bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epstein-Barr Virus Rta-Mediated Accumulation of DNA Methylation Interferes with CTCF Binding in both Host and Viral Genomes
Authors: Chen Yen-Ju , Chen Yu-Lian , Chang Yao , Wu Chung-Chun , Ko Ying-Chieh , Tsao Sai Wah , Chen Jen-Yang , Lin Su-Fang 
Published: May 2017

ABSTRACT

Rta, an Epstein-Barr virus (EBV) immediate-early protein, reactivates viral lytic replication that is closely associated with tumorigenesis. In previous studies, we demonstrated that in epithelial cells Rta efficiently induced cellular senescence, which is an irreversible G
1
arrest likely to provide a favorable environment for productive replications of EBV and Kaposi's sarcoma-associated herpesvirus (KSHV). To restrict progression of the cell cycle, Rta simultaneously upregulates CDK inhibitors and downregulates MYC, CCND1, and JUN, among others. Rta has long been known as a potent transcriptional activator, thus its role in gene repression is unexpected.
In silico
analysis revealed that the promoter regions of
MYC
,
CCND1
, and
JUN
are common in (i) the presence of CpG islands, (ii) strong chromatin immunoprecipitation (ChIP) signals of CCCTC-binding factor (CTCF), and (iii) having at least one Rta binding site. By combining ChIP assays and DNA methylation analysis, here we provide evidence showing that Rta binding accumulated CpG methylation and decreased CTCF occupancy in the regulatory regions of
MYC
,
CCND1
, and
JUN
, which were associated with downregulated gene expression. Stable residence of CTCF in the viral latency and reactivation control regions is a hallmark of viral latency. Here, we observed that Rta-mediated decreased binding of CTCF in the viral genome is concurrent with virus reactivation. Via interfering with CTCF binding, in the host genome Rta can function as a transcriptional repressor for gene silencing, while in the viral genome Rta acts as an activator for lytic gene loci by removing a topological constraint established by CTCF.

IMPORTANCE
CTCF is a multifunctional protein that variously participates in gene expression and higher-order chromatin structure of the cellular and viral genomes. In certain loci of the genome, CTCF occupancy and DNA methylation are mutually exclusive. Here, we demonstrate that the Epstein-Barr virus (EBV) immediate-early protein, Rta, known to be a transcriptional activator, can also function as a transcriptional repressor. Via enriching CpG methylation and decreasing CTCF reloading, Rta binding efficiently shut down the expression of
MYC
,
CCND1
, and
JUN
, thus impeding cell cycle progression. Rta-mediated disruption of CTCF binding was also detected in the latency/reactivation control regions of the EBV genome, and this in turn led to viral lytic cycle progression. As emerging evidence indicates that a methylated EBV genome is a preferable substrate for EBV Zta, the other immediate-early protein, our results suggest a mechanistic link in understanding the molecular processes of viral latent-lytic switch.
Subcategories of tendinopathy using ultrasound tissue characterization (utc): dorsal mid-portion achilles tendinopathy is more severe than ventral achilles tendinopathy
Authors: Wynter Bee W , Ubhi J , Kumar B 
Published: May 2017

