecting which could be the most aggressive trains for a particular structure based onpure geometrical considerations is discussed. Finally, the applicability of the theoretical derivations is shownthrough the numerical analysis of two real bridges belonging to the Swedish railway network., QC 20200916

The Caribbean and Western Atlantic region hosts one of the world’s most diverse geopolitical regions and a unique marine biota distinct from tropical seas in the Pacific and Indian Oceans. While this region varies in human population density, GDP and wealth, coral reefs, and their associated ecosystem services, are central to people’s livelihoods. Unfortunately, the region’s reefs have experienced extensive degradation over the last several decades. This degradation has been attributed to a combination of disease, overfishing, and multiple pressures from other human activities. Furthermore, the Caribbean region has experienced rapid ocean warming and acidification as a result of climate change that will continue and accelerate throughout the 21st century. It is evident that these changes will pose increasing threats to Caribbean reefs unless imminent actions are taken at the local, regional and global scale. Active management is required to sustain Caribbean reefs and increase their resilience to recover from acute stress events. Here, we propose local and regional solutions to halt and reverse Caribbean coral reef degradation under ongoing ocean warming and acidification. Because the Caribbean has already experienced high coral reef degradation, we suggest that this region may be suitable for more aggressive interventions than might be suitable for other regions. Solutions with direct ecological benefits highlighted here build on existing knowledge of factors that can contribute to reef restoration and increased resilience in the Caribbean: (1) management of water quality, (2) reduction of unsustainable fishing practices, (3) application of ecological engineering, and (4) implementing marine spatial planning. Complementary socioeconomic and governance solutions include: (1) increasing communication and leveraging resources through the establishment of a regional reef secretariat, (2) incorporating reef health and sustainability goals into the blue economy plans for