DEAD-box helicase DP103 defines metastatic potential of human breast cancers

Despite advancement in breast cancer treatment, 30% of patients with early breast cancers experience relapse with distant metastasis. It is a challenge to identify patients at risk for relapse; therefore, the identification of markers and therapeutic targets for metastatic breast cancers is imperative. Here, we identified DP103 as a biomarker and metastasis-driving oncogene in human breast cancers and determined that DP103 elevates matrix metallopeptidase 9 (MMP9) levels, which are associated with metastasis and invasion through activation of NF-κB. In turn, NF-κB signaling positively activated DP103 expression. Furthermore, DP103 enhanced TGF-β-activated kinase-1 (TAK1) phosphorylation of NF-κB-activating IκB kinase 2 (IKK2), leading to increased NF-κB activity. Reduction of DP103 expression in invasive breast cancer cells reduced phosphorylation of IKK2, abrogated NF-κB-mediated MMP9 expression, and impeded metastasis in a murine xenograft model. In breast cancer patient tissues, elevated levels of DP103 correlated with enhanced MMP9, reduced overall survival, and reduced survival after relapse. Together, these data indicate that a positive DP103/NF-κB feedback loop promotes constitutive NF-κB activation in invasive breast cancers and activation of this pathway is linked to cancer progression and the acquisition of chemotherapy resistance. Furthermore, our results suggest that DP103 has potential as a therapeutic target for breast cancer treatment.

Inhabiting Sound: Tactile-sonic links in musical meaning

Connections can be suggested between music’s occupation of physical space, its relative ‘presence’ (using Edward Hall’s notion of proxemics), and the various senses of movement which pervade it. Movement might be seen to operate with respect to music at a variety of levels of metaphorisation – as increasingly complex chains of analogy which point back to our early physical experience of the world. But of course music is, fundamentally, action. Humans put energy into systems - external or internal to themselves - which transduce that energy into the movement of air. At the acoustic level music is, emphatically and unmetaphorically, movement. Perhaps such simple physical perceptions form one route through which we might understand and explore shared senses of meaning and their capacity for ‘transduction’ between multiple individuals. Our (developmentally) early sensory models of the world, built from encounters with its physical resistances and affordances, might be a route to understanding our more clearly encultured and abstracted ('higher' level) understandings of music.

Environmental Operations Management and its links with Proactivity and Performance: A study of the UK Food Industry

Two important strands of research within the literature on Environmental Operations Management (EOM) relate to environmental approach and performance. Often in this research the links between environmental approach, environmental performance and EOM are considered separately with little consideration given to the interrelationships between them. This study develops and tests a theoretical framework that combines these two strands to explore how UK food manufacturers approach EOM. The framework considers the relationships between an environmentally pro-active strategic orientation, EOM and environmental and cost performance. A cross-sectional survey was developed to collect data from a sample of 1200 food manufacturing firms located within the UK. Responses were sought from production and operations managers who are knowledgeable about the environmental operations practices within their firms. A total of 149 complete and useable responses were obtained. The reliability and validity of the scales used in the survey were tested using exploratory factor analysis, prior to the testing of the hypotheses underpinning the theoretical framework using hierarchical regression analysis. Our results generate support for a link between environmental proactivity, environmental practices and performance, consistent with the natural resource-based view (NRBV) and a number of studies in the extant literature. In considering environmental proactivity as a standalone concept that influences the implementation of environmental practices outlined in the NRBV, our study generates some novel insights into these links. Further our results provide some interesting insights for managers within the food industry who can identify the potential benefits of certain practices for performance within this unique context.

Protocol: A randomised controlled trial evaluation of Cancer Focus NI’s ‘Dead Cool’ smoking prevention programme in post-primary schools

This paper presents a research protocol for a randomised controlled efficacy trial of the ‘Dead Cool’ smoking prevention programme. Dead Cool is a three to four-hour programme designed to be used by teachers with Year 9 students in Northern Ireland. The main outcome of the programme is to prevent students from starting to smoke. The protocol reports a research design intended to test the efficacy of the programme in 20 post-primary school settings. Selected schools included those from secondary /grammar/integrated/single sex/coeducational, rural and urban schools from both the maintained and controlled state sector and independent sector schools. Outcome measures include self-reported behaviours, monitoring of carbon monoxide (CO) in exhaled breath and focus groups designed to assess implementation fidelity and opinions on efficacy in intervention schools and explore the ‘counterfactual’ potential treatments in control schools.

Is the Schwabe organ a retained larval eye? Anatomical and behavioural studies of a novel sense organ in adult leptochiton asellus (Mollusca, Polyplacophora) indicate links to larval photoreceptors

The discovery of a sensory organ, the Schwabe organ, was recently reported as a unifying feature of chitons in the order Lepidopleurida. It is a patch of pigmented tissue located on the roof of the pallial cavity, beneath the velum on either side of the mouth. The epithelium is densely innervated and contains two types of potential sensory cells. As the function of the Schwabe organ remains unknown, we have taken a cross-disciplinary approach, using anatomical, histological and behavioural techniques to understand it. In general, the pigmentation that characterises this sensory structure gradually fades after death; however, one particular concentrated pigment dot persists. This dot is positionally homologous to the larval eye in chiton trochophores, found in the same neuroanatomical location, and furthermore the metamorphic migration of the larval eye is ventral in species known to possess Schwabe organs. Here we report the presence of a discrete subsurface epithelial structure in the region of the Schwabe organ in Leptochiton asellus that histologically resembles the chiton larval eye. Behavioural experiments demonstrate that Leptochiton asellus with intact Schwabe organs actively avoid an upwelling light source, while Leptochiton asellus with surgically ablated Schwabe organs and a control species lacking the organ (members of the other extant order, Chitonida) do not (Kruskal-Wallis, H = 24.82, df = 3, p < 0.0001). We propose that the Schwabe organ represents the adult expression of the chiton larval eye, being retained and elaborated in adult lepidopleurans.

