Over the last five decades, remarkable progress has been achieved in the field of earthquake engineering, especially in the following areas: seismic design philosophy, earthquake protective systems, seismic design and performance evaluation of structures, and theory of structural optimization. The progress achieved and products developed in these areas can be integrated to develop a desired computer-aided optimum structural design framework. Accordingly, a probabilistic performance-based optimum seismic design (PPBOSD) framework is proposed and first illustrated and validated on a simplified single- degree-of-freedom (SDOF) bridge model optimized (i.e., rated) for a target seismic loss hazard curve. The feasibility and optimality of seismic isolation is investigated for a California High-Speed Rail (CHSR) prototype bridge testbed using the proposed PPBOSD framework, balancing the beneficial and detrimental effects of seismic isolation for such a bridge. Towards this goal, a three-dimensional detailed nonlinear finite element model of the CHSR prototype bridge, including soil -pile-structure interaction and rail-structure interaction, is developed in OpenSees. The seismic response of the isolated bridge is compared to that of the corresponding non-isolated bridge both in deterministic and probabilistic terms. A comprehensive parametric probabilistic demand hazard analysis is carried out to investigate the effects of the seismic isolator properties on the seismic risk of the CHSR prototype bridge. To enable the computationally intensive probabilistic seismic response analyses, a cloud-based optimization framework was used integrating cloud computing resources with the high throughput computing in PPBOSD methodology. Furthermore, some well-posed practical optimization problems are formulated and investigated for seismic isolation in CHSR bridges. In summary, the unique contributions and findings are summarized as follows : (1) A PPBOSD framework is proposed, illustrated, and validated using a nonlinear SDOF bridge model; (2) Compared to a non -isolated bridge, the seismic isolation increases the deck displacement and rail stress demands, while it reduces the seismic demand in the bridge substructure in both the deterministic and probabilistic sense; (3) A cloud-based computing platform is developed for PPBOSD to address the high computational cost; (4) The feasibility and optimality of seismic isolation for the prototype bridge is achieved using the PPBOSD framework, reaching various performance objectives considering the relevant sources of uncertainty

Background: Adverse stress exposure during the early neonatal period has been shown to cause aberrant development, resulting in an increased risk of adult disease. We tested the hypothesis that neonatal exposure to lipopolysaccharide (LPS) does not alter heart function at rest condition but causes heart dysfunction under stress stimulation later in life. Methods: Saline control or LPS were administered to neonatal rats via intraperitoneal injection. Experiments were conducted in 6 week-old male and female rats. Isolated hearts were perfused in a Langendorff preparation. Results: Neonatal LPS exposure exhibited no effects on the body weight of the developing rats, but induced decreases in the left ventricle (LV) to the body weight ratio in male rats. Neonatal LPS exposure showed no effects on the baseline heart function determined by in vivo and ex vivo experiments, but caused decreases in the post-ischemic recovery of the LV function in male but not female rats. Neonatal LPS-mediated LV dysfunction was associated with an increase in myocardial infarct size and the LDH release in the male rats. Conclusion: The present study provides novel evidence that neonatal immune challenges could induce gender-dependent long-term effects on cardiac development and heart function, which reinforces the notion that adverse stress exposure during the early neonatal period can aggravate heart functions and the development of a heart ischemia-sensitive phenotype later in life.

Wind waves, which frequently occur on large surface water bodies such as lakes, may temporarily alter flow patterns in a subsurface zone and the corresponding water and nutrient interactions between surface waters and shallow groundwaters. To better understand these processes, soil flume experiments were carried out to investigate wind wave-driven water and chloride interactions across the lake–groundwater interface, and the Hydrus-2D model was used to analyze and evaluate the observed experimental results. Two interaction cases between the lake and groundwater systems were considered: groundwater discharging into a lake (the GDL case), and lake water recharging groundwater (the LRG case). For comparison, no-wave conditions for both the GDL and LRG cases were also analyzed. The results revealed that, similarly to no-wave conditions, water and chloride exchange fluxes between the lake and groundwater systems under wave conditions occurred mainly within narrow bands near the intersection of the water level in the lake and the interface in both the GDL and LRG cases, and then exponentially decreased along the interface. Most water and chloride that infiltrated into the subsurface zone through the upper part of the interface during a wave crest returned to the lake through the lower part during a wave trough in both the GDL and LRG cases, creating local recirculation zones in the subsurface near the interface. Such recirculation produced a more frequent exchange of water and solute across the interface compared with those under no-wave conditions. During a one-day period after wind waves started, the total exchange fluxes of water and chloride to the lake decreased by 36.2% and 71.9%, respectively, compared to the no-wave conditions in the GDL case. In the LRG case, the total exchange water fluxes to the subsurface increased by 89.7%, while the total exchange chloride fluxes increased only slightly (4.5%) compared to the no-wave conditions due to the difference in chloride concentrations between the upper and lower parts of the interface. The sensitivity analysis revealed that the hydraulic conductivity of the lakeshore zone and the characteristics of the waves were important factors influencing water and chloride exchange between the lake and groundwater systems. The simulated results helped us to better understand water and solute interactions in the lake–groundwater system during windy periods.

