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.

A review of rationale for allocating costs and payments in producing and supplying public sector information PART A of 2 Parts – Chapters 1, 2 and 3) 13 March 2011 version

This work reviews the rationale and processes for raising revenue and allocating funds to perform information intensive activities that are pertinent to the work of democratic government. ‘Government of the people, by the people, for the people’ expresses an idea that democratic government has no higher authority than the people who agree to be bound by its rules. Democracy depends on continually learning how to develop understandings and agreements that can sustain voting majorities on which democratic law making and collective action depends. The objective expressed in constitutional terms is to deliver ‘peace, order and good government’. Meeting this objective requires a collective intellectual authority that can understand what is possible; and a collective moral authority to understand what ought to happen in practice. Facts of life determine that a society needs to retain its collective competence despite a continual turnover of its membership as people die but life goes on. Retaining this ‘collective competence’ in matters of self-government depends on each new generation: • acquiring a collective knowledge of how to produce goods and services needed to sustain a society and its capacity for self-government; • Learning how to defend society diplomatically and militarily in relation to external forces to prevent overthrow of its self-governing capacity; and • Learning how to defend society against divisive internal forces to preserve the authority of representative legislatures, allow peaceful dispute resolution and maintain social cohesion.

Evaluation of the year 1 literacy and numeracy checkpoints assessments trial - 2010

The draft Year 1 Literacy and Numeracy Checkpoints Assessments were in open and supported trial during Semester 2, 2010. The purpose of these trials was to evaluate the Year 1 Literacy and Numeracy Checkpoints Assessments (hereafter the Year 1 Checkpoints) that were designed in 2009 as a way to incorporate the use of the Year 1 Literacy and Numeracy Indicators as formative assessment in Year 1 in Queensland Schools. In these trials there were no mandated reporting requirements. The processes of assessment were related to future teaching decisions. As such the trials were trials of materials and the processes of using those materials to assess students, plan and teach in year 1 classrooms. In their current form the Year 1 Checkpoints provide assessment resources for teachers to use in February, June and October. They aim to support teachers in monitoring children's progress and making judgments about their achievement of the targeted P‐3 Literacy and Numeracy Indicators by the end of Year 1 (Queensland Studies Authority, 2010 p. 1). The Year 1 Checkpoints include support materials for teachers and administrators, an introductory statement on assessment, work samples, and a Data Analysis Assessment Record (DAAR) to record student performance. The Supported Trial participants were also supported with face‐to‐face and on‐line training sessions, involvement in a moderation process after the October Assessments, opportunities to participate in discussion forums as well as additional readings and materials. The assessment resources aim to use effective early years assessment practices in that the evidence is gathered from hands‐on teaching and learning experiences, rather than more formal assessment methods. They are based in a model of assessment for learning, and aim to support teachers in the “on‐going process of determining future learning directions” (Queensland Studies Authority, 2010 p. 1) for all students. Their aim is to focus teachers on interpreting and analysing evidence to make informed judgments about the achievement of all students, as a way to support subsequent planning for learning and teaching. The Evaluation of the Year 1 Literacy and Numeracy Checkpoints Assessments Supported Trial (hereafter the Evaluation) aimed to gather information about the appropriateness, effectiveness and utility of the Year 1 Checkpoints Assessments from early years’ teachers and leaders in up to one hundred Education Queensland schools who had volunteered to be part of the Supported Trial. These sample schools represent schools across a variety of Education Queensland regions and include schools with:  - A high Indigenous student population; - Urban, rural and remote school locations; - Single and multi‐age early phase classes; - A high proportion of students from low SES backgrounds. The purpose of the Evaluation was to: Evaluate the materials and report on the views of school‐based staff involved in the trial on the process, materials, and assessment practices utilised. The Evaluation has reviewed the materials, and used surveys, interviews, and observations of processes and procedures to collect relevant data to help present an informed opinion on the Year 1 Checkpoints as assessment for the early years of schooling. Student work samples and teacher planning and assessment documents were also collected. The evaluation has not evaluated the Year 1 Checkpoints in any other capacity than as a resource for Year 1 teachers and relevant support staff.

