Chronic activation of the low affinity site of β1-adrenoceptors stimulates haemodynamics but exacerbates pressure-overload cardiac remodelling

Background and Purpose The β1-adrenoceptor has at least two binding sites, high and low affinity sites (β1H and β1L, respectively), which mediate cardiostimulation. While β1H-adrenoceptor can be blocked by all clinically used β-blockers, β1L-adrenoceptor is relatively resistant to blockade. Thus, chronic β1L-adrenoceptor activation may mediate persistent cardiostimulation, despite the concurrent blockade of β1H-adrenoceptors. Hence, it is important to determine the potential significance of β1L-adrenoceptors in vivo, particularly in pathological situations. Experimental Approach C57Bl/6 male mice were used. Chronic (4 or 8 weeks) β1L-adrenoceptor activation was achieved by treatment, via osmotic mini pumps, with (-)-CGP12177 (10 mg·kg−1·day−1). Cardiac function was assessed by echocardiography and micromanometry. Key Results (-)-CGP12177 treatment of healthy mice increased heart rate and left ventricular (LV) contractility. (-)-CGP12177 treatment of mice subjected to transverse aorta constriction (TAC), during weeks 4–8 or 4–12 after TAC, led to a positive inotropic effect and exacerbated fibrogenic signalling while cardiac hypertrophy tended to be more severe. (-)-CGP12177 treatment of mice with TAC also exacerbated the myocardial expression of hypertrophic, fibrogenic and inflammatory genes compared to untreated TAC mice. Washout of (-)-CGP12177 revealed a more pronounced cardiac dysfunction after 12 weeks of TAC. Conclusions and Implications β1L-adrenoceptor activation provides functional support to the heart, in both normal and pathological (pressure overload) situations. Sustained β1L-adrenoceptor activation in the diseased heart exacerbates LV remodelling and therefore may promote disease progression from compensatory hypertrophy to heart failure.

Simultaneous estimation of hunting pressure, harvest and hunter success rates using WinBUGS

The use of hierarchical Bayesian spatial models in the analysis of ecological data is increasingly prevalent. The implementation of these models has been heretofore limited to specifically written software that required extensive programming knowledge to create. The advent of WinBUGS provides access to Bayesian hierarchical models for those without the programming expertise to create their own models and allows for the more rapid implementation of new models and data analysis. This facility is demonstrated here using data collected by the Missouri Department of Conservation for the Missouri Turkey Hunting Survey of 1996. Three models are considered, the first uses the collected data to estimate the success rate for individual hunters at the county level and incorporates a conditional autoregressive (CAR) spatial effect. The second model builds upon the first by simultaneously estimating the success rate and harvest at the county level, while the third estimates the success rate and hunting pressure at the county level. These models are discussed in detail as well as their implementation in WinBUGS and the issues arising therein. Future areas of application for WinBUGS and the latest developments in WinBUGS are discussed as well.

Pulse-coupled neural network performance for real-time identification of vegetation during forced landing

Safety concerns in the operation of autonomous aerial systems require safe-landing protocols be followed during situations where the mission should be aborted due to mechanical or other failure. This article presents a pulse-coupled neural network (PCNN) to assist in the vegetation classification in a vision-based landing site detection system for an unmanned aircraft. We propose a heterogeneous computing architecture and an OpenCL implementation of a PCNN feature generator. Its performance is compared across OpenCL kernels designed for CPU, GPU, and FPGA platforms. This comparison examines the compute times required for network convergence under a variety of images to determine the plausibility for real-time feature detection.

Using pulse transit delay in Z-scan to discriminate between excited-state absorption and other nonlinear processes in ZnO nanocones

We report a new approach that uses the single beam Z-scan technique, to discriminate between excited state absorption (ESA) and two and three photon nonlinear absorption. By measuring the apparent delay or advance of the pulse in reaching the detector, the nonlinear absorption can be unambiguously identified as either instantaneous or transient. The simple method does not require a large range of input fluences or sophisticated pulse-probe experimental apparatus. The technique is easily extended to any absorption process dependent on pulse width and to nonlinear refraction measurements. We demonstrate in particular, that the large nonlinear absorption in ZnO nanocones when exposed to nanosecond 532 nm pulses, is due mostly to ESA, not pure two-photon absorption.

