Research on foundation response to seismic shaking has shown that full mobilisation of bearing capacity and the promotion of rocking foundation response may be beneficial for structural integrity – ...particularly in the case of seismic motions that exceed design limits. Full mobilisation of foundation bearing capacity acts as a safety valve, limiting the inertia loading on the structure. While most research has focused on rocking shallow or embedded foundations, a rocking pile group foundation has attracted much less attention. Today, the growing need for retrofit of existing structures, which were typically designed and constructed long before the adoption of modern seismic design provisions, makes such a rocking pile group design an appealing solution, as it allows optimisation (or even complete avoidance) of foundation retrofit, which can be a major operation, especially in dense urban environments. Compared to the bearing capacity of surface shallow or embedded foundations, the failure modes of a rocking pile group are more complex. They may involve structural damage below the ground level, which is perceived as something to avoid, as it is difficult to repair or even detect. To shed more light on the problem, the present study develops a finite element (FE) model of an idealised yet realistic single bridge pier supported by a rocking 2x2 pile group. The FE model employs a carefully calibrated and thoroughly validated kinematic hardening model for the soil, combined with the concrete damaged plasticity (CDP) model for the reinforced (RC) piles and pier. The FE model is subjected to pushover and preliminary dynamic time history analysis. It is shown that the rocking pile group exhibits a ductile response.
Although early detection of toxicant induced kidney injury during drug development and chemical safety testing is still limited by the lack of sensitive and reliable biomarkers of nephrotoxicity, ...omics technologies have brought enormous opportunities for improved detection of toxicity and biomarker discovery. Thus, transcription profiling has led to the identification of several candidate kidney biomarkers such as kidney injury molecule (Kim-1), clusterin, lipocalin-2, and tissue inhibitor of metalloproteinase 1 (Timp-1), and metabonomic analysis of urine is increasingly used to indicate biochemical perturbations due to renal toxicity. This study was designed to assess the value of a combined 1H-NMR and gas chromatography–mass spectrometry (GC-MS) metabonomics approach and a set of novel urinary protein markers for early detection of nephrotoxicity following treatment of male Wistar rats with gentamicin (60 and 120 mg/kg bw, sc) for 7 days. Time- and dose-dependent separation of gentamicin-treated animals from controls was observed by principal component analysis of 1H-NMR and GC-MS data. The major metabolic alterations responsible for group separation were linked to the gut microflora, thus related to the pharmacology of the drug, and increased glucose in urine of gentamicin-treated animals, consistent with damage to the S1 and S2 proximal tubules, the primary sites for glucose reabsorption. Altered excretion of urinary protein biomarkers Kim-1 and lipocalin-2, but not Timp-1 and clusterin, was detected before marked changes in clinical chemistry parameters were evident. The early increase in urine, which correlated with enhanced gene and protein expression at the site of injury, provides further support for lipocalin-2 and Kim-1 as sensitive, noninvasive biomarkers of nephrotoxicity.
Summary
The paper studies the performance of a typical overpass bridge, with continuous deck and monolithic pier‐deck connections, subjected to strike‐slip faulting. A three‐dimensional (3D) finite ...element (FE) model of the entire bridge–foundation–abutment–soil system is developed, accounting for soil, structure and geometric nonlinearities. Soil behaviour is simulated with a thoroughly validated strain softening constitutive model. The concrete damaged plasticity (CDP) model is implemented for piers, accounting for the interaction between axial force N, bending moment M, shear force Q and torsion T (NMQT); the model is validated against experimental results from the literature. The location of the fault rupture is parametrically investigated, confirming the vulnerability of indeterminate structural systems to large tectonic deformation. The deck is shown to sustain both in‐plane and out‐of‐plane bending moments, as well as torsion; the piers are subjected to biaxial bending, shear and torsion. The response is highly dependent on the location of the fault rupture, emphasizing the need to develop cost‐effective modelling techniques. Four such techniques are developed (with and without decoupling) and comparatively assessed using the detailed 3D FE model as benchmark. The best prediction is achieved by a coupled model, which includes the bridge superstructure, detailed 3D modelling of the soil‐foundation system only for the pier directly affected by the fault, and nonlinear springs representing the foundations of all other piers. The proposed technique offers a computationally efficient means to parametrically analyse long multispan bridges subjected to faulting, for which full 3D FE modelling is impractical.
