Experimental dataset on water levels, sediment depths and wave front celerity values in the study of multiphase shock wave for different initial up- and down-stream conditions

This data article presents a rich original experimental video sources and wide collections of laboratory data on water levels, sediment depths and wave front celerity values arose from different multiphase dam-break scenarios. The required data of dam-break shock waves in highly silted-up reservoirs with various initial up- and down-stream hydraulic conditions is obtained directly from high-quality videos. The multi-layer shock waves were recorded by three professional cameras mounted along the laboratory channel. The extracted video images were rigorously scrutinized, and the datasets were obtained through the images via image processing method. Different sediment depths in the upstream reservoir and dry- or wet-bed downstream conditions were considered as initial conditions, compromising a total of 32 different scenarios. A total of 198 original experimental videos are made available online in the public repository "Mendeley Data" in 8 groups based on 8 different initial upstream sediment depths [1], [2], [3], [4], [5], [6], [7], [8]. 20 locations along the flume and 15 time snaps after the dam breaks were considered for data collecting. Consequently, a total of 18,000 water level and sediment depth data points were collected to prepare four datasets, which are uploaded in the public repository "Mendeley Data". A total of 9600 water level data points could be accessed in [9], [10], while 8400 sediment depth data points are available online in [11], [12] and could be utilized for validation and practical purposes by other researchers. This data article is related to another research article entitled "Experimental study and numerical verification of silted-up dam-break" [13]

Cross-species gene expression analysis of species specific differences in the preclinical assessment of pharmaceutical compounds

Animals are frequently used as model systems for determination of safety and efficacy in pharmaceutical research and development. However, significant quantitative and qualitative differences exist between humans and the animal models used in research. This is as a result of genetic variation between human and the laboratory animal. Therefore the development of a system that would allow the assessment of all molecular differences between species after drug exposure would have a significant impact on drug evaluation for toxicity and efficacy. Here we describe a cross-species microarray methodology that identifies and selects orthologous probes after cross-species sequence comparison to develop an orthologous cross-species gene expression analysis tool. The assumptions made by the use of this orthologous gene expression strategy for cross-species extrapolation is that; conserved changes in gene expression equate to conserved pharmacodynamic endpoints. This assumption is supported by the fact that evolution and selection have maintained the structure and function of many biochemical pathways over time, resulting in the conservation of many important processes. We demonstrate this cross-species methodology by investigating species specific differences of the peroxisome proliferatoractivator receptor (PPAR) a response in rat and human

Analysis of Gene Regulatory Networks in the Mammalian Circadian Rhythm

Circadian rhythm is fundamental in regulating a wide range of cellular, metabolic, physiological, and behavioral activities in mammals. Although a small number of key circadian genes have been identified through extensive molecular and genetic studies in the past, the existence of other key circadian genes and how they drive the genomewide circadian oscillation of gene expression in different tissues still remains unknown. Here we try to address these questions by integrating all available circadian microarray data in mammals. We identified 41 common circadian genes that showed circadian oscillation in a wide range of mouse tissues with a remarkable consistency of circadian phases across tissues. Comparisons across mouse, rat, rhesus macaque, and human showed that the circadian phases of known key circadian genes were delayed for 4–5 hours in rat compared to mouse and 8–12 hours in macaque and human compared to mouse. A systematic gene regulatory network for the mouse circadian rhythm was constructed after incorporating promoter analysis and transcription factor knockout or mutant microarray data. We observed the significant association of cis-regulatory elements: EBOX, DBOX, RRE, and HSE with the different phases of circadian oscillating genes. The analysis of the network structure revealed the paths through which light, food, and heat can entrain the circadian clock and identified that NR3C1 and FKBP/HSP90 complexes are central to the control of circadian genes through diverse environmental signals. Our study improves our understanding of the structure, design principle, and evolution of gene regulatory networks involved in the mammalian circadian rhythm

Megalin/LRP2 Expression Is Induced by Peroxisome Proliferator-Activated Receptor -Alpha and -Gamma: Implications for PPARs' Roles in Renal Function

BACKGROUND: Megalin is a large endocytic receptor with relevant functions during development and adult life. It is expressed at the apical surface of several epithelial cell types, including proximal tubule cells (PTCs) in the kidney, where it internalizes apolipoproteins, vitamins and hormones with their corresponding carrier proteins and signaling molecules. Despite the important physiological roles of megalin little is known about the regulation of its expression. By analyzing the human megalin promoter, we found three response elements for the peroxisomal proliferator-activated receptor (PPAR). The objective of this study was to test whether megalin expression is regulated by the PPARs. METHODOLOGY/PRINCIPAL FINDINGS: Treatment of epithelial cell lines with PPARα or PPARγ ligands increased megalin mRNA and protein expression. The stimulation of megalin mRNA expression was blocked by the addition of specific PPARα or PPARγ antagonists. Furthermore, PPAR bound to three PPAR response elements located in the megalin promoter, as shown by EMSA, and PPARα and its agonist activated a luciferase construct containing a portion of the megalin promoter and the first response element. Accordingly, the activation of PPARα and PPARγ enhanced megalin expression in mouse kidney. As previously observed, high concentrations of bovine serum albumin (BSA) decreased megalin in PTCs in vitro; however, PTCs pretreated with PPARα and PPARγ agonists avoided this BSA-mediated reduction of megalin expression. Finally, we found that megalin expression was significantly inhibited in the PTCs of rats that were injected with BSA to induce tubulointerstitial damage and proteinuria. Treatment of these rats with PPARγ agonists counteracted the reduction in megalin expression and the proteinuria induced by BSA. CONCLUSIONS: PPARα/γ and their agonists positively control megalin expression. This regulation could have an important impact on several megalin-mediated physiological processes and on pathophysiologies such as chronic kidney disease associated with diabetes and hypertension, in which megalin expression is impaired

