Inhibition of the JAK2/STAT3 pathway in ovarian cancer results in the loss of cancer stem cell-like characteristics and a reduced tumor burden

Background Current treatment of ovarian cancer patients with chemotherapy leaves behind a residual tumor which results in recurrent ovarian cancer within a short time frame. We have previously demonstrated that a single short-term treatment of ovarian cancer cells with chemotherapy in vitro resulted in a cancer stem cell (CSC)-like enriched residual population which generated significantly greater tumor burden compared to the tumor burden generated by control untreated cells. In this report we looked at the mechanisms of the enrichment of CSC-like residual cells in response to paclitaxel treatment. Methods The mechanism of survival of paclitaxel-treated residual cells at a growth inhibitory concentration of 50% (GI50) was determined on isolated tumor cells from the ascites of recurrent ovarian cancer patients and HEY ovarian cancer cell line by in vitro assays and in a mouse xenograft model. Results Treatment of isolated tumor cells from the ascites of ovarian cancer patients and HEY ovarian cancer cell line with paclitaxel resulted in a CSC-like residual population which coincided with the activation of Janus activated kinase 2 (JAK2) and signal transducer and activation of transcription 3 (STAT3) pathway in paclitaxel surviving cells. Both paclitaxel-induced JAK2/STAT3 activation and CSC-like characteristics were inhibited by a low dose JAK2-specific small molecule inhibitor CYT387 (1 μM) in vitro. Subsequent, in vivo transplantation of paclitaxel and CYT387-treated HEY cells in mice resulted in a significantly reduced tumor burden compared to that seen with paclitaxel only-treated transplanted cells. In vitro analysis of tumor xenografts at protein and mRNA levels demonstrated a loss of CSC-like markers and CA125 expression in paclitaxel and CYT387-treated cell-derived xenografts, compared to paclitaxel only-treated cell-derived xenografts. These results were consistent with significantly reduced activation of JAK2 and STAT3 in paclitaxel and CYT387-treated cell-derived xenografts compared to paclitaxel only-treated cell derived xenografts. Conclusions This proof of principle study demonstrates that inhibition of the JAK2/STAT3 pathway by the addition of CYT387 suppresses the ‘stemness’ profile in chemotherapy-treated residual cells in vitro, which is replicated in vivo, leading to a reduced tumor burden. These findings have important implications for ovarian cancer patients who are treated with taxane and/or platinum-based therapies. Keywords: Ovarian carcinoma, Cancer stem cell, Metastasis, Ascites, Chemoresistance, Recurrence, JAK2/STAT3 pathway

Real-time monitoring of nucleation-growth cycle of carbon nanoparticles in acetylene plasmas

Quantum cascade laserabsorption spectroscopy was used to measure the absolute concentration of acetylene in situ during the nanoparticle growth in Ar + C2H2 RF plasmas. It is demonstrated that the nanoparticle growth exhibits a periodical behavior, with the growth cycle period strongly dependent on the initial acetylene concentration in the chamber. Being 300 s at 7.5% of acetylene in the gas mixture, the growth cycle period decreases with the acetylene concentration increasing; the growth eventually disappears when the acetylene concentration exceeds 32%. During the nanoparticle growth, the acetylene concentration is small and does not exceed 4.2% at radio frequency (RF) power of 4 W, and 0.5% at RF power of 20 W. An injection of a single acetylene pulse into the discharge also results in the nanoparticlenucleation and growth. The absorption spectroscopy technique was found to be very effective for the time-resolved measurement of the hydrocarbon content in nanoparticle-generatingplasmas.

Arterial short-term travel time prediction using Bluetooth data

This project recognized lack of data analysis and travel time prediction on arterials as the main gap in the current literature. For this purpose it first investigated reliability of data gathered by Bluetooth technology as a new cost effective method for data collection on arterial roads. Then by considering the similarity among varieties of daily travel time on different arterial routes, created a SARIMA model to predict future travel time values. Based on this research outcome, the created model can be applied for online short term travel time prediction in future.

