bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA2: Navigating the balance of INK4/ARF expression in cancer: ncRNAs as sensors and regulators of transcription
Authors: Walsh Martin J. , Aguilo Francesca , Li SiDe , Yap Kyoko , Gil Jesus , Zhou Ming-Ming 
Published: April 2013

Abstract
The INK/ARF (CDKN2A) locus expresses p15Ink4B, p16Ink4A, p14Arf and is under control of Polycomb Repressive Complexes PRC1 and PRC2 to impose transcriptional silencing to bypass cellular senescence upon oncogenic stress. Previously, we had identified a constituent member of human PRC1, known as the chromobox protein 7 (CBX7), is endowed the capacity to bind specifically to elements of the long non-coding RNA identified as the non-coding anti-sense RNA of the INK locus (ANRIL) RNA transcript as a mature processed polyadenylated RNA transcript. ANRIL represent a large heterogeneous population of individual transcripts and their isoforms arising from the localized genomic region overlapping INK/ARF. These transcripts reveal independent patterns of expression dependent on the state of cell growth and differentiation. Moreover, specific transcripts overlapping the ANRIL region of chromosome 9p21.3 provide strict correlation to human embryonic stem cell pluripotency and self-renewal versus differentiation. We recently identify specific ANRIL transcripts and isoforms that are correlative with human prostate tumor stages and states of malignancy. We had previously shown that certain transcripts correlate with PRC1 is organized on the INK/ARF locus through the interaction between CBX7 and the nascent ANRIL transcript to help establish and maintain repressive histone H3K27 methylation and H2AK119 monoubiquitination. Both PRC1 and PRC2 can interact with different ANRIL transcript regions and it remains unclear whether this activity is cooperative. This activity is abrogated in the absence of RNA polymerase II activity thereby requiring nascent transcription of anti-sense transcripts of INK/ARF by RNA polymerase II (RNA POLII). Interestingly, TAF15/TAFII68 can be tethered to CBX7 in prostate carcinoma cells where the ANRIL ncRNA transcripts are elevated. Our recent finding is that specific ANRIL transcripts directed by RNAPOLII are influenced by RNA polymerase III (RNA POLIII) as measured through the depletion of the core RNA POLIII factor BRF1. This evidence suggests that RNA POLIII may populate RNA synthesis of shorter transcripts to influence PRC1 and PRC2 binding thereby instructing the behavior of RNA POLII synthesis. This provides a rational mechanism whereby RNA POLIII with RNAPOLIII provide the genomic RNA context to instruct PRC1 and PRC2 to exert antisense transcription at the expense of transcriptional activity of INK/ARF.
Citation Format: Martin J. Walsh, Francesca Aguilo, SiDe Li, Kyoko Yap, Jesus Gil, Ming-Ming Zhou. Navigating the balance of INK4/ARF expression in cancer: ncRNAs as sensors and regulators of transcription [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr IA2.
Chemoprevention of Lung Squamous Cell Carcinoma by Ginseng
Authors: Pan Jing , Zhang Qi , Li Kezhen , Liu Qian , Wang Yian , You Ming 
Published: April 2013

