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Axially loaded piles in liquefiable soils can undergo severe settlement due to an earthquake event. During shaking, the settlement is caused by the decreased shaft and tip capacity from excess pore pressures (ue) generated around the pile. Post shaking, soil settlement from the reconsolidation of liquefied soil surrounding the pile results in the development of additional load (known as drag load), causing downdrag settlement of the pile. Estimating the axial load distribution and pile settlement is essential for designing and evaluating the performance of axially loaded piles in liquefiable soils. In practice, a simplified neutral plane solution method is used, where the liquefied soils are modeled as a consolidating layer without considering the effect of ue generation/dissipation. A TzQzLiq analysis models the load and settlement response of axially loaded piles in liquefiable soils by accounting for the effect of excess pore pressure (ue) generation/dissipation on the shaft and tip capacity. This paper presents the deficiencies of the simplified neutral plane method in predicting the drag load as well as the downdrag settlement by comparing it with the TzQzLiq analysis validated with hypergravity model tests. The results show that the drag load and the downdrag settlement predicted by the neutral plane method might be over- or under-estimated depending on the pile load, the rate of ue dissipation, and the soil settlement. For the cases studied, it was found that most of the pile settlement occurs during shaking due to the decrease in the pile's tip resistance from the development of ue in the soil surrounding it. While large drag loads develop during reconsolidation, the resulting downdrag settlement is small. While the neutral plane method generally predicted a downdrag settlement comparable to that of the TzQzLiq analysis, it overpredicted drag load and could not predict co-seismic settlement. Finally, the study advocates for the development and use of a displacement-based procedure (accounting for all the mechanisms occurring during and after an earthquake event) such as based on TzQzLiq analysis in accurately evaluating the performance of the pile (i.e., the pile settlement and the maximum load), thus providing an overall safe, efficient, and optimized design.

RNase R (encoded by the rnr gene) is a highly processive 3' → 5' exoribonuclease essential for the growth of the psychrotrophic bacterium P. syringae Lz4W at low temperature. The cell death of a rnr deletion mutant at low temperature has been previously attributed to the processing defects in 16S rRNA, defective ribosomal assembly and inefficient protein synthesis. We recently showed that RNase R is required to protect P. syringae Lz4W from DNA damage and oxidative stress, independent of its exoribonuclease activity. Here, we show that the processing defect in 16S rRNA does not cause cell death of the rnr mutant of P. syringae at low temperature. Our results demonstrate that the rnr mutant of P. syringae Lz4W, complemented with a RNase R deficient in exoribonuclease function (RNase RD284A) is defective in 16S rRNA processing but can grow at 4 oC. This suggested that the processing defect in ribosomal RNAs is not a cause of the cold sensitivity of the rnr mutant. We further show that the rnr mutant accumulates copies of the indigenous plasmid of P. syringae Lz4W, pLz4W, that bears a type II toxin-antitoxin system (psA-psT). This phenotype was rescued by over-expressing antitoxin psA in the rnr mutant, suggesting that activation of the type II toxin-antitoxin system leads to cold sensitivity of the rnr mutant of P. syringae Lz4W. Here, we report a previously unknown functional relationship between the cold sensitivity of the rnr mutant and a type II toxin-antitoxin system in P. syringae Lz4W.