Integrating 40Ar-39Ar, 87Rb-87Sr and 147Sm-143Nd geochronology of authigenic illite to evaluate tectonic reactivation in an intraplate setting, central Australia

The Warburton-Cooper basins, central Australia, include a multitude of reactivated fracture-fault networks related to a complex, and poorly understood, tectonic evolution. We investigated authigenic illites from a granitic intrusion and sedimentary rocks associated with prominent structural features (Gidgealpa-Merrimelia-Innamincka Ridge and the Nappamerri Trough). These were analysed by 40Ar-39Ar, 87Rb-87Sr and 147Sm-143Nd geochronology to explore the thermal and tectonic histories of central Australian basins. The combined age data provide evidence for three major periods of fault reactivation throughout the Phanerozoic. While Carboniferous (323.3 ± 9.4 Ma) and Late Triassic ages (201.7 ± 9.3 Ma) derive from basin-wide hydrothermal circulation, Cretaceous ages (~128 to ~86 Ma) reflect episodic fluid flow events restricted to the synclinal Nappamerri Trough. Such events result from regional extensional tectonism derived from the transferral of far-field stresses to mechanically and thermally weakened regions of the Australian continent. Specifically, Cretaceous ages reflect continent-wide transmission of tensional stress from a > 2500 km long rifting event on the Eastern (and southern) Australian margin associated with break-up of Gondwana and opening of the Tasman Sea. By integrating 40Ar-39Ar, 87Rb-87Sr and 147Sm-143Nd dating, this study highlights the use of authigenic illite in temporally constraining the tectonic evolution of intracontinental basins that would otherwise remain unknown. Furthermore, combining Sr- and Ar-isotopic systems enables more accurate dating of authigenesis whilst significantly reducing geochemical pitfalls commonly associated with these radioisotopic dating methods.

Mifepristone in the central nucleus of the amygdala reduces yohimbine stress-induced reinstatement of ethanol-seeking

Chronic ethanol exposure leads to dysregulation of the hypothalamic-pituitary-adrenal axis, leading to changes in glucocorticoid release and function that have been proposed to maintain pathological alcohol consumption and increase vulnerability to relapse during abstinence. The objective of this study was to determine whether mifepristone, a glucocorticoid receptor antagonist, plays a role in ethanol self-administration and reinstatement. Male, Long-Evans rats were trained to self-administer either ethanol or sucrose in daily 30 min operant self-administration sessions using a fixed ratio 3 schedule of reinforcement. Following establishment of stable baseline responding, we examined the effects of mifepristone on maintained responding and yohimbine-induced increases in responding for ethanol and sucrose. Lever responding was extinguished in separate groups of rats and animals were tested for yohimbine-induced reinstatement and corticosterone release. We also investigated the effects of local mifepristone infusions into the central amygdala (CeA) on yohimbine-induced reinstatement of ethanol- and sucrose-seeking. In addition, we infused mifepristone into the basolateral amygdala (BLA) in ethanol-seeking animals as an anatomical control. We show that both systemic and intra-CeA (but not BLA) mifepristone administration suppressed yohimbine-induced reinstatement of ethanol-seeking, while only systemic injections attenuated sucrose-seeking. In contrast, baseline consumption, yohimbine-induced increases in responding, and circulating CORT levels were unaffected. The data indicate that the CeA plays an important role in the effects of mifepristone on yohimbine-induced reinstatement of ethanol-seeking. Mifepristone may be a valuable pharmacotherapeutic strategy for preventing relapse to alcohol use disorders and, as it is FDA approved, may be a candidate for clinical trials in the near future.

