bluuebunny/crossref_metadata_2025_split huggingface dataset:
legaSCi
Authors: Schumacher Christoph , Weinstock Jan Henrik , Leupers Rainer , Ascheid Gerd , Tosoratto Laura , Lonardo Alessandro , Petras Dietmar , Hoffmann Andreas 
Published: December 2014

Architects and developers use virtual prototypes of computer systems to receive early feedback on hardware design decisions as well as to develop and debug system software. This is facilitated by the comprehensive inspection capabilities virtual prototypes offer. For virtual prototypes, execution speed is crucial to support the users' productivity. Parallel simulation techniques are employed to offset the speed impact of the increasing number of cores that need to be simulated in virtual prototypes of parallel and embedded systems.
SystemC is the de facto industry standard library for virtual platform modeling. Since currently no parallel SystemC library is commonly available, typical SystemC models are coded for execution in sequential simulation environments. Simply putting such models into parallel simulators may lead to thread-safety issues and may additionally cause nondeterministic simulator behavior.

This article proposes a methodology to support simulation creators to face the challenge of integrating such legacy models into parallel SystemC environments. The feasibility of the proposed method is evaluated by parallelizing the latest instance of the EU FP7 project EURETILE embedded platform simulator. Using
legaSCi
, on four host processor cores a speedup of 2.13× is demonstrated, without having to change the individual models of the simulator.
Now what?
Authors: Stout Jane , Camp Tracy 
Published: December 2014

Our culture is currently paying a great deal of attention to issues of diversity in computing and technology. More specifically, society wonders why there are not more women involved in computing. Statistics on women's representation in all levels of the postsecondary academic pipeline, and in professions outside of the academy, have been bleak for decades. In response to this, social scientists have taken great interest in understanding why this cultural phenomenon exists. Although women's underrepresentation may seem intractable due to many years of stagnancy, we urge readers to take heart, and capitalize on the cultural climate, which places great emphasis on promoting gender equity and diversity in computing.
In this article, we review a number of factors that explain women's low participation in and attrition from computing, which have been developed through empirical research. We then articulate actionable items that can be implemented "on the ground" in classrooms and professional settings, as well as "on the books" at the administrative and public policy level. We conclude by urging readers to consider this a "people's issue" rather than a "women's issue", because all people can benefit from environments, cultural beliefs and policies that espouse inclusivity and equity.
DNMT1–MicroRNA126 Epigenetic Circuit Contributes to Esophageal Squamous Cell Carcinoma Growth via ADAM9–EGFR–AKT Signaling
Authors: Liu Ronghua , Gu Jie , Jiang Pei , Zheng Yijie , Liu Xiaoming , Jiang Xuechao , Huang Enyu , Xiong Shudao , Xu Fengkai , Liu Guangwei , Ge Di , Chu Yiwei 
Published: December 2014

Abstract
Purpose: MicroRNAs (miRNA) are involved in and are controlled by epigenetic regulation, and thereby form a reciprocal regulatory circuit. Using next-generation sequencing (NGS)–based miRNA profiling, this study aimed to discover esophageal squamous cell carcinoma (ESCC)–specific miRNAs and miRNA-related epigenetic modulations.
Experimental Design: NGS-based miRNA profiles were generated for four pairs of ESCC tissues and adjacent normal tissues. In situ hybridization was used to assess miRNA expression and its correlation with prognosis. miRNA-related DNA methylations were identified using bisulfite genomic sequencing, and the role of DNA methyltransferase 1 (DNMT1) was investigated using RNA interference. miRNA targets were screened by mRNA sequencing, and functional validation was performed in vitro and in vivo.
Results: NGS-based miRNA profiling identified 78 differentially expressed miRNAs in ESCC. Among them, microRNA126-3p (miR-126) was significantly downregulated, and its downregulation correlated with poor ESCC prognosis. Downregulation of miR-126 was due to promoter hypermethylation of its host gene, Egfl7. DNMT1 was aberrantly upregulated in ESCC and responsible for the hypermethylation of Egfl7. Intriguingly, DNMT1 was suppressed by overexpression of miR-126, indicating the existence of a regulatory feedback circuit. ADAM9 was identified as a key target of miR-126. Ectopic expression of miR-126 or silencing of ADAM9 reduced ESCC cell proliferation and migration by inhibiting epidermal growth factor receptor–AKT signaling.
Conclusions: Our results indicate that miR-126 is a potential prognostic indicator for ESCC and suggest that a novel “DNMT1–miR-126 epigenetic circuit” is involved in ESCC progression. Consequently, miR-126–based epigenetic modulations may provide a basic rationale for new approaches to antitumor therapeutics. Clin Cancer Res; 21(4); 854–63. ©2014 AACR.
Identification of Novel Radiosensitizers in a High-Throughput, Cell-Based Screen for DSB Repair Inhibitors
Authors: Goglia Alexander G. , Delsite Robert , Luz Antonio N. , Shahbazian David , Salem Ahmed F. , Sundaram Ranjini K. , Chiaravalli Jeanne , Hendrikx Petrus J. , Wilshire Jennifer A. , Jasin Maria , Kluger Harriet M. , Glickman J. Fraser , Powell Simon N. , Bindra Ranjit S. 
Published: December 2014

