Inhibitors of human immunodeficiency virus type 1 reverse transcriptase target distinct phases of early reverse transcription

Early HIV-1 reverse transcription can be separated into initiation and elongation phases. Here we show, using PCR analysis of negative-strand strong-stop DNA [(−)ssDNA] synthesis in intact virus, that different reverse transcriptase (RT) inhibitors affect distinct phases of early natural endogenous reverse transcription (NERT). The effects of nevirapine on NERT were consistent with a mechanism of action including both specific and nonspecific binding events. The nonspecific component of this inhibition targeted the elongation reaction, whereas the specific effect seemed principally to be directed at very early events (initiation or the initiation-elongation switch). In contrast, foscarnet and the nucleoside analog ddATP inhibited both early and late (−)ssDNA synthesis in a similar manner. We also examined compounds that targeted other viral proteins and found that Ro24-7429 (a Tat antagonist) and rosmarinic acid (an integrase inhibitor) also directly inhibited RT. Our results indicate that NERT can be used to identify and evaluate compounds that directly target the reverse transcription complex.

Strategizing public sector human resource management : the implications of working network

Networks have come to the fore as a means by which government can achieve its strategic objectives, particularly when addressing complex or “wicked” issues. Such joined-up arrangements differ in their operations from other forms of organizing as they require collaborative effort to deliver the collaborative advantage. Strategic Human Resource Management is concerned with the matching of human resource practices to the strategic direction of organizations. It is argued that the strategic direction of government has been towards network involvement and that, as a result, a reconfiguration of Human Resource Management practices is needed to support this new direction. Drawing on eight network case studies findings are presented in relation to the roles government is expected to play in networks and conclusions are drawn about what types of human resource management practices would best support those roles. Implications for Strategic Human Resource Management are posited.

Vastu Purusha Mandala : A human ecological framework for designing living environments

This paper aims to present ‘vastu purusha mandala’(VPM), a symbolic diagram used in the indigenous system of Indian architecture as a human ecologic frame work for designing living environments. The article begins with an attempt to provide a working definition for the ‘living environment’ based on the theories developed by Rapoport (2005) and Lawrence (2001). It then discusses the symbolism and the human ecologic significance of VPM. This is substantiated through the works of Kramrisch (1976), Moore (1989), Shukla (1996) and Chakrabarthi (1998). Some recent papers on Vastu Shastra are also examined. Furthermore, VPM is compared with the livability guidelines developed for high-rise living by the Centre for Subtropical Design, Queensland University of Technology, Brisbane, Australia. A meaningful interpretation of vastushastra which is free from mysticism and symbolism is proffered through this paper.

Formal complaints of workplace sexual harassment lodged with Australian Human Rights and Equal Opportunity Commissions - 1 July 2009 - 31 December 2009

This report presents an analysis of quantitative data collected from the Australian Human Rights Commission, the Anti-Discrimination Commission of Queensland, the Victorian Equal Opportunity and Human Rights Commission, the Anti-Discrimination Board of New South Wales, the Equal Opportunity Commission of South Australia, the Australian Capital Territory Human Rights Commission, the Equal Opportunity Commission Western Australia, the Northern Territory Anti-Discrimination Commission, and the Office of the Anti-Discrimination Commissioner (Tasmania) (hereafter referred to as the Commissions). The data comprise formal complaints lodged under the various federal, state and territory anti-discrimination laws in the period 1 July 2009 to 31 December 2009 where a complainant had alleged sexual harassment in the area of employment.

Embedding human expert cognition and real-time trajectory planning in autonomous UAS

This thesis presents a new approach to compute and optimize feasible three dimensional (3D) flight trajectories using aspects of Human Decision Making (HDM) strategies, for fixed wing Unmanned Aircraft (UA) operating in low altitude environments in the presence of real time planning deadlines. The underlying trajectory generation strategy involves the application of Manoeuvre Automaton (MA) theory to create sets of candidate flight manoeuvres which implicitly incorporate platform dynamic constraints. Feasible trajectories are formed through the concatenation of predefined flight manoeuvres in an optimized manner. During typical UAS operations, multiple objectives may exist, therefore the use of multi-objective optimization can potentially allow for convergence to a solution which better reflects overall mission requirements and HDM preferences. A GUI interface was developed to allow for knowledge capture from a human expert during simulated mission scenarios. The expert decision data captured is converted into value functions and corresponding criteria weightings using UTilite Additive (UTA) theory. The inclusion of preferences elicited from HDM decision data within an Automated Decision System (ADS) allows for the generation of trajectories which more closely represent the candidate HDM’s decision strategies. A novel Computationally Adaptive Trajectory Decision optimization System (CATDS) has been developed and implemented in simulation to dynamically manage, calculate and schedule system execution parameters to ensure that the trajectory solution search can generate a feasible solution, if one exists, within a given length of time. The inclusion of the CATDS potentially increases overall mission efficiency and may allow for the implementation of the system on different UAS platforms with varying onboard computational capabilities. These approaches have been demonstrated in simulation using a fixed wing UAS operating in low altitude environments with obstacles present.

