The low-affinity site of the β1-adrenoceptor and its relevance to cardiovascular pharmacology

β-Adrenoceptor blocking agents (β-blockers) that at low concentrations antagonize cardiostimulant effects of catecholamines, but at high concentrations also cause cardiostimulation, have been appearing since the late 1960s. These cardiostimulant β-blockers, coined non-conventional partial agonists, antagonize the effects of catecholamines through a high-affinity site (β1HAR), but cause cardiostimulation mainly through a low-affinity site (β1LAR) of the myocardial β1-adrenoceptor. The experimental non-conventional partial agonist (−)-CGP12177 increases cardiac L-type Ca2+ current density and Ca2+ transients, shortens action potential duration but augments action potential plateau, increases heart rate and force, as well as causes arrhythmic Ca2+ transients and arrhythmic cardiocyte contractions. Other β-blockers, which do not cause cardiostimulation, consistently have lower affinity for β1LAR than β1HAR. These sites were verified and the cardiac pharmacology of non-conventional partial agonists confirmed on recombinant β1-adrenoceptors and on β1-adrenoceptors overexpressed into the heart. A targeted mutation of Asp138 to Glu138 virtually abolished the pharmacology of β1HAR but left intact the pharmacology of β1LAR. Non-conventional partial agonists may be beneficial for the treatment of peripheral autonomic neuropathy but probably due to their arrhythmic propensities, may be harmful for the treatment of chronic heart failure.

meso-Porphyrinylphosphine Oxides: Mono- and Bidentate Ligands for Supramolecular Chemistry and the Crystal Structures of Monomeric [10,20-Diphenylporphyrinatonickel(II)-5,15-diyl]-bis-[P(O)Ph2] and Polymeric Self-Coordinated ([10,20-Diphenylporphyrinatozinc(II)-5,15-diyl]-bis-[P(O)Ph2])

A series of porphyrins substituted in one or two meso-positions by diphenylphosphine oxide groups has been prepared by the palladium catalysed reaction of diphenylphosphine or its oxide with the corresponding bromoporphyrins. Compounds {MDPP-[P(O)Ph2]n} (M = H2, Ni, Zn; H2DPP = 5,15-diphenylporphyrin; n = 1, 2) were isolated in yields of 60-95%. The reaction is believed to proceed via the conventional oxidative addition, phosphination and reductive elimination steps, as the stoichiometric reaction of η1-palladio(II) porphyrin [PdBr(H2DPP)(dppe)] (H2DPP = 5,15-diphenylporphyrin; dppe = 1,2-bis(diphenylphosphino)ethane) with diphenylphosphine oxide also results in the desired mono-porphyrinylphosphine oxide [H2DPP-P(O)Ph2]. Attempts to isolate the tertiary phosphines failed due to their extreme air-sensitivity. Variable temperature 1H NMR studies of [H2DPP-P(O)Ph2] revealed an intrinsic lack of symmetry, while fluorescence spectroscopy showed that the phosphine oxide group does not behave as a "heavy atom" quencher. The electron withdrawing effect of the phosphine oxide group was confirmed by voltammetry. The ligands were characterised by multinuclear NMR and UV-visible spectroscopy as well as mass spectrometry. Single crystal X-ray crystallography showed that the bis(phosphine oxide) nickel(II) complex {[NiDPP-[P(O)Ph2]2} is monomeric in the solid state, with a ruffled porphyrin core and the two P=O fragments on the same side of the average plane of the molecule. On the other hand, the corresponding zinc(II) complex formed infinite chains through coordination of one Ph2PO substituent to the neighbouring zinc porphyrin through an almost linear P=O---Zn unit, leaving the other Ph2PO group facing into a parallel channel filled with disordered water molecules. These new phosphine oxides are attractive ligands for supramolecular porphyrin chemistry.

An evaluation framework for sustaining the impact of educational development

Notwithstanding significant efforts by international aid agencies, aid ineffectiveness became apparent in 1990s as the impact of continued development intervention did not endure the expected outcomes. Conventional monitoring and evaluation by those agencies is critiqued for focusing on measuring project outcomes and giving little attention to aspects of sustainability. As a result, devising a rigorous evaluation framework for educational development has been sought in light of recent paradigm shifts in international development. This paper reports on a case study of an Egyptian educational development project highlighting the importance of transforming the evaluation procedures to process evaluation so as to enhance project impact and longevity. This requires building evaluation capacity of the aid recipient country.

