Generation and characterisation of Cisplatin-resistant non-small cell lung cancer cell lines displaying a stem-like signature

Introduction: Inherent and acquired cisplatin resistance reduces the effectiveness of this agent in the management of non-small cell lung cancer (NSCLC). Understanding the molecular mechanisms underlying this process may result in the development of novel agents to enhance the sensitivity of cisplatin. Methods: An isogenic model of cisplatin resistance was generated in a panel of NSCLC cell lines (A549, SKMES-1, MOR, H460). Over a period of twelve months, cisplatin resistant (CisR) cell lines were derived from original, age-matched parent cells (PT) and subsequently characterized. Proliferation (MTT) and clonogenic survival assays (crystal violet) were carried out between PT and CisR cells. Cellular response to cisplatin-induced apoptosis and cell cycle distribution were examined by FACS analysis. A panel of cancer stem cell and pluripotent markers was examined in addition to the EMT proteins, c-Met and β-catenin. Cisplatin-DNA adduct formation, DNA damage (γH2AX) and cellular platinum uptake (ICP-MS) was also assessed. Results: Characterisation studies demonstrated a decreased proliferative capacity of lung tumour cells in response to cisplatin, increased resistance to cisplatin-induced cell death, accumulation of resistant cells in the G0/G1 phase of the cell cycle and enhanced clonogenic survival ability. Moreover, resistant cells displayed a putative stem-like signature with increased expression of CD133+/CD44+cells and increased ALDH activity relative to their corresponding parental cells. The stem cell markers, Nanog, Oct-4 and SOX-2, were significantly upregulated as were the EMT markers, c-Met and β-catenin. While resistant sublines demonstrated decreased uptake of cisplatin in response to treatment, reduced cisplatin-GpG DNA adduct formation and significantly decreased γH2AX foci were observed compared to parental cell lines. Conclusion: Our results identified cisplatin resistant subpopulations of NSCLC cells with a putative stem-like signature, providing a further understanding of the cellular events associated with the cisplatin resistance phenotype in lung cancer. © 2013 Barr et al.

Prenatal Vitamin D deficiency induces an early and more severe experimental autoimmune encephalomyelitis in the second generation

In a previous study, we demonstrated that mouse adult F(1) offspring, exposed to a vitamin d deficiency during pregnancy, developed a less severe and delayed Experimental Autoimmune Encephalomyelitis (EAE), when compared with control offspring. We then wondered whether a similar response was observed in the subsequent generation. To answer this question, we assessed F(2) females whose F(1) parents (males or females) were vitamin d-deprived when developing in the uterus of F(0) females. Unexpectedly, we observed that the vitamin d deficiency affecting the F(0) pregnant mice induced a precocious and more severe EAE in the F(2) generation. This paradoxical finding led us to assess its implications for the epidemiology of Multiple Sclerosis (MS) in humans. Using the REFGENSEP database for MS trios (the patient and his/her parents), we collected the parents' dates of birth and assessed a potential season of birth effect that could potentially be indicative of the vitamin d status of the pregnant grandmothers. A trend for a reduced number of births in the Fall for the parents of MS patients was observed but statistical significance was not reached. Further well powered studies are warranted to validate the latter finding.

Preparing the next generation of HRM professionals : an international comparison of tertiary HRM programs

The future of the HRM profession depends to at least some extent on the quality of preparation of the next generation of HR professionals. This paper examines bachelor degree programs in HRM and the role of professional associations as influencers of curricula. Some 39% of the 599 AACSB and EQUIS-accredited institutions sampled offer undergraduate degrees in HRM. The programs vary in emphasis on HRM competencies. Unsurprisingly, all include foundation work (perhaps a third of the content) in business management. Grouping degree content by regions globally allows benchmarking of degrees against international trends, along with consideration of the increasingly significant influence on curricula by professional bodies, in preparing the next generation of HRM practitioners to manage in organisations that will require strategic thinking, specialist technical skills, and interpersonal competence.

Joint Ventures Law in Australia (3rd ed.)

Following on from the 2nd edition published in 2005, this new edition updates its predecessor and adds considerable new material as a result of changes in the law generally and commercial approaches to financing joint ventures in particular. Of special note, Financing of Joint Ventures has been completely re-written with considerable additions to take account of the new legislative regimes such as the Personal Property Securities. The impact of climate change legislation has been covered, specifically carbon pricing with additional material on structuring generally and particularly in relation to large joint ventures with governments through Public Private Partnerships. A new Chapter has been added called Resources Joint Ventures and undertakes a thorough analysis of a typical resources joint venture and is heavily cross referenced into the chapter on Default which has also been updated. In addition, International Joint Ventures now includes additional material on structuring and dispute resolution and Joint Ventures and the Competition and Consumer Act has been substantially re-written to take account of 2009 legislative amendments on cartel conduct, and the impact of changes wrought by the Competition and Consumer Act 2010. All other chapters and material has been updated to accommodate other legislative changes and new case law over the seven years since the last edition.

Essential elements for recruitment and retention : Generation Y

Purpose: Generation Y (Gen Y) is the newest and largest generation entering the workforce. Gen Y may differ from previous generations in work-related characteristics which may have recruitment and retention repercussions. Currently, limited theoretically-based research exists regarding Gen Y’s work expectations and goals in relation to undergraduate students and graduates. Design/methodology/approach: This study conducted a theoretically-based investigation of the work expectations and goals of student- and working-Gen Y individuals based within a framework incorporating both expectancy-value and goal setting theories. N = 398 provided useable data via an on-line survey. Findings: Overall, some support was found for predictions with career goals loading on a separate component to daily work expectations and significant differences between student- and working- Gen Y on career goals. No significant differences were found, however, between the two groups in daily work expectations. Research limitations/implications: Future research may benefit from adopting a theoretical framework which assesses both daily work expectations and career goals when examining the factors which motivate Gen Y’s decisions to join and remain at a particular organisation. Practical implications: At a practical level, based on the findings, some examples are provided of the means by which organisations may draw upon daily work expectations and career goals of importance to Gen Y and, in doing so, influence the likelihood that a Gen Y individual will join and remain at their particular organisation. Originality/value: This research has demonstrated the utility of adopting a sound theoretical framework in furthering understanding about the motivations which influence organisations’ ability to recruit and retain Gen Y, among both student Gen Y as well as those Gen Y individuals who are already working.