Fire resistance rating of light gauge steel frame walls exposed to realistic design fires : a review and development of time equivalent approach

This paper presents the details of research undertaken on the development of an energy based time equivalent approach for light gauge steel frame (LSF) walls. This research utilized an energy based time equivalent approach to obtain the fire resistance ratings (FRR) of LSF walls exposed to realistic design fires with respect to standard fire exposure [1]. It is based on the equal area concept of fire severity and relates to the amount of energy transferred to the member. The proposed method was used to predict the fire resistance of single and double plasterboard lined and externally insulated LSF walls. The predicted fire resistance ratings were compared with the results from finite element analyses and fire design rules for three different wall configurations. This paper presents the review of the available time equivalent approaches and the development of energy based time equivalent approach for the prediction of fire resistance ratings of LSF walls exposed to realistic design fires.

Time to analgesia for care delivered by nurse practitioners in the emergency department: A retrospective chart audit

Objectives To evaluate quality of care delivered to patients presenting to the emergency department (ED) with pain and managed by emergency nurse practitioners by measuring: 1) Evaluate time to analgesia from initial presentation 2) Evaluate time from being seen to next analgesia 3) Pain score documentation Background The delivery of quality care in the emergency department (ED) is emerging as one of the most important service indicators being measured by health services. Emergency nurse practitioner services are designed to improve timely, quality care for patients. One of the goals of quality emergency care is the timely and effective delivery of analgesia for patients. Timely analgesia is an important indicator of ED service performance. Methods A retrospective explicit chart review of 128 consecutive patients with pain and managed by emergency nurse practitioners was conducted. Data collected included demographics, presenting complaint, pain scores, and time to first dose of analgesia. Patients were identified from the ED Patient Information System (Cerner log) and data were extracted from electronic medical records Results Pain scores were documented in 67 (52.3%; 95% CI: 43.3-61.2) patients. The median time to analgesia from presentation was 60.5 (IQR 30-87) minutes, with 34 (26.6%; 95% CI: 19.1-35.1) patients receiving analgesia within 30 minutes of presentation to hospital. There were 22 (17.2%; 95% CI: 11.1-24.9) patients who received analgesia prior to assessment by a nurse practitioner. Among patients that received analgesia after assessment by a nurse practitioner, the median time to analgesia after assessment was 25 (IQR 12-50) minutes, with 65 (61.3%; 95% CI: 51.4-70.6) patients receiving analgesia within 30 minutes of assessment. Conclusions The majority of patients assessed by nurse practitioners received analgesia within 30 minutes after assessment. However, opportunities for substantial improvement in such times along with documentation of pain scores were identified and will be targeted in future research.

Mid-Aged Adults' Sitting Time in Three Contexts

BACKGROUND: To develop evidence-based approaches for reducing sedentary behavior, there is a need to identify the specific settings where prolonged sitting occurs, associated factors, and variations. PURPOSE: To examine the sociodemographic and health factors associated with mid-aged adults' sitting time in three contexts and variations between weekdays and weekend days. METHODS: A mail survey was sent to 17,000 adults (aged 40-65 years) in 2007; 11,037 responses were received (68.5%); and 7719 were analyzed in 2010. Respondents indicated time spent sitting on a usual weekday and weekend day for watching TV, general leisure, and home computer use. Multivariate linear mixed models with area-level random intercepts were used to examine (1) associations between sociodemographic and health variables and sitting time, and (2) interaction effects of weekday/weekend day with each of gender, age, education, and employment status, on sitting time. RESULTS: For each context, longer sitting times were reported by those single and living alone, and those whose health restricted activity. For watching TV, longer sitting times were reported by men; smokers; and those with high school or lower education, not in paid employment, in poor health, and with BMI ≥25. For general leisure, longer sitting times were reported by women, smokers, and those not employed full-time. For home computer use, longer sitting times were reported by men; and those aged 40-44 years, with university qualifications; in the mid-income range; and with BMI ≥30. Sitting times tended to be longer on weekend days than weekdays, although the extent of this differed among sociodemographic groups. CONCLUSIONS: Sociodemographic and health factors associated with sitting time differ by context and between weekdays and weekend days.

