Computer assisted synthesis and in-vitro cytotoxic evaluation of new pyrazole-fused isoquinolinoquinones derivatives as PI3K receptor antagonist with promising antitumoral activity

The importance of pyrazole and isoquinoline-5,8-dione scaffolds in medical chemistry is underlined by the high number of drugs currently on trading that contains these active ingredients. Due to their cytotoxic capability, the interest of medicinal chemists in these heterocyclic rings has grown exponentially especially, for cancer therapy. In this project, the first synthesis of pyrazole-fused isoquinoline-5,8-diones has been developed. 1,3-Dipolar cycloaddition followed by oxidative aromatization, established by our research group, has been employed. Screening of reaction conditions and characterization studies about the regioselectivity have been successfully performed. A remote control of regioselectivity, to achieve the two possible regioisomers has been accomplished. Through Molecular Docking studies, Structure-Activity relationship of differently substituted scaffolds containing our central core proved that a family of PI3K inhibitors have been discovered. Finally, in order to verify the promising antitumor activity, a first test of cell viability in vitro on T98G cell line of a solid brain tumor, the Glioblastoma Multiforme, showed cytotoxic inhibition comparable to currently trade anticancer drugs.

The medico-legal importance of establishing human identity by palatal rugoscopy: evaluation of the immutability and individuality of palatal rugae under the influence of ante mortem orthodontic treatment

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Longitudinal Student Evaluations of a Postgraduate Unit Using Importance-Performance Analysis

The Australian tourism tertiary education sector operates in a competitive and dynamic environment, which necessitates a market orientation to be successful. Academic staff and management in the sector must regularly assess the perceptions of prospective and current students, and monitor the satisfaction levels of current students. This study is concerned with the setting and monitoring of satisfaction levels of current students, reporting the results of three longitudinal investigations of student satisfaction in a postgraduate unit. The study also addresses a limitation of a university’s generic teaching evaluation instrument. Importance-performance analysis (IPA) has been recommended as a simple but effective tool for overcoming the deficiencies of many student evaluation studies, which have generally measured only attribute importance or importance at the end of a semester. IPA was used to compare student expectations of the unit at the beginning of semester with their perceptions of performance ten weeks later. The first stage documented key benchmarks for which amendments to the unit based on student feedback could be evaluated during subsequent teaching periods.

The public management issues of access to electronic gaming machines (EGMs) : a case study of policy in Victoria, its effects and requirements for evaluation

Wynne and Schaffer (2003) have highlighted both the strong growth of gambling activity in recent years, and the revenue streams this has generated for governments and communities. Gambling activities and the revenues derived from them have, unsurprisingly, therefore also been seen as a way in which to increase economic development in deprived areas (Jinkner-Lloyd, 1996). Consequently, according to Brown et al (2003), gambling is now a large taxation revenue earner for many western governments, at both federal and state levels, worldwide (for example UK, USA, Australia). In size and importance, the Australian gambling industry in particular has grown significantly over the last three decades, experiencing a fourfold increase in real gambling turnover. There are, however, also concerns expressed about gambling and Electronic Gaming in particular, as illustrated in economic, social and ethical terms in Oddo (1997). There are also spatial aspects to understanding these issues. Marshall’s (1998) study, for example, highlights that benefits from gambling are more likely to accrue at the macro as opposed to the local level, because of centralised tax gathering and spending of tax revenues, whilst localities may suffer from displacement of activities with higher multipliers than the institutions with EGMs that replace them. This also highlights a regional context of costs, where benefits accrue to the centre, but the costs accrue to the regions and localities, as simultaneously resources leave those communities through both the gambling activities themselves (in the form of revenue for the EGM owners), and the government (through taxes).

An institutional understanding of triple bottom line evaluations and the use of social and environmental metrics

Measuring social and environmental metrics of property is necessary for meaningful triple bottom line (TBL) assessments. This paper demonstrates how relevant indicators derived from environmental rating systems provide for reasonably straightforward collations of performance scores that support adjustments based on a sliding scale. It also highlights the absence of a corresponding consensus of important social metrics representing the third leg of the TBL tripod. Assessing TBL may be unavoidably imprecise, but if valuers and managers continue to ignore TBL concerns, their assessments may soon be less relevant given the emerging institutional milieu informing and reflecting business practices and society expectations.

