A reference method for the evaluation of femoral head joint center location technique based on external markers

Accurate localization of joint centers is essential in movement analysis. However, joint centers cannot be directly palpated and alternative methods must be used. To assess the relative merits of these methods, a medical image based reference should be used. The EOS1 system, a new low dose bi-planar X-rays imaging technique may be considered. The aim of this study was to evaluate the accuracy of hip joint center (HJC) localization using the EOS1 system. Seventeen healthy young adults participated in the study. Femoral heads and pelvic external markers were localized using the EOS1 system and the HJCs were expressed in the movement analysis coordinate system. Results showed that external marker localization was reliable within 0.15 mm for trained assessors. Mean accuracy for HJC localization was 2.9 mm (SD: 1.3, max: 6.2). The EOS based method therefore appeared reliable and may be used for femoral head localization or as a reference to assess the accuracy of other methods for HJC localization.The authors are grateful to VICON (OMG-UK) for the loan of a motion capture system necessary for the overall study

Manipulation of JAK/STAT Signalling by High-Risk HPVs: Potential Therapeutic Targets for HPV-Associated Malignancies

Human papillomaviruses (HPVs) are small, DNA viruses that cause around 5% of all cancers in humans, including almost all cervical cancer cases and a significant proportion of anogenital and oral cancers. The HPV oncoproteins E5, E6 and E7 manipulate cellular signalling pathways to evade the immune response and promote virus persistence. The Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway has emerged as a key mediator in a wide range of important biological signalling pathways, including cell proliferation, cell survival and the immune response. While STAT1 and STAT2 primarily drive immune signalling initiated by interferons, STAT3 and STAT5 have widely been linked to the survival and proliferative potential of a number of cancers. As such, the inhibition of STAT3 and STAT5 may offer a therapeutic benefit in HPV-associated cancers. In this review, we will discuss how HPV manipulates JAK/STAT signalling to evade the immune system and promote cell proliferation, enabling viral persistence and driving cancer development. We also discuss approaches to inhibit the JAK/STAT pathway and how these could potentially be used in the treatment of HPV-associated diseas

Autocrine STAT3 activation in HPV positive cervical cancer through a virus-driven Rac1-NFκB-IL-6 signalling axis.

Persistent human papillomavirus (HPV) infection is the leading cause of cervical cancer. Although the fundamental link between HPV infection and oncogenesis is established, the specific mechanisms of virus-mediated transformation are not fully understood. We previously demonstrated that the HPV encoded E6 protein increases the activity of the proto-oncogenic transcription factor STAT3 in primary human keratinocytes; however, the molecular basis for STAT3 activation in cervical cancer remains unclear. Here, we show that STAT3 phosphorylation in HPV positive cervical cancer cells is mediated primarily via autocrine activation by the pro-inflammatory cytokine Interleukin 6 (IL-6). Antibody-mediated blockade of IL-6 signalling in HPV positive cells inhibits STAT3 phosphorylation, whereas both recombinant IL-6 and conditioned media from HPV positive cells leads to increased STAT3 phosphorylation within HPV negative cervical cancer cells. Interestingly, we demonstrate that activation of the transcription factor NFκB, involving the small GTPase Rac1, is required for IL-6 production and subsequent STAT3 activation. Our data provides new insights into the molecular re-wiring of cancer cells by HPV E6. We reveal that activation of an IL-6 signalling axis drives the autocrine and paracrine phosphorylation of STAT3 within HPV positive cervical cancers cells and that activation of this pathway is essential for cervical cancer cell proliferation and survival. Greater understanding of this pathway provides a potential opportunity for the use of existing clinically approved drugs for the treatment of HPV-mediated cervical cancer

HOX genes as potential markers of circulating tumour cells

YesCirculating tumour cells (CTCs) have significant diagnostic potential as they can reflect both the presence and recurrence of a wide range of cancers. However, this potential continues to be limited by the lack of robust and accessible isolation technologies. An alternative to isolation might be their direct detection amongst other peripheral blood cells, although this would require markers that allow them to be distinguished from an exceptionally high background signal. This review assesses the potential role of HOX genes, a family of homeodomain containing transcription factors with key roles in both embryonic development and oncogenesis, as unique and possibly disease specific markers of CTCs