2-(4-Aminophenyl)-1-phenyldiazenium 2,4,6-trinitrophenolate

In the structure of the title salt, C12H12N3+ C6H2N3O7-, the diazenyl group of the 4-(phenyldiazenyl)aniline molecule is protonated and forms a hydrogen bond with the phenolate O acceptor of the picrate anion. Structure extension occurs through two symmetrical inter-ion three-centre amine N---H...O,O'(nitro) hydrogen-bonding associations [graph set R2/1(4)] giving a convoluted two-dimensional network structure.

The legal role of medical professionals in decisions to withhold or withdraw life-sustaining treatment : Part 1 (New South Wales)

This is the first article in a series of three that examines the legal role of medical professionals in decisions to withhold or withdraw life-sustaining treatment from adults who lack capacity. This article considers the position in New South Wales. A review of the law in this State reveals that medical professionals play significant legal roles in these decisions. However, the law is problematic in a number of respects and this is likely to impede medical professionals’ legal knowledge in this area. The article examines the level of training medical professionals receive on issues such as advance directives and substitute decision-making, and the available empirical evidence as to the state of medical professionals’ knowledge of the law at the end of life. It concludes that there are gaps in legal knowledge and that law reform is needed in New South Wales.

Road safety issues for older road users : CARRS-Q Monograph 1

[Selection of papers from the Older Road User Safety Symposium, 26 November 2000, Brisbane, Australia.]----- This publication is a selection of papers on older road user safety which were presented at the Older Road User Safety Symposium on Sunday 26 November 2000 at the Sheraton Brisbane Hotel, Queensland, Australia. The Symposium was held on the day before Australia’s annual Road Safety Research, Policing and Education Conference, which provided an opportunity to garner both presenters and participants from the wider road safety community in Australia. Road safety is a large and diverse area of scholarship and practice, and many disciplines are drawn on in the processes of understanding and addressing road safety problems. The safety of older road users is no different. As this selection shows, work on older road user safety can be informed by demography, research on the mental and physical effects of ageing, social research on older people as road users, evaluation of educational and behavioural interventions, road crash analysis, engineering research and practice, and reviews of policy approaches within Australia and elsewhere. It is possible to summarise these into four constellations, which are reflected in the papers selected for this publication: social impacts and responses; physical and cognitive capability; specific road use performance; and environment/ecology. Though three years have passed since the Symposium, the issues raised in these papers remain current.

Sonic loom (Volume 1)

Sonic Loom is a purpose built classroom tool for teachers and students of drama that will enable them to explore the use of music in live performance in theory and practice. It’s intended as a resource for drama classrooms, to encourage communication and exchange about the way music works on us so we can find new ways we can make it work for us. Working to consciously attend to music and how it’s used, particularly in cinema (as a popular way in to styles of western theatre and live performance) will allow students and teachers to use music in more subtle and complex ways an aid to narrative in performance. Sonic Loom encourages active listening, (aided but not encumbered by traditional musicology) so students (and teachers) can develop a ‘critical ear’ in the transformation and adaptation of music for their own artistic purposes, whether it’s soundtracking existing scene work, or acting as a pre-text for scenes which have yet to be created.

Analysis of Object-Specific Authorization Protocol (OSAP) using coloured petri nets - Version 1.0

Analyzing security protocols is an ongoing research in the last years. Different types of tools are developed to make the analysis process more precise, fast and easy. These tools consider security protocols as black boxes that can not easily be composed. It is difficult or impossible to do a low-level analysis or combine different tools with each other using these tools. This research uses Coloured Petri Nets (CPN) to analyze OSAP trusted computing protocol. The OSAP protocol is modeled in different levels and it is analyzed using state space method. The produced model can be combined with other trusted computing protocols in future works.

