Mobile silencing in plants: what is the signal and what defines the target

RNA-mediated silencing in plants can spread from cell to cell and over a long distance, and such mobile silencing has been extensively studied in the past decade. However, major questions remain as to what is the exact nature of the mobile silencing signals, how the components of the RNA-directed DNA methylation pathway are involved, and why systemic spread of silencing has only been observed for transgenes but not endogenous genes. In this review, we provide an overview of the current knowledge on mobile gene silencing in plants and present a model where systemic silencing involves long nuclear RNA transcripts that serve as a template to amplify primary siRNA signals.

Queensland’s high risk foot database : tracking the length and width of Queensland’s foot ulcers

Background Foot ulcers are a leading cause of avoidable hospital admissions and lower extremity amputations. However, large clinical studies describing foot ulcer presentations in the ambulatory setting are limited. The aim of this descriptive observational paper is to report the characteristics of ambulatory foot ulcer patients managed across 13 of 17 Queensland Health & Hospital Services. Methods Data on all foot ulcer patients registered with a Queensland High Risk Foot Form (QHRFF) was collected at their first consult in 2012. Data is automatically extracted from each QHRFF into a Queensland high risk foot database. Descriptive statistics display age, sex, ulcer types and co-morbidities. Statewide clinical indicators of foot ulcer management are also reported. Results Overall, 2,034 people presented with a foot ulcer in 2012. Mean age was 63(±14) years and 67.8% were male. Co-morbidities included 85% had diabetes, 49.7% hypertension, 39.2% dyslipidaemia, 25.6% cardiovascular disease, 13.7% kidney disease and 12.2% smoking. Foot ulcer types included 51.6% neuropathic, 17.8% neuro-ischaemic, 7.2% ischaemic, 6.6% post-surgical and 16.8% other; whilst 31% were infected. Clinical indicator results revealed 98% had their wound categorised, 51% received non-removable offloading, median ulcer healing time was 6-weeks and 37% had ulcer recurrence. Conclusion This paper details the largest foot ulcer database reported in Australia. People presenting with foot ulcers appear predominantly older, male with several co-morbidities. Encouragingly it appears most patients are receiving best practice care. These results may be a factor in the significant reduction of Queensland diabetes foot-related hospitalisations and amputations recently reported.

The velocity synchronous discrete Fourier transform for order tracking in the field of rotating machinery

Diagnostics of rotating machinery has developed significantly in the last decades, and industrial applications are spreading in different sectors. Most applications are characterized by varying velocities of the shaft and in many cases transients are the most critical to monitor. In these variable speed conditions, fault symptoms are clearer in the angular/order domains than in the common time/frequency ones. In the past, this issue was often solved by synchronously sampling data by means of phase locked circuits governing the acquisition; however, thanks to the spread of cheap and powerful microprocessors, this procedure is nowadays rarer; sampling is usually performed at constant time intervals, and the conversion to the order domain is made by means of digital signal processing techniques. In the last decades different algorithms have been proposed for the extraction of an order spectrum from a signal sampled asynchronously with respect to the shaft rotational velocity; many of them (the so called computed order tracking family) use interpolation techniques to resample the signal at constant angular increments, followed by a common discrete Fourier transform to shift from the angular domain to the order domain. A less exploited family of techniques shifts directly from the time domain to the order spectrum, by means of modified Fourier transforms. This paper proposes a new transform, named velocity synchronous discrete Fourier transform, which takes advantage of the instantaneous velocity to improve the quality of its result, reaching performances that can challenge the computed order tracking.

Order tracking for discrete-random separation in variable speed conditions

The transmission path from the excitation to the measured vibration on the surface of a mechanical system introduces a distortion both in amplitude and in phase. Moreover, in variable speed conditions, the amplification/attenuation and the phase shift, due to the transfer function of the mechanical system, varies in time. This phenomenon reduces the effectiveness of the traditionally tachometer based order tracking, compromising the results of a discrete-random separation performed by a synchronous averaging. In this paper, for the first time, the extent of the distortion is identified both in the time domain and in the order spectrum of the signal, highlighting the consequences for the diagnostics of rotating machinery. A particular focus is given to gears, providing some indications on how to take advantage of the quantification of the disturbance to better tune the techniques developed for the compensation of the distortion. The full theoretical analysis is presented and the results are applied to an experimental case.

