Recent advances in cancer therapy targeting proteins involved in DNA double-strand break repair

Damage to genetic material represents a persistent and ubiquitous threat to genomic stability. Once DNA damage is detected, a multifaceted signaling network is activated that halts the cell cycle, initiates repair, and in some instances induces apoptotic cell death. In this article, we will review DNA damage surveillance networks, which maintain the stability of our genome, and discuss the efforts underway to identify chemotherapeutic compounds targeting the core components of DNA double-strand breaks (DSB) response pathway. The majority of tumor cells have defects in maintaining genomic stability owing to the loss of an appropriate response to DNA damage. New anticancer agents are exploiting this vulnerability of cancer cells to enhance therapeutic indexes, with limited normal tissue toxicity. Recently inhibitors of the checkpoint kinases Chk1 and Chk2 have been shown to sensitize tumor cells to DNA damaging agents. In addition, the treatment of BRCA1- or BRCA2-deficient tumor cells with poly(ADP-ribose) polymerase (PARP) inhibitors also leads to specific tumor killing. Due to the numerous roles of p53 in genomic stability and its defects in many human cancers, therapeutic agents that restore p53 activity in tumors are the subject of multiple clinical trials. In this article we highlight the proteins mentioned above and catalog several additional players in the DNA damage response pathway, including ATM, DNA-PK, and the MRN complex, which might be amenable to pharmacological interventions and lead to new approaches to sensitize cancer cells to radio- and chemotherapy. The challenge is how to identify those patients most receptive to these treatments.

Cultivating Innovation through Social Relationships: A Qualitative Study of Outstanding Australian Innovators in Science, Technology and the Creative Industries

In this chapter, we describe and explore social relationship patterns associated with outstanding innovation. In doing so, we draw upon the findings of 16 in-depth interviews with award-winning Australian innovators from science & technology and the creative industries. The interviews covered topics relating to various influences on individual innovation capacity and career development. We found that for all of the participants, innovation was a highly social process. Although each had been recognised individually for their innovative success, none worked in isolation. The ability to generate innovative outcomes was grounded in certain types of interaction and collaboration. We outline the distinctive features of the social relationships which seem to be important to innovation, and ask which ‘social network capabilities’ might underlie the ability to create an optimal pattern of interpersonal relationships. We discuss the implications of these findings for universities, which we argue play a key role in the development of nascent innovators.

The concept of 'Organismic Asymmetry' in sport science

The concept of organismic asymmetry refers to an inherent bias for seeking explanations of human performance and behaviour based on internal mechanisms and referents. A weakness in this tendency is a failure to consider the performer–environment relationship as the relevant scale of analysis. In this paper we elucidate the philosophical roots of the bias and discuss implications of organismic asymmetry for sport science and performance analysis, highlighting examples in psychology, sports medicine and biomechanics.

Student autonomy enhancing science learning : Observations from a Primary Connections implementation

This case study involved a detailed analysis of the changes in beliefs and teaching practices of teachers who adopted the Primary Connections program as a professional development initiative. When implementing an inquiry-based learning model, teachers observed that their students learnt more when they intervened less. By scaffolding open-ended nquiries they achieved more diverse, complex and thorough learning outcomes than previously achieved with teacher-led discussions or demonstrations. Initially, student autonomy presented erceived threats to teachers, including possible selection of topics outside the teachers’ science knowledge. In practice, when such issues arose, resolving them became a stimulating part of the earning for both teachers and students. The teachers’ observation of enhanced student learning became a powerful motivator for change in their beliefs and practices. Implications for developers of PD programs are (1) the importance of modeling student-devised inquiries, and (2) recognising the role of successful classroom implementation in facilitating change.

School-based experiences : developing primary science preservice teachers' practice

Reviews into teacher education emphasise the need for preservice teachers to have more school-based experiences. In this study, a school-based experience was organised within a nine-week science curriculum university unit that allowed preservice teachers’ repeated experiences in teaching primary science. This research uses a survey, questionnaire with extended written responses, and researcher observations to investigate preservice teachers’ (n=38) learning experiences in two school settings. Survey results indicated that the majority of these preservice teachers either agreed or strongly agreed that school-based experiences developed their: personal-professional skill development (100%); system requirements (range: 81-100%); teaching practices (81-100%); student behaviour management (range: 94-100%); providing student feedback (89-94%); and reflection on practice (92-100%). Qualitative data provided insights into their development particularly for science content knowledge and receiving positive reinforcement on effective teaching behaviours. According to these preservice teachers, the school-based experiences facilitated “teachable moments – having the knowledge or skills to run with students’ questions or ideas” and allowed preservice teachers to “critically reflect between groups to make the task flow better”. Embedding school-based experiences needs to be part of each and every preservice teacher education unit so preservice teachers can develop confidence, knowledge and skills within authentic school contexts.

Generalising across borders : policy and the limits of educational science.

AERA Distinguished Lecture, Annual Meetings of the American Educational Research Association, New Orleans, 8 April 2011. How well does educational policy, innovation and science cross borders? What are the parameters of a generalisable cultural science of education? What constitutes a principled policy 'borrowing'?