AimTo evaluate the association between tendon structure and clinical severity. Looking specifically at location of pathology, comparing ventral versus dorsal tendinopathy.MethodsPatients were recruited from a tertiary tendinopathy center between Jan 2015 – June 2016. Inclusion criteria included patients with midportion Achilles tendinopathy, aged between 1870. Patients with insertional Achilles tendinopathy or other suspected etiology were excluded. Patients were assessed using ultrasound tissue characterization (UTC) scanning. UTC software was used to analyse a 2 cm block 24 cm from the calcaneum for percentage of echo type I, II, III and IV. With percentage echo type I+II used as the primary outcome. A doctor also categorised patients into predominately dorsal or ventral pathology based on UTC imaging. VISAA and VAS scores were used for clinical outcome measures. Statistics were undertaken using SPSS, data was not normally distributedResultsOverall 33 tendons with mid portion Achilles tendinopathy were analysed, the overall percentage echo type I+II showed no correlation to either VISAA (p=0.745, r=0.0600) or VAS (p=0.157, r=0.248). When divided into dorsal and ventral Achilles tendinopathy there was a significant difference between baseline VISAA scores with a lower VISAA score 35 (SD±19) in dorsal group compared with the ventral group 60 (SD±17.1) (p=0.009). There was also a higher VAS score in the dorsal group (mean = 6, SD±2.28) at baseline compared with ventral (mean = 5, SD±3.07), although this was not significant (p=0.416).ConclusionsThis highlights the possibility of using UTC to subcategories patients into ventral and dorsal which seems to correlate to increased clinical severity in the dorsal group. This is perhaps due to increased tension and stretching acting through this part of the tendon on loading and thus more nociceptive stimulation and greater dysfunction of the tendon. This could be used to help determine differing rehabilitation interventions in future with differing intensities for the two groups. It further highlights as previous studies1,2have that there is no direct correlation between overall structure and clinical severity.
Multimorbidity as an important issue among women: results of a gender difference investigation in a large population-based cross-sectional study in West Asia
Authors: Alimohammadian Masoomeh , Majidi Azam , Yaseri Mehdi , Ahmadi Batoul , Islami Farhad , Derakhshan Mohammad , Delavari Alireza , Amani Mohammad , Feyz-Sani Akbar , Poustchi Hossein , Pourshams Akram , Sadjadi Amir Mahdi , Khoshnia Masoud , Qaravi Samad , Abnet Christian C , Dawsey Sanford , Brennan Paul , Kamangar Farin , Boffetta Paolo , Sadjadi Alireza , Malekzadeh Reza 
Published: May 2017

ObjectivesTo investigate the impact of gender on multimorbidity in northern Iran.DesignA cross-sectional analysis of the Golestan cohort data.SettingGolestan Province, Iran.Study population49 946 residents (age 40–75 years) of Golestan Province, Iran.Main outcome measuresResearchers collected data related to multimorbidity, defined as co-existence of two or more chronic diseases in an individual, at the beginning of a representative cohort study which recruited its participants from 2004 to 2008. The researchers utilised simple and multiple Poisson regression models with robust variances to examine the simultaneous effects of multiple factors.ResultsWomen had a 25.0% prevalence of multimorbidity, whereas men had a 13.4% prevalence (p<0.001). Women of all age-groups had a higher prevalence of multimorbidity. Of note, multimorbidity began at a lower age (40–49 years) in women (17.3%) compared with men (8.6%) of the same age (p<0.001). This study identified significant interactions between gender as well as socioeconomic status, ethnicity, physical activity, marital status, education level and smoking (p<0.01).ConclusionPrevention and control of multimorbidity requires health promotion programmes to increase public awareness about the modifiable risk factors, particularly among women.
Health status and needs of cancer survivors attending the Sydney Survivorship Centre clinics and programmes: a protocol for longitudinal evaluation of the centre’s services
Authors: Vardy Janette L , Tan Cindy , Turner Jane D , Dhillon Haryana 
Published: May 2017