PITX2 and non-canonical Wnt pathway interaction in metastatic prostate cancer

The non-canonical Wnt pathway, a regulator of cellular motility and morphology, is increasingly implicated in cancer metastasis. In a quantitative PCR array analysis of 84 Wnt pathway associated genes, both non-canonical and canonical pathways were activated in primary and metastatic tumors relative to normal prostate. Expression of the Wnt target gene PITX2 in a prostate cancer (PCa) bone metastasis was strikingly elevated over normal prostate (over 2,000-fold) and primary prostate cancer (over 200-fold). The elevation of PITX2 protein was also evident on tissue microarrays, with strong PITX2 immunostaining in PCa skeletal and, to a lesser degree, soft tissue metastases. PITX2 is associated with cell migration during normal tissue morphogenesis. In our studies, overexpression of individual PITX2A/B/C isoforms stimulated PC-3 PCa cell motility, with the PITX2A isoform imparting a specific motility advantage in the presence of non-canonical Wnt5a stimulation. Furthermore, PITX2 specific shRNA inhibited PC-3 cell migration toward bone cell derived chemoattractant. These experimental results support a pivotal role of PITX2A and non-canonical Wnt signaling in enhancement of PCa cell motility, suggest PITX2 involvement in homing of PCa to the skeleton, and are consistent with a role for PITX2 in PCa metastasis to soft and bone tissues. Our findings, which significantly expand previous evidence that PITX2 is associated with risk of PCa biochemical recurrence, indicate that variation in PITX2 expression accompanies and may promote prostate tumor progression and metastasis.

Cyclic mechanical strain guides capillary-like morphology in vitro

Introduction Stretching of tissue stimulates angiogenesis but increased motion at a fracture site hinders revascularisation. In vitro studies have indicated that mechanical stimuli promote angiogenic responses in endothelial cells, but can either inhibit or enhance responses when applied directly to angiogenesis assays. We anticipated that cyclic tension applied during endothelial network assembly would increase vascular structure formation up to a certain threshold. Methods Fibroblast/HUVEC co-cultures were subjected to cyclic equibiaxial strain (1 Hz; 6 h/day; 7 days) using the FlexerCell FX-4000T system and limiting rings for simultaneous application of multiple strain magnitudes (0–13%). Cells were labelled using anti-PECAM-1, and image analysis provided measures of endothelial network length and numbers of junctions. Results Cyclic stretching had no significant effect on the total length of endothelial networks (P > 0.2) but resulted in a strain-dependent decrease in branching and localised alignments of endothelial structures, which were in turn aligned with the supporting fibroblastic construct. Conclusion The organisation of endothelial networks under cyclic strain is dominated by structural adaptation to the supporting construct. It may be that, in fracture healing, the formation and integrity of the granulation tissue and callus is ultimately critical in revascularisation and its failure under severe strain conditions.

The Implications of Activity Based Funding for Emergency Departments : A Comprehensive Literature Review