Nitrogen (N) pollution is a global environmental problem that has greatly increased the risks of both the eutrophication of surface waters and contamination of ground waters. The majority of N pollution mainly comes from agricultural fields, in particular during rice growing seasons. In recent years, a gradual shift from the transplanting rice cultivation method to the direct seeding method has occurred, which results in different water and N losses from paddy fields and leads to distinct impacts on water environments. The N transport and transformations in an experimental direct-seeded-rice (DSR) field in the Taihu Lake Basin of east China were observed during two consecutive seasons, and simulated using Hydrus-1D model. The observed crop N uptake, ammonia volatilization (AV), N concentrations in soil, and N leaching were used to calibrate and validate the model parameters. The two most important inputs of N, i.e., fertilization and mineralization, were considered in the simulations with 220 and 145.5kgha-1 in 2008 and 220 and 147.8kgha-1 in 2009, respectively. Ammonia volatilization and nitrate denitrification were the two dominant pathways of N loss, accounting for about 16.0% and 38.8% of the total N input (TNI), respectively. Both nitrification and denitrification processes mainly occurred in the root zone. N leaching at 60 and 120cm depths accounted for about 6.8% and 2.7% of TNI, respectively. The crop N uptake was 32.1% and 30.8% of TNI during the 2008 and 2009 seasons, respectively, and ammonium was the predominant form (74% of the total N uptake on average). Simulated N concentrations and fluxes in soil matched well with the corresponding observed data. Hydrus-1D could simulate the N transport and transformations in the DSR field, and could thus be a good tool for designing optimal fertilizer management practices in the future.

Available water resources for agricultural irrigation have decreased worldwide in recent decades, prompting advances in water saving methods. In this study, soil water regime and water balance in a transplanted rice field with reduced irrigation (multiple shallow depth irrigations) in the Taihu Lake Basin of East China were observed and then evaluated using Hydrus-1D model during two consecutive growing seasons. During the 2008 season, irrigation water accounted for 48% of the total water input (TWI, 94.6 cm), but only 20% of TWI (120.4 cm) during the 2009 season. Due to heavy rainfalls during the wet 2009 season, surface runoff accounted for about 6.4% of the TWI, whereas during the much drier 2008 season with higher controlled irrigation inputs, no surface runoff occurred. Simulated evapotranspiration during the 2008 and 2009 seasons accounted for 67.4% and 54.9% of TWIs, respectively. Measured and simulated results indicate that water percolation (approximately 32.5% and 37.6% of TWIs during the 2008 and 2009 seasons, respectively) was the main path of water losses from the transplanted rice fields, suggesting that long and high standing water during the 2009 season increased water percolation. Water productivities evaluated from total irrigations and TWIs were 2.08 and 0.99 kg.m-3 during the 2008 season and 3.85 and 0.77 kg.m-3 during the 2009 season, respectively, and were 1.47 and 1.40 kg.m-3, respectively, when evaluated from modeled evapotranspiration fluxes. The cultivation method with multiple shallow depth irrigation efficiently used rainfall water and reduced the losses due to water percolation and surface runoff by stabilizing rice yields.