Adaptive GPS duty cycling and radio ranging for energy-efficient localization

This paper addresses the tradeoff between energy consumption and localization performance in a mobile sensor network application. The focus is on augmenting GPS location with more energy-efficient location sensors to bound position estimate uncertainty in order to prolong node lifetime. We use empirical GPS and radio contact data from a largescale animal tracking deployment to model node mobility, GPS and radio performance. These models are used to explore duty cycling strategies for maintaining position uncertainty within specified bounds. We then explore the benefits of using short-range radio contact logging alongside GPS as an energy-inexpensive means of lowering uncertainty while the GPS is off, and we propose a versatile contact logging strategy that relies on RSSI ranging and GPS lock back-offs for reducing the node energy consumption relative to GPS duty cycling. Results show that our strategy can cut the node energy consumption by half while meeting application specific positioning criteria.

Secure data aggregation in wireless sensor networks

A Wireless Sensor Network (WSN) is a set of sensors that are integrated with a physical environment. These sensors are small in size, and capable of sensing physical phenomena and processing them. They communicate in a multihop manner, due to a short radio range, to form an Ad Hoc network capable of reporting network activities to a data collection sink. Recent advances in WSNs have led to several new promising applications, including habitat monitoring, military target tracking, natural disaster relief, and health monitoring. The current version of sensor node, such as MICA2, uses a 16 bit, 8 MHz Texas Instruments MSP430 micro-controller with only 10 KB RAM, 128 KB program space, 512 KB external ash memory to store measurement data, and is powered by two AA batteries. Due to these unique specifications and a lack of tamper-resistant hardware, devising security protocols for WSNs is complex. Previous studies show that data transmission consumes much more energy than computation. Data aggregation can greatly help to reduce this consumption by eliminating redundant data. However, aggregators are under the threat of various types of attacks. Among them, node compromise is usually considered as one of the most challenging for the security of WSNs. In a node compromise attack, an adversary physically tampers with a node in order to extract the cryptographic secrets. This attack can be very harmful depending on the security architecture of the network. For example, when an aggregator node is compromised, it is easy for the adversary to change the aggregation result and inject false data into the WSN. The contributions of this thesis to the area of secure data aggregation are manifold. We firstly define the security for data aggregation in WSNs. In contrast with existing secure data aggregation definitions, the proposed definition covers the unique characteristics that WSNs have. Secondly, we analyze the relationship between security services and adversarial models considered in existing secure data aggregation in order to provide a general framework of required security services. Thirdly, we analyze existing cryptographic-based and reputationbased secure data aggregation schemes. This analysis covers security services provided by these schemes and their robustness against attacks. Fourthly, we propose a robust reputationbased secure data aggregation scheme for WSNs. This scheme minimizes the use of heavy cryptographic mechanisms. The security advantages provided by this scheme are realized by integrating aggregation functionalities with: (i) a reputation system, (ii) an estimation theory, and (iii) a change detection mechanism. We have shown that this addition helps defend against most of the security attacks discussed in this thesis, including the On-Off attack. Finally, we propose a secure key management scheme in order to distribute essential pairwise and group keys among the sensor nodes. The design idea of the proposed scheme is the combination between Lamport's reverse hash chain as well as the usual hash chain to provide both past and future key secrecy. The proposal avoids the delivery of the whole value of a new group key for group key update; instead only the half of the value is transmitted from the network manager to the sensor nodes. This way, the compromise of a pairwise key alone does not lead to the compromise of the group key. The new pairwise key in our scheme is determined by Diffie-Hellman based key agreement.

Remote monitoring of outdoor performance of low scale dye sensitized solar cells for nanosensors nodes

This is the first outdoor test of small-scale dye sensitized solar cells (DSC) powering a standalone nanosensor node. A solar cell test station (SCTS) has been developed using standard DSC to power a gas nanosensor, a radio transmitter, and the control electronics (CE) for battery charging. The station is remotely monitored through wired (Ethernet cable) or wireless connection (radio transmitter) in order to evaluate in real time the performance of the solar cells powering a nanosensor and a transmitter under different weather conditions. We analyze trends of energy conversion efficiency after 60 days of operation. The 408 cm2 active surface module produces enough energy to power a gas nanosensor and a radio transmitter during the day and part of the night. Also, by using a variable programmable load we keep the system working on the maximum power point (MPP) quantifying the total energy generated and stored in a battery. Although this technology is at an early stage of development, these experiments provide useful data for future outdoor applications such as nanosensor network nodes.

Reproducing successful rituals in bad times : exploring interactions of a new science teacher

Teaching is emotional work. This is especially the case in the first years of teaching when new teachers are particularly vulnerable. By understanding changes in teacher emotions in the early years of teaching we hope to identify strategies that might ultimately reduce teacher attrition. As part of a larger study of the transition of new teachers to the profession, this ethnographic case study explores how a new science teacher produced and reproduced positive emotional interaction rituals with her students in her first year of teaching. We show how dialogical interactions were positive and satisfying experiences for the teacher, and how they were reproduced successfully in different contexts. We also illustrate how both teacher and students used humor to create a structure for dialogical interactions. During these successful interactions the students used shared resources to satisfy their teacher that they were engaging in the relevant science content. The implications of what we have learned for the professional development of new teachers are discussed in relation to an expanded understanding of teacher emotions.