Design Pressure Test 2013 Workshop

Design Pressure Test 2013 was a full-day intensive design immersion creative event run on Saturday 3 August 2013, at the QUT Faculty of Creative Industries J Block Design Lab Workshop in Brisbane, Australia, for 25 self-selected high-achieving junior and middle school (year 5-9) students, as part of the Queensland Academies ‘Young Scholars’ Program. Facilitated by tertiary interior design, fashion design and industrial design educators, technicians and six tertiary interior design and fashion design students, the workshop explored design process, environmental impact, the material properties and structural integrity of cardboard, construction techniques, and the production and evaluation of furniture design prototypes. This action research study aimed to facilitate an awareness in young people, of the role and scope of design within our society, the environmental ramifications of design decisions, and the value of design thinking skills in generating strategies to solve basic to complex challenges. It also aimed to investigate the value of collaboration between junior and middle school students, tertiary design educators and students and industry professionals in design awareness, and inspiring post-secondary pathways and idea generation for education. During the creative event, students utilised mathematics skills and developed sketching, making, communication, presentation and collaboration skills to improve their design process, while considering social, cultural and environmental opportunities. Through a series of hands-on collaborative design experiments, participants explored in teams of five, the opportunities available using cardboard as a material – inspiring both functional and aesthetic design solutions. Underpinned by the State Library of Queensland Design Minds Website ‘inquire, ideate and implement’ model of design thinking, the experiments culminated in the development of a detailed client brief, the design and fabrication of a furniture item for seating, and then a team presentation of prototypes to a panel of judges from the professions of architecture, interior design and industrial design, viewed also by parents. The final test for structural integrity was measured by the hoisting down of an adult body weight onto the fabricated seat. The workshop was filmed for the television program ‘Totally Wild’ for dissemination nationally (over 200,000 viewing audience) of the value of design and the Design Minds model to a wider target youth audience.

High pressure in situ diffraction studies of metal–hydrogen systems

“Hybrid” hydrogen storage, where hydrogen is stored in both the solid material and as a high pressure gas in the void volume of the tank can improve overall system efficiency by up to 50% compared to either compressed hydrogen or solid materials alone. Thermodynamically, high equilibrium hydrogen pressures in metal–hydrogen systems correspond to low enthalpies of hydrogen absorption–desorption. This decreases the calorimetric effects of the hydride formation–decomposition processes which can assist in achieving high rates of heat exchange during hydrogen loading—removing the bottleneck in achieving low charging times and improving overall hydrogen storage efficiency of large hydrogen stores. Two systems with hydrogenation enthalpies close to −20 kJ/mol H2 were studied to investigate the hydrogenation mechanism and kinetics: CeNi5–D2 and ZrFe2−xAlx (x = 0.02; 0.04; 0.20)–D2. The structure of the intermetallics and their hydrides were studied by in situ neutron powder diffraction at pressures up to 1000 bar and complementary X-ray diffraction. The deuteration of the hexagonal CeNi5 intermetallic resulted in CeNi5D6.3 with a volume expansion of 30.1%. Deuterium absorption filled three different types of interstices, Ce2Ni2 and Ni4 tetrahedra, and Ce2Ni3 half-octahedra and was accompanied by a valence change for Ce. Significant hysteresis was observed between deuterium absorption and desorption which profoundly decreased on a second absorption cycle. For the Al-modified Laves-type C15 ZrFe2−xAlx intermetallics, deuteration showed very fast kinetics of H/D exchange and resulted in a volume increase of the FCC unit cells of 23.5% for ZrFe1.98Al0.02D2.9(1). Deuterium content, hysteresis of H/D uptake and release, unit cell expansion and stability of the hydrides systematically change with the amount of Al content. In the deuteride D atoms exclusively occupy the Zr2(Fe,Al)2 tetrahedra. Observed interatomic distances are Zr–D = 1.98–2.11; (Fe, Al)–D = 1.70–1.75A˚ . Hydrogenation slightly increases the magnetic moment of the Fe atoms in ZrFe1.98Al0.02 and ZrFe1.96Al0.04 from 1.9 �B at room temperature for the alloy to 2.2 �B for its deuteride.