Multiuser relaying over mixed RF/FSO links

A multiuser dual-hop relaying system over mixed radio frequency/free-space optical (RF/FSO) links is investigated. Specifically, the system consists of m single-antenna sources, a relay node equipped with n≥ m receive antennas and a single photo-aperture transmitter, and one destination equipped with a single photo-detector. RF links are used for the simultaneous data transmission from multiple sources to the relay. The relay operates under the decode-and-forward protocol and utilizes the popular V-BLAST technique by successively decoding each user's transmitted stream. Two common norm-based orderings are adopted, i.e., the streams are decoded in an ascending or a descending order. After V-BLAST, the relay retransmits the decoded information to the destination via a point-to-point FSO link in m consecutive timeslots. Analytical expressions for the end-to-end outage probability and average symbol error probability of each user are derived, while closed-form asymptotic expressions are also presented. Capitalizing on the derived results, some engineering insights are manifested, such as the coding and diversity gain of each user, the impact of the pointing error displacement on the FSO link and the V-BLAST ordering effectiveness at the relay.

The histone demethylase JMJD2A/KDM4A links ribosomal RNA transcription to nutrients and growth factors availability

The interplay between methylation and demethylation of histone lysine residues is an essential component of gene expression regulation and there is considerable interest in elucidating the roles of proteins involved. Here we report that histone demethylase KDM4A/JMJD2A, which is involved in the regulation of cell proliferation and is overexpressed in some cancers, interacts with RNA Polymerase I, associates with active ribosomal RNA genes and is required for serum-induced activation of rDNA transcription. We propose that KDM4A controls the initial stages of transition from 'poised', non-transcribed rDNA chromatin into its active form. We show that PI3K, a major signalling transducer central for cell proliferation and survival, controls cellular localization of KDM4A and consequently its association with ribosomal DNA through the SGK1 downstream kinase. We propose that the interplay between PI3K/SGK1 signalling cascade and KDM4A constitutes a mechanism by which cells adapt ribosome biogenesis level to the availability of growth factors and nutrients.

Step by step: reconstruction of terrestrial animal movement paths by dead-reckoning

BACKGROUND: Research on wild animal ecology is increasingly employing GPS telemetry in order to determine animal movement. However, GPS systems record position intermittently, providing no information on latent position or track tortuosity. High frequency GPS have high power requirements, which necessitates large batteries (often effectively precluding their use on small animals) or reduced deployment duration. Dead-reckoning is an alternative approach which has the potential to 'fill in the gaps' between less resolute forms of telemetry without incurring the power costs. However, although this method has been used in aquatic environments, no explicit demonstration of terrestrial dead-reckoning has been presented.

RESULTS: We perform a simple validation experiment to assess the rate of error accumulation in terrestrial dead-reckoning. In addition, examples of successful implementation of dead-reckoning are given using data from the domestic dog Canus lupus, horse Equus ferus, cow Bos taurus and wild badger Meles meles.

CONCLUSIONS: This study documents how terrestrial dead-reckoning can be undertaken, describing derivation of heading from tri-axial accelerometer and tri-axial magnetometer data, correction for hard and soft iron distortions on the magnetometer output, and presenting a novel correction procedure to marry dead-reckoned paths to ground-truthed positions. This study is the first explicit demonstration of terrestrial dead-reckoning, which provides a workable method of deriving the paths of animals on a step-by-step scale. The wider implications of this method for the understanding of animal movement ecology are discussed.

Exploiting Direct Links for Physical Layer Security in Multi-User Multi-Relay Networks

We present two physical layer secure transmission schemes for multi-user multi-relay networks, where the communication from M users to the base station is assisted by direct links and by N decode-and-forward relays. In this network, we consider that a passive eavesdropper exists to overhear the transmitted information, which entails exploiting the advantages of both direct and relay links for physical layer security enhancement. To fulfill this requirement, we investigate two criteria for user and relay selection and examine the achievable secrecy performance. Criterion I performs a joint user and relay selection, while Criterion II performs separate user and relay selections, with a lower implementation complexity. We derive a tight lower bound on the secrecy outage probability for Criterion I and an accurate analytical expression for the secrecy outage probability for Criterion II. We further derive the asymptotic secrecy outage probabilities at high transmit signal-to-noise ratios and high main-to-eavesdropper ratios for both criteria. We demonstrate that the secrecy diversity order is min (MN, M + N) for Criterion I, and N for Criterion II. Finally, we present numerical and simulation results to validate the proposed analysis, and show the occurrence condition of the secrecy outage probability floor