A study of laughter in science lessons

Laughter is a fundamental human phenomenon. Yet there is little educational research on the potential functions of laughter on the enacted (lived) curriculum. In this study, we identify the functions of laughter in a beginning science teacher’s classroom throughout her first year of teaching. Our study shows that laughter is more than a gratuitous phenomenon. It is the result of a collective interactive achievement of the classroom participants that offsets the seriousness of science as a discipline. Laughter, whereas it challenges the seriousness of science, also includes the dialectical inversion of the challenge: it simultaneously reinforces the idea of science as serious business.

The power of educational podcasting : using short-format podcasts to reinforce tertiary student learning experiences in science

In 2007 I introduced short-format educational podcast resources that reinforced conceptual teaching and learning in an interdisciplinary tertiary science study area (biochemistry). This study aims to determine student attitudes to the perceived usefulness and benefit of short-format educational podcasts, and presents the findings (qualitative and quantitative) from surveys obtained from three offerings of the science teaching unit (2007, 2008 and 2009). Podcasts were recorded (MP3 audio files) separately from the instructive lecture sessions, and subsequent to the weekly lecture, short-format podcasts summarising the key learning objectives were integrated within the resources presented through the students learning management system (Blackboard). The vast majority (>88%) of students utilised the podcast resources, indicating a high level of acceptance and uptake for this portable educational technology. The respondents reported that podcasts focused their attention to core learning concepts and supported their understanding and learning of the lecture material. Furthermore, the data showed that respondents agreed strongly that podcasts assisted with study and revision for examinations and, somewhat surprisingly, there was a perception that podcasts positively impacted on examination performance. Overall, student users perceived that podcasting is as an effective and valuable educational tool that offers convenience and flexibility for their learning and understanding of a tertiary science study area, such as biochemistry.

Re-engaging adolescent students in science : an experienced teachers' classroom

Adolescents are both aware of and have the impetuous to exploit aspects of Science, Technology, Engineering and Mathematics (STEM) within their personal lives. Whether they are surfing, cycling, skateboarding or shopping, STEM concepts impact their lives. However science, mathematics, engineering and technology are still treated in the classroom as separate fragmented entities in the educational environment where most classroom talk is seemingly incomprehensible to the adolescent senses. The aim of this study was to examine the experiences of young adolescents with the aim of transforming school learning at least of science into meaningful experiences that connected with their lives using a self-study approach. Over a 12-month period, the researcher, an experienced secondary-science teacher, designed, implemented and documented a range of pedagogical practices with his Year-7 secondary science class. Data for this case study included video recordings, journals, interviews and surveys of students. By setting an environment empathetic to adolescent needs and understandings, students were able to actively explore phenomena collaboratively through developmentally appropriate experiences. Providing a more contextually relevant environment fostered meta-cognitive practices, encouraged new learning through open dialogue, multi-modal representations and assessments that contributed to building upon, re-affirming, or challenging both the students' prior learning and the teacher’s pedagogical content knowledge. A significant outcome of this study was the transformative experiences of an insider, the teacher as researcher, whose reflections provided an authentic model for reforming pedagogy in STEM classes.

Developing an IS-Impact decision tool : a literature based design science roadmap

This paper derives from research-in-progress intending both Design Research (DR) and Design Science (DS) outputs; the former a management decision tool based in IS-Impact (Gable et al. 2008) kernel theory; the latter being methodological learnings deriving from synthesis of the literature and reflection on the DR ‘case study’ experience. The paper introduces a generic, detailed and pragmatic DS ‘Research Roadmap’ or methodology, deriving at this stage primarily from synthesis and harmonization of relevant concepts identified through systematic archival analysis of related literature. The scope of the Roadmap too has been influenced by the parallel study aim to undertake DR applying and further evolving the Roadmap. The Roadmap is presented in attention to the dearth of detailed guidance available to novice Researchers in Design Science Research (DSR), and though preliminary, is expected to evolve and gradually be substantiated through experience of its application. A key distinction of the Roadmap from other DSR methods is its breadth of coverage of published DSR concepts and activities; its detail and scope. It represents a useful synthesis and integration of otherwise highly disparate DSR-related concepts.

A design science research roadmap

This paper proposes and synthesizes from previous design science(DS) methodological literature a structured and detailed DS Roadmap for the conduct of DS research. The Roadmap is a general guide for researchers to carry out DS research by suggesting reasonably detailed activities.Though highly tentative, it is believed the Roadmap usefully inter-relates many otherwise seemingly disparate, overlapping or conflicting concepts. It is hoped the DS Roadmap will aid in the planning, execution and communication of DS research,while also attracting constructive criticism, improvements and extensions. A key distinction of the Roadmap from other DS research methods is its breadth of coverage of DS research aspects and activities; its detail and scope. We demonstrate and evaluate the Roadmap by presenting two case studies in terms of the DS Roadmap.