Functional role of cell surface CUB domain-containing protein 1 in tumour cell dissemination

The function of CUB domain-containing protein 1 (CDCP1), a recently described transmembrane protein expressed on the surface of hematopoietic stem cells and normal and malignant cells of different tissue origin, is not well defined. The contribution of CDCP1 to tumor metastasis was analyzed by using HeLa carcinoma cells overexpressing CDCP1 (HeLa-CDCP1) and a high-disseminating variant of prostate carcinoma PC-3 naturally expressing high levels of CDCP1 (PC3-hi/diss). CDCP1 expression rendered HeLa cells more aggressive in experimental metastasis in immunodeficient mice. Metastatic colonization by HeLa-CDCP1 was effectively inhibited with subtractive immunization-generated, CDCP1-specific monoclonal antibody (mAb) 41-2, suggesting that CDCP1 facilitates relatively late stages of the metastatic cascade. In the chick embryo model, time- and dose-dependent inhibition of HeLa-CDCP1 colonization by mAb 41-2 was analyzed quantitatively to determine when and where CDCP1 functions during metastasis. Quantitative PCR and immunohistochemical analyses indicated that CDCP1 facilitated tumor cell survival soon after vascular arrest. Live cell imaging showed that the function-blocking mechanism of mAb 41-2 involved enhancement of tumor cell apoptosis, confirmed by attenuation of mAb 41-2–mediated effects with the caspase inhibitor z-VAD-fmk. Under proapoptotic conditions in vitro, CDCP1 expression conferred HeLa-CDCP1 cells with resistance to doxorubicin-induced apoptosis, whereas ligation of CDCP1 with mAb 41-2 caused additional enhancement of the apoptotic response. The functional role of naturally expressed CDCP1 was shown by mAb 41-2–mediated inhibition of both experimental and spontaneous metastasis of PC3-hi/diss. These findings confirm that CDCP1 functions as an antiapoptotic molecule and indicate that during metastasis CDCP1 facilitates tumor cell survival likely during or soon after extravasation.

Managing wetlands sustainably as ecosystems : The contribution of the law (part 1)

The ways in which a society set standards of behaviour and of conduct for its members vary hugely. For example, accepted practices, recognised customs, spiritually or morally inspired norms, judicially declared rules, executively formulated edicts, formal legislative enactments or constitutionally embedded rights and duties. Whatever form they assume, these standards are the artificial construction of the human mind. Accordingly the law - whatever its form - can do no more and no less than regulate or set standards for human behaviour, human conduct, and human decision-making. The law cannot regulate the environment. It can only regulate human activities that impact directly or indirectly upon the environment. This applies as much to wetlands as components of the environment as it does to any other components of the environment or the environment at large. The capacity of the law to protect the environment and therefore wetlands is thus totally dependent upon the capacity of the law to regulate human behaviour, human conduct and human decision-making. At the same time the law needs to reflect the specific nature, functions and locations of wetlands. A wetland is an ecosystem by itself; it comprises a range of ecosystems within it; and it is part of a wider set of ecosystems. Hence, the significant ecological functions performed by wetlands. Then there are the benefits flowing to humans from wetlands. These may be social, economic, cultural, aesthetic, or a combination of some or of all of these. It is a challenge for a society acting through its legal system to find the appropriate balance between these ecological and these human values. But that is what sustainability requires.The ways in which a society set standards of behaviour and of conduct for its members vary hugely. For example, accepted practices, recognised customs, spiritually or morally inspired norms, judicially declared rules, executively formulated edicts, formal legislative enactments or constitutionally embedded rights and duties. Whatever form they assume, these standards are the artificial construction of the human mind. Accordingly the law - whatever its form - can do no more and no less than regulate or set standards for human behaviour, human conduct, and human decision-making. The law cannot regulate the environment. It can only regulate human activities that impact directly or indirectly upon the environment. This applies as much to wetlands as components of the environment as it does to any other components of the environment or the environment at large. The capacity of the law to protect the environment and therefore wetlands is thus totally dependent upon the capacity of the law to regulate human behaviour, human conduct and human decision-making. At the same time the law needs to reflect the specific nature, functions and locations of wetlands. A wetland is an ecosystem by itself; it comprises a range of ecosystems within it; and it is part of a wider set of ecosystems. Hence, the significant ecological functions performed by wetlands. Then there are the benefits flowing to humans from wetlands. These may be social, economic, cultural, aesthetic, or a combination of some or of all of these. It is a challenge for a society acting through its legal system to find the appropriate balance between these ecological and these human values. But that is what sustainability requires.