The roles of JK-1 (FAM134B) expressions in colorectal cancer

The aims of the present study are to investigate the clinicopathological correlations of JK-1(FAM134B) expression and its relationship to carcinogenesis in a colorectal adenoma-adenocarcinoma model. JK-1(FAM134B) protein expression was studied in a colon cancer cell line by Western blot and immunocytochemistry. JK-1(FAM134B) expression profiles at mRNA and protein levels were investigated in cancer tissues from 236 patients with colorectal adenocarcinoma and 32 patients with colorectal adenoma using real-time polymerase chain reaction and immunohistochemistry. The findings were then correlated with the clinicopathological features of these tumours. JK-1(FAM134B) protein was demonstrated in the colon cancer cells by Western blot. The protein was located in the nuclei of the tumour cells at both cellular and tissue levels. In colorectal adenocarcinomas, lower levels of JK-1(FAM134B) protein expression were associated with younger age (p=0.032), larger tumour size (p=0.004), advanced cancer stages (p=0.016) and higher rates of cancer recurrence (p=0.04). Also, lower levels of JK-1(FAM134B) mRNA expression were associated with advanced cancer stages (p=0.02) and presence of lymphovascular invasion (p=0.014). Higher JK-1(FAM134B) mRNA and protein expression levels were identified in adenomas and non-neoplastic mucosae, compared to carcinomas (p=0.005). To conclude, JK-1(FAM134B) mRNA expression and JK1 (FAM134B) protein levels varied with the different stages of progression of colorectal tumours. The expression levels of the gene were associated with clinicopathological features in patients with colorectal adenocarcinoma suggesting that JK-1(FAM134B) gene has roles in controlling some steps in the development of the invasive phenotypes from colorectal adenoma to early staged as well as advanced staged colorectal adenocarcinomas.

Regulation of microRNA-1288 in colorectal cancer : altered expression and its clinicopathological significance

We aim to examine the miR-1288 expression in cancer cell lines and a large cohort of patients with colorectal cancer. Two colon cancer cell lines (SW480 and SW48) and one normal colonic epithelial cell line (FHC) were recruited. The miRNA expressions of miR-1288 were tested on these cell lines by using quantitative real-time polymerase chain reaction (qRT-PCR). An exogenous miR-1288 (mimic) was used to detect cell proliferation and cell cycle changes in SW480 using MTT calorimetric assay and flow cytometry, respectively. In addition, tissues from 122 patients with surgical resection of colorectum (82 adenocarcinomas, 20 adenomas, and 20 non-neoplastic tissues) were tested for miR-1288 expression by qRT-PCR. The colon cancer cell lines showed reduced expression of miR-1288 compared to normal colonic epithelial cell line. Over expression of miR-1288 in SW480 cell line showed increased cell proliferation and increased G2-M phase cells. In tissues, reduced miR-1288 expression was noted in majority of colorectal adenocarcinoma compared to colorectal adenoma and non-neoplastic tissues. Reduced or absent expression of miR-1288 was noted in 76% (n = 62/82) of the cancers. The expression levels of miR-1288 were higher in distal colorectal adenocarcinomas (P = 0.013) and in cancers of lower T staging (P = 0.033). To conclude, alternation of miR-1288 expression is important in the progression of colorectal cancer. The differential regulation of miR-1288 was found to be related to cancer location and pathological staging in colorectal cancers.