A New DER coordination in LV network based on the concept of distributed control

Given the paradigm of smart grid as the promising backbone for future network, this paper uses this paradigm to propose a new coordination approach for LV network based on distributed control algorithm. This approach divides the LV network into hierarchical communities where each community is controlled by a control agent. Different level of communication has been proposed for this structure to control the network in different operation modes.

Common DC link in residential LV network to improve the penetration level of Small-Scale Embedded Generators

This paper presents a new approach for network upgrading to improve the penetration level of Small Scale Generators in residential feeders. In this paper, it is proposed that a common DC link can be added to LV network to alleviate the negative impact of increased export power on AC lines, allowing customers to inject their surplus power with no restrictions to the common DC link. In addition, it is shown that the proposed approach can be a pathway from current AC network to future DC network.

Supplementary Information : Hogan, Holland, Holloway, Petit and Read : Read Classification for Next Generation Sequencing, ESANN 2013, April 2013

This item provides supplementary materials for the paper mentioned in the title, specifically a range of organisms used in the study. The full abstract for the main paper is as follows: Next Generation Sequencing (NGS) technologies have revolutionised molecular biology, allowing clinical sequencing to become a matter of routine. NGS data sets consist of short sequence reads obtained from the machine, given context and meaning through downstream assembly and annotation. For these techniques to operate successfully, the collected reads must be consistent with the assumed species or species group, and not corrupted in some way. The common bacterium Staphylococcus aureus may cause severe and life-threatening infections in humans,with some strains exhibiting antibiotic resistance. In this paper, we apply an SVM classifier to the important problem of distinguishing S. aureus sequencing projects from alternative pathogens, including closely related Staphylococci. Using a sequence k-mer representation, we achieve precision and recall above 95%, implicating features with important functional associations.

Trip generation in Australia : Practical issues

An online survey was conducted to investigate the views and experiences of Australian traffic and transport professionals about practical problems and issues in terms of trip generation and trip chaining for use in Transport Impact Assessment (TIA). Findings from this survey revealed that there is a shortage of appropriate data related to trip generation estimation for use in TIAs in Australia. Establishing a National Trip Generation Database (NTGD) with a centralised responsible organisation for collecting and publishing trip generation data based on federal and state governments’ contribution was found the most accepted solution for resolving this shortage as well as providing national standards and guidelines associated with trip generation definitions, data collection methodology, and TIA preparation process based on updated research. Finally, the study recognised the importance of the trip chaining effects on trip generation estimation and identified most prevalent land uses subject to trip chaining in terms of TIA.

Peer assisted learning, skills development and Generation Y : a case study of a first year undergraduate law unit

The majority of current first year university students belong to Generation Y. Consequently, research suggests that, in order to more effectively engage them, their particular learning preferences should be acknowledged in the organisation of their learning environments and in the support provided. These preferences are reflected in the Torts Student Peer Mentor Program, which, as part of the undergraduate law degree at the Queensland University of Technology, utilises active learning, structured sessions and teamwork to supplement student understanding of the substantive law of Torts with the development of life-long skills. This article outlines the Program, and its relevance to the learning styles and experiences of Generation Y first year law students transitioning to university, in order to investigate student perceptions of its effectiveness – both generally and, more specifically, in terms of the Program’s capacity to assist students to develop academic and work-related skills.

Decentralized detector generation in cooperative intrusion detection system

We consider Cooperative Intrusion Detection System (CIDS) which is a distributed AIS-based (Artificial Immune System) IDS where nodes collaborate over a peer-to-peer overlay network. The AIS uses the negative selection algorithm for the selection of detectors (e.g., vectors of features such as CPU utilization, memory usage and network activity). For better detection performance, selection of all possible detectors for a node is desirable but it may not be feasible due to storage and computational overheads. Limiting the number of detectors on the other hand comes with the danger of missing attacks. We present a scheme for the controlled and decentralized division of detector sets where each IDS is assigned to a region of the feature space. We investigate the trade-off between scalability and robustness of detector sets. We address the problem of self-organization in CIDS so that each node generates a distinct set of the detectors to maximize the coverage of the feature space while pairs of nodes exchange their detector sets to provide a controlled level of redundancy. Our contribution is twofold. First, we use Symmetric Balanced Incomplete Block Design, Generalized Quadrangles and Ramanujan Expander Graph based deterministic techniques from combinatorial design theory and graph theory to decide how many and which detectors are exchanged between which pair of IDS nodes. Second, we use a classical epidemic model (SIR model) to show how properties from deterministic techniques can help us to reduce the attack spread rate.

Civil procedure : commentary and materials (3rd ed.)

This book provides a comprehensive analysis of the practical and theoretical issues encountered in Australian civil procedure, including alternative dispute resolution. Each chapter features in-depth questions and notes together with lists of further reading to aid understanding of the issue. It also examines and discusses each substantive and procedural step in the trial process. Topics include jurisdiction of a court to consider a matter, alternative dispute resolution. limitations of actions, commencing proceedings, pleading, gathering evidence, trial and appeal, costs and practice directions. The procedures in the Supreme Courts of each of the states and Territories are covered, as well as those of the Federal Court of Australia.