Revisiting the conceptualization and measurement of service quality

Since the 1980s, industries and researchers have sought to better understand the quality of services due to the rise in their importance (Brogowicz, Delene and Lyth 1990). More recent developments with online services, coupled with growing recognition of service quality (SQ) as a key contributor to national economies and as an increasingly important competitive differentiator, amplify the need to revisit our understanding of SQ and its measurement. Although ‘SQ’ can be broadly defined as “a global overarching judgment or attitude relating to the overall excellence or superiority of a service” (Parasuraman, Berry and Zeithaml 1988), the term has many interpretations. There has been considerable progress on how to measure SQ perceptions, but little consensus has been achieved on what should be measured. There is agreement that SQ is multi-dimensional, but little agreement as to the nature or content of these dimensions (Brady and Cronin 2001). For example, within the banking sector, there exist multiple SQ models, each consisting of varying dimensions. The existence of multiple conceptions and the lack of a unifying theory bring the credibility of existing conceptions into question, and beg the question of whether it is possible at some higher level to define SQ broadly such that it spans all service types and industries. This research aims to explore the viability of a universal conception of SQ, primarily through a careful re-visitation of the services and SQ literature. The study analyses the strengths and weaknesses of the highly regarded and widely used global SQ model (SERVQUAL) which reflects a single-level approach to SQ measurement. The SERVQUAL model states that customers evaluate SQ (of each service encounter) based on five dimensions namely reliability, assurance, tangibles, empathy and responsibility. SERVQUAL, however, failed to address what needs to be reliable, assured, tangible, empathetic and responsible. This research also addresses a more recent global SQ model from Brady and Cronin (2001); the B&C (2001) model, that has potential to be the successor of SERVQUAL in that it encompasses other global SQ models and addresses the ‘what’ questions that SERVQUAL didn’t. The B&C (2001) model conceives SQ as being multidimensional and multi-level; this hierarchical approach to SQ measurement better reflecting human perceptions. In-line with the initial intention of SERVQUAL, which was developed to be generalizable across industries and service types, this research aims to develop a conceptual understanding of SQ, via literature and reflection, that encompasses the content/nature of factors related to SQ; and addresses the benefits and weaknesses of various SQ measurement approaches (i.e. disconfirmation versus perceptions-only). Such understanding of SQ seeks to transcend industries and service types with the intention of extending our knowledge of SQ and assisting practitioners in understanding and evaluating SQ. The candidate’s research has been conducted within, and seeks to contribute to, the ‘IS-Impact’ research track of the IT Professional Services (ITPS) Research Program at QUT. The vision of the track is “to develop the most widely employed model for benchmarking Information Systems in organizations for the joint benefit of research and practice.” The ‘IS-Impact’ research track has developed an Information Systems (IS) success measurement model, the IS-Impact Model (Gable, Sedera and Chan 2008), which seeks to fulfill the track’s vision. Results of this study will help future researchers in the ‘IS-Impact’ research track address questions such as: • Is SQ an antecedent or consequence of the IS-Impact model or both? • Has SQ already been addressed by existing measures of the IS-Impact model? • Is SQ a separate, new dimension of the IS-Impact model? • Is SQ an alternative conception of the IS? Results from the candidate’s research suggest that SQ dimensions can be classified at a higher level which is encompassed by the B&C (2001) model’s 3 primary dimensions (interaction, physical environment and outcome). The candidate also notes that it might be viable to re-word the ‘physical environment quality’ primary dimension to ‘environment quality’ so as to better encompass both physical and virtual scenarios (E.g: web sites). The candidate does not rule out the global feasibility of the B&C (2001) model’s nine sub-dimensions, however, acknowledges that more work has to be done to better define the sub-dimensions. The candidate observes that the ‘expertise’, ‘design’ and ‘valence’ sub-dimensions are supportive representations of the ‘interaction’, physical environment’ and ‘outcome’ primary dimensions respectively. The latter statement suggests that customers evaluate each primary dimension (or each higher level of SQ classification) namely ‘interaction’, physical environment’ and ‘outcome’ based on the ‘expertise’, ‘design’ and ‘valence’ sub-dimensions respectively. The ability to classify SQ dimensions at a higher level coupled with support for the measures that make up this higher level, leads the candidate to propose the B&C (2001) model as a unifying theory that acts as a starting point to measuring SQ and the SQ of IS. The candidate also notes, in parallel with the continuing validation and generalization of the IS-Impact model, that there is value in alternatively conceptualizing the IS as a ‘service’ and ultimately triangulating measures of IS SQ with the IS-Impact model. These further efforts are beyond the scope of the candidate’s study. Results from the candidate’s research also suggest that both the disconfirmation and perceptions-only approaches have their merits and the choice of approach would depend on the objective(s) of the study. Should the objective(s) be an overall evaluation of SQ, the perceptions-only approached is more appropriate as this approach is more straightforward and reduces administrative overheads in the process. However, should the objective(s) be to identify SQ gaps (shortfalls), the (measured) disconfirmation approach is more appropriate as this approach has the ability to identify areas that need improvement.

