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.

A new approach for evaluating the benefits of smart grid development

In this paper, the inherent mechanism of 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 taken as pressures. The improvements of the performance and efficiency of power system operation are taken as states. The effects of smart grid development on society are taken as responses. Then, a novel method for evaluating social benefits in energy saving and CO2 emission reduction from smart grid development is presented. Finally, the benefits in a province in northwest China is carried out by employing the developed evaluation system, and reasonable evaluation results are attained.

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.

Ambient ionisation mass spectrometry for the characterisation of polymers and polymer additives : A review

The purpose of this review is to showcase the present capabilities of ambient sampling and ionisation technologies for the analysis of polymers and polymer additives by mass spectrometry (MS) while simultaneously highlighting their advantages and limitations in a critical fashion. To qualify as an ambient ionisation technique, the method must be able to probe the surface of solid or liquid samples while operating in an open environment, allowing a variety of sample sizes, shapes, and substrate materials to be analysed. The main sections of this review will be guided by the underlying principle governing the desorption/extraction step of the analysis; liquid extraction, laser ablation, or thermal desorption, and the major component investigated, either the polymer itself or exogenous compounds (additives and contaminants) present within or on the polymer substrate. The review will conclude by summarising some of the challenges these technologies still face and possible directions that would further enhance the utility of ambient ionisation mass spectrometry as a tool for polymer analysis. (C) 2013 Elsevier B. V. All rights reserved.

A finite volume method for solving the two-sided time-space fractional advection-dispersion equation

We present a finite volume method to solve the time-space two-sided fractional advection-dispersion equation on a one-dimensional domain. The spatial discretisation employs fractionally-shifted Grünwald formulas to discretise the Riemann-Liouville fractional derivatives at control volume faces in terms of function values at the nodes. We demonstrate how the finite volume formulation provides a natural, convenient and accurate means of discretising this equation in conservative form, compared to using a conventional finite difference approach. Results of numerical experiments are presented to demonstrate the effectiveness of the approach.

A rule-based hybrid method for anomaly detection in online-social-network graphs

Detecting anomalies in the online social network is a significant task as it assists in revealing the useful and interesting information about the user behavior on the network. This paper proposes a rule-based hybrid method using graph theory, Fuzzy clustering and Fuzzy rules for modeling user relationships inherent in online-social-network and for identifying anomalies. Fuzzy C-Means clustering is used to cluster the data and Fuzzy inference engine is used to generate rules based on the cluster behavior. The proposed method is able to achieve improved accuracy for identifying anomalies in comparison to existing methods.

Novel sequential methods in dose-finding designs : extensions of the continual reassessment method

Dose-finding trials are a form of clinical data collection process in which the primary objective is to estimate an optimum dose of an investigational new drug when given to a patient. This thesis develops and explores three novel dose-finding design methodologies. All design methodologies presented in this thesis are pragmatic. They use statistical models, incorporate clinicians' prior knowledge efficiently, and prematurely stop a trial for safety or futility reasons. Designing actual dose-finding trials using these methodologies will minimize practical difficulties, improve efficiency of dose estimation, be flexible to stop early and reduce possible patient discomfort or harm.

Tethering for Selective Synthesis of 2,2′-Biphenols : the Acetal Method

2,2'-Biphenols are a large and diverse group of compounds with exceptional properties both as ligands and bioactive agents. Traditional methods for their synthesis by oxidative dimerisation are often problematic and lead to mixtures of ortho- and para-connected regioisomers. To compound these issues, an intermolecular dimerisation strategy is often inappropriate for the synthesis of heterodimers. The ‘acetal method’ provides a solution for these problems: stepwise tethering of two monomeric phenols enables heterodimer synthesis, enforces ortho regioselectivity and allows relatively facile and selective intramolecular reactions to take place. The resulting dibenzo[1,3]dioxepines have been analysed by quantum chemical calculations to obtain information about the activation barrier for ring flip between the enantiomers. Hydrolytic removal of the dioxepine acetal unit revealed the 2,2′-biphenol target.