Abstract
Ginseng has been used as a medicinal herb to maintain physical vitality for thousands of years, and it has also been shown to be a nonorgan-specific cancer preventive agent by several epidemiologic studies. However, the chemopreventive effects of Korea white ginseng (KWG) in lung squamous cell carcinoma (SCC) have not been tested. In this study, we investigated the chemopreventive activity of KWG in a mouse lung SCC model. N-nitroso-trischloroethylurea (NTCU) was used to induce lung tumors in female Swiss mice, and KWG was given orally. KWG significantly reduced the percentage of lung SCCs from 26.5% in the control group to 9.1% in the KWG group and in the meantime, increased the percentage of normal bronchial and hyperplasia. KWG was also found to greatly reduce squamous cell lung tumor area from an average of 9.4% in control group to 1.5% in the KWG group. Treatment with KWG decreased Ki-67 staining, suggesting that the lung tumor inhibitory effects of KWG were partly through inhibition of proliferation. High-performance liquid chromatography/mass spectrometry identified 10 ginsenosides from KWG extracts, Rb1 and Rd being the most abundant as detected in mouse blood and lung tissue. The tumor inhibitory effects of KWG are mediated by inhibition of activator protein (AP-1), as showed by in vitro study conducted on AP-1/NF-κB–dependent mouse non–small cell lung carcinoma cell lines. Western blotting of lung tissues also indicated that NTCU upregulated AP-1 through phosphorylation of c-jun-NH2-kinase, which was downregulated by KWG in concurrence with its chemoprevention function. These results suggest that KWG could be a potential chemopreventive agent for lung SCC. Cancer Prev Res; 6(6); 530–9. ©2013 AACR.
Succinate Dehydrogenase Mutation Underlies Global Epigenomic Divergence in Gastrointestinal Stromal Tumor
Authors: Killian J. Keith , Kim Su Young , Miettinen Markku , Smith Carly , Merino Maria , Tsokos Maria , Quezado Martha , Smith William I. , Jahromi Mona S. , Xekouki Paraskevi , Szarek Eva , Walker Robert L. , Lasota Jerzy , Raffeld Mark , Klotzle Brandy , Wang Zengfeng , Jones Laura , Zhu Yuelin , Wang Yonghong , Waterfall Joshua J. , O'Sullivan Maureen J. , Bibikova Marina , Pacak Karel , Stratakis Constantine , Janeway Katherine A. , Schiffman Joshua D. , Fan Jian-Bing , Helman Lee , Meltzer Paul S. 
Published: April 2013

Abstract
Gastrointestinal stromal tumors (GIST) harbor driver mutations of signal transduction kinases such as KIT, or, alternatively, manifest loss-of-function defects in the mitochondrial succinate dehydrogenase (SDH) complex, a component of the Krebs cycle and electron transport chain. We have uncovered a striking divergence between the DNA methylation profiles of SDH-deficient GIST (n = 24) versus KIT tyrosine kinase pathway–mutated GIST (n = 39). Infinium 450K methylation array analysis of formalin-fixed paraffin-embedded tissues disclosed an order of magnitude greater genomic hypermethylation relative to SDH-deficient GIST versus the KIT-mutant group (84.9 K vs. 8.4 K targets). Epigenomic divergence was further found among SDH-mutant paraganglioma/pheochromocytoma (n = 29), a developmentally distinct SDH-deficient tumor system. Comparison of SDH-mutant GIST with isocitrate dehydrogenase-mutant glioma, another Krebs cycle–defective tumor type, revealed comparable measures of global hypo- and hypermethylation. These data expose a vital connection between succinate metabolism and genomic DNA methylation during tumorigenesis, and generally implicate the mitochondrial Krebs cycle in nuclear epigenomic maintenance.
Significance: This study shows that SDH deficiency underlies pervasive DNA hypermethylation in multiple tumor lineages, generally defining the Krebs cycle as mitochondrial custodian of the methylome. We propose that this phenomenon may result from a failure of maintenance CpG demethylation, secondary to inhibition of the TET 5-methylcytosine dioxgenase demethylation pathway, by inhibitory metabolites that accumulate in tumors with Krebs cycle dysfunction. Cancer Discov; 3(6); 648–57. ©2013 AACR.
This article is highlighted in the In This Issue feature, p. 591
Obesity and the Risk of Intracerebral Hemorrhage
Authors: Pezzini Alessandro , Grassi Mario , Paciaroni Maurizio , Zini Andrea , Silvestrelli Giorgio , Iacoviello Licia , Di Castelnuovo Augusto , Del Zotto Elisabetta , Caso Valeria , Nichelli Paolo Frigio , Giossi Alessia , Volonghi Irene , Simone Anna Maria , Lanari Alessia , Costa Paolo , Poli Loris , Pentore Roberta , Falzone Francesca , Gamba Massimo , Morotti Andrea , Ciccone Alfonso , Ritelli Marco , Guido Davide , Colombi Marina , De Gaetano Giovanni , Agnelli Giancarlo , Padovani Alessandro 
Published: April 2013

Background and Purpose—
The effect of obesity on the risk of intracerebral hemorrhage (ICH) may depend on the pathophysiology of vessel damage. To further address this issue, we investigated and quantified the correlations between obesity and obesity-related conditions in the causal pathways leading to ICH.