In the recent decade, increasing costs of labor, water, and fertilizers around the world led to a change in the method of crop establishment from traditional transplanted rice (TPR) to direct-seeded rice (DSR) and to a substantial rise in the DSR-managed area. Since water management in areas with DSR is quite different from those with TPR, vertical water movement and water and nutrient losses during the crop season may be different as well. Water flow and water losses in a DSR field in the Taihu Lake Basin of east China were monitored and evaluated using Hydrus-1D during two seasons with different rainfalls and irrigation managements. While during the 2008 season, irrigation accounted for 57% of the total water input (TWI), during the 2009 season, it accounted for only 32%. Due to large rainfall during the wet, 2009 rice season, surface runoff accounted for about 17.0% of TWI. During the much drier 2008 rice season with higher irrigation inputs, surface runoff (4.6% of TWI) could be controlled much better. Modeled evapotranspiration during the 2008 and 2009 seasons accounted for 54.6% and 44.6% of TWIs, respectively. Measured and simulated results indicate that water leaching (approximately 42.7% and 34.9% of TWIs in the 2008 and 2009 seasons, respectively) was the main path of water loss from the DSR fields, which implies that frequent irrigation increases water leaching. The plough sole layer played a major buffering role for water flow during both dry and wet seasons. Water productivities evaluated from TWIs during the 2008 and 2009 seasons were 0.71 and 0.59kg/m3, respectively; they were 1.30 and 1.33kg/m3 when evaluated from modeled evapotranspiration fluxes. Pressure heads and vertical fluxes simulated using Hydrus-1D matched measured data well. The Hydrus-1D can be used to simulate water flow and water balance in the DSR fields. © 2014 Elsevier B.V.

Cerebral edema, primarily caused by disruption of the blood-brain barrier (BBB), is one of the serious complications associated with brain injury in neonatal hypoxic-ischemic encephalopathy (HIE). Our recent study demonstrated that the hypoxic-ischemic (HI) treatment significantly increased microRNA-210 (miR-210) in the neonatal rat brain and inhibition of miR-210 provided neuroprotection in neonatal HI brain injury. The present study aims to determine the role of miR-210 in the regulation of BBB integrity in the developing brain. miR-210 mimic was administered via intracerebroventricular injection (i.c.v.) into the brain of rat pups. Forty-eight hours after the injection, a modified Rice-Vannucci model was conducted to produce HI brain injury. Post-assays included cerebral edema analysis, western blotting, and immunofluorescence staining for serum immunoglobulin G (IgG) leakage. The results showed that miR-210 mimic exacerbated cerebral edema and IgG leakage into the brain parenchyma. In contrast, inhibition of miR-210 with its complementary locked nucleic acid oligonucleotides (miR-210-LNA) significantly reduced cerebral edema and IgG leakage. These findings suggest that miR-210 negatively regulates BBB integrity i n the neonatal brain. Mechanistically, the seed sequences of miR-210 were identified complementary to the 3' untranslated region (3' UTR) of the mRNA transcripts of tight junction protein occludin and adherens junction protein β-catenin, indicating downstream targets of miR-210. This was further validated by in vivo data showing that miR-210 mimic significantly reduced the expression of these junction proteins in rat pup brains. Of importance, miR-210-LNA preserved the expression of junction proteins occludin and β-catenin from neonatal HI insult. Altogether, the present study reveals a novel mechanism of miR-210 in impairing BBB integrity that contributes to cerebral edema formation after neonatal HI insult, and provides new insights in miR-210-LNA mediated neuroprotection in neonatal HI brain injury.

The catalytic mechanism of N2 fixation by nitrogenase remains unresolved in how the strong N≡N bond is activated and why the reductive elimination of H2 is required. Here, we use density functional theory and physiologically relevant thermal simulations to elucidate the mechanism of the complete nitrogenase catalytic cycle. Over the accumulation of four reducing equivalents, we find that protons and electrons transfer to the FeMo cofactor to weaken and break its bridge Fe–S bond, leading to temporary H2S formation that exposes the Fe sites to weakly bind N2. Remarkably, we find that subsequent H2 formation is responsible for chemical activation to an N=N double bond accompanied by a low barrier for H2 release. We emphasize that finite temperature effects smooth out mechanistic differences between DFT functionals observed at 0 K, thus leading to a consistent understanding as to why H formation is an obligatory step in N2 adsorption and activation.

The cAMP cascade is increasingly recognized to transduce physiological effects locally through spatially limited cAMP gradients. However, little is known about how adenylyl cyclase enzymes that initiate cAMP gradients are localized. Here we address this question in physiologically relevant striatal neurons and investigate how AC localization impacts downstream signaling function. We show that the major striatal AC isoforms are differentially sorted between ciliary and extraciliary domains of the plasma membrane, and that one isoform, AC9, is uniquely concentrated in endosomes. We identify key sorting determinants in the N-terminal cytoplasmic domain responsible for isoform-specific localization. We further show that AC9-containing endosomes accumulate activated dopamine receptors and form an elaborately intertwined network with juxtanuclear PKA stores bound to Golgi membranes. Finally, we provide evidence that endosomal localization enables AC9 to selectively elevate PKA activity in the nucleus relative to the cytoplasm. Together, these results reveal a precise spatial landscape of the cAMP cascade in neurons and a key role of AC localization in directing downstream PKA signaling to the nucleus.