IntroductionThe care of cancer survivors after primary adjuvant treatment is recognised as a distinct phase of the cancer journey. Recent research highlights the importance of lifestyle factors in treating symptoms, potentially decreasing risk of a cancer recurrence and modifying the risk of developing other chronic illnesses that are increased in the cancer population. Survivorship services aim to deliver care that addresses these issues. The overall aims are to determine the health status of cancer survivors and to evaluate the services offered by the Sydney Survivorship Centre (SSC).Methods and analysisThis is an observational single-centre study evaluating the longitudinal physical and psychological health, symptoms, quality of life and lifestyle (physical activity and nutrition) of early stage cancer survivors attending the multidisciplinary Sydney Survivorship Clinic and survivors (at any stage of the cancer journey) and caregivers participating in SSC courses. Evaluation of patient satisfaction is included. Patient-reported outcomes and patient characteristics will be summarised using descriptive statistics with Spearman rank sum correlation coefficients to determine associations between patient-reported outcomes. Regression modelling may be used to further evaluate associations and to investigate risk factors and predictors of health outcomes. Qualitative data will be analysed using thematic analysis to identify themes. Sample size will be determined by attendance of consenting patients at clinics and courses.Ethics and disseminationThe study has received ethics approval from the Concord Repatriation General Hospital Human Research Ethics Committee (HREC/14/CRGH/23). The results will be published and presented at appropriate conferences.This study will provide important information regarding the health status and needs of Australian cancer survivors and the ability of the survivorship centre to address these needs. These data will shape the future direction of survivorship care in Australia and facilitate the design of interventions or measures to provide better quality of care to this patient population.
The BRCA1 c. 5096G>A p.Arg1699Gln (R1699Q) intermediate risk variant: breast and ovarian cancer risk estimation and recommendations for clinical management from the ENIGMA consortium
Authors: Moghadasi Setareh , Meeks Huong D , Vreeswijk Maaike PG , Janssen Linda AM , Borg Åke , Ehrencrona Hans , Paulsson-Karlsson Ylva , Wappenschmidt Barbara , Engel Christoph , Gehrig Andrea , Arnold Norbert , Hansen Thomas Van Overeem , Thomassen Mads , Jensen Uffe Birk , Kruse Torben A , Ejlertsen Bent , Gerdes Anne-Marie , Pedersen Inge Søkilde , Caputo Sandrine M , Couch Fergus , Hallberg Emily J , van den Ouweland Ans MW , Collée Margriet J , Teugels Erik , Adank Muriel A , van der Luijt Rob B , Mensenkamp Arjen R , Oosterwijk Jan C , Blok Marinus J , Janin Nicolas , Claes Kathleen BM , Tucker Kathy , Viassolo Valeria , Toland Amanda Ewart , Eccles Diana E , Devilee Peter , Van Asperen Christie J , Spurdle Amanda B , Goldgar David E , García Encarna Gómez 
Published: May 2017

BackgroundWe previously showed that the BRCA1 variant c.5096G>A p.Arg1699Gln (R1699Q) was associated with an intermediate risk of breast cancer (BC) and ovarian cancer (OC). This study aimed to assess these cancer risks for R1699Q carriers in a larger cohort, including follow-up of previously studied families, to further define cancer risks and to propose adjusted clinical management of female BRCA1*R1699Q carriers.MethodsData were collected from 129 BRCA1*R1699Q families ascertained internationally by ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) consortium members. A modified segregation analysis was used to calculate BC and OC risks. Relative risks were calculated under both monogenic model and major gene plus polygenic model assumptions.ResultsIn this cohort the cumulative risk of BC and OC by age 70 years was 20% and 6%, respectively. The relative risk for developing cancer was higher when using a model that included the effects of both the R1699Q variant and a residual polygenic component compared with monogenic model (for BC 3.67 vs 2.83, and for OC 6.41 vs 5.83).ConclusionOur results confirm that BRCA1*R1699Q confers an intermediate risk for BC and OC. Breast surveillance for female carriers based on mammogram annually from age 40 is advised. Bilateral salpingo-oophorectomy should be considered based on family history.
Fermilab proton accelerator complex status and improvement plans
Authors: Shiltsev Vladimir 
Published: May 2017