Wind pressure measurements on a cube subjected to pulsed impinging jet flow

A pulsed impinging jet is used to simulate the gust front of a thunderstorm downburst. This work concentrates on investigating the peak transient loading conditions on a 30 mm cubic model submerged in the simulated downburst flow. The outflow induced pressures are recorded and compared to those from boundary layer and steady wall jet flow. Given that peak winds associated with downburst events are often located in the transient frontal region, the importance of using a non-stationary modelling technique for assessing peak downburst wind loads is highlighted with comparisons.

A framework for testing robust autonomy of UAS during design and certification

As the number of Uninhabited Airborne Systems (UAS) proliferates in civil applications, industry is increasingly putting pressure on regulation authorities to provide a path for certification and allow UAS integration into regulated airspace. The success of this integration depends on developments in improved UAS reliability and safety, regulations for certification, and technologies for operational performance and safety assessment. This paper focusses on the last topic and describes a framework for quantifying robust autonomy of UAS, which quantifies the system's ability to either continue operating in the presence of faults or safely shut down. Two figures of merit are used to evaluate vehicle performance relative to mission requirements and the consequences of autonomous decision making in motion control and guidance systems. These figures of merit are interpreted within a probabilistic framework, which extends previous work in the literature. The valuation of the figures of merit can be done using stochastic simulation scenarios during both vehicle development and certification stages with different degrees of integration of hardware-in-the-loop simulation technology. The objective of the proposed framework is to aid in decision making about the suitability of a vehicle with respect to safety and reliability relative to mission requirements.

Direct repression of MYB by ZEB1 suppresses proliferation and epithelial gene expression during epithelial-to-mesenchymal transition of breast cancer cells

Introduction Epithelial-to-mesenchymal transition (EMT) promotes cell migration and is important in metastasis. Cellular proliferation is often downregulated during EMT, and the reverse transition (MET) in metastases appears to be required for restoration of proliferation in secondary tumors. We studied the interplay between EMT and proliferation control by MYB in breast cancer cells. Methods MYB, ZEB1, and CDH1 expression levels were manipulated by lentiviral small-hairpin RNA (shRNA)-mediated knockdown/overexpression, and verified with Western blotting, immunocytochemistry, and qRT-PCR. Proliferation was assessed with bromodeoxyuridine pulse labeling and flow cytometry, and sulforhodamine B assays. EMT was induced with epidermal growth factor for 9 days or by exposure to hypoxia (1% oxygen) for up to 5 days, and assessed with qRT-PCR, cell morphology, and colony morphology. Protein expression in human breast cancers was assessed with immunohistochemistry. ZEB1-MYB promoter binding and repression were determined with Chromatin Immunoprecipitation Assay and a luciferase reporter assay, respectively. Student paired t tests, Mann–Whitney, and repeated measures two-way ANOVA tests determined statistical significance (P < 0.05). Results Parental PMC42-ET cells displayed higher expression of ZEB1 and lower expression of MYB than did the PMC42-LA epithelial variant. Knockdown of ZEB1 in PMC42-ET and MDA-MB-231 cells caused increased expression of MYB and a transition to a more epithelial phenotype, which in PMC42-ET cells was coupled with increased proliferation. Indeed, we observed an inverse relation between MYB and ZEB1 expression in two in vitro EMT cell models, in matched human breast tumors and lymph node metastases, and in human breast cancer cell lines. Knockdown of MYB in PMC42-LA cells (MYBsh-LA) led to morphologic changes and protein expression consistent with an EMT. ZEB1 expression was raised in MYBsh-LA cells and significantly repressed in MYB-overexpressing MDA-MB-231 cells, which also showed reduced random migration and a shift from mesenchymal to epithelial colony morphology in two dimensional monolayer cultures. Finally, we detected binding of ZEB1 to MYB promoter in PMC42-ET cells, and ZEB1 overexpression repressed MYB promoter activity. Conclusions This work identifies ZEB1 as a transcriptional repressor of MYB and suggests a reciprocal MYB-ZEB1 repressive relation, providing a mechanism through which proliferation and the epithelial phenotype may be coordinately modulated in breast cancer cells.