Executive Summary Emergency Departments (EDs) locally, nationally and internationally are becoming increasingly busy. Within this context, it can be challenging to deliver a health service that is safe, of high quality and cost-effective. Whilst various models are described within the literature that aim to measure ED ‘work’ or ‘activity’, they are often not linked to a measure of costs to provide such activity. It is important for hospital and ED managers to understand and apply this link so that optimal staffing and financial resourcing can be justifiably sought. This research is timely given that Australia has moved towards a national Activity Based Funding (ABF) model for ED activity. ABF is believed to increase transparency of care and fairness (i.e. equal work receives equal pay). ABF involves a person-, performance- or activity-based payment system, and thus a move away from historical “block payment” models that do not incentivise efficiency and quality. The aim of the Statewide Workforce and Activity-Based Funding Modelling Project in Queensland Emergency Departments (SWAMPED) is to identify and describe best practice Emergency Department (ED) workforce models within the current context of ED funding that operates under an ABF model. The study is comprised of five distinct phases. This monograph (Phase 1) comprises a systematic review of the literature that was completed in June 2013. The remaining phases include a detailed survey of Queensland hospital EDs’ resource levels, activity and operational models of care, development of new resource models, development of a user-friendly modelling interface for ED mangers, and production of a final report that identifies policy implications. The anticipated deliverable outcome of this research is the development of an ABF based Emergency Workforce Modelling Tool that will enable ED managers to profile both their workforce and operational models of care. Additionally, the tool will assist with the ability to more accurately inform adequate staffing numbers required in the future, inform planning of expected expenditures and be used for standardisation and benchmarking across similar EDs. Summary of the Findings Within the remit of this review of the literature, the main findings include: 1. EDs are becoming busier and more congested Rising demand, barriers to ED throughput and transitions of care all contribute to ED congestion. In addition requests by organisational managers and the community require continued broadening of the scope of services required of the ED and further increases in demand. As the population live longer with more lifestyle diseases their propensity to require ED care continues to grow. 2. Various models of care within EDs exist Models often vary to account for site specific characteritics to suit staffing profile, ED geographical location (e.g. metropolitan or rural site), and patient demographic profile (e.g. paediatrics, older persons, ethnicity). Existing and new models implemented within EDs often depend on the target outcome requiring change. Generally this is focussed on addressing issues at the input, throughput or output areas of the ED. Even with models targeting similar demographic or illness, the structure and process elements underpinning the model can vary, which can impact on outcomes and variance to the patient and carer experience between and within EDs. Major models of care to manage throughput inefficiencies include: A. Workforce Models of Care focus on the appropriate level of staffing for a given workload to provide prompt, timely and clinically effective patient care within an emergency care setting. The studies reviewed suggest that the early involvement of senior medical decision maker and/or specialised nursing roles such as Emergency Nurse Practitioners and Clinical Initiatives Nurse, primary contact or extended scope Allied Health Practitioners can facilitate patient flow and improve key indicators such as length of stay and reducing the number of those who did not wait to be seen amongst others. B. Operational Models of Care within EDs focus on mechanisms for streaming (e.g. fast-tracking) or otherwise grouping patient care based on acuity and complexity to assist with minimising any throughput inefficiencies. While studies support the positive impact of these models in general, it appears that they are most effective when they are adequately resourced. 3. Various methods of measuring ED activity exist Measuring ED activity requires careful consideration of models of care and staffing profile. Measuring activity requires the ability to account for factors including: patient census, acuity, LOS, intensity of intervention, department skill-mix plus an adjustment for non-patient care time. 4. Gaps in the literature Continued ED growth calls for new and innovative care delivery models that are safe, clinically effective and cost effective. New roles and stand-alone service delivery models are often evaluated in isolation without considering the global and economic impact on staffing profiles. Whilst various models of accounting for and measuring health care activity exist, costing studies and cost effectiveness studies are lacking for EDs making accurate and reliable assessments of care models difficult. There is a necessity to further understand, refine and account for measures of ED complexity that define a workload upon which resources and appropriate staffing determinations can be made into the future. There is also a need for continued monitoring and comprehensive evaluation of newly implemented workforce modelling tools. This research acknowledges those gaps and aims to: • Undertake a comprehensive and integrated whole of department workforce profiling exercise relative to resources in the context of ABF. • Inform workforce requirements based on traditional quantitative markers (e.g. volume and acuity) combined with qualitative elements of ED models of care; • Develop a comprehensive and validated workforce calculation tool that can be used to better inform or at least guide workforce requirements in a more transparent manner.