Ultrafast near infrared sintering of TiO2 layers on metal substrates for dye-sensitized solar cells

A limiting step to roll-to-roll production of dye-sensitized solar cells on metals is TiO2 sintering (10-30 min). Near infrared (NIR) heating is a novel process innovation which directly heats titanium substrates giving rapid binder removal and sintering. NIR heating (for 12.5 s) at varying power gave titanium temperatures of 545, 685 and 817 degrees Celsius yielding cells with efficiencies of 2.9, 2.8 and 2.5%. Identical cells prepared in a conventional oven (1800 s) at 500, 600 and 800 degrees Celsius gave 2.9, 2.6 and 0.2% efficiency. NIR sintering is ultrafast and has a wide process window making it ideal for rapid manufacturing on metals.

Thin film solar cells based on CU2ZnSnS4 absorber

Cu2ZnSnS4 (CZTS) is considered to be one of the most promising light absorbing materials for low cost, high efficiency thin film solar cells. Compared to conventional CuIn(S, Se)2 (CIS) and Cu(InGa)(S,Se)2 (CIGS) as well as CdTe light absorber, CZTS is only composed of earth-abundant non-toxic elements, ensuring the price competitiveness of this kind of solar cell in the future PV market. However, the research in this area is very limited compared to CIS and CIGS. Detailed studies of both the material and the device are rare, which significantly restricts the development in this area. This paper reviews the progress in the research field of CZTS, particularly the methods which were employed to prepare CZTS absorber material.

Cluster analysis of movement patterns in multiarticular actions: A tutorial

The present paper proposes a technical analysis method for extracting information about movement patterning in studies of motor control, based on a cluster analysis of movement kinematics. In a tutorial fashion, data from three different experiments are presented to exemplify and validate the technical method. When applied to three different basketball-shooting techniques, the method clearly distinguished between the different patterns. When applied to a cyclical wrist supination-pronation task, the cluster analysis provided the same results as an analysis using the conventional discrete relative phase measure. Finally, when analyzing throwing performance constrained by distance to target, the method grouped movement patterns together according to throwing distance. In conclusion, the proposed technical method provides a valuable tool to improve understanding of coordination and control in different movement models, including multiarticular actions.

Natural balancing of flying capacitor voltages in multicell inverter under PD carrier-based PWM

The flying capacitor multicell inverter (FCMI) possesses natural balancing property. With the phase-shifted (PS) carrier-based scheme, natural balancing can be achieved in a straightforward manner. However, to achieve natural balancing with the harmonically optimal phase-disposition (PD) carrierbased scheme, the conventional approaches require (n-1) x (n-1) trapezoidal carrier signals for an n-level inverter, which is (n-1) x (n-2) times more than that in the standard PD scheme. This paper proposes two improved natural balancing strategies for FMI under PD scheme, which use the same (n-1) carrier signals as used in the standard PD scheme. In the first scheme, on-line detection is performed of the band in which the modulation signal is located, corresponding period number of the carrier, and rising or falling half cycle of the carrier waveform to generate the switching signals based on certain rules. In the second strategy, the output voltage level selection is first processed and the switching signals are then generated according to a rule based on preferential cell selection algorithm. These methods are easy to use and can be simply implemented as compared to the other available methods. Simulation and experimental results are presented for a five-level inverter to verify these proposed schemes.

Inclusion of PMU current phasor measurements in a power system state estimator

Three different methods of inclusion of current measurements by phasor measurement units (PMUs) in a power sysetm state estimator is investigated. A comprehensive formulation of the hybrid state estimator incorporating conventional, as well as PMU measurements, is presented for each of the three methods. The behaviour of the elements because of the current measurements in the measurement Jacobian matrix is examined for any possible ill-conditioning of the state estimator gain matrix. The performance of the state estimators are compared in terms of the convergence properties and the varian in the estimated states. The IEEE 14-bus and IEEE 300-bus systems are used as test beds for the study.

