Single-stranded DNA-binding protein hSSB1 is critical for genomic stability

Single-strand DNA (ssDNA)-binding proteins (SSBs) are ubiquitous and essential for a wide variety of DNA metabolic processes, including DNA replication, recombination, DNA damage detection and repair1. SSBs have multiple roles in binding and sequestering ssDNA, detecting DNA damage, stimulating nucleases, helicases and strand-exchange proteins, activating transcription and mediating protein–protein interactions. In eukaryotes, the major SSB, replication protein A (RPA), is a heterotrimer1. Here we describe a second human SSB (hSSB1), with a domain organization closer to the archaeal SSB than to RPA. Ataxia telangiectasia mutated (ATM) kinase phosphorylates hSSB1 in response to DNA double-strand breaks (DSBs). This phosphorylation event is required for DNA damage-induced stabilization of hSSB1. Upon induction of DNA damage, hSSB1 accumulates in the nucleus and forms distinct foci independent of cell-cycle phase. These foci co-localize with other known repair proteins. In contrast to RPA, hSSB1 does not localize to replication foci in S-phase cells and hSSB1 deficiency does not influence S-phase progression. Depletion of hSSB1 abrogates the cellular response to DSBs, including activation of ATM and phosphorylation of ATM targets after ionizing radiation. Cells deficient in hSSB1 exhibit increased radiosensitivity, defective checkpoint activation and enhanced genomic instability coupled with a diminished capacity for DNA repair. These findings establish that hSSB1 influences diverse endpoints in the cellular DNA damage response.

Assessment of critical constructability activities among Malaysian building contractors

After the primary researches on constructability issue which were implemented in United States, United Kingdom and Australia, more explorations were applied on that in order to assess this unique scientific fact in East Asian country of Malaysia. Based on the latest researches done on constructability concept in Malaysia, the most Critical Constructability Activities (CCAs) are defined according to amount of contractors’ participation in each activity and amount of gap between actual and potential effects of each of them on achieving the overall objectives of the construction projects with more cost and time savings and better quality which is the whole aim of a beneficial constructability activity. The present research aims to assess the current findings on CCAs in order to identify the types of contractors and projects which these CCAs are getting performed in and also the types of contracts is used in these CCAs. Finally it was found that there are some significant differences in amount of contractors’ involvement in CCAs among various considered independent variables. This study uses the former researches to help Malaysian construction stakeholders to find out the barriers of constructability implementation in building projects via giving more details on application of CCAs among different IVs.

A Modified inverse integer Cholesky decorrelation method and the performance on ambiguity resolution

One of the research focuses in the integer least squares problem is the decorrelation technique to reduce the number of integer parameter search candidates and improve the efficiency of the integer parameter search method. It remains as a challenging issue for determining carrier phase ambiguities and plays a critical role in the future of GNSS high precise positioning area. Currently, there are three main decorrelation techniques being employed: the integer Gaussian decorrelation, the Lenstra–Lenstra–Lovász (LLL) algorithm and the inverse integer Cholesky decorrelation (IICD) method. Although the performance of these three state-of-the-art methods have been proved and demonstrated, there is still a potential for further improvements. To measure the performance of decorrelation techniques, the condition number is usually used as the criterion. Additionally, the number of grid points in the search space can be directly utilized as a performance measure as it denotes the size of search space. However, a smaller initial volume of the search ellipsoid does not always represent a smaller number of candidates. This research has proposed a modified inverse integer Cholesky decorrelation (MIICD) method which improves the decorrelation performance over the other three techniques. The decorrelation performance of these methods was evaluated based on the condition number of the decorrelation matrix, the number of search candidates and the initial volume of search space. Additionally, the success rate of decorrelated ambiguities was calculated for all different methods to investigate the performance of ambiguity validation. The performance of different decorrelation methods was tested and compared using both simulation and real data. The simulation experiment scenarios employ the isotropic probabilistic model using a predetermined eigenvalue and without any geometry or weighting system constraints. MIICD method outperformed other three methods with conditioning improvements over LAMBDA method by 78.33% and 81.67% without and with eigenvalue constraint respectively. The real data experiment scenarios involve both the single constellation system case and dual constellations system case. Experimental results demonstrate that by comparing with LAMBDA, MIICD method can significantly improve the efficiency of reducing the condition number by 78.65% and 97.78% in the case of single constellation and dual constellations respectively. It also shows improvements in the number of search candidate points by 98.92% and 100% in single constellation case and dual constellations case.