Methods—
A total of 777 ICH cases ≥55 years of age (287 lobar ICH and 490 deep ICH) were consecutively enrolled as part of the Multicenter Study on Cerebral Hemorrhage in Italy and compared with 2083 control subjects by a multivariate path analysis model. Separate analyses were conducted for deep and lobar ICH.

Results—
Obesity was not independently associated with an increased risk of lobar ICH (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.58–1.01) or deep ICH (OR, 1.18; 95% CI, 0.95–1.45) when compared with control subjects. The path analysis confirmed the nonsignificant total effect of obesity on the risk of lobar ICH (OR, 0.77; 95% CI, 0.58–1.02) but demonstrated a significant indirect effect on the risk of deep ICH (OR, 1.28; 95% CI, 1.03–1.57), mostly determined by hypertension (OR, 1.07; 95% CI, 1.04–1.11) and diabetes mellitus (OR, 1.04; 95% CI, 1.01–1.07). Obesity was also associated with an increased risk of deep ICH when compared with lobar ICH (OR, 1.62; 95% CI, 1.14–2.31).

Conclusions—
Obesity increases the risk of deep ICH, mostly through an indirect effect on hypertension and other intermediate obesity-related comorbidities, but has no major influence on the risk of lobar ICH. This supports the hypothesis of different, vessel-specific, biological mechanisms underlying the relationship between obesity and cerebral hemorrhage.
Favorable Vascular Profile is an Independent Predictor of Outcome
Authors: Schellinger Peter D. , Köhrmann Martin , Liu Songling , Dillon William P. , Nogueira Raul G. , Shuaib Ashfaq , Liebeskind David S. ,   for the SENTIS Trial Investigators
Published: April 2013

Background and Purpose—
We hypothesized that a favorable vascular profile (FVP) defined as anatomic intactness of the Circle of Willis combined with a stable cerebral perfusion pressure (mean arterial blood pressure>65 mm Hg) is a prerequisite for collateral recruitment and maintenance and may improve outcome. We performed post hoc analyses of a subset of the Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke (SENTIS) trial data set to identify whether FVP is associated with independent outcome.

Methods—
SENTIS was a randomized, controlled device trial comparing hemodynamic augmentation with the NeuroFlo device to best medical treatment. We identified all patients from the primary dataset (n=515 patients) with available intracranial vascular imaging at baseline. Vascular imaging data were read blind to clinical and treatment data. We performed univariate and multivariate analyses to identify predictors of independent outcome (modified Rankin Scale 0–2) at 90 days.

Results—

A total of 192/515 SENTIS subjects had available baseline vascular imaging (91 treated/101 controls). Baseline characteristics did not differ between groups. Overall, FVP was seen in 89.6% of patients and predicted independent outcome in univariate (odds ratio, 7.46; 95% confidence interval, 1.68–33.18;
P
=0.0082) and multiple logistic regression analyses (odds ratio, 10.22; 95% confidence interval, 1.78–58.57;
P
=0.0091). Aside from FVP, only baseline National Institutes of Health Stroke Scales (NIHSS; odds ratio, 0.74; 95% confidence interval, 0.67–0.82,
P
<0.0001) entered the predictive model. There was no interaction with randomization to treatment or control.

Conclusions—
FVP and baseline NIHSS independently predicted outcome in this subset of the SENTIS population. FVP is a novel parameter to predict outcome of acute stroke patients and further studies will establish its potential role for selection of optimal candidates for hemodynamic augmentation.

Clinical Trial Registration Information—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00119717
Using System Dynamics Modelling to Understand and Address the Systemic Issues on Complex Engineering Projects
Authors: Stupples David W 
Published: April 2013

As our world becomes ever more complex, engineering solutions to meet our needs become more difficult to realise. These solutions are born through projects that, because of this complexity, have been increasingly difficult to deliver on time and to budget. There is not a week goes by without reports of yet another project disaster, or another embarrassment for government! What is going wrong? Our ability to design and construct complex engineering solutions is improving, mainly through the formal application of systems engineering, but there is another entity in play that is not benefiting from the same degree of attention — the delivery mechanism or, as it is more commonly termed the “project”. This project can be as complex as the engineering solution, with behaviour that is extremely dynamic in nature. The application of system dynamics modelling is currently the only way by which this behaviour can be understood and ultimately controlled. System dynamics may therefore be the missing ingredient for successful projects.
Industrial Symbiosis in the Kwinana Industrial Area (Western Australia)
Authors: Harris Steve 
Published: April 2013