An evaluation of viability of public private partnerships in social infrastructure procurement projects in Queensland, Australia

Public private partnerships (PPP) have been widely used as a method for public infrastructure project delivery not only locally and internationally, however the adoption of PPPs in social infrastructure procurement has still been very limited. The objective of this paper is to investigate the potential of implementation of current PPP framework in social affordable housing projects in South East Queensland. Data were collected from 22 interviewees with rich experiences in the industry. The findings of this study show that affordable housing investment have been considered by the industry practitioners as a risky business in comparison to other private rental housing investment. The main determents of the adoption of PPPs in social infrastructure project are the tenant-related factors, such as the inability of paying rent and the inability of caring the property. The study also suggests the importance of seeking strategic partnership with community-based organisation that has experiences in managing similar tenants’ profiles. Current PPP guideline is also viewed as inappropriate for the affordable housing projects, but the principle of VFM framework and risk allocation in PPPs still be applied to the affordable housing projects. This study helps to understand the viability of PPP in social housing procurement projects, and point out the importance of developing guideline for multi-stakeholder partnership and the expansion of the current VFM and PPPs guidelines.

Sustainable urban development : a quadruple bottom line assessment framework

Sustainable development has long been promoted as the best answer to the world's environmental problems. This term has generated mass appeal as it implies that the development of the built environment and its associated resource consumption can both be achieved without jeopardising the natural environment. In the urban context, sustainability issues have been reflected in the pomotion of sustainable urbanisation in a manner that allows future generations to repeat this process. This paper attempts to highlight an increasing urgency in formulating a suitable model for assessing sustainability at urban level, because this is where the bulk of a nation's population reside, and where sustainability problems mostly occur. It will also point out to the increasing importance of governance in facilitating urban sustainability research. This assessment involves the use of physical, social, environmental and goverance aspects in assessing the extent to which development of an urban settlement is sustainable. Specifically, this assessment model is carried out to determine whether or not sustainable urban development pratice is implemented in the provision of residential development, and in particular whether the development of master-planned residential communities have more desireable outcomes compared to traditional residential subdivision.

Evaluation of contextual influences on the medication administration practice of paediatric nurses

Aim. This paper is a report of a study conducted to explore the impact of preidentified contextual themes (related to work environment and socialization) on nursing medication practice. Background. Medication administration is a complex aspect of paediatric nursing and an important component of day-to-day nursing practice. Many attempts are being made to improve patient safety, but many errors remain. Identifying and understanding factors that influence medication administration errors are of utmost importance. Method. A cross-sectional survey was conducted with a sample of 278 paediatric nurses from the emergency department, intensive care unit and medical and surgical wards of an Australian tertiary paediatric hospital in 2004. The response rate was 67%. Result. Contextual influences were important in determining how closely medication policy was followed. Completed questionnaires were returned by 185 nurses (67%). Younger nurses aged <34 years thought that their medication administration practice could be influenced by the person with whom they checked the drugs (P = 0·001), and that there were daily circumstances when it was acceptable not to adhere strictly to medication policy (P < 0·001), including choosing between following policy and acting in the best interests of the child (P = 0·002). Senior nurses agreed that senior staff dictate acceptable levels of medication policy adherence through role modelling (P = 0·01). Less experienced nurses reported greater confidence with computer literacy (P < 0·001). Conclusions. Organizations need to employ multidisciplinary education programmes to promote universal understanding of, and adherence to, medication policies. Skill mix should be closely monitored to ensure adequate support for new and junior staff.