Abstract
Most cancer therapies involve a component of treatment that inflicts DNA damage in tumor cells, such as double-strand breaks (DSBs), which are considered the most serious threat to genomic integrity. Complex systems have evolved to repair these lesions, and successful DSB repair is essential for tumor cell survival after exposure to ionizing radiation (IR) and other DNA-damaging agents. As such, inhibition of DNA repair is a potentially efficacious strategy for chemo- and radiosensitization. Homologous recombination (HR) and nonhomologous end-joining (NHEJ) represent the two major pathways by which DSBs are repaired in mammalian cells. Here, we report the design and execution of a high-throughput, cell-based small molecule screen for novel DSB repair inhibitors. We miniaturized our recently developed dual NHEJ and HR reporter system into a 384-well plate-based format and interrogated a diverse library of 20,000 compounds for molecules that selectively modulate NHEJ and HR repair in tumor cells. We identified a collection of novel hits that potently inhibit DSB repair, and we have validated their functional activity in a comprehensive panel of orthogonal secondary assays. A selection of these inhibitors was found to radiosensitize cancer cell lines in vitro, which suggests that they may be useful as novel chemo- and radio sensitizers. Surprisingly, we identified several FDA-approved drugs, including the calcium channel blocker mibefradil dihydrochloride, that demonstrated activity as DSB repair inhibitors and radiosensitizers. These findings suggest the possibility for repurposing them as tumor cell radiosensitizers in the future. Accordingly, we recently initiated a phase I clinical trial testing mibefradil as a glioma radiosensitizer. Mol Cancer Ther; 14(2); 326–42. ©2014 AACR.
p53 Mutation Directs AURKA Overexpression via miR-25 and FBXW7 in Prostatic Small Cell Neuroendocrine Carcinoma
Authors: Li Zhen , Sun Yin , Chen Xufeng , Squires Jill , Nowroozizadeh Behdokht , Liang Chaozhao , Huang Jiaoti 
Published: December 2014

Abstract
Prostatic small cell neuroendocrine carcinoma (SCNC) is a rare but aggressive form of prostate cancer that is negative for androgen receptor (AR) and not responsive to hormonal therapy. The molecular etiology of this prostate cancer variant is not well understood; however, mutation of the p53 (TP53) tumor suppressor in prostate neuroendocrine cells inactivates the IL8–CXCR2–p53 pathway that normally inhibits cellular proliferation, leading to the development of SCNC. SCNC also overexpresses Aurora kinase A (AURKA) which is considered to be a viable therapeutic target. Therefore, the relationship of these two molecular events was studied, and we show that p53 mutation leads to increased expression of miR-25 and downregulation of the E3 ubiquitin ligase FBXW7, resulting in elevated levels of Aurora kinase A. This study demonstrates an intracellular pathway by which p53 mutation leads to Aurora kinase A expression, which is critically important for the rapid proliferation and aggressive behavior of prostatic SCNC.
Implications: The pathogenesis of prostatic SCNC involves a p53 and Aurora Kinase A signaling mechanism, both potentially targetable pathways. Mol Cancer Res; 13(3); 584–91. ©2014 AACR.
Sexual Activity and Counseling in the First Month After Acute Myocardial Infarction Among Younger Adults in the United States and Spain
Authors: Lindau Stacy Tessler , Abramsohn Emily M. , Bueno Héctor , D’Onofrio Gail , Lichtman Judith H. , Lorenze Nancy P. , Mehta Sanghani Rupa , Spatz Erica S. , Spertus John A. , Strait Kelly , Wroblewski Kristen , Zhou Shengfan , Krumholz Harlan M. 
Published: December 2014

