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.

Using scenarios to explore the social aspects of design led innovations

Emerging technologies have redefined the way people go about everyday life. An increasing array of online and on-the-go solutions supporting remote work, entertainment on demand, information sharing, social communication, telehealth and beyond, are now available at the touch of a screen. This paper discusses concept of scenarios as a design tool that can be successfully employed by organisations as an innovative design led approach to: (i) understand people’s everyday practices in current social contexts in order to identify opportunities and emerging markets, and (ii) reveal stakeholder relationships existing in the provision of services within current everyday practices. To illustrate this approach, two case studies will be presented: the first focusing on a real industry project exploring opportunities for the development of future health care services, the second focusing on people’s access to services as part of a transport journey experience. This paper aims to demonstrate the use of scenarios as part of a design led innovation approach to understand the social aspects and their complexities of new designs in an increasing everyday technological driven context.

Damage detection in slab-on-girder bridges using vibration characteristics

This paper develops and applies a multi-criteria procedure, incorporating changes in natural frequencies, modal flexibility and the modal strain energy, for damage detection in slab-on-girder bridges. The proposed procedure is first validated through experimental testing of a model bridge. Numerically simulated modal data obtained through finite element analyses are then used to evaluate the vibration parameters before and after damage and used as the indices for assessment of the state of structural health. The procedure is illustrated by its application to full scale slab-on-girder bridges under different damage scenarios involving single and multiple damages on the deck and girders.

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.

Intratherapist reliability in the rating of scapula posture in multiple planes of reference

Background: Evaluation of scapular posture is a fundamental component in the clinical evaluation of the upper quadrant. This study examined the intrarater reliability of scapular posture ratings. Methods: A test-retest reliability investigation was undertaken with one week between assessment sessions. At each session physical therapists conducted visual assessments of scapula posture (relative to the thorax) in five different scapula postural planes (plane of scapula, sagittal plane, transverse plane, horizontal plane, and vertical plane). These five plane ratings were performed for four different scapular posture perturbating conditions (rest, isometric shoulder; flexion, abduction, and external rotation). Results. A total of 100 complete scapular posture ratings (50 left, 50 right) were undertaken at each assessment. The observed agreement between the test and retest postural plane ratings ranged from 59% to 87%; 16 of the 20 plane-condition combinations exceeded 75% observed agreement. Kappa (and prevalence adjusted bias adjusted kappa) values were inconsistent across the postural planes and perturbating conditions. Conclusions: This investigation generally revealed fair to moderate intrarater reliability in the rating of scapular posture by visual inspection. However, enough disagreement between assessments was present to warrant caution when interpreting perceived changes in scapula position between longitudinal assessments using visual inspection alone.

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.

Fine-mapping identifies multiple prostate cancer risk loci on 5p15 some associating with TERT expression

Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease.

A framework for automated identification of attack scenarios on IT infrastructures

Due to increased complexity, scale, and functionality of information and telecommunication (IT) infrastructures, every day new exploits and vulnerabilities are discovered. These vulnerabilities are most of the time used by ma¬licious people to penetrate these IT infrastructures for mainly disrupting business or stealing intellectual pro¬perties. Current incidents prove that it is not sufficient anymore to perform manual security tests of the IT infra¬structure based on sporadic security audits. Instead net¬works should be continuously tested against possible attacks. In this paper we present current results and challenges towards realizing automated and scalable solutions to identify possible attack scenarios in an IT in¬frastructure. Namely, we define an extensible frame¬work which uses public vulnerability databases to identify pro¬bable multi-step attacks in an IT infrastructure, and pro¬vide recommendations in the form of patching strategies, topology changes, and configuration updates.

Speaker attribution of multiple telephone conversations using a complete-linkage clustering approach

In this paper we propose and evaluate a speaker attribution system using a complete-linkage clustering method. Speaker attribution refers to the annotation of a collection of spoken audio based on speaker identities. This can be achieved using diarization and speaker linking. The main challenge associated with attribution is achieving computational efficiency when dealing with large audio archives. Traditional agglomerative clustering methods with model merging and retraining are not feasible for this purpose. This has motivated the use of linkage clustering methods without retraining. We first propose a diarization system using complete-linkage clustering and show that it outperforms traditional agglomerative and single-linkage clustering based diarization systems with a relative improvement of 40% and 68%, respectively. We then propose a complete-linkage speaker linking system to achieve attribution and demonstrate a 26% relative improvement in attribution error rate (AER) over the single-linkage speaker linking approach.

Slide attacks on the Sfinks stream cipher

Sfinks is a shift register based stream cipher designed for hardware implementation and submitted to the eSTREAM project. In this paper, we analyse the initialisation process of Sfinks. We demonstrate a slid property of the loaded state of the Sfinks cipher, where multiple key-IV pairs may produce phase shifted keystream sequences. The state update functions of both the initialisation process and keystream generation and also the pattern of the padding affect generation of the slid pairs.

Robots move : bootstrapping the development of object representations using sensorimotor coordination

This paper is concerned with the unsupervised learning of object representations by fusing visual and motor information. The problem is posed for a mobile robot that develops its representations as it incrementally gathers data. The scenario is problematic as the robot only has limited information at each time step with which it must generate and update its representations. Object representations are refined as multiple instances of sensory data are presented; however, it is uncertain whether two data instances are synonymous with the same object. This process can easily diverge from stability. The premise of the presented work is that a robot's motor information instigates successful generation of visual representations. An understanding of self-motion enables a prediction to be made before performing an action, resulting in a stronger belief of data association. The system is implemented as a data-driven partially observable semi-Markov decision process. Object representations are formed as the process's hidden states and are coordinated with motor commands through state transitions. Experiments show the prediction process is essential in enabling the unsupervised learning method to converge to a solution - improving precision and recall over using sensory data alone.

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.