WaterFieldWork : a working lexicon for critical refugia in arid landscapes

Algebuckina Waterhole exists as a permanent waterhole near a north-south dirt road and an old trainline on the Oodnadatta Track - lines that once opened up the arid lands of central South Australia but are now bypassed. It also exists as the final and largest freshwater waterhole at the end of the Neales River system. It is a critical biodiversity site, a cultural place and a working environment. It is seen to need a resilient management plan that encompasses diverse interests and impacts. Its managers sense that the theories and practices emerging out of landscape disciplinary systems may be of help. Work-in-progress research towards a management methodology are presented through posing scenarios on how landscape thinking and design, informed by an emergent textual and visual lexicon for water landscapes, can intersect with scientific fieldwork to produce useful and transferable outcomes for Algebuckina.

Raman spectroscopy of hydrogen arsenate group (AsO3OH)2− in solid-state compounds: cobalt-containing zinc arsenate mineral, koritnigite (Zn,Co)(AsO3OH)·H2O

Raman spectra of two well-defined types of koritnigite crystals from the Jáchymov ore district, Czech Republic, were recorded and interpreted. No substantial differences were observed between both crystal types. Observed Raman bands were attributed to the (AsO3OH)2- stretching and bending vibrations, stretching and bending vibrations of water molecules and hydroxyl ions. Non-interpreted Raman spectra of koritnigite from the RRUFF database, and published infrared spectra of cobaltkoritnigite were used for comparison. The O-H...O hydrogen bond lengths in the crystal structure of koritnigite were inferred from the Raman spectra and compared with those derived from the X-ray single crystal refinement. The presence of (AsO3OH)2- units in the crystal structure of koritnigite was proved from the Raman spectra which supports the conclusions of the X-ray structure analysis.

Punitiveness and the criminalisation of the other : State wards, unlawful non-citizens and Indigenous youth

This paper explores the genealogies of bio-power that cut across punitive state interventions aimed at regulating or normalising several distinctive ‘problem’ or ‘suspect’ deviant populations, such as state wards, non-lawful citizens and Indigenous youth. It begins by making some general comments about the theoretical approach to bio-power taken in this paper. It then outlines the distinctive features of bio-power in Australia and how these intersected with the emergence of penal welfarism to govern the unruly, unchaste, unlawful, and the primitive. The paper draws on three examples to illustrate the argument – the gargantuan criminalisation rates of Aboriginal youth, the history of incarcerating state wards in state institutions, and the mandatory detention of unlawful non-citizens and their children. The construction of Indigenous people as a dangerous presence, alongside the construction of the unruly neglected children of the colony — the larrikin descendants of convicts as necessitating special regimes of internal controls and institutions, found a counterpart in the racial and other exclusionary criteria operating through immigration controls for much of the twentieth century. In each case the problem child or population was expelled from the social body through forms of bio-power, rationalised as strengthening, protecting or purifying the Australian population.

Children re-read and re-write their neighborhoods : critical literacies and identity work

This chapter considers the complex literate repertoires of 21st century children in multicultural primary classrooms in Adelaide South Australia. It draws on the curricular and pedagogical work of two experienced primary school teachers who explore culture, race and class, by positioning children as textual producers across a variety of media. In particular we discuss two child-authored texts – A is for Arndale – a local alphabet book co-authored by children aged between eight and ten, and – Cooking Afghani Style - a magazine style film produced by a multi-aged class of children (aged eight to thirteen) recently arrived in Australia. In the process of making these texts, primary children engaged in reading as a cultural practice – re-reading and re-writing their neighbourhoods and identities (both individual and collective). This involved frequent excursions to local key sites, both familiar and unfamiliar to the children. They investigated how diverse children experienced and lived their lives in particular places within changing communities.