Innovation networks in the construction arena : the strategic management of mixed enterprises

The building and construction sector is one of the five largest contributors to the Australian economy and is a key performance component in the economy of many other jurisdictions. However, the ongoing viability of this sector is increasingly reliant on its ability to foster and transfer innovated products and practices. Interorganisational networks, which bring together key industry stakeholders and facilitate the flows of information, resources and trust necessary to secure innovation, have emerged as a key growth strategy within this and other arenas. The blending of organisations, resources and purposes creates new, hybrid institutional forms that draw on a mix of contract, structure and interpersonal relationship as integration processes. This paper argues that hybrid networked arrangements, because they incorporate relational elements, require management strategies and techniques that not always synonymous with conventional management approaches, including those used within the building and construction sector. It traces the emergence of the Construction Innovation Project in Australia as a hybrid institutional arrangement moulding public, private and academic stakeholders of the building and construction industry into a coherent collective force aimed at fostering innovation and its application within all levels of the industry. Specifically, the paper examines the Construction Innovation Project to ascertain the impact of relational governance and its management to harness and leverage the skills, resources and capacities of members to secure innovative outcomes. Finally, the paper offers some prospects to guide the ongoing work of this body and any other charged with a similar integrative responsibility.

Shear tests of Litesteel beams with web openings

This paper presents the details of experimental studies on the shear strength of a recently developed, cold-formed steel beam known as LiteSteel Beam (LSB) with web openings. The innovative LSB sections have the beneficial characteristics of torsionally rigid closed rectangular flanges combined with economical fabrication processes from a single strip of high strength steel. They combine the stability of hot-rolled steel sections with the high strength to weight ratio of conventional cold-formed steel sections. The LSB sections are commonly used as flexural members in the building industry. Current practice in flooring systems is to include openings in the web element of floor joists or bearers so that building services can be located within them. Shear behaviour of LSBs with web openings is more complicated while their shear strengths are considerably reduced by the presence of web openings. However, limited research has been undertaken on the shear behaviour and strength of LSBs with web openings. Therefore a detailed experimental study involving 26 shear tests was undertaken to investigate the shear behaviour and strength of different LSB sections. Simply supported test specimens of LSBs with an aspect ratio of 1.5 were loaded at midspan until failure. This paper presents the details of this experimental study and the results. Experimental results showed that the current design rules in cold-formed steel structures design codes (AS/NZS 4600) [1] are very conservative for the shear design of LSBs with web openings. Improved design equations have been proposed for the shear strength of LSBs with web openings based on experimental results from this study.

Test and evaluation system for multi-protocol sampled value protection schemes

Proposed transmission smart grids will use a digital platform for the automation of substations operating at voltage levels of 110 kV and above. The IEC 61850 series of standards, released in parts over the last ten years, provide a specification for substation communications networks and systems. These standards, along with IEEE Std 1588-2008 Precision Time Protocol version 2 (PTPv2) for precision timing, are recommended by the both IEC Smart Grid Strategy Group and the NIST Framework and Roadmap for Smart Grid Interoperability Standards for substation automation. IEC 61850-8-1 and IEC 61850-9-2 provide an inter-operable solution to support multi-vendor digital process bus solutions, allowing for the removal of potentially lethal voltages and damaging currents from substation control rooms, a reduction in the amount of cabling required in substations, and facilitates the adoption of non-conventional instrument transformers (NCITs). IEC 61850, PTPv2 and Ethernet are three complementary protocol families that together define the future of sampled value digital process connections for smart substation automation. This paper describes a specific test and evaluation system that uses real time simulation, protection relays, PTPv2 time clocks and artificial network impairment that is being used to investigate technical impediments to the adoption of SV process bus systems by transmission utilities. Knowing the limits of a digital process bus, especially when sampled values and NCITs are included, will enable utilities to make informed decisions regarding the adoption of this technology.