In vitro cultivation of adult human chondrocytes : importance of culture system, oxygen and zonal differences

Articular cartilage exhibits limited intrinsic regenerative capacity and focal tissue defects can lead to the development of osteoarthritis (OA), a painful and debilitating loss of cartilage tissue. In Australia, 1.4 million people are affected by OA and its prevalence is increasing in line with current demographics. As treatment options are limited, new therapeutic approaches are being investigated including biological resurfacing of joints with tissue-engineered cartilage. Despite some progress in the field, major challenges remain to be addressed for large scale clinical success. For example, large numbers of chondrogenic cells are required for cartilage formation, but chondrocytes lose their chondrogenic phenotype (dedifferentiate) during in vitro propagation. Additionally, the zonal organization of articular cartilage is critical for normal cartilage function, but development of zonal structure has been largely neglected in cartilage repair strategies. Therefore, we hypothesised that culture conditions for freshly isolated human articular chondrocytes from non-OA and OA sources can be improved by employing microcarrier cultures and a reduced oxygen environment and that oxygen is a critical factor in the maintenance of the zonal chondrocyte phenotype. Microcarriers have successfully been used to cultivate bovine chondrocytes, and offer a potential alternative for clinical expansion of human chondrocytes. We hypothesised that improved yields can be achieved by propagating human chondrocytes on microcarriers. We found that cells on microcarriers acquired a flattened, polygonal morphology and initially proliferated faster than monolayercultivated cells. However, microcarrier cultivation over four weeks did not improve growth rates or the chondrogenic potential of non-OA and OA human articular chondrocytes over conventional monolayer cultivation. Based on these observations, we aimed to optimise culture conditions by modifying oxygen tension, to more closely reflect the in vivo environment. We found that propagation at 5% oxygen tension (moderate hypoxia) did not improve proliferation or redifferentiation capacity of human osteoarthritic chondrocytes. Moderate hypoxia increased the expression of chondrogenic markers during redifferentiation. However, osteoarthritic chondrocytes cultivated on microcarriers exhibited lower expression levels of chondrogenic surface marker proteins and had at best equivalent redifferentiation capacities compared to monolayer-cultured cells. This suggests that monolayer culture with multiple passaging potentially selects for a subpopulation of cells with higher differentiation capacity, which are otherwise rare in osteoarthritic, aged cartilage. However, fibroblastic proteins were found to be highly expressed in all cultures of human osteoarthritic chondrocytes indicating the presence of a high proportion of dedifferentiated, senescent cells with a chondrocytic phenotype that was not rescued by moderate hypoxia. The different zones of cartilage support chondrocyte subpopulations, which exhibit characteristic protein expression and experience varying oxygen tensions. We, therefore, hypothesised that oxygen tension affects the zonal marker expression of human articular chondrocytes isolated from the different cartilage layers. We found that zonal chondrocytes maintained these phenotypic differences during in vitro cultivation. Low oxygen environments favoured the expression of the zonal marker proteoglycan 4 in superficial cells, most likely through the promotion of chondrogenesis. The putative zonal markers clusterin and cartilage intermediate layer protein were found to be expressed by all subpopulations of human osteoarthritic chondrocytes ex vivo and, thus, may not be reliable predictors of in vitro stratification using these clinically relevant cells. The findings in this thesis underline the importance of considering low oxygen conditions and zonal stratification when creating native-like cartilaginous constructs. We have not yet found the right cues to successfully cultivate clinically-relevant human osteoarthritic chondrocytes in vitro. A more thorough understanding of chondrocyte biology and the processes of chondrogenesis are required to ensure the clinical success of cartilage tissue engineering.