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.

Mesenchymal stem cells

Cell based therapies as they apply to tissue engineering and regenerative medicine, require cells capable of self renewal and differentiation, and a prerequisite is to be able to prepare an effective dose of ex vivo expanded cells for autologous transplants. The in vivo identification of a source of physiologically relevant cell types suitable for cell therapies therefore figures as an integral part of tissue engineering. Stem cells serve as a reserve for biological repair, having the potential to differentiate into a number of specialised cell types within the body; they therefore represent the most useful candidates for cell based therapies. The primary goal of stem cell research is to produce cells that are both patient specific, as well as having properties suitable for the specific conditions for which they are intended to remedy. From a purely scientific perspective, stem cells allow scientists to gain a deeper understanding of developmental biology and regenerative therapies. Stem cells have acquired a number of uses for applications in regenerative medicine, immunotherapy, gene therapy, but it is in the area of tissue engineering that they generate most excitement, primarily as a result of their capacity for self-renewal and pluripotency. A unique feature of stem cells is their ability to maintain an uncommitted quiescent state in vivo and then, once triggered by conditions such as disease, injury or natural wear or tear, serve as a reservoir and natural support system to replenish lost cells. Although these cells retain the plasticity to differentiate into various tissues, being able to control this differentiation process is still one of the biggest challenges facing stem cell research. In an effort to harness the potential of these cells a number of studies have been conducted using both embryonic/foetal and adult stem cells. The use of embryonic stem cells (ESC) have been hampered by strong ethical and political concerns, this despite their perceived versatility due to their pluripotency. Ethical issues aside, other concerns raised with ESCs relates to the possibility of tumorigenesis, immune rejection and complications with immunosuppressive therapies, all of which adds layers of complications to the application ESC in research and which has led to the search for alternative sources for stem cells. The adult tissues in higher organisms harbours cells, termed adult stem cells, and these cells are reminiscent of unprogrammed stem cells. A number of sources of adult stem cells have been described. Bone marrow is by far the most accessible source of two potent populations of adult stem cells, namely haematopoietic stem cells (HSCs) and bone marrow mesenchymal stem cells (BMSCs). Autologously harvested adult stem cells can, in contrast to embryonic stem cells, readily be used in autografts, since immune rejection is not an issue; and their use in scientific research has not attracted the ethical concerns which have been the case with embryonic stem cells. The major limitation to their use, however, is the fact that adult stem cells are exceedingly rare in most tissues. This fact makes identifying and isolating these cells problematic; bone marrow being perhaps the only notable exception. Unlike the case of HSCs, there are as yet no rigorous criteria for characterizing MSCs. Changing acuity about the pluripotency of MSCs in recent studies has expanded their potential application; however, the underlying molecular pathways which impart the features distinctive to MSCs remain elusive. Furthermore, the sparse in vivo distribution of these cells imposes a clear limitation to their study in vitro. Also, when MSCs are cultured in vitro, there is a loss of the in vivo microenvironment, resulting in a progressive decline in proliferation potential and multipotentiality. This is further exacerbated with increased passage numbers in culture, characterized by the onset of senescence related changes. As a consequence, it is necessary to establish protocols for generating large numbers of MSCs but without affecting their differentiation potential. MSCs are capable of differentiating into mesenchymal tissue lineages, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Recent findings indicate that adult bone marrow may also contain cells that can differentiate into the mature, nonhematopoietic cells of a number of tissues, including cells of the liver, kidney, lung, skin, gastrointestinal tract, and myocytes of heart and skeletal muscle. MSCs can readily be expanded in vitro and can be genetically modified by viral vectors and be induced to differentiate into specific cell lineages by changing the microenvironment–properties which makes these cells ideal vehicles for cellular gene therapy. MSCs can also exert profound immunosuppressive effects via modulation of both cellular and innate immune pathways, and this property allows them to overcome the issue of immune rejection. Despite the many attractive features associated with MSCs, there are still many hurdles to overcome before these cells are readily available for use in clinical applications. The main concern relates to in vivo characterization and identification of MSCs. The lack of a universal biomarker, sparse in vivo distribution, and a steady age related decline in their numbers, makes it an obvious need to decipher the reprogramming pathways and critical molecular players which govern the characteristics unique to MSCs. This book presents a comprehensive insight into the biology of adult stem cells and their utility in current regeneration therapies. The adult stem cell populations reviewed in this book include bone marrow derived MSCs, adipose derived stem cells (ASCs), umbilical cord blood stem cells, and placental stem cells. The features such as MSC circulation and trafficking, neuroprotective properties, and the nurturing roles and differentiation potential of multiple lineages have been discussed in details. In terms of therapeutic applications, the strengths of MSCs have been presented and their roles in disease treatments such as osteoarthritis, Huntington’s disease, periodontal regeneration, and pancreatic islet transplantation have been discussed. An analysis comparing osteoblast differentiation of umbilical cord blood stem cells and MSCs has been reviewed, as has a comparison of human placental stem cells and ASCs, in terms of isolation, identification and therapeutic applications of ASC in bone, cartilage regeneration, as well as myocardial regeneration. It is my sincere hope that this book will update the reader as to the research progress of MSC biology and potential use of these cells in clinical applications. It will be the best reward to all contributors of this book, if their efforts herein may in some way help the readers in any part of their study, research, and career development.