Background—
United States and European cardiovascular society guidelines recommend physicians counsel patients about resuming sexual activity after acute myocardial infarction (AMI), but little is known about patients’ experience with counseling about sexual activity after AMI.

Methods and Results—
The prospective, longitudinal Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study, conducted at 127 hospitals in the United States and Spain, was designed, in part, to evaluate gender differences in baseline sexual activity, function, and patient experience with physician counseling about sexual activity after an AMI. This study used baseline and 1-month data collected from the 2:1 sample of women (N=2349) and men (N=1152) ages 18 to 55 years with AMI. Median age was 48 years. Among those who reported discussing sexual activity with a physician in the month after AMI (12% of women, 19% of men), 68% were given restrictions: limit sex (35%), take a more passive role (26%), and/or keep the heart rate down (23%). In risk-adjusted analyses, factors associated with not discussing sexual activity with a physician included female gender (relative risk, 1.07; 95% confidence interval, 1.03–1.11), age (relative risk, 1.05 per 10 years; 95% confidence interval, 1.02–1.08), and sexual inactivity at baseline (relative risk, 1.11; 95% confidence interval, 1.08–1.15). Among patients who received counseling, women in Spain were significantly more likely to be given restrictions than U.S. women (relative risk; 1.36, 95% confidence interval, 1.11–1.66).

Conclusions—
Very few patients reported counseling for sexual activity after AMI. Those who did were commonly given restrictions not supported by evidence or guidelines.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00597922.
Regional Structure of the Indian Summer Monsoon in Observations, Reanalysis, and Simulation
Authors: Cash Benjamin A. , Kinter James L. , Adams Jennifer , Altshuler Eric , Huang Bohua , Jin Emilia K. , Manganello Julia , Marx Larry , Jung Thomas 
Published: December 2014

Abstract
Regional variations in seasonal mean Indian summer monsoon rainfall and circulation for the period 1979–2009 are investigated using multiple data products. The focus is on four separate regions: the Western Ghats (WG), the Ganges basin (GB), the Bay of Bengal (BB), and Bangladesh–northeastern India (BD). Data reliability varies strongly by region, with particularly low correlations between different products for the BB and BD regions. Correlations between regions are generally not statistically significant, indicating rainfall varies independently in these four regions. The diagnosed associations between rainfall, circulation, and sea surface temperatures can be sensitive to the choice of rainfall product, and multiple precipitation products may need to be analyzed in this region to ensure that the results are robust.
Enhanced precipitation in the BD region is associated with anomalous anticyclonic circulation at 850 mb and westerly anomalies along the foothills of the Tibetan Plateau, while precipitation in the other regions is associated with cyclonic flow and easterlies. These associations provide a dynamical explanation for previously reported weak, negative correlations between BD and the other regions.
In addition to observed products, atmosphere-only simulations made using the European Centre for Medium-Range Weather Forecasts (ECMWF) Integrated Forecast System (IFS) during Project Athena are analyzed. While the simulations do not reproduce the observed interannual variations in rainfall, the fidelity of the simulated precipitation and circulation structure is comparable to or even outperforms the different state-of-the-art reanalysis products considered. Accuracy in representing interannual variability and regional structure thus appears to be independent.
Vertical Structure of Ocean Pressure Variations with Application to Satellite-Gravimetric Observations
Authors: Piecuch Christopher G. , Fukumori Ichiro , Ponte Rui M. , Wang Ou 
Published: December 2014