Geophysical investigations of a geothermal anomaly at Wadi Ghadir, eastern Egypt

During regional heat flow studies a geothermal anomaly was discovered approximately 2 km from the Red Sea coast at Wadi Ghadir, in the Red Sea Hills of Eastern Egypt. A temperature gradient of 55 C/km was measured in a 150 m drillhole at this location, indicating a heat flow of approximately 175 mw/sqm, approximately four times the regional background heat flow for Egypt. Gravity and magnetic data were collected along Wadi Ghadir, and combined with offshore gravity data, to investigate the source of the thermal anomaly. Magnetic anomalies in the profile do not coincide with the thermal anomaly, but were observed to correlate with outcrops of basic rocks. Other regional heat flow and gravity data indicate that the transition from continental to oceanic type lithosphere occurs close to the Red Sea margin, and that the regional thermal anomaly is possibly related to the formation of the Red Sea

A Special Homotopy Continuation Method For A Class of Polynomial Systems

A special homotopy continuation method, as a combination of the polyhedral homotopy and the linear product homotopy, is proposed for computing all the isolated solutions to a special class of polynomial systems. The root number bound of this method is between the total degree bound and the mixed volume bound and can be easily computed. The new algorithm has been implemented as a program called LPH using C++. Our experiments show its efficiency compared to the polyhedral or other homotopies on such systems. As an application, the algorithm can be used to find witness points on each connected component of a real variety

Mechanisms of Nuclear Export in Cancer and Resistance to Chemotherapy

YesTumour suppressor proteins, such as p53, BRCA1, and ABC, play key roles in preventing the development of a malignant phenotype, but those that function as transcriptional regulators need to enter the nucleus in order to function. The export of proteins between the nucleus and cytoplasm is complex. It occurs through nuclear pores and exported proteins need a nuclear export signal (NES) to bind to nuclear exportin proteins, including CRM1 (Chromosomal Region Maintenance protein 1), and the energy for this process is provided by the RanGTP/RanGDP gradient. Due to the loss of DNA repair and cell cycle checkpoints, drug resistance is a major problem in cancer treatment, and often an initially successful treatment will fail due to the development of resistance. An important mechanism underlying resistance is nuclear export, and a number of strategies that can prevent nuclear export may reverse resistance. Examples include inhibitors of CRM1, antibodies to the nuclear export signal, and alteration of nuclear pore structure. Each of these are considered in this review

Instrumenting the Musician: Measuring and Enhancing A ective and Behavioural Interaction During Collaborative Music Making

Modern sensor technologies facilitate the measurement and interpretation of human affective and behavioural signals, and have consequently become widely used tools in the fields of affective computing, social signal processing and psychophysiology. This thesis investigates the use and development of these tools for measuring and enhancing aff ective and behavioural interaction during collaborative music making. Drawing upon work in the aforementioned fields, an exploratory study is designed, where self-report and continuous behavioural and physiological measures are collected from pairs of improvising percussionists. The findings lead to the selection of gaze, motion, and cardiac activity as input measures in the design of a device to enhance affective and behavioural interaction between co-present musicians. The device provides musicians with real-time visual feedback on the glances or body motions of their co-performers, whilst also recording cardiac activity as a potential measure of musical decision making processes. Quantitative evidence is found for the effects of this device on the communicative behaviours of collaborating musicians during an experiment designed to test the device in a controlled environment. This study also reports findings on discrete and time series relationships between cardiac activity and musical decision-making. A further, qualitative study is designed to evaluate the appropriation and impact of the device during long-term use in naturalistic settings. The results provide insights into earlier findings and contribute towards an empirical understanding of affective and behavioural interaction during collaborative music making, as well as implications for the design and deployment of sensor-based technologies to enhance such interactions. This thesis advances the dominant single-user paradigm within human-computer interaction and affective computing research, towards multi-user scenarios, where the concern is human-human interaction. It achieves this by focusing on the emotionally rich, and under-studied context of co-present musical collaboration; contributing new methods and findings that pave the way for further research and real-world applications.This work was funded by the Engineering and Physical Sciences Research Council (EPSRC) as part of the Centre for Doctoral Training in Media and Arts Technology at Queen Mary University of London (ref: EP/G03723X/1)