Critical literacies in place : teachers who work for just and sustainable communities

This chapter draws upon theories of social justice, critical literacy and place-based pedagogies and two research projects to discuss how teachers are working ethically and creatively towards a sustainable and just society in their place(s).

Critical reading comprehension in an era of accountability

This paper argues for the need for critical reading comprehension in an era of accountability that often promotes reading comprehension as readily assessable through students answering multiple choice questions of unseen texts. Based upon a 1 year study investigating literacy in Years 4–9 the ways strong-performing primary schools develop serious and in-depth reading for learning are explored. School and teacher features which allow for the development of sophisticated pedagogical repertoires and space for critical reading comprehension, without losing the complexity of curriculum offerings, are outlined. How one experienced middle primary teacher operates strategically, ethically and critically in supporting her ESL students to learn to read is illustrated. The teacher’s work is situated within the complex accountability demands faced by classroom teachers. This was accomplished by a teacher whose pedagogical repertoire has been assembled across a career teaching in low-SES high ESL communities in a school with a balanced literacy program and high level of collegial support. Risks for schools and teachers whose circumstances work against their capacities for prioritisation and strategic decision-making are identified and discussed.

What are the real costs of major trauma?

Background This economic evaluation reports the results of a detailed study of the cost of major trauma treated at Princess Alexandra Hospital (PAH), Australia. Methods A bottom-up approach was used to collect and aggregate the direct and indirect costs generated by a sample of 30 inpatients treated for major trauma at PAH in 2004. Major trauma was defined as an admission for Multiple Significant Trauma with an Injury Severity Score >15. Direct and indirect costs were amalgamated from three sources, (1) PAH inpatient costs, (2) Medicare Australia, and (3) a survey instrument. Inpatient costs included the initial episode of inpatient care including clinical and outpatient services and any subsequent representations for ongoing-related medical treatment. Medicare Australia provided an itemized list of pharmaceutical and ambulatory goods and services. The survey instrument collected out-of-pocket expenses and opportunity cost of employment forgone. Inpatient data obtained from a publically funded trauma registry were used to control for any potential bias in our sample. Costs are reported in Australian dollars for 2004 and 2008. Results The average direct and indirect costs of major trauma incurred up to 1-year postdischarge were estimated to be A$78,577 and A$24,273, respectively. The aggregate costs, for the State of Queensland, were estimated to range from A$86.1 million to $106.4 million in 2004 and from A$135 million to A$166.4 million in 2008. Conclusion These results demonstrate that (1) the costs of major trauma are significantly higher than previously reported estimates and (2) the cost of readmissions increased inpatient costs by 38.1%.

Nation-state or country-state : how do we discuss belonging in an age of fluidity?

This is the opening article of a two-part exchange between Jean-Paul Gagnon and Michael Gardiner on the nation-state.