Existing simplified procedures for evaluating soil liquefaction potential or for estimating excess pore pressures during earthquakes are typically based on undrained cyclic tests performed on saturated soil samples under controlled loading and boundary conditions. Under such conditions, the effect of excess pore pressure (ue) dissipation and redistribution to neighboring soil layers cannot be accounted for. Existing simplified procedures treat liquefiable layers as isolated soil layers without any boundary conditions even if dense and loose layers are very thin, permeable, and adjacent to each other. However, redistribution is likely to increase and decrease ue in the neighboring dense and loose layers respectively. Until now, no procedure short of fully coupled numerical analysis is available to estimate the importance of redistribution. This paper presents an approximate analytical procedure for assessing the effects of ue redistribution in (1) soil layers that would have liquefied if they were undrained, and (2) soil layers that would have not liquefied even if undrained. It is found that a layer that is initially assumed liquefied under undrained conditions might not even liquefy accounting for the ue redistribution to neighboring layers. On the other hand, a layer initially assumed to not liquefy can develop significant ue and can even liquefy due to pore pressure migration from the neighboring layers. Thus, accounting for redistributed ue is important for liquefaction consequence assessment quantification, particularly in systems that span the depth of these effects like deep foundations. Migration of u toward the tip of a pile can reduce its capacity, even if the tip is embedded in a dense sand layer. On the other hand, if redistribution can result in the reduction of ue in initially assumed liquefied layers, risks associated with liquefaction might be avoided. A criterion is also developed to evaluate the thicknesses of a layer below which redistribution could prevent liquefaction even if the layer is deemed liquefied according to the existing liquefaction-triggering procedures. Finally, the proposed procedure is illustrated by application to selected shaking events of centrifuge tests involving liquefaction of layered soil profiles. The predictions from the procedure matched the centrifuge test results reasonably.

Background and aimsWe previously reported that Oxy210, an oxysterol-based drug candidate, exhibits antifibrotic and anti-inflammatory properties. We also showed that, in mice, it ameliorates hepatic hallmarks of non-alcoholic steatohepatitis (NASH), including inflammation and fibrosis, and reduces adipose tissue inflammation. Here, we aim to investigate the effects of Oxy210 on atherosclerosis, an inflammatory disease of the large arteries that is linked to NASH in epidemiologic studies, shares many of the same risk factors, and is the major cause of mortality in people with NASH.MethodsOxy210 was studied in vivo in APOE*3-Leiden.CETP mice, a humanized mouse model for both NASH and atherosclerosis, in which symptoms are induced by consumption of a high fat, high cholesterol "Western" diet (WD). Oxy210 was also studied in vitro using two cell types that are important in atherogenesis: human aortic endothelial cells (HAECs) and macrophages treated with atherogenic and inflammatory agents.ResultsOxy210 reduced atherosclerotic lesion formation by more than 50% in hyperlipidemic mice fed the WD for 16 weeks. This was accompanied by reduced plasma cholesterol levels and reduced macrophages in lesions. In HAECs and macrophages, Oxy210 reduced the expression of key inflammatory markers associated with atherosclerosis, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand 2 (CCL2), vascular cell adhesion molecule-1 (VCAM-1), and E-Selectin. In addition, cholesterol efflux was significantly enhanced in macrophages treated with Oxy210.ConclusionsThese findings suggest that Oxy210 could be a drug candidate for targeting both NASH and atherosclerosis, as well as chronic inflammation associated with the manifestations of metabolic syndrome.

Axially loaded piles in liquefiable soils can undergo severe settlements due to a shaking event. During shaking, the settlement is caused by the reduction of its shaft and tip capacity from the excess pore pressures generated around the pile. Post shaking, additional pile settlement is caused by the surrounding soil settling due to reconsolidation and the associated development of drag load. A new displacement-based method is developed using a TzQzLiq analysis for designing axially loaded piles subject to seismic loading and liquefaction-induced downdrag. The new displacement-based design method offers several advancements to the state of practice forced-based design procedure by AASHTO's force-based design procedure by reasonably accounting for the mechanisms that occur on axially loaded piles during and post shaking. It accounts for the initial drag load on the pile, redistribution effects resulting in large excess pore pressures in the non-liquefied layers, and reduction in the pile's shaft and tip capacity from excess pore pressures around the pile. The new design procedure estimates the pile settlement and axial load distribution during the entire shaking event, i.e., during shaking and reconsolidation. Design steps are provided describing the procedure for obtaining design curves on the settlement and drag load on piles with varying pile lengths. The length of the piles is then selected based on serviceability criteria and the pile's structural strength. Finally, the new design procedure is applied on piles used in centrifuge model tests, and results are compared, followed by an example design problem that illustrates the applicability of the new method in practice.