Problems for which it is impossible to make a precise causal prediction are commonly tackled with statistical analysis. Although fairly simple, the problem of a rocking block on a rigid base ...subjected to seismic excitation exhibits a fascinating, complex response, making it extremely difficult to validate numerical models against experimental results, thus calling for a statistical approach. In this context, this paper statistically studies the rocking behaviour of rigid blocks, excited by synthetic far‐field ground motions. A total of 50 million analyses are performed, considering rocking blocks of height ranging from 1 to 20 m and slenderness angle ranging from 0.1 to 0.35 rad. The results are used to explore the performance of different ground motion intensity measures (IMs), in terms of their ability to predict the maximum rocking rotation. By comparing the efficiency, sufficiency and proficiency of the IMs, it is found that the peak ground velocity (PGV) performs optimally. Then, fragility curves are constructed using different IMs, concluding again that the PGV is the most efficient IM. Impressively, the fragility curves for different block sizes collapse to a single curve, if a non‐dimensional IM that involves PGV and the block geometry is used. Finally, the results produced on the basis of far‐field synthetic motions are compared to results based on recorded ground motions.
The simplest 3D extension of Housner's planar rocking model is a rocking (wobbling) cylinder allowed to uplift and roll on its circumference, but constrained not to roll out of its initial position. ...The model is useful for the description of bridges that use rocking as a seismic isolation technique, in an effort to save material by reducing the design moment and the size of the foundations. This paper shows that describing wobbling motion in terms of displacements rather than rotations is more useful. It unveils that a remarkable property of planar rocking bodies extends to 3D motion: A small and a large wobbling cylinder of the same slenderness will sustain roughly equal top displacement, as long as they are not close to overturning. This allows for using the response of an infinitely large wobbling cylinder of slenderness α as a proxy to compute the response of all cylinders having the same slenderness, irrespectively of their size. Thus, the dimensionality of the problem is reduced by one. Moreover, this paper shows that the median wobbling response to sets of ground motions can be described as an approximate function of only two non‐dimensional parameters, namely (gtanα/PGA,u/PGD)or (gtanα/PGA,uPGA/PGV2) where u is the top displacement of the wobbling body.
Summary
Recognizing the beneficial effect of nonlinear soil–foundation response has led to a novel design concept, termed ‘rocking isolation’. The analysis and design of such rocking structures ...require nonlinear dynamic time history analyses. Analyzing the entire soil–foundation–structure system is computationally demanding, impeding the application of rocking isolation in practice. Therefore, there is an urgent need to develop efficient simplified analysis methods. This paper assesses the robustness of two simplified analysis methods, using (i) a nonlinear and (ii) a bilinear rocking stiffness combined with linear viscous damping. The robustness of the simplified methods is assessed by (i) one‐to‐one comparison with a benchmark finite element (FE) analysis using a selection of ground motions and (ii) statistical comparison of probability distributions of response quantities, which characterize the time history response of rocking systems. A bridge pier (assumed rigid) supported on a square foundation, lying on a stiff clay stratum, is used as an illustrative example. Nonlinear dynamic FE time history analysis serves as a benchmark. Both methods yield reasonably accurate predictions of the maximum rotation θmax. Their stochastic comparison with respect to the empirical cumulative distribution function of θmax reveals that the nonlinear and the bilinear methods are not biased. Thus, both can be used to estimate probabilities of exceeding a certain threshold value of θ. Developed in this paper, the bilinear method is much easier to calibrate than the nonlinear, offering similar performance.