Hybrid multi-channel cooperative spectrum sensing to satisfy channel target

Spectrum sensing of multiple primary user channels is a crucial function in cognitive radio networks. In this paper we propose an optimal, sensing resource allocation algorithm for multi-channel cooperative spectrum sensing. The channel target is implemented as an objective and constraint to ensure a pre-determined number of empty channels are detected for secondary user network operations. Based on primary user traffic parameters, we calculate the minimum number of primary user channels that must be sensed to satisfy the channel target. We implement a hybrid sensing structure by grouping secondary user nodes into clusters and assign each cluster to sense a different primary user channels. We then solve the resource allocation problem to find the optimal sensing configuration and node allocation to minimise sensing duration. Simulation results show that the proposed algorithm requires the shortest sensing duration to achieve the channel target compared to existing studies that require long sensing and cannot guarantee the target.

Vision-based docking using an autonomous surface vehicle

This paper describes the development of a novel vision-based autonomous surface vehicle with the purpose of performing coordinated docking manoeuvres with a target, such as an autonomous underwater vehicle, at the water's surface. The system architecture integrates two small processor units; the first performs vehicle control and implements a virtual force based docking strategy, with the second performing vision-based target segmentation and tracking. Furthermore, the architecture utilises wireless sensor network technology allowing the vehicle to be observed by, and even integrated within an ad-hoc sensor network. Simulated and experimental results are presented demonstrating the autonomous vision- based docking strategy on a proof-of-concept vehicle.

Tracking-based moving object detection

We present a novel approach for multi-object detection in aerial videos based on tracking. The proposed method mainly involves three steps. Firstly, the spatial-temporal saliency is employed to detect moving objects. Secondly, the detected objects are tracked by mean shift in the subsequent frames. Finally, the saliency results are fused with the weight map generated by tracking to get refined detection results, and in turn the modified detection results are used to update the tracking models. The proposed algorithm is evaluated on VIVID aerial videos, and the results show that our approach can reliably detect moving objects even in challenging situations. Meanwhile, the proposed method can process videos in real time, without the effect of time delay.

Ghrelin and the brain-gut axis as a pharmacological target for appetite control

Appetite regulation is highly complex and involves a large number of orexigenic and anorexigenic peptide hormones. These are small, processed, secreted peptides derived from larger prepropeptide precursors. These peptides are important targets for the development of therapeutics for obesity, a global health epidemic. As a case study, we consider the ghrelin axis. The ghrelin axis is likely to be a particularly useful drug target, as it also plays a role in energy homeostasis, adipogenesis, insulin regulation and reward associated with food intake. Ghrelin is the only known circulating gut orexigenic peptide hormone. As it appears to play a role in diet-induced obesity, blocking the action of ghrelin is likely to be effective for treating and preventing obesity. The ghrelin peptide has been targeted using a number of approaches, with ghrelin mirror-image oligonucleotides (Spiegelmers) and immunotherapy showing some promise. The ghrelin receptor, the growth hormone secretagogue receptor, may also provide a useful target and a number of antagonists and inverse agonists have been developed. A particularly promising new target is the enzyme which octanoylates ghrelin, ghrelin O-acyltransferase (GOAT), and drugs that inhibit GOAT are likely to circumvent pharmacological issues associated with approaches that directly target ghrelin or its receptor.

Tracking spatio temporal movement of human in terms of space utilization using media access control address data