The Kwinana Industrial Area of Western Australia has emerged as a world leading example of industrial symbiosis. This involves businesses in close proximity exchanging by-product material, water and energy. Utilisation of a previously discarded resource as an alternative input to another company can help improve both business and sustainability performance of the participating companies. For example, the exchange can reduce disposal costs and provide a cheaper input for the receiving company. The environmental benefits can include reduced collective resource consumption and waste generation, whilst the social benefits may include new employment opportunities and reduction of emission (e.g. water or traffic) to the local community. This article presents the integrated research programme undertaken at the Centre of Excellence in Cleaner Production, Curtin University of Technology which seeks to enhance the uptake of industrial symbiosis in Australian heavy industrial areas. The case of Kwinana is discussed with illustrative case studies of industrial symbiosis exchanges. International interest in the creation of industrial symbiosis continues to grow and the article concludes with a discussion on the emerging role of measurement and control technolo
Hydrogen Induced Stress Cracking (HISC) and DNV-RP-F112
Authors: Solnørdal Morten , Wästberg Stig , Heiberg Gustav , Hauås-Eide Odd 
Published: April 2013

Duplex stainless steels are widely used in subsea petroleum production installation. In many instances such steels are a robust solution to the design and manufacturing challenges. However, a number of failures have occurred, which were attributed to Hydrogen Induced Stress Cracking (HISC). Several failure investigations and extensive testing have been carried out over the last 5–10 years, and a design guideline has been established; DNV-RP-F112. The article presents HISC as a failure mode, with a brief summary of the necessary conditions and failure characteristics. The testing and research effort into HISC is described. Finally DNV-RP-F112 “Design of Duplex Stainless Steel Subsea Equipment Exposed to Cathodic Protection” is introduced and the main features are outlined.
Safety Panel: An Introduction
Authors: Howard Colin 
Published: April 2013

Over the past 25 years there have been a number of initiatives worldwide to develop guidelines and standards to enable the safe exploitation of programmable electronic systems (PESs) used for safety applications. In the context of industrial applications (to distinguish from aerospace and military applications) a major initiative has been focussed on IEC 61508, and other standards based on IEC 61508, have emerged as a key international standards. This paper considers some of the key features of IEC 61508, which has now been available for over 10 years, and indicates some of the issues that are being considered in the current revision of the standard.
The Science of Physical Archaeology
Authors: Hatherly P.A. 
Published: April 2013

All too often, the theory and practice of archaeology, and heritage in general, are seen as the preserve of the humanities and are interpretative and subjective rather than objectively measured. However, as we will discuss in this paper, measurement technology and physical science are vital to archaeological interpretation in many areas. To illustrate the point, we will examine the techniques used in a case study investigating the properties of Roman pigments. We will look at some of the physical science techniques applied, the kind of physical properties determined and how the outcomes have aided the understanding, interpretation and validation of artefacts.
Fostering Forensic Innovation
Authors: Mennell Julie 
Published: April 2013

Forensic science has a significant current and future role in crime detection, policing and the criminal justice system. Government and societal drivers, police priorities and advances in science and technology are demanding, as well as providing opportunities, for its impact and potential to be expanded, evaluated and assessed further. Within this, there is a need for the Criminal Justice System to be clear what it is looking for in respect of forensic science and to identify what the priorities, opportunities and processes are for development and possible expansion (of some areas, such as Digital Forensics, Biometrics and Imaging technologies). For example, if the police service's primary forensic science requirements are for reductions in unit costs, improvements in detection rates or faster turn-around times then this should be clearly specified to internal and external providers, while recognising that such requirements could have consequences for the development and delivery of forensic science, as well as policing, in other ways. A key area of agreement within the forensic community is the importance of establishing a vehicle for identifying future possibilities, potential and priorities which fosters innovation, maintains investment and shapes (rather than directs) the forensic science market; together with the need for engagement with the broader based academic community, in relation to research and development.
From Submarines to Sunspots: Challenges in Ship Position Control
Authors: Stephens Richard I. 
Published: April 2013