Arts-based research in design education

There is an urgent need in terms of changing world conditions to move beyond the dualist paradigm that has traditionally informed design research, education and practice. Rather than attempt to reduce uncertainty, novelty and complexity as is the conventional approach, an argument is presented in this article that seeks to exploit these qualities through a reconceptualisation of design in creative as well as systematic, rigorous and ethical terms. Arts-based research, which 'brings together the systematic and rigorous qualities of inquiry with the creative and imaginative qualities of the arts', is presented as being central to this reconceptualisation. This is exemplified in the application of art-informed inquiry in a research unit for graduating tertiary-level interior design students. The application is described in this article and is shown to rely substantially on the image and its capacity to open up and reveal new possibilities and meaning.

Towards the adoption of low-cost rail level crossing warning devices in regional areas of Australia : a review of current technologies and reliability issues

This paper discusses major obstacles for the adoption of low cost level crossing warning devices (LCLCWDs) in Australia and reviews those trialed in Australia and internationally. The argument for the use of LCLCWDs is that for a given investment, more passive level crossings can be treated, therefore increasing safety benefits across the rail network. This approach, in theory, reduces risk across the network by utilizing a combination of low-cost and conventional level crossing interventions, similar to what is done in the road environment. This paper concludes that in order to determine if this approach can produce better safety outcomes than the current approach, involving the incremental upgrade of level crossings with conventional interventions, it is necessary to perform rigorous risk assessments and cost-benefit analyses of LCLCWDs. Further research is also needed to determine how best to differentiate less reliable LCCLWDs from conventional warning devices through the use of different warning signs and signals. This paper presents a strategy for progressing research and development of LCLCWDs and details how the Cooperative Research Centre (CRC) for Rail Innovation is fulfilling this strategy through the current and future affordable level crossing projects.

Trans digital storytelling : everyday activism, mutable identity and the problem of visibility

Mainstream representations of trans people typically run the gamut from victim to mentally ill and are almost always articulated by non-trans voices. The era of user-generated digital content and participatory culture has heralded unprecedented opportunities for trans people who wish to speak their own stories in public spaces. Digital Storytelling, as an easy accessible autobiographic audio-visual form, offers scope to play with multi-dimensional and ambiguous representations of identity that contest mainstream assumptions of what it is to be ‘male’ or ‘female’. Also, unlike mainstream media forms, online and viral distribution of Digital Stories offer potential to reach a wide range of audiences, which is appealing to activist oriented storytellers who wish to confront social prejudices. However, with these newfound possibilities come concerns regarding visibility and privacy, especially for storytellers who are all too aware of the risks of being ‘out’ as trans. This paper explores these issues from the perspective of three trans storytellers, with reference to the Digital Stories they have created and shared online and on DVD. These examplars are contextualised with some popular and scholarly perspectives on trans representation, in particular embodied and performed identity. It is contended that trans Digital Stories, while appearing in some ways to be quite conventional, actually challenge common notions of gender identity in ways that are both radical and transformative.

Immunohistochemical analysis of structural changes in collagen for the assessment of osteoarthritis

Collagen fibrillation within articular cartilage (AC) plays a key role in joint osteoarthritis (OA) progression and, therefore, studying collagen synthesis changes could be an indicator for use in the assessment of OA. Various staining techniques have been developed and used to determine the collagen network transformation under microscopy. However, because collagen and proteoglycan coexist and have the same index of refraction, conventional methods for specific visualization of collagen tissue is difficult. This study aimed to develop an advanced staining technique to distinguish collagen from proteoglycan and to determine its evolution in relation to OA progression using optical and laser scanning confocal microscopy (LSCM). A number of AC samples were obtained from sheep joints, including both healthy and abnormal joints with OA grades 1 to 3. The samples were stained using two different trichrome methods and immunohistochemistry (IHC) to stain both colourimetrically and with fluorescence. Using optical microscopy and LSCM, the present authors demonstrated that the IHC technique stains collagens only, allowing the collagen network to be separated and directly investigated. Fluorescently-stained IHC samples were also subjected to LSCM to obtain three-dimensional images of the collagen fibres. Changes in the collagen fibres were then correlated with the grade of OA in tissue. This study is the first to successfully utilize the IHC staining technique in conjunction with laser scanning confocal microscopy. This is a valuable tool for assessing changes to articular cartilage in OA.