Overhead electricity line connector tester

Assessment of the condition of connectors in the overhead electricity network has traditionally relied on the heat dissipation or voltage drop from existing load current (50Hz) as a measurable parameter to differentiate between satisfactory and failing connectors. This research has developed a technique which does not rely on the 50Hz current and a prototype connector tester has been developed. In this system a high frequency signal is injected into the section of line under test and measures the resistive voltage drop and the current at the test frequency to yield the resistance in micro-ohms. From the value of resistance a decision as to whether a connector is satisfactory or approaching failure can be made. Determining the resistive voltage drop in the presence of a large induced voltage was achieved by the innovative approach of using a representative sample of the magnetic flux producing the induced voltage as the phase angle reference for the signal processing rather than the phase angle of the current, which can be affected by the presence of nearby metal objects. Laboratory evaluation of the connector tester has validated the measurement technique. The magnitude of the load current (50Hz) has minimal effect on the measurement accuracy. Addition of a suitable battery based power supply system and isolated communications, probably radio and refinement of the printed circuit board design and software are the remaining development steps to a production instrument.

Performance evaluation of an adaptive travel time prediction model

This paper presents a travel time prediction model and evaluates its performance and transferability. Advanced Travelers Information Systems (ATIS) are gaining more and more importance, increasing the need for accurate, timely and useful information to the travelers. Travel time information quantifies the traffic condition in an easy to understand way for the users. The proposed travel time prediction model is based on an efficient use of nearest neighbor search. The model is calibrated for optimal performance using Genetic Algorithms. Results indicate better performance by using the proposed model than the presently used naïve model.

Evaluation of risk factors leading to cost overrun in delivery of highway construction projects

Accurate owner budget estimates are critical to the initial decision-to-build process for highway construction projects. However, transportation projects have historically experienced significant construction cost overruns from the time the decision to build has been taken by the owner. This paper addresses the problem of why highway projects overrun their predicted costs. It identifies the owner risk variables that contribute to significant cost overrun and then uses factor analysis, expert elicitation, and the nominal group technique to establish groups of importance ranked owner risks. Stepwise multivariate regression analysis is also used to investigate any correlation of the percentage of cost overrun with risks, together with attributes such as highway project type, indexed cost, geographics location, and project delivery method. The research results indicate a correlation between the reciprocal of project budgets size and percentage cost overrun. This can be useful for owners in determining more realistic decision-to-build highway budget estimates by taking into account the economies of scale associated with larger projects.

An evaluation methodology for the tangible and intangible assets of city-regions : the 6K1C framework

Together with hard and soft networks tangible and intangible regional assets play an important role in the knowledge-based development of competing city-regions. The aim of this paper, therefore, is to investigate the best ways of managing invaluable tangible and intangible assets of city-regions. The paper explores the importance of asset management of city-regions by giving special emphasis on their knowledge asset base. This paper develops and introduces a theoretical framework to conceptualise a new approach to articulate the strategic planning mechanism, so called the 6K1C framework. The 6K1C framework is part of the strategic planning process of continuous improvement of overall public sector performance. The framework provides a proactive check-list approach integrated for managing and harnessing tangible and intangible assets of the post-industrial city-regions.

Evaluation on service quality of railway timetable

From the business viewpoint, the railway timetable is a list of the products presented by the railway transportation operators to the customers, specifying the schedules of all the train services on a railway line or network. In order to evaluate the quality of the train service schedules, a number of indices are proposed in this paper. These indices primarily take the passengers’ needs, such as waiting time, transfer time and transport capacity into consideration. Delay rate is usually used in post-evaluation. In this study, we propose to give an evaluation on the probability that the scheduled train services are likely to be delayed and the recovery ability of the timetable after delay has occurred. The evaluation identifies the possible problems in the services, such as excessive waiting time, non-seamless transfer, and high possibility of delay. This paper also discusses the improvement of these problems through certain adjustments on the timetable. The indices for evaluation and the adjustment method on timetable are then applied to a case study on the Hu-Ning-Hang railway in China, followed by the discussions of the merits of the proposed indices for timetable evaluation and possible improvement.