Fermilab carries out an extensive program of accelerator-based high energy particle physics research at the Intensity Frontier that relies on the operation of 8 GeV and 120 GeV proton beamlines for a number of fixed target experiments. Routine operation with a world-record 700 kW of average 120 GeV beam power on the neutrino target was achieved in 2017 as a result of the Proton Improvement Plan (PIP) upgrade. There are plans to further increase the power from 900–1000 kW. The next major upgrade of the FNAL accelerator complex, called PIP-II, is under development. It aims at 1.2 MW beam power on target at the start of the LBNF/DUNE experiment in the middle of the next decade and assumes replacement of the existing 40 years old 400 MeV normal-conducting Linac with a modern 800 MeV superconducting RF linear accelerator. There are several concepts to further double the beam power to [Formula: see text] 2.4 MW after replacement of the existing 8 GeV Booster synchrotron. In this review, we discuss current performance of the Fermilab proton accelerator complex, the upgrade plans for the next two decades and the accelerator R&D program to address cost and performance risks for these upgrades.
A study of coFeB magnetic yoke based on planar electromagnet
Authors: Qin L. , Li Q. , Yuan Yong J. 
Published: May 2017

This paper studies the fabrication of a novel planar electromagnet consisting of a planar copper coil and a magnetic yoke. CoFeB was used as the magnetic yoke material instead of the traditional permanent magnets. The planar electromagnet was fabricated and optimized to maximize the electromagnetic force, especially with varying CoFeB thickness. The micro-planar electromagnet was fabricated successfully by the traditional micro-electro-mechanical-system (MEMS) techniques and XRD, VSM were used to characterize the performance of the electromagnet. The planar electromagnet exhibits superior perpendicular magnetic anisotropy (PMA) and 0.006 emu of [Formula: see text] was achieved following 2 min deposition of CoFeB thin film. By integrating with other micro apparatuses, it is anticipated that the planar electromagnet will have potential applications in areas such as biosensors, biological medicine, drug delivery, chemical analysis and environmental monitoring.
Advanced Economic Control of Electricity-Based Space Heating Systems in Domestic Coalitions with Shared Intermittent Energy Resources
Authors: Panagopoulos Athanasios Aris , Maleki Sasan , Rogers Alex , Venanzi Matteo , Jennings Nicholas R. 
Published: May 2017

Over the past few years, Domestic Heating Automation Systems (DHASs) that optimize the domestic space heating control process with minimum user input, utilizing appropriate occupancy prediction technology, have emerged as commercial products (e.g., the smart thermostats from Nest and Honeywell). At the same time, many houses are being equipped with, potentially grid-connected, Intermittent Energy Resources (IERs), such as rooftop photovoltaic systems and/or small wind turbine generators. Now, in many regions of the world, such houses can sell energy to the grid but at a lower price than the price of buying it. In this context, and given the anticipated increase in electrification of heating, the next generation DHASs need to incorporate Advanced Economic Control (AEC). Such AEC can exploit the energy buffer that heating loads provide, in order to shift the consumption of electricity-based heating systems to follow the intermittent energy generation of the house. By so doing, the energy imported from the grid can be minimized and considerable monetary gains for the household can be achieved, without affecting the occupants’ schedule. These benefits can be amplified still further in domestic coalitions, where a number of houses come together and share their IER generation to minimize their cumulative grid energy import.
Given the above, in this work we extend a state-of-the-art DHAS, to propose AdaHeat+, a practical DHAS, that, for the first time, incorporates AEC. Our work is applicable to both individual houses and domestic coalitions and comes complete with an allocation mechanism to share the coalition gains. Importantly, we propose an effective heuristic heating schedule planning approach for collective AEC that (i) has a complexity that scales in a linear and parallelizable manner with the coalition size, and (ii) enables AdaHeat+ to handle the distinct preferences, in balancing heating cost and thermal discomfort, of the households. Our approach relies on stochastic IER power output predictions. In this context, we propose a simple and effective formulation for the site-specific calibration of such predictions based on adaptive Gaussian process modeling. Finally, we demonstrate the effectiveness of AdaHeat+ through real data evaluation, to show that collective AEC can improve heating cost-efficiency by up to 60%, compared to independent AEC (and even more when compared to no-AEC).
Debugging Embedded Systems Requirements Before The Design Begins
Authors: Gaucher Fabien , Génevaux Yves 
Published: May 2017