Ship position control is enabling extraction of oil and gas from hitherto inaccessible locations and in extreme conditions. It is now also assisting in the deployment and maintenance of installations for the burgeoning offshore renewable energy industry. The paper examines the systems and control engineering challenges of providing safe ship positioning in an inhospitable environment. It looks at the shortcomings of a number of technologies and underlines the need for multiple diverse techniques to be brought together in a single system.
A Solution to Measure the Flow Rate of Wet Gas
Authors: Niblett Mark , Robertson Ian 
Published: April 2013

Traditionally the mixture of fluids at the wellhead is separated into its various phases. Proper separation and accurate measurement of each of the component phases is critical in determining production capabilities. Gas is separated from the liquid by passing the emitted well fluids through a separator. The phases are then further separated and measured independently. Using a flowmeter rather than separators to determine the gas and liquid phases gives a very significant reduction in CAPEX in the evaluation of new wells. This paper covers the key benefits that wet gas meters provide in comparison with expensive separators, multiphase metering and traditional single phase DP producing devices such as orifice plates.
West Delta Deep Marine — Offshore Mono Ethylene Glycol Injection
Authors: Smith David A. 
Published: April 2013

In 1999 INTECSEA (Previously INTEC) commenced a FEED study in a concession called West Delta Deep Marine (WDDM), offshore Egypt in the Mediterranean Sea. The development was to be operated by the Burullus Gas Company, a Joint Venture comprising BG Egypt, Edison Gas and EGPC (the Egyptian General Petroleum Company). Since that time Edison Gas have sold their share to PICL (Egypt) Corporation Ltd (Wholly owned by PETRONAS). The development was the first deepwater development offshore Egypt, an area with no experience in deepwater developments with little associated infrastructure. The development was also to be pioneering as it was, at that time, one of the longest tie-backs to shore at 90 km initially with the Scarab /Saffron fields. Since those early days, INTECSEA have continued working alongside Burullus Gas, delivering a number of Phases of the development, with the expansion being further, 105 km, from shore and in deeper water, 1024 m. This article describes our work associated with the need to provide reliable subsea Mono Ethylene Glycol (MEG) injection and some of the issues experienced from those early days to the present.
Real-Time Optical Aircraft Detection
Authors: Revell James , Buchanan Rod , Dixon Rob 
Published: April 2013

The routine use of Uninhabited Air Systems (UAS) in non-segregated airspace presents many technological and regulatory challenges to the aerospace industry. This paper gives an overview of the collision avoidance problem facing UAS designers and provides a discussion of the current optical aircraft detection and tracking approaches. In addition, the paper describes several important challenges for a computer vision based aircraft detection approach that is designed to form part of an optical UAS collision avoidance system. Some initial flight trial results are presented from our prototype and conclusions drawn.
Conditional Based Monitoring of an Three Column Gas Chromatograph
Authors: Sutan Anwar , Laidlaw Jason 
Published: April 2013

Chromatography is an analytical technique which facilitates the separation of components in a mixture for subsequent use or analysis. On-line Gas Chromatography is frequently used within the oil and gas sector to obtain the composition of natural gas for the purposes of such things as allocation, fiscal reporting and sales/custody transfer. The composition measured by the Gas Chromatograph (GC) is therefore likely to come under the direct scrutiny of the buyer(s), the seller(s) and the regulator. The GC is widely known as a device that conducts its measuring functions recurrently and it is imperative that the instrument remains stable and repeatable. The requirement for high repeatability makes the setting of the GC valve timing fundamentally important to accurate chromatography and hence there is a requirement to detect the presence of potential drift before the measurement becomes compromised. The composition measured by the GC may be used to calculate various parameters, however, the gas calorific value is commonly used as the basis for financial transactions and as such the accuracy of this measurement is critically important. The author has performed a live test, which, in the absence of condition based monitoring, would have resulted in an undetected problem with the GC settings that would have caused an error of up to 1.4% in the calorific value. For the case in question, the monetary value of this error would have been in excess of £300,000 per month. It is very clear that failure to calibrate and operate a GC to its full potential can be very costly and result in significant financial exposure for all the parties involved. This paper presents a condition based monitoring strategy aimed at ensuring that the GC performance is maintained and that any potential problems are identified early to prevent erroneous measurement.