Career paths in the third sector : implications for human resource management

My interest in career paths in the third sector came from three early observations. First, the majority of workers appear to be women, in fact 77% of community sector community services in NSW (O'Donnell, 1985). Second, when asked about their career, most workers express the opinion that they have none. Third, when I examined the individual career paths of community sector workers I was struck by the stop and start nature of their paid work. Even, or perhaps especially, well qualified workers would move out of a position after about two years often to a more difficult position in a new area, with little or no salary increase and little prospect of future promotion. Indeed, there appears to be little career path available. These observations raise a number of important questions, some of which will be explored in this paper. What is the structure of the third sector labour market? What is the staff structure of third sector organisations? Is it true that career paths are unavailable, either within organisations or within the sector? If none exists, why do workers stay in the field? What motivates them? If there is a high turnover of staff, is this the reason? What are the implications of all this? If some sort of career path does exist, why do workers deny having a career? What do we mean by `career' anyway?

Application of a human bone engineering platform to an in vitro and in vivo breast cancer metastasis model

Breast cancer in its advanced stage has a high predilection to the skeleton. Currently, treatment options of breast cancer-related bone metastasis are restricted to only palliative therapeutic modalities. This is due to the fact that mechanisms regarding the breast cancer celI-bone colonisation as well as the interactions of breast cancer cells with the bone microenvironment are not fully understood, yet. This might be explained through a lack of appropriate in vitro and in vivo models that are currently addressing the above mentioned issue. Hence the hypothesis that the translation of a bone tissue engineering platform could lead to improved and more physiological in vitro and in vivo model systems in order to investigate breast cancer related bone colonisation was embraced in this PhD thesis. Therefore the first objective was to develop an in vitro model system that mimics human mineralised bone matrix to the highest possible extent to examine the specific biological question, how the human bone matrix influences breast cancer cell behaviour. Thus, primary human osteoblasts were isolated from human bone and cultured under osteogenic conditions. Upon ammonium hydroxide treatment, a cell-free intact mineralised human bone matrix was left behind. Analyses revealed a similar protein and mineral composition of the decellularised osteoblast matrix to human bone. Seeding of a panel of breast cancer cells onto the bone mimicking matrix as well as reference substrates like standard tissue culture plastic and collagen coated tissue culture plastic revealed substrate specific differences of cellular behaviour. Analyses of attachment, alignment, migration, proliferation, invasion, as well as downstream signalling pathways showed that these cellular properties were influenced through the osteoblast matrix. The second objective of this PhD project was the development of a human ectopic bone model in NOD/SCID mice using medical grade polycaprolactone tricalcium phosphate (mPCL-TCP) scaffold. Human osteoblasts and mesenchymal stem cells were seeded onto an mPCL-TCP scaffold, fabricated using a fused deposition modelling technique. After subcutaneous implantation in conjunction with the bone morphogenetic protein 7, limited bone formation was observed due to the mechanical properties of the applied scaffold and restricted integration into the soft tissue of flank of NOD/SCID mice. Thus, a different scaffold fabrication technique was chosen using the same polymer. Electrospun tubular scaffolds were seeded with human osteoblasts, as they showed previously the highest amount of bone formation and implanted into the flanks of NOD/SCID mice. Ectopic bone formation with sufficient vascularisation could be observed. After implantation of breast cancer cells using a polyethylene glycol hydrogel in close proximity to the newly formed bone, macroscopic communication between the newly formed bone and the tumour could be observed. Taken together, this PhD project showed that bone tissue engineering platforms could be used to develop an in vitro and in vivo model system to study cancer cell colonisation in the bone microenvironment.

Polycaprolactone-based scaffold plus recombinant human bone morphogenetic protein (rhBMP-2) in an ovine model of anterior spinal fusion

Synthetic scaffolds combined with growth factors have the potential to replace allograft or autograft as a graft material for spinal interbody fusion. Such tissue engineering approaches may be useful in Adolescent Idiopathic Scoliosis (AIS) surgery, however there are no studies to date examining the use of such biodegradable implants in combination with biologics in a thoracic spine model. This in vivo study examines the use of biodegradable polycaprolactone (PCL) based scaffolds with rhBMP-2 as a bone graft substitute in a sheep thoracic fusion model, where an anterior approach is used to simulate minimally invasive surgical deformity correction in the setting of AIS.