AbstractThe nature of ocean bottom pressure () variability is considered on large spatial scales and long temporal scales. Monthly gridded estimates from the Gravity Recovery and Climate Experiment (GRACE) Release-05 and the new version 4 bidecadal ocean state estimate of the Consortium for Estimating the Circulation and Climate of the Ocean (ECCO) are used. Estimates of from GRACE and ECCO are generally in good agreement, providing an independent measure of the quality of both products. Diagnostic fields from the state estimate are used to compute barotropic (depth independent) and baroclinic (depth dependent) components. The relative roles of baroclinic and barotropic processes are found to vary with latitude and time scale: variations in at higher latitudes and shorter periods are affected by barotropic processes, whereas fluctuations at lower latitudes and longer periods can be influenced by baroclinic effects, broadly consistent with theoretical scaling arguments. Wind-driven Rossby waves and coupling of baroclinic and barotropic modes due to flow–topography interactions appear to be important influences on the baroclinic variability. Decadal simulations of monthly variability based on purely barotropic frameworks are expected to be in error by about 30% on average ( in the tropical ocean and at higher latitudes). Results have implications for applying GRACE observations to problems such as estimating transports of the Antarctic Circumpolar Current.
Characteristics of antidepressant medication users in a cohort of mid-age and older Australians
Authors: Paige Ellie , Korda Rosemary J , Kemp Anna , Rodgers Bryan , Banks Emily 
Published: December 2014

Objectives: We aimed to investigate antidepressant use, including the class of antidepressant, in mid-age and older Australians according to sociodemographic, lifestyle and physical and mental health-related factors. Methods: Baseline questionnaire data on 111,705 concession card holders aged ⩾45 years from the 45 and Up Study—a population-based cohort study from New South Wales, Australia—were linked to administrative pharmaceutical data. Current- and any-antidepressant users were those dispensed medications with Anatomical Therapeutic Chemical classification codes beginning N06A, within ⩽6 months and ⩽19 months before baseline, respectively; non-users had no antidepressants dispensed ⩽19 months before baseline. Multinomial logistic regression was used to calculate adjusted relative risk ratios (aRRRs) for predominantly self-reported factors in relation to antidepressant use. Results: Some 19% of the study population (15% of males and 23% of females) were dispensed at least one antidepressant during the study period; 40% of participants used selective serotonin reuptake inhibitors (SSRIs) only and 32% used tricyclic antidepressants (TCAs) only. Current antidepressant use was markedly higher in those reporting: severe versus no physical impairment (aRRR 3.86(95%CI 3.67–4.06)); fair/poor versus excellent/very good self-rated health (4.04(3.83–4.25)); high/very high versus low psychological distress (7.22(6.81–7.66)); ever- versus never-diagnosis of depression by a doctor (18.85(17.95–19.79)); low-dose antipsychotic use versus no antipsychotic use (12.26(9.85–15.27)); and dispensing of ⩾10 versus <5 other medications (5.97(5.62–6.34)). Sociodemographic and lifestyle factors were also associated with use, although to a lesser extent. Females, older people, those with lower education and those with poorer health were more likely to be current antidepressant users than non-users and were also more likely to use TCAs-only versus SSRIs-only. Conclusions: Use of antidepressants is substantially higher in those with physical ill-health and in those reporting a range of adverse mental health measures. In addition, sociodemographic factors, including sex, age and education were also associated with antidepressant use and the class of antidepressant used.
Experience With the Enlite Sensor in a Multicenter Pediatric Study
Authors: Evans Keira , Richardson Christine , Landry Alanna , Muileboom Janice , Cormack Lynne , Lawson Margaret L. ,   On behalf of the CGM TIME Trial Study Group and the JDRF Canadian Clinical Trials Network CCTN1101
Published: December 2014

Purpose The purpose of this article is to outline the experience of certified diabetes educators (CDEs) using the Enlite continuous glucose monitoring sensor system in a pediatric multicenter randomized controlled trial. Continuous glucose monitoring (CGM) is becoming popular as a tool for educators and families to improve glycemic control. CGM can be a valuable educational tool to demonstrate to the user the impact of insulin dosing and effects of physical activity, food intake, and other life events such as work, illness, and stress on their glycemic control. The authors will share education tips and practical applications for diabetes educators to facilitate education and sustained use of Enlite glucose sensors in children and adolescents using insulin pump therapy. Conclusions The Enlite glucose sensor is a comfortable and user-friendly device. Improvements to both the insertion device and the Enlite glucose sensor have resulted in improved level of comfort on insertion and with ongoing wear, which may translate into greater adherence and effectiveness.
Altered Lower Extremity Movement Variability in Female Soccer Players During Side-Step Cutting After Anterior Cruciate Ligament Reconstruction
Authors: Pollard Christine D. , Stearns Kristen M. , Hayes Andy T. , Heiderscheit Bryan C. 
Published: December 2014