Clinical impacts of mammalian target of rapamycin expression in human colorectal cancers

This study investigated the clinicopathologic roles of mammalian target of rapamycin (mTOR) expression and its relationship to carcinogenesis and tumor progression in a colorectal adenoma-adenocarcinoma model. Two colon cancer cell lines with different pathologic stages (SW480 and SW48) and 1 normal colonic epithelial cell line (FHC) were used, in addition to 119 colorectal adenocarcinomas and 32 adenomas. mTOR expression profiles at messenger RNA (mRNA) and protein levels were investigated in the cells and tissues using real-time quantification polymerase chain reaction and immunohistochemistry. The findings were correlated with the clinicopathologic features of the tumors. The colon cell line from stage III cancer (SW48) showed higher expression of mTOR mRNA than that from stage II cancer (SW480). At the tissue level, mTOR showed higher mRNA and protein expression in colorectal carcinoma than in adenoma. The mRNA and protein expression was correlated with each other in approximately one-third of the carcinomas and adenomas. High levels of mTOR mRNA expression were noted more in carcinoma or adenoma arising from the distal portion of the large intestine (P = .025 and .019, respectively). Within the colorectal cancer population, a high level of expression of mTOR mRNA was related to the presence of lymph node metastases (P = .031), advanced pathologic stage (P = .05), and presence of persistent disease or tumor recurrence (P = .035). To conclude, the study has indicated that mTOR is likely to be involved in the development and progression of colorectal cancer and is linked to cancer initiation, invasiveness, and progression.

Exploring Bodies in Time and Space

While the body, time and space are fundamental to human experience, comparatively little attention has been given to the connections between them. Here scholars from a wide range of disciplines explore important themes of embodied life in time and space across cultures, activities and bodymind states. Motivated by a common desire to deepen and extend our comprehension of these phenomena and the connections and conversations between them, this book emerged from intense inter-disciplinary dialogue during the 1st Global Conferences on Time, Space and the Body and Body Horror. A plenitude of theoretical approaches and media are deployed to investigate assumptions and pose problems, to creatively deconstruct and reconstruct the terms through which experience is rendered meaningful, pleasurable, and functional. These investigations, pursued through various research methods in fields of the arts, social and psychological sciences and humanities, invite readers into a genuinely pluralistic conversation around the most basic and profound aspects of being.

Introduction : Understanding Connections between Time, Space and the Body

The experiences and constructs of time, space and bodies saturate human discourse—naturally enough, since they are fundamental to existence—yet there has long been a tendency for the terms to be approached somewhat independently, belying the depth of their interconnections. It was a desire to address that apparent shortcoming that inspired this book, and the interdisciplinary meetings from which it was born, the 1st Global Conferences on ‘Time, Space and the Body’ and ‘Body Horror’ held in Sydney in February 2013. Following the lively, often provocative, exchange of ideas throughout those meetings, the writing here crosses conventional boundaries inhabiting everyday life and liminal experiences, across cultures, life circumstances, and bodily states. Through numerous theoretical frameworks and with reference to a variety of media, the authors problematize or deconstruct commonplace assumptions to reveal challenging new perspectives on the diverse cultures and communities which make our world. If there is an overarching theme of this collection it is diversity itself. The writers here come from numerous academic fields, but a good number of them also draw on first-hand cultural production in the arts: photography, sculpture and fine art instillation, for example. Of course, however laudable it might be, there is a potential problem in such diversity: does it produce fruitful dialogue moving toward creative, workable syntheses or simply a cacophony of competing, incomprehensible, barely comprehending voices? To a large degree this depends upon the intellectual, existential ambitions as well as the old-fashioned goodnatured tolerance of both writers and readers. But we hope three unifying characteristics are discernable in the following chapters viewed as a whole: firstly, a genuine concern for the world humans inhabit and the communities they form as bodies in space and time; secondly, an emphasis upon the experience of the human subject, exemplified perhaps by the number of chapters drawing on phenomenology; thirdly, an adventurous, explorative impulse associated with an underlying sense that being, since it is inseparable from the body’s temporality, is always becoming, and here the presence of poststructuralist influences is unmistakable, often explicit. Our challenge as editors has been to present the enormous variety of subjects and views in a way that would render the book coherent and at the same time encourage readers to make explorations themselves into realms they might usually consider beyond their field of interest. To that end we have divided the book into six sections around loosely defined themes, each offering different angles on how time and/or space unfold in and around bodies.