Influence of Neonatal Hypothyroidism on Hepatic Gene Expression and Lipid Metabolism in Adulthood

Thyroid hormones are required for normal growth and development in mammals. Congenital-neonatal hypothyroidism (CH) has a profound impact on physiology, but its specific influence in liver is less understood. Here, we studied how CH influences the liver gene expression program in adulthood. Pregnant rats were given the antithyroid drug methimazole (MMI) from GD12 until PND30 to induce CH in male offspring. Growth defects due to CH were evident as reductions in body weight and tail length from the second week of life. Once the MMI treatment was discontinued, the feed efficiency increased in CH, and this was accompanied by significant catch-up growth. On PND80, significant reductions in body mass, tail length, and circulating IGF-I levels remained in CH rats. Conversely, the mRNA levels of known GH target genes were significantly upregulated. The serum levels of thyroid hormones, cholesterol, and triglycerides showed no significant differences. In contrast, CH rats showed significant changes in the expression of hepatic genes involved in lipid metabolism, including an increased transcription of PPARα and a reduced expression of genes involved in fatty acid and cholesterol uptake, cellular sterol efflux, triglyceride assembly, bile acid synthesis, and lipogenesis. These changes were associated with a decrease of intrahepatic lipids. Finally, CH rats responded to the onset of hypothyroidism in adulthood with a reduction of serum fatty acids and hepatic cholesteryl esters and to T3 replacement with an enhanced activation of malic enzyme. In summary, we provide in vivo evidence that neonatal hypothyroidism influences the hepatic transcriptional program and tissue sensitivity to hormone treatment in adulthood. This highlights the critical role that a euthyroid state during development plays on normal liver physiology in adulthood

Application of RBF-DQ Method to Time-Dependent Analysis of Unsaturated Seepage

Richards’ equation is a nonlinear partial differential equation governing unsteady seepage flow through unsaturated porous media. This paper investigates applicability of radial basis function-based differential quadrature (RBF-DQ), as a meshless method, to simulate one-dimensional flow processes in the unsaturated zone under different initial and boundary conditions. Fourth-order Runge–Kutta scheme has been adopted for time integration. Results of solving three numerical examples using RBF-DQ are compared with those of analytical, numerical, and experimental solutions presented in the literature. The comparison indicates that RBF-DQ can provide more accurate results comparing with traditional FDM or FEM without the need to discretize the computational domain. Moreover, the merit of mesh-free characteristic in RBF-DQ makes it suitable not only for solving nonlinear problems but also for dealing with multidimensional problems since meshless methods are not restricted to dimensional limitations. A key parameter in utilizing multiquadratic approximation in RBF-DQ method is the user-defined shape parameter C, which may significantly affect solution accuracy. Thus, a sensitivity analysis has been conducted to study possible effects of shape parameter on achieved results

Groundwater sustainability: Developing a non-cooperative optimal management scenario in shared groundwater resources under water bankruptcy conditions.

Groundwater level drawdown changes the hydrological cycle and poses challenges such as land subsidence and reduction of the groundwater quality. In this study, a new approach using a simulation-optimization framework was developed for shared groundwater management under water bankruptcy conditions (where water demand is greater than the allowable discharge capacity of water resources). The novelty of this study lies in using bankruptcy rules and a game model to manage a bankrupted shared groundwater resource considering aquifer sustainability. Accordingly, groundwater flow in the aquifer was numerically simulated by a finite-differences model (MODFLOW). Then, the repeated performance code of the finite-differences model was run for different discharge scenarios, and the results were applied to develop an MLP-ANN meta-model. By coupling the meta-model with a non-dominated sorting genetic algorithm II (NSGA-II)-based multi-objective optimization model, an optimized cultivation pattern under water bankruptcy conditions was achieved. Then, six different bankruptcy methods were utilized to specify groundwater allocation between three stakeholders. To manage the water bankruptcy conditions, different scenarios considering various groundwater extraction rates and cultivation areas were defined, and the optimization model was recoded for each scenario to find the corresponding optimized cultivation pattern. To consider the competition between stakeholders for groundwater extraction, a non-cooperative 3-player game was applied to achieve a compromise for different combinations of management strategies, which maximizes the profit and yields the best cultivation scenario. Applicability of the proposed methodology was investigated in an aquifer system located in Golestan Province, Iran, including three regions (Minudasht, Azadshahr, and Gonbade-kavus). Results show that the proposed method is capable of managing the bankruptcy conditions by generating greater agricultural profit and reducing groundwater drawdowns