Background: Anterior cruciate ligament (ACL) reconstruction (ACLR) is common after an ACL tear and is thought to restore functional stability to the knee. A recent investigation demonstrated that individuals who have undergone ACLR exhibited increased lower extremity coupling variability during gait, suggestive of altered dynamic stability. However, little is known about whether they exhibit alterations in lower extremity variability during dynamic sport-specific tasks. Purpose: To determine if female soccer players who have had an ACLR demonstrate differences in lower extremity coupling variability as compared with athletes with no history of knee injury during a side-step cutting maneuver. Study Design: Controlled laboratory study. Methods: Ten female soccer players who had undergone ACLR served as the experimental group, and 10 female soccer players with no history of knee ligament injury composed the control group (CON). Three-dimensional kinematics and ground-reaction forces were collected while each participant performed a side-step cutting maneuver. Based on known ACL loading patterns, 7 lower extremity intralimb couplings were created. With use of a vector-coding technique, the coordination variability was calculated for each coupling. Independent t tests were used to determine group differences in variability for each coupling ( P ≤ .05). Results: Individuals who had undergone ACLR exhibited increased lower extremity variability during side-step cutting as compared with control subjects in the following couplings: hip rotation/knee abduction-adduction (27.2° ± 11.5° [ACLR] vs 19.7° ± 6.8° [CON]; P = .04), hip flexion-extension/knee abduction-adduction (26.0° ± 13.3° [ACLR] vs 18.6° ± 5.3° [CON]; P = .05), knee abduction-adduction/knee flexion-extension (13.5° ± 5.7° [ACLR] vs 7.3° ± 2.7° [CON]; P < .01), and knee abduction-adduction/knee rotation (26.4° ± 10.8° [ACLR] vs 19.3° ± 4.5° [CON]; P = .03). In addition, there was a trend toward increased variability in the hip rotation/ankle inversion-eversion coupling (22.9° ± 9.3° [ACLR] vs 18.0° ± 6.7° [CON]; P = .09) and knee abduction-adduction/ankle inversion-eversion coupling (25.9° ± 10.0° [ACLR] vs 20.2° ± 9.7° [CON]; P = .10). Conclusion: Female soccer players who have undergone ACLR and returned to sports participation exhibit altered lower extremity coupling variability during side-step cutting. Clinical Relevance: While individuals who have had an ACLR exhibit mechanical knee stability before returning to sports, the observed increased movement variability during side-step cutting is likely reflective of altered neuromuscular control and may contribute to the known increased risk for ACL reinjury and knee osteoarthritis after return to sports participation. Improving the understanding of altered lower extremity coupling variability after ACLR will aid in the development of more effective rehabilitation programs.
Assessing the risk of imminent aggression in mentally ill young offenders
Authors: Kasinathan John , Marsland Christopher , Batterham Philip , Gaskin Claire , Adams Jonathon , Daffern Michael 
Published: December 2014

Objectives: Aggression in adolescents presents a significant problem for psychiatric units. The Dynamic Appraisal of Situational Aggression (DASA) is an empirically validated measure designed to appraise the risk of imminent aggression (within the next 24 hours) in adult patients. Our aim was to examine the predictive validity of the DASA: Youth Version (DASA:YV) with youth-specific items, in young offenders hospitalised with a mental illness. Methods: This prospective validation study involved 4440 DASA:YV ratings of mentally ill adolescents in a secure hospital. At 24 hours post-assessment, the nursing staff documented whether patients had behaved aggressively: physically, verbally or towards property. Predictive accuracy was assessed using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Results: The DASA:YV significantly predicted any imminent aggression (AUC = 0.754). Additional youth-specific items conferred a greater predictive yield, as compared to adult-derived items ( p = 0.014). Conclusions: It is possible to monitor the risk state of hospitalised mentally ill youth, so that heightened states can be detected early, thus facilitating interventions to reduce the risk of violence.