Using Media-Access-Control (MAC) address for data collection and tracking is a capable and cost effective approach as the traditional ways such as surveys and video surveillance have numerous drawbacks and limitations. Positioning cell-phones by Global System for Mobile communication was considered an attack on people's privacy. MAC addresses just keep a unique log of a WiFi or Bluetooth enabled device for connecting to another device that has not potential privacy infringements. This paper presents the use of MAC address data collection approach for analysis of spatio-temporal dynamics of human in terms of shared space utilization. This paper firstly discuses the critical challenges and key benefits of MAC address data as a tracking technology for monitoring human movement. Here, proximity-based MAC address tracking is postulated as an effective methodology for analysing the complex spatio-temporal dynamics of human movements at shared zones such as lounge and office areas. A case study of university staff lounge area is described in detail and results indicates a significant added value of the methodology for human movement tracking. By analysis of MAC address data in the study area, clear statistics such as staff’s utilisation frequency, utilisation peak periods, and staff time spent is obtained. The analyses also reveal staff’s socialising profiles in terms of group and solo gathering. The paper is concluded with a discussion on why MAC address tracking offers significant advantages for tracking human behaviour in terms of shared space utilisation with respect to other and more prominent technologies, and outlines some of its remaining deficiencies.

How much information can be obtained from tracking the position of the leading edge in a scratch assay?

Moving cell fronts are an essential feature of wound healing, development and disease. The rate at which a cell front moves is driven, in part, by the cell motility, quantified in terms of the cell diffusivity $D$, and the cell proliferation rate �$\lambda$. Scratch assays are a commonly-reported procedure used to investigate the motion of cell fronts where an initial cell monolayer is scratched and the motion of the front is monitored over a short period of time, often less than 24 hours. The simplest way of quantifying a scratch assay is to monitor the progression of the leading edge. Leading edge data is very convenient since, unlike other methods, it is nondestructive and does not require labeling, tracking or counting individual cells amongst the population. In this work we study short time leading edge data in a scratch assay using a discrete mathematical model and automated image analysis with the aim of investigating whether such data allows us to reliably identify $D$ and $\lambda$�. Using a naıve calibration approach where we simply scan the relevant region of the ($D$;$\lambda$�) parameter space, we show that there are many choices of $D$ and $\lambda$� for which our model produces indistinguishable short time leading edge data. Therefore, without due care, it is impossible to estimate $D$ and $\lambda$� from this kind of data. To address this, we present a modified approach accounting for the fact that cell motility occurs over a much shorter time scale than proliferation. Using this information we divide the duration of the experiment into two periods, and we estimate $D$ using data from the first period, while we estimate �$\lambda$ using data from the second period. We confirm the accuracy of our approach using in silico data and a new set of in vitro data, which shows that our method recovers estimates of $D$ and $\lamdba$� that are consistent with previously-reported values except that that our approach is fast, inexpensive, nondestructive and avoids the need for cell labeling and cell counting.

A multi-genome analysis approach enables tracking of the invasion of a single Russian wheat aphid (Diuraphis noxia) clone throughout the New World

This study investigated the population genetics, demographic history and pathway of invasion of the Russian wheat aphid (RWA) from its native range in Central Asia, the Middle East and Europe to South Africa and the Americas. We screened microsatellite markers, mitochondrial DNA and endosymbiont genes in 504 RWA clones from nineteen populations worldwide. Following pathway analyses of microsatellite and endosymbiont data, we postulate that Turkey and Syria were the most likely sources of invasion to Kenya and South Africa, respectively. Furthermore, we found that one clone transferred between South Africa and the Americas was most likely responsible for the New World invasion. Finally, endosymbiont DNA was found to be a high resolution population genetic marker, extremely useful for studies of invasion over a relatively short evolutionary history time frame. This study has provided valuable insights into the factors that may have facilitated the recent global invasion by this damaging pest.

Control of an underactuated-slender-hull unmanned underwater vehicle using Port-Hamiltonian theory

This paper presents a control design for tracking of attitude and speed of an underactuated slender-hull unmanned underwater vehicle (UUV). The control design is based on Port-Hamiltonian theory. The target dynamics (desired dynamic response) is shaped with particular attention to the target mass matrix so that the influence of the unactuated dynamics on the controlled system is suppressed. This results in achievable dynamics independent of uncontrolled states. Throughout the design, insight of the physical phenomena involved is used to propose the desired target dynamics. The performance of the design is demonstrated through simulation with a high-fidelity model.