Police officer in-vehicle discomfort : appointments carriage method and vehicle seat features

Musculoskeletal pain is commonly reported by police officers. A potential cause of officer discomfort is a mismatch between vehicle seats and the method used for carrying appointments. Twenty-five police officers rated their discomfort while seated in: (1) a standard police vehicle seat, and (2) a vehicle seat custom-designed for police use. Discomfort was recorded in both seats while wearing police appointments on: (1) a traditional appointments belt, and (2) a load-bearing vest / belt combination (LBV). Sitting in the standard vehicle seat and carrying appointments on a traditional appointments belt were both associated with significantly elevated discomfort. Four vehicle seat features were most implicated as contributing to discomfort: back rest bolster prominence; lumbar region support; seat cushion width; and seat cushion bolster depth. Authorising the carriage of appointments using a LBV is a lower cost solution with potential to reduce officer discomfort. Furthermore, the introduction of custom-designed vehicle seats should be considered.

Spatially-explicit modelling of grassland classes - an improved method of integrating a climate-based classification model with interpolated climate surfaces

Spatially-explicit modelling of grassland classes is important to site-specific planning for improving grassland and environmental management over large areas. In this study, a climate-based grassland classification model, the Comprehensive and Sequential Classification System (CSCS) was integrated with spatially interpolated climate data to classify grassland in Gansu province, China. The study area is characterized by complex topographic features imposed by plateaus, high mountains, basins and deserts. To improve the quality of the interpolated climate data and the quality of the spatial classification over this complex topography, three linear regression methods, namely an analytic method based on multiple regression and residues (AMMRR), a modification of the AMMRR method through adding the effect of slope and aspect to the interpolation analysis (M-AMMRR) and a method which replaces the IDW approach for residue interpolation in M-AMMRR with an ordinary kriging approach (I-AMMRR), for interpolating climate variables were evaluated. The interpolation outcomes from the best interpolation method were then used in the CSCS model to classify the grassland in the study area. Climate variables interpolated included the annual cumulative temperature and annual total precipitation. The results indicated that the AMMRR and M-AMMRR methods generated acceptable climate surfaces but the best model fit and cross validation result were achieved by the I-AMMRR method. Twenty-six grassland classes were classified for the study area. The four grassland vegetation classes that covered more than half of the total study area were "cool temperate-arid temperate zonal semi-desert", "cool temperate-humid forest steppe and deciduous broad-leaved forest", "temperate-extra-arid temperate zonal desert", and "frigid per-humid rain tundra and alpine meadow". The vegetation classification map generated in this study provides spatial information on the locations and extents of the different grassland classes. This information can be used to facilitate government agencies' decision-making in land-use planning and environmental management, and for vegetation and biodiversity conservation. The information can also be used to assist land managers in the estimation of safe carrying capacities which will help to prevent overgrazing and land degradation.

An efficient and effective localization method for networked disjoint top-view cameras

Disjoint top-view networked cameras are among the most commonly utilized networks in many applications. One of the open questions for these cameras' study is the computation of extrinsic parameters (positions and orientations), named extrinsic calibration or localization of cameras. Current approaches either rely on strict assumptions of the object motion for accurate results or fail to provide results of high accuracy without the requirement of the object motion. To address these shortcomings, we present a location-constrained maximum a posteriori (LMAP) approach by applying known locations in the surveillance area, some of which would be passed by the object opportunistically. The LMAP approach formulates the problem as a joint inference of the extrinsic parameters and object trajectory based on the cameras' observations and the known locations. In addition, a new task-oriented evaluation metric, named MABR (the Maximum value of All image points' Back-projected localization errors' L2 norms Relative to the area of field of view), is presented to assess the quality of the calibration results in an indoor object tracking context. Finally, results herein demonstrate the superior performance of the proposed method over the state-of-the-art algorithm based on the presented MABR and classical evaluation metric in simulations and real experiments.