Over the last two decades, there has been a real movement towards requirements engineering [1]. However, the various tools that have been developed with the aim of improving the specifications development are mostly focused on requirements management and traceability, and there was no easy-to-use requirements validation tool available for checking their functional consistency before any design or coding takes place. As a result, 40 to 60% of design bugs are caused by faulty requirements that generate costly iterations of the development process.
Argosim's ambition is to change this situation by providing STIMULUS [2], the very first requirements simulation tool for real-time embedded systems. STIMULUS combines the ability to write requirements into a formal yet simple textual language, but also and even more importantly, to simulate them by generating the possible behaviours of the specified system in the form of execution plots. The analysis of simulation results allows for the quick and early detection of ambiguous, incorrect, incomplete or even conflicting requirements.
In practice, STIMULUS integrates seamlessly into the agile development processes [3]. It allows for the concurrent development and validation of both the requirements and their test scenarios in a very incremental way.
Once validated at the specification level, both requirements and test scenarios can be reused to validate the design implementation.Test scenarios make it possible to generate many test vectors automatically, while requirements are reused as test observers, or test oracles, in order to automatically check that the system satisfies its requirements.
This paper describes the major innovation offered by STIMULUS in the field of requirements engineering. It will first present its operating principles and then briefly illustrate both the requirements validation and software validation workflows with an example from the automotive domain.
Dispelling the myth that habitual caffeine consumption influences the performance response to acute caffeine supplementation
Authors: Gonçalves Lívia de Souza , Painelli Vitor de Salles , Yamaguchi Guilherme , Oliveira Luana Farias de , Saunders Bryan , da Silva Rafael Pires , Maciel Erika , Artioli Guilherme Giannini , Roschel Hamilton , Gualano Bruno 
Published: May 2017

This study investigates the influence of habitual caffeine intake on aerobic exercise-performance responses to acute caffeine supplementation. A double-blind, crossover, counterbalanced study was performed. Forty male endurance-trained cyclists were allocated into tertiles, according to their daily caffeine intake: low (58 ± 29 mg/d), moderate (143 ± 25 mg/d), and high (351 ± 139 mg/d) consumers. Participants completed three trials in which they performed simulated cycling time trials (TTs) in the fastest time possible following ingestion of the following: caffeine (CAF: 6 mg/kg body mass), placebo (PLA), and no supplement (CON). A mixed-model analysis revealed that TT performance was significantly improved in CAF compared with PLA and CON (29.92 ± 2.18 vs. 30.81 ± 2.67 and 31.14 ± 2.71 min, respectively; P = 0.0002). Analysis of covariance revealed no influence of habitual caffeine intake as a covariate on exercise performance ( P = 0.47). TT performance was not significantly different among tertiles ( P = 0.75). No correlation was observed between habitual caffeine intake and absolute changes (CAF − CON) in TT performance with caffeine ( P = 0.524). Individual analysis showed that eight, seven, and five individuals improved above the variation of the test in CAF in the low, moderate, and high tertiles, respectively. A Fisher’s exact test did not show any significant differences in the number of individuals who improved in CAF among the tertiles ( P > 0.05). Blood lactate and ratings of perceived exertion were not different between trials and tertiles ( P > 0.05). Performance effects of acute caffeine supplementation during an ~30-min cycling TT performance were not influenced by the level of habitual caffeine consumption. NEW & NOTEWORTHY There has been a long-standing paradigm that habitual caffeine intake may influence the ergogenicity of caffeine supplementation. Low, moderate, and high caffeine consumers showed similar absolute and relative improvements in cycling time-trial performance following acute supplementation of 6 mg/kg body mass caffeine. Performance effects of acute caffeine were not influenced by the level of habitual caffeine consumption, suggesting that high habitual caffeine intake does not negate the benefits of acute caffeine supplementation.