The geostationary orbit : a critical legal geography of space’s most valuable real estate

This chapter attends to the legal and political geographies of one of Earth's most important, valuable, and pressured spaces: the geostationary orbit. Since the first, NASA, satellite entered it in 1964, this small, defined band of Outer Space, 35,786km from the Earth's surface, and only 30km wide, has become a highly charged legal and geopolitical environment, yet it remains a space which is curiously unheard of outside of specialist circles. For the thousands of satellites which now underpin the Earth's communication, media, and data industries and flows, the geostationary orbit is the prime position in Space. The geostationary orbit only has the physical capacity to hold approximately 1500 satellites; in 1997 there were approximately 1000. It is no overstatement to assert that media, communication, and data industries would not be what they are today if it was not for the geostationary orbit. This chapter provides a critical legal geography of the geostationary orbit, charting the topography of the debates and struggles to define and manage this highly-important space. Drawing on key legal documents such as the Outer Space Treaty and the Moon Treaty, the chapter addresses fundamental questions about the legal geography of the orbit, questions which are of growing importance as the orbit’s available satellite spaces diminish and the orbit comes under increasing pressure. Who owns the geostationary orbit? Who, and whose rules, govern what may or may not (literally) take place within it? Who decides which satellites can occupy the orbit? Is the geostationary orbit the sovereign property of the equatorial states it supertends, as these states argued in the 1970s? Or is it a part of the res communis, or common property of humanity, which currently legally characterises Outer Space? As challenges to the existing legal spatiality of the orbit from launch states, companies, and potential launch states, it is particularly critical that the current spatiality of the orbit is understood and considered. One of the busiest areas of Outer Space’s spatiality is international territorial law. Mentions of Space law tend to evoke incredulity and ‘little green men’ jokes, but as Space becomes busier and busier, international Space law is growing in complexity and importance. The chapter draws on two key fields of research: cultural geography, and critical legal geography. The chapter is framed by the cultural geographical concept of ‘spatiality’, a term which signals the multiple and dynamic nature of geographical space. As spatial theorists such as Henri Lefebvre assert, a space is never simply physical; rather, any space is always a jostling composite of material, imagined, and practiced geographies (Lefebvre 1991). The ways in which a culture perceives, represents, and legislates that space are as constitutive of its identity--its spatiality--as the physical topography of the ground itself. The second field in which this chapter is situated—critical legal geography���derives from cultural geography���s focus on the cultural construction of spatiality. In his Law, Space and the Geographies of Power (1994), Nicholas Blomley asserts that analyses of territorial law largely neglect the spatial dimension of their investigations; rather than seeing the law as a force that produces specific kinds of spaces, they tend to position space as a neutral, universally-legible entity which is neatly governed by the equally neutral 'external variable' of territorial law (28). 'In the hegemonic conception of the law,' Pue similarly argues, 'the entire world is transmuted into one vast isotropic surface' (1990: 568) on which law simply acts. But as the emerging field of critical legal geography demonstrates, law is not a neutral organiser of space, but is instead a powerful cultural technology of spatial production. Or as Delaney states, legal debates are “episodes in the social production of space” (2001, p. 494). International territorial law, in other words, makes space, and does not simply govern it. Drawing on these tenets of the field of critical legal geography, as well as on Lefebvrian concept of multipartite spatiality, this chapter does two things. First, it extends the field of critical legal geography into Space, a domain with which the field has yet to substantially engage. Second, it demonstrates that the legal spatiality of the geostationary orbit is both complex and contested, and argues that it is crucial that we understand this dynamic legal space on which the Earth’s communications systems rely.

The genesis of 'the new geography and the new imperialism : 1870-1918', or 'how I came to Jamaica and joined the UWI Geography Department

In this article, Brian Hudson relates how he came to write the paper published in the journal Antipode, for which he gained recognition as a radical geographer in the late 1970's. It is a tale of a journey in which the loves of his life, geography, history, travel and his wife of over 40 years, came together through living in a number of different places: the United Kingdom, Ghana, Hong Kong, and Jamaica. After leaving UWI, Brian and his family settled in Brisbane, Australia where he taught at Queensland University of Technology until his retirement.