A sub‒domain smoothed Galerkin method for solid mechanics problems

A sub‒domain smoothed Galerkin method is proposed to integrate the advantages of mesh‒free Galerkin method and FEM. Arbitrarily shaped sub‒domains are predefined in problems domain with mesh‒free nodes. In each sub‒domain, based on mesh‒free Galerkin weak formulation, the local discrete equation can be obtained by using the moving Kriging interpolation, which is similar to the discretization of the high‒order finite elements. Strain smoothing technique is subsequently applied to the nodal integration of sub‒domain by dividing the sub‒domain into several smoothing cells. Moreover, condensation of DOF can also be introduced into the local discrete equations to improve the computational efficiency. The global governing equations of present method are obtained on the basis of the scheme of FEM by assembling all local discrete equations of the sub‒domains. The mesh‒free properties of Galerkin method are retained in each sub‒domain. Several 2D elastic problems have been solved on the basis of this newly proposed method to validate its computational performance. These numerical examples proved that the newly proposed sub‒domain smoothed Galerkin method is a robust technique to solve solid mechanics problems based on its characteristics of high computational efficiency, good accuracy, and convergence.

Health monitoring of short-and medium-spen bridges using an improved modal strain energy method

Increasing the importance and use of infrastructures such as bridges, demands more effective structural health monitoring (SHM) systems. SHM has well addressed the damage detection issues through several methods such as modal strain energy (MSE). Many of the available MSE methods either have been validated for limited type of structures such as beams or their performance is not satisfactory. Therefore, it requires a further improvement and validation of them for different types of structures. In this study, an MSE method was mathematically improved to precisely quantify the structural damage at an early stage of formation. Initially, the MSE equation was accurately formulated considering the damaged stiffness and then it was used for derivation of a more accurate sensitivity matrix. Verification of the improved method was done through two plane structures: a steel truss bridge and a concrete frame bridge models that demonstrate the framework of a short- and medium-span of bridge samples. Two damage scenarios including single- and multiple-damage were considered to occur in each structure. Then, for each structure, both intact and damaged, modal analysis was performed using STRAND7. Effects of up to 5 per cent noise were also comprised. The simulated mode shapes and natural frequencies derived were then imported to a MATLAB code. The results indicate that the improved method converges fast and performs well in agreement with numerical assumptions with few computational cycles. In presence of some noise level, it performs quite well too. The findings of this study can be numerically extended to 2D infrastructures particularly short- and medium-span bridges to detect the damage and quantify it more accurately. The method is capable of providing a proper SHM that facilitates timely maintenance of bridges to minimise the possible loss of lives and properties.

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.

A simple method for EPID-based in vivo dosimetry for radiotherapy treatments of head-and-neck cancers

This study used a homogeneous water-equivalent model of an electronic portal imaging device (EPID), contoured as a structure in a radiotherapy treatment plan, to produce reference dose images for comparison with in vivo EPID dosimetry images. Head and neck treatments were chosen as the focus of this study, due to the heterogeneous anatomies involved and the consequent difficulty of rapidly obtaining reliable reference dose images by other means. A phantom approximating the size and heterogeneity of a typical neck, with a maximum radiological thickness of 8.5 cm, was constructed for use in this study. This phantom was CT scanned and a simple treatment including five square test fields and one off-axis IMRT field was planned. In order to allow the treatment planning system to calculate dose in a model EPID positioned a distance downstream from the phantom to achieve a source-to-detector distance (SDD) of 150 cm, the CT images were padded with air and the phantom’s “body” contour was extended to encompass the EPID contour. Comparison of dose images obtained from treatment planning calculations and experimental irradiations showed good agreement, with more than 90% of points in all fields passing a gamma evaluation, at γ (3%, 3mm )Similar agreement was achieved when the phantom was over-written with air in the treatment plan and removed from the experimental beam, suggesting that water EPID model at 150 cm SDD is capable of providing accurate reference images for comparison with clinical IMRT treatment images, for patient anatomies with radiological thicknesses ranging from 0 up to approximately 9 cm. This methodology therefore has the potential to be used for in vivo dosimetry during treatments to tissues in the neck as well as the oral and nasal cavities, in the head-and-neck region.