Synthesis of MgB2 at low temperature and autogenous pressure

High quality, micron-sized interpenetrating grains of MgB2 with high density are produced at low temperatures (~420oC < T < ~500oC) under autogenous pressure by pre-mixing Mg powder and NaBH4 and heating in an Inconel 601 alloy reactor for 5−15 hours. Optimum production of MgB2 with yields greater than 75% occurs for autogenous pressure in the range 1.0 MPa to 2.0 MPa with the reactor at ~500oC. Autogenous pressure is induced by the decomposition of NaBH4 in the presence of Mg and/or other Mg-based compounds. The morphology, transition temperature and magnetic properties of MgB2 are dependent on the heating regime. Significant improvement in physical properties accrues when the reactor temperature is held at 250oC for >20minutes prior to a hold at 500oC.

Quantitative sensory measures distinguish office workers with varying levels of neck pain and disability

This study was undertaken to investigate any relationship between sensory features and neck pain in female office workers using quantitative sensory measures to better understand neck pain in this group. Office workers who used a visual display monitor for more than four hours per day with varying levels of neck pain and disability were eligible for inclusion. There were 85 participants categorized according to their scores on the neck disability index (NDI): 33 with no pain (NDI < 8); 38 with mild levels of pain and disability (NDI 9–29); 14 with moderate levels of pain (NDI ⩾ 30). A fourth group of women without neck pain (n = 22) who did not work formed the control group. Measures included: thermal pain thresholds over the posterior cervical spine; pressure pain thresholds over the posterior neck, trapezius, levator scapulae and tibialis anterior muscles, and the median nerve trunk; sensitivity to vibrotactile stimulus over areas of the hand innervated by the median, ulnar and radial nerves; sympathetic vasoconstrictor response. All tests were conducted bilaterally. ANCOVA models were used to determine group differences between the means for each sensory measure. Office workers with greater self-reported neck pain demonstrated hyperalgesia to thermal stimuli over the neck, hyperalgesia to pressure stimulation over several sites tested; hypoaesthesia to vibration stimulation but no changes in the sympathetic vasoconstrictor response. There is evidence of multiple peripheral nerve dysfunction with widespread sensitivity most likely due to altered central nociceptive processing initiated and sustained by nociceptive input from the periphery.

Pressure state response-based method for evaluating social benefits from smart grid development

In this paper, the inherent mechanism of social benefits associated with smart grid development is examined based on the pressure state response (PSR) model from resource economics. The emerging types of technology brought up by smart grid development are regarded as pressures. The improvements of the performance and efficiency of power system operation, such as the enhanced capability of accommodating renewable energy generation, are regarded as states. The effects of smart grid development on society are regarded as responses. Then, a novel method for evaluating social benefits from smart grid development is presented. Finally, the social benefits from smart grid development in a province in northwest China are carried out by using the developed evaluation system, and reasonable evaluation results are attained.

Time pressure and coworker support mediate the curvilinear relationship between age and occupational well-being

As the proportion of older employees in the workforce is growing, researchers have become increasingly interested in the association between age and occupational well-being. The curvilinear nature of relationships between age and job satisfaction and between age and emotional exhaustion is well-established in the literature, with employees in their late 20s to early 40s generally reporting lower levels of occupational well-being than younger and older employees. However, the mechanisms underlying these curvilinear relationships are so far not well understood due to a lack of studies testing mediation effects. Based on an integration of role theory and research from the adult development and career literatures, this study examined time pressure, work–home conflict, and coworker support as mediators of the relationships between age and job satisfaction and between age and emotional exhaustion. Data came from 771 employees between 17 and 74 years of age in the construction industry. Results showed that employees in their late 20s to early 40s had lower job satisfaction and higher emotional exhaustion than younger and older employees. Time pressure and coworker support fully mediated both the U-shaped relationship between age and job satisfaction and the inversely U-shaped relationship between age and emotional exhaustion. These findings suggest that organizational interventions may help increase the relatively low levels of occupational well-being in certain age groups.