Children and the environment

Children and the environment cover a broad, interdisciplinary field of research and practice. The social sciences often use the word “environment” to mean the social, political, or economic context of children’s lives, but this bibliography covers physical settings. It focuses on a place-based scale that children can see, hear, taste, smell, touch, and navigate: not large, abstract scales such as national identities or population dynamics, or small scales such as environmental impacts on genes or cell functions. Attention to the everyday settings of children’s lives grew in the 18th century, when Romantic literature introduced the theme of children and nature. In the 19th century, concern for children’s welfare included an interest in conditions for children in burgeoning industrial cities, and justifications for early streetcar and railroad suburbs included claims that they would save children from the dangers of cities and provide the healthful benefits of natural surroundings. In the 20th century, academic disciplines developed different lines of inquiry about the impact of the physical environment on children and how children relate to places: ethnographic studies of children in different parts of the world in the fields of anthropology and geography; sociological studies of different populations of children in different settings; educational research on the learning opportunities that different school and out-of-school settings afford; medical research to understand disease vectors and the impact of pollutants on children; and efforts in the field of environment and behavior research more broadly, to understand how built and designed environments affect children physically, cognitively, socially, and emotionally. At the beginning of the 21st century, children and the environment is an active area of inquiry seeking to understand rapidly changing conditions for children as the world urbanizes, opportunities for free play outdoors and independent mobility erode in many parts of the world, media environments consume more of children’s time, and awareness grows that children need opportunities to contribute to creating sustainable societies.

Human proximal tubule epithelial cells modulate autologous dendritic cell function

Background We have previously demonstrated that human kidney proximal tubule epithelial cells (PTEC) are able to modulate autologous T and B lymphocyte responses. It is well established that dendritic cells (DC) are responsible for the initiation and direction of adaptive immune responses and that these cells occur in the renal interstitium in close apposition to PTEC under inflammatory disease settings. However, there is no information regarding the interaction of PTEC with DC in an autologous human context. Methods Human monocytes were differentiated into monocyte-derived DC (MoDC) in the absence or presence of primary autologous activated PTEC and matured with polyinosinic:polycytidylic acid [poly(I:C)], while purified, pre-formed myeloid blood DC (CD1c+ BDC) were cultured with autologous activated PTEC in the absence or presence of poly(I:C) stimulation. DC responses were monitored by surface antigen expression, cytokine secretion, antigen uptake capacity and allogeneic T-cell-stimulatory ability. Results The presence of autologous activated PTEC inhibited the differentiation of monocytes to MoDC. Furthermore, MoDC differentiated in the presence of PTEC displayed an immature surface phenotype, efficient phagocytic capacity and, upon poly(I:C) stimulation, secreted low levels of pro-inflammatory cytokine interleukin (IL)-12p70, high levels of anti-inflammatory cytokine IL-10 and induced weak Th1 responses. Similarly, pre-formed CD1c+ BDC matured in the presence of PTEC exhibited an immature tolerogenic surface phenotype, strong endocytic and phagocytic ability and stimulated significantly attenuated T-cell proliferative responses. Conclusions Our data suggest that activated PTEC regulate human autologous immunity via complex interactions with DC. The ability of PTEC to modulate autologous DC function has important implications for the dampening of pro-inflammatory immune responses within the tubulointerstitium in renal injuries. Further dissection of the mechanisms of PTEC modulation of autologous immune responses may offer targets for therapeutic intervention in renal medicine.

A human-simulated immune evolutionary computation approach

Premature convergence to local optimal solutions is one of the main difficulties when using evolutionary algorithms in real-world optimization problems. To prevent premature convergence and degeneration phenomenon, this paper proposes a new optimization computation approach, human-simulated immune evolutionary algorithm (HSIEA). Considering that the premature convergence problem is due to the lack of diversity in the population, the HSIEA employs the clonal selection principle of artificial immune system theory to preserve the diversity of solutions for the search process. Mathematical descriptions and procedures of the HSIEA are given, and four new evolutionary operators are formulated which are clone, variation, recombination, and selection. Two benchmark optimization functions are investigated to demonstrate the effectiveness of the proposed HSIEA.

Environmental rights or a right to the environment? Exploring the nexus between human rights and environmental protection.

The importance of the environment to the fulfilment of human rights is widely accepted at international law. What is less well-accepted is the proposition that we, as humans, possess rights to the environment beyond what is necessary to support our basic human needs. The suggestion that a human right to a healthy environment may be emerging at international law raises a number of theoretical and practical challenges for human rights law, with such challenges coming from both within and outside the human rights discourse. It is argued that human rights law can make a positive contribution to environmental protection, but the precise nature of the connection between the environment and human rights warrants more critical analysis. This short paper considers the different ways that the environment is conceptualised in international human rights law and analyses the proposition that a right to a healthy environment is emerging. It identifies some of the challenges which would need to be overcome before such a right could be recognised, including those which draw on the disciplines of deep ecology and earth jurisprudence.