The InnoMed PredTox consortium was formed to evaluate whether conventional preclinical safety assessment can be significantly enhanced by incorporation of molecular profiling (“omics”) technologies. ...In short-term toxicological studies in rats, transcriptomics, proteomics and metabolomics data were collected and analyzed in relation to routine clinical chemistry and histopathology. Four of the sixteen hepato- and/or nephrotoxicants given to rats for 1, 3, or 14
days at two dose levels induced similar histopathological effects. These were characterized by bile duct necrosis and hyperplasia and/or increased bilirubin and cholestasis, in addition to hepatocyte necrosis and regeneration, hepatocyte hypertrophy, and hepatic inflammation. Combined analysis of liver transcriptomics data from these studies revealed common gene expression changes which allowed the development of a potential sequence of events on a mechanistic level in accordance with classical endpoint observations. This included genes implicated in early stress responses, regenerative processes, inflammation with inflammatory cell immigration, fibrotic processes, and cholestasis encompassing deregulation of certain membrane transporters. Furthermore, a preliminary classification analysis using transcriptomics data suggested that prediction of cholestasis may be possible based on gene expression changes seen at earlier time-points. Targeted bile acid analysis, based on LC-MS metabonomics data demonstrating increased levels of conjugated or unconjugated bile acids in response to individual compounds, did not provide earlier detection of toxicity as compared to conventional parameters, but may allow distinction of different types of hepatobiliary toxicity. Overall, liver transcriptomics data delivered mechanistic and molecular details in addition to the classical endpoint observations which were further enhanced by targeted bile acid analysis using LC/MS metabonomics.
Scope: Furan, a food contaminant formed during heat processing, induces hepatocellular tumors in rodents and high incidences of cholangiocarcinomas in rats even at the lowest dose (2 mg/kg b.w.) ...administered. Initial estimates suggested that human intake of furan may be as high as 3.5 μg/kg b.w./day, indicating a relatively narrow margin of exposure. The aim of this study was to establish dose-response data for cytotoxicity, regenerative cell proliferation and secondary oxidative DNA damage in livers of male F344 rats treated with furan at doses ≤2 mg/kg b.w. for 28 days. Methods and results: No significant signs of hepatotoxicity other than a mild, dose‐dependent increase in serum cholesterol and unconjugated bile acids, and no evidence of oxidative DNA damage were seen. Histopathological alterations and proliferative changes were restricted to subcapsular areas of the left and caudate liver lobes. Conclusion: Although statistically significant effects were only seen at the 2 mg/kg b.w. dose during the course of our study, a ∼two and ∼threefold increase in 5‐bromo‐2′‐deoxyuridine labeling index was observed at 0.1 and 0.5 mg/kg b.w., respectively, suggesting that chronic exposure to doses even below 2 mg/kg b.w. may cause proliferative changes in rat liver and highlighting the need to assess furan carcinogenicity at lower doses.
The InnoMed PredTox consortium was formed to evaluate whether conventional preclinical safety assessment can be significantly enhanced by incorporation of molecular profiling (aomicsa) technologies. ...In short-term toxicological studies in rats, transcriptomics, proteomics and metabolomics data were collected and analyzed in relation to routine clinical chemistry and histopathology. Four of the sixteen hepato- and/or nephrotoxicants given to rats for 1, 3, or 14days at two dose levels induced similar histopathological effects. These were characterized by bile duct necrosis and hyperplasia and/or increased bilirubin and cholestasis, in addition to hepatocyte necrosis and regeneration, hepatocyte hypertrophy, and hepatic inflammation. Combined analysis of liver transcriptomics data from these studies revealed common gene expression changes which allowed the development of a potential sequence of events on a mechanistic level in accordance with classical endpoint observations. This included genes implicated in early stress responses, regenerative processes, inflammation with inflammatory cell immigration, fibrotic processes, and cholestasis encompassing deregulation of certain membrane transporters. Furthermore, a preliminary classification analysis using transcriptomics data suggested that prediction of cholestasis may be possible based on gene expression changes seen at earlier time-points. Targeted bile acid analysis, based on LC-MS metabonomics data demonstrating increased levels of conjugated or unconjugated bile acids in response to individual compounds, did not provide earlier detection of toxicity as compared to conventional parameters, but may allow distinction of different types of hepatobiliary toxicity. Overall, liver transcriptomics data delivered mechanistic and molecular details in addition to the classical endpoint observations which were further enhanced by targeted bile acid analysis using LC/MS metabonomics.
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