Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat diet

Glucocorticoid hormones are critical to respond and adapt to stress. Genetic variations in the glucocorticoid receptor (GR) gene alter hypothalamic-pituitary-adrenal (HPA) axis activity and associate with hypertension and susceptibility to metabolic disease. Here we test the hypothesis that reduced GR density alters blood pressure and glucose and lipid homeostasis and limits adaption to obesogenic diet. Heterozygous GR βgeo/+ mice were generated from embryonic stem (ES) cells with a gene trap integration of a β-galactosidase-neomycin phosphotransferase (βgeo) cassette into the GR gene creating a transcriptionally inactive GR fusion protein. Although GRβgeo/+ mice have 50% less functional GR, they have normal lipid and glucose homeostasis due to compensatory HPA axis activation but are hypertensive due to activation of the renin-angiotensin- aldosterone system (RAAS). When challenged with a high-fat diet, weight gain, adiposity, and glucose intolerance were similarly increased in control and GRβgeo/+ mice, suggesting preserved control of intermediary metabolism and energy balance. However, whereas a high-fat diet caused HPA activation and increased blood pressure in control mice, these adaptions were attenuated or abolished in GRβgeo/+ mice. Thus, reduced GR density balanced by HPA activation leaves glucocorticoid functions unaffected but mineralocorticoid functions increased, causing hypertension. Importantly, reduced GR limits HPA and blood pressure adaptions to obesogenic diet.

Genotoxicity of inorganic lead salts and disturbance of microtubule function

Lead compounds are known genotoxicants, principally affecting the integrity of chromosomes. Lead chloride and lead acetate induced concentration-dependent increases in micronucleus frequency in V79 cells, starting at 1.1 μM lead chloride and 0.05 μM lead acetate. The difference between the lead salts, which was expected based on their relative abilities to form complex acetato-cations, was confirmed in an independent experiment. CREST analyses of the micronuclei verified that lead chloride and acetate were predominantly aneugenic (CREST-positive response), which was consistent with the morphology of the micronuclei (larger micronuclei, compared with micronuclei induced by a clastogenic mechanism). The effects of high concentrations of lead salts on the microtubule network of V79 cells were also examined using immunofluorescence staining. The dose effects of these responses were consistent with the cytotoxicity of lead(II), as visualized in the neutral-red uptake assay. In a cell-free system, 20-60 μM lead salts inhibited tubulin assembly dose-dependently. The no-observed-effect concentration of lead(II) in this assay was 10 μM. This inhibitory effect was interpreted as a shift of the assembly/disassembly steady-state toward disassembly, e.g., by reducing the concentration of assembly-competent tubulin dimers. The effects of lead salts on microtubule-associated motor-protein functions were studied using a kinesin-gliding assay that mimics intracellular transport processes in vitro by quantifying the movement of paclitaxel-stabilized microtubules across a kinesin-coated glass surface. There was a dose-dependent effect of lead nitrate on microtubule motility. Lead nitrate affected the gliding velocities of microtubules starting at concentrations above 10 μM and reached half-maximal inhibition of motility at about 50 μM. The processes reported here point to relevant interactions of lead with tubulin and kinesin at low dose levels.

Determination of preventive maintenance lead time using hybrid analysis

The time for conducting Preventive Maintenance (PM) on an asset is often determined using a predefined alarm limit based on trends of a hazard function. In this paper, the authors propose using both hazard and reliability functions to improve the accuracy of the prediction particularly when the failure characteristic of the asset whole life is modelled using different failure distributions for the different stages of the life of the asset. The proposed method is validated using simulations and case studies.

Feasibility studies on using microwave-heating techniques for recycling lead waste

Lead is present everywhere in the environment and has been defined as one of the greatest threats to the human health. In this paper, attempts have been made to study a way of recycling the lead produced from waste usage and disposed of in such a way as to avoid degrading the surrounding environment. In order to contain the waste, recycled asphalt material is mixed with the lead and then heated with microwave energy. This is an attempt to solidify and reduce the lead contaminants and use the final product as sub-base material in road pavement construction. The microwave heating of the specimens is carried out with 30%, 50%, 80% and 100% of power at 800W. The optimum power mode is used to compare with the conventional heating of asphalt with sulfur additive. The results are characterized by compact density, permeability, and subjected to toxicity test with regards to lead concentration. A mechanical test to evaluate the stability is also performed on the three methods of solidification and to prove that microwave zapping method allow to convert into an environmentally stable material for recycling without having to be deposited in a landfill site.

Stretching-induced orientation to improve mechanical properties of electrospun pan nanocomposites

Partially aligned and oriented polyacrylonitrile(PAN)-based nanofibers were electrospun from PAN and SWNTs/PAN in the solution of dimethylformamide(DMF) to make the carbon nanofibers. The as-spun nanofibers were hot-stretched in an oven to enhance its orientation and crystallinity. Then it were stabilized at 250 square under a stretched stress, and carbonized at 1000 square in N-2 atmosphere by fixing the length of the stabilized nanofiber to convert them into carbon nanofibers. With this hot-stretched process and with the introduction of SWNTs, the mechanical properties will be enhanced correspondingly. The crystallinity of the stretched fibers confirmed by X-ray diffraction has also increased. For PAN nanofibers, the improved fiber alignment and crystallinity resulted in the increased mechanical properties, such as the modulus and tensile strength of the nanofibers. It was concluded that the hot-stretched nanofiber and the SWNTs/PAN nanofibers can be used as a potential precursor to produce high-performance carbon composites.

Dynamic matrix control on wind-induced vibration of spatial latticed structures [Chinese title = 空间网壳结构风振抑制的动态矩阵预测控制分析]

Ameliorated strategies were put forward to improve the model predictive control in reducing the wind induced vibration of spatial latticed structures. The dynamic matrix control (DMC) predictive method was used and the reference trajectory which is called the decaying functions was suggested for the analysis of spatial latticed structure (SLS) under wind loads. The wind-induced vibration control model of SLS with improved DMC model predictive control was illustrated, then the different feedback strategies were investigated and a typical SLS was taken as example to investigate the reduction of wind-induced vibration. In addition, the robustness and reliability of DMC strategy were discussed by varying the model configurations.

Safety culture research, lead indicators, and the development of safety effectiveness indicators in the construction sector

Construction sector application of Lead Indicators generally and Positive Performance Indicators (PPIs) particularly, are largely seen by the sector as not providing generalizable indicators of safety effectiveness. Similarly, safety culture is often cited as an essential factor in improving safety performance, yet there is no known reliable way of measuring safety culture. This paper proposes that the accurate measurement of safety effectiveness and safety culture is a requirement for assessing safe behaviours, safety knowledge, effective communication and safety performance. Currently there are no standard national or international safety effectiveness indicators (SEIs) that are accepted by the construction industry. The challenge is that quantitative survey instruments developed for measuring safety culture and/ or safety climate are inherently flawed methodologically and do not produce reliable and representative data concerning attitudes to safety. Measures that combine quantitative and qualitative components are needed to provide a clear utility for safety effectiveness indicators.