Modelling total duration of traffic incidents including incident detection and recovery time

Traffic incidents are key contributors to non-recurrent congestion, potentially generating significant delay. Factors that influence the duration of incidents are important to understand so that effective mitigation strategies can be implemented. To identify and quantify the effects of influential factors, a methodology for studying total incident duration based on historical data from an ‘integrated database’ is proposed. Incident duration models are developed using a selected freeway segment in the Southeast Queensland, Australia network. The models include incident detection and recovery time as components of incident duration. A hazard-based duration modelling approach is applied to model incident duration as a function of a variety of factors that influence traffic incident duration. Parametric accelerated failure time survival models are developed to capture heterogeneity as a function of explanatory variables, with both fixed and random parameters specifications. The analysis reveals that factors affecting incident duration include incident characteristics (severity, type, injury, medical requirements, etc.), infrastructure characteristics (roadway shoulder availability), time of day, and traffic characteristics. The results indicate that event type durations are uniquely different, thus requiring different responses to effectively clear them. Furthermore, the results highlight the presence of unobserved incident duration heterogeneity as captured by the random parameter models, suggesting that additional factors need to be considered in future modelling efforts.

Using informative priors in the estimation of mixtures over time with application to aerosol particle size distributions

The issue of using informative priors for estimation of mixtures at multiple time points is examined. Several different informative priors and an independent prior are compared using samples of actual and simulated aerosol particle size distribution (PSD) data. Measurements of aerosol PSDs refer to the concentration of aerosol particles in terms of their size, which is typically multimodal in nature and collected at frequent time intervals. The use of informative priors is found to better identify component parameters at each time point and more clearly establish patterns in the parameters over time. Some caveats to this finding are discussed.

Editorial : is it the time for railway industry to reinvent itself?

Editorial: is it the time for railway industry to reinvent itself? Railway infrastructure plays a critical role in urban development, mobility, and economic growth of society. This focus issue of the Electronic Journal of Structural Engineering is devoted to a special theme, “Advances in Rail Track Infrastructure and Practice - ARTRP”. It contains articles, which were rigorously peer reviewed and accepted from a list of invited manuscripts that demonstrate significant innovation in the area of the structural engineering aspects of the rail track infrastructure...

A runtime integrity monitoring framework for real-time relative positioning systems based on GPS and DSRC

This paper provides a three-layered framework to monitor the positioning performance requirements of Real-time Relative Positioning (RRP) systems of the Cooperative Intelligent Transport Systems (C-ITS) that support Cooperative Collision Warning (CCW) applications. These applications exploit state data of surrounding vehicles obtained solely from the Global Positioning System (GPS) and Dedicated Short-Range Communications (DSRC) units without using other sensors. To this end, the paper argues the need for the GPS/DSRC-based RRP systems to have an autonomous monitoring mechanism, since the operation of CCW applications is meant to augment safety on roads. The advantages of autonomous integrity monitoring are essential and integral to any safety-of-life system. The autonomous integrity monitoring framework proposed necessitates the RRP systems to detect/predict the unavailability of their sub-systems and of the integrity monitoring module itself, and, if available, to account for effects of data link delays and breakages of DSRC links, as well as of faulty measurement sources of GPS and/or integrated augmentation positioning systems, before the information used for safety warnings/alarms becomes unavailable, unreliable, inaccurate or misleading. Hence, a monitoring framework using a tight integration and correlation approach is proposed for instantaneous reliability assessment of the RRP systems. Ultimately, using the proposed framework, the RRP systems will provide timely alerts to users when the RRP solutions cannot be trusted or used for the intended operation.