bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exercise serum increases GLUT4 in human adipocytes
Authors: Flores‐Opazo Marcelo , Raajendiran Arthe , Watt Matthew J. , Hargreaves Mark 
Published: February 2019

New Findings
What is the central question of this study?
Do circulating factors mediate exercise‐induced effects on adipose tissue GLUT4 expression?

What is the main finding and its importance?
Serum (10%) obtained from human volunteers immediately after a single exercise bout increased GLUT4 protein levels in human adipocytes in culture. This result suggests that circulating factors might mediate the effects of exercise on adipose tissue GLUT4 and prompts further effort to identify the specific factor(s) and tissue(s) of origin.

AbstractIn this study, we tested the hypothesis that circulating factors generated during exercise increase adipose tissue GLUT4 expression. Serum was obtained from eight healthy subjects before and after 60 min of cycling exercise, and primary adipocytes were cultured from stromal vascular fractions that were isolated from subcutaneous abdominal adipose tissue samples from one healthy, male volunteer. A 48 h exposure of human primary adipocytes to 10% serum obtained after exercise increased GLUT4 protein expression, on average, by 12% compared with exposure to 10% serum obtained at rest, before exercise. GLUT4 mRNA levels were increased after 12 h of exposure to exercise serum but were unchanged after 6 and 24 h of exposure. Our results suggest that circulating factors might mediate the effects of exercise on adipose tissue GLUT4 expression and encourage further efforts to identify the potential factor(s), tissue(s) of origin and physiological relevance.
Resting metabolic rate prediction equations and the validity to assess energy deficiency in the athlete population
Authors: Schofield K. L. , Thorpe H. , Sims S. T. 
Published: February 2019

New Findings
What is the topic of this review?We review the issues with using predicted resting metabolic rate equations in athletic populations.
What advances does it highlight?The use of dated predicted resting metabolic rate equations is not appropriate for athletic populations until more studies have been conducted among these unique populations.
AbstractResting metabolic rate (RMR) is the amount of energy the body uses at rest. A suppressed RMR has been correlated with low energy availability and therefore used as an indicator of an individual's energy state. Furthermore, confounding identification of low energy availability within an athletic population are the physiological measures required, which can be time consuming and require professional expertise. To negate the demands of laboratory protocols in measuring RMR, predicted RMR (pRMR) equations were developed. Caution should be exercised when applying the pRMR equations for determining low energy availability in athletes owing to the population used to develop the equations and the higher metabolic cost of fat‐free mass, thus elevated RMR, associated with athletes. Moreover, a low ratio of measured RMR to pRMR is often used as an alternative marker for energy deficiency. Predictive equations should implement fat‐free mass within the algorithm when estimating RMR in athletic populations. The purpose of this paper is to describe pRMR equation development and the issues associated with use of pRMR equations for athletic populations. As professional sport increases, validation of pRMR equations in the modern athlete population is needed to monitor energy availability for athletic health and performance.
Numerical constructions of optimal feedback in models of chemotherapy of a malignant tumor
Authors: Novoselova Natalia G. 
Published: February 2019

In this paper, a problem of chemotherapy of a malignant tumor is considered. Dynamics is piecewise monotone and a therapy function has two maxima. The aim of therapy is to minimize the number of tumor cells at the given final instance. The main result of this work is the construction of optimal feedbacks in the chemotherapy task. The construction of optimal feedback is based on the value function in the corresponding problem of optimal control (therapy). The value function is represented as a minimax generalized solution of the Hamilton–Jacobi–Bellman equation. It is proved that optimal feedback is a discontinuous function and the line of discontinuity satisfies the Rankin–Hugoniot conditions. Other results of the work are illustrative numerical examples of the construction of optimal feedbacks and Rankin–Hugoniot lines.
Remote sensing applications in the Fars Region of the Zagros Mountains of Iran
Authors: Ginés Jorge , Edwards Rowan , Lohr Tina , Larkin Hayley , Holley Rachel 
Published: February 2019

Abstract
The Zagros Mountains in Iran are an active fold-and-thrust belt that contains world-class examples of folding and salt tectonics. The Fars Region is an excellent location for testing remote sensing methods and applications of satellite data due to its dry climate and superb exposure of geological features. Recent advances in satellite technology and image acquisition have resulted in high-quality global datasets at increasing resolution that provide a highly valuable source of data for structural analysis of fold-and-thrust belts. Oblique lineaments like the Razak Line in eastern Fars can be identified by changes in the dimensions of anticlines, presence of deflected folds, offsets in the alignment of structures, location of anticlinal plunges and exposures of salt. Drainage analysis can show propagation and coalescence of anticlines. We review several methods using optical data, digital elevation models and interferometric synthetic-aperture radar. We integrate those methods and generate detailed geological maps, structural cross-sections, identify structural steps and hidden basement features, and compare to seismological data and their effect on the exposed geology.
Clearing the clouds
Authors: Ferdman Michael , Adileh Almutaz , Kocberber Onur , Volos Stavros , Alisafaee Mohammad , Jevdjic Djordje , Kaynak Cansu , Popescu Adrian Daniel , Ailamaki Anastasia , Falsafi Babak 
Published: February 2019

Emerging scale-out workloads require extensive amounts of computational resources. However, data centers using modern server hardware face physical constraints in space and power, limiting further expansion and calling for improvements in the computational density per server and in the per-operation energy. Continuing to improve the computational resources of the cloud while staying within physical constraints mandates optimizing server efficiency to ensure that server hardware closely matches the needs of scale-out workloads.
In this work, we introduce CloudSuite, a benchmark suite of emerging scale-out workloads. We use performance counters on modern servers to study scale-out workloads, finding that today's predominant processor micro-architecture is inefficient for running these workloads. We find that inefficiency comes from the mismatch between the workload needs and modern processors, particularly in the organization of instruction and data memory systems and the processor core micro-architecture. Moreover, while today's predominant micro-architecture is inefficient when executing scale-out workloads, we find that continuing the current trends will further exacerbate the inefficiency in the future. In this work, we identify the key micro-architectural needs of scale-out workloads, calling for a change in the trajectory of server processors that would lead to improved computational density and power efficiency in data centers.
Data races vs. data race bugs
Authors: Kasikci Baris , Zamfir Cristian , Candea George 
Published: February 2019

Even though most data races are harmless, the harmful ones are at the heart of some of the worst concurrency bugs. Alas, spotting just the harmful data races in programs is like finding a needle in a haystack: 76%-90% of the true data races reported by state-of-the-art race detectors turn out to be harmless [45]. We present Portend, a tool that not only detects races but also automatically classifies them based on their potential consequences: Could they lead to crashes or hangs? Could their effects be visible outside the program? Are they harmless? Our proposed technique achieves high accuracy by efficiently analyzing multiple paths and multiple thread schedules in combination, and by performing symbolic comparison between program outputs.
We ran Portend on 7 real-world applications: it detected 93 true data races and correctly classified 92 of them, with no human effort. 6 of them are harmful races. Portend's classification accuracy is up to 88% higher than that of existing tools, and it produces easy-to-understand evidence of the consequences of harmful races, thus both proving their harmfulness and making debugging easier. We envision Portend being used for testing and debugging, as well as for automatically triaging bug reports.
Torque-planning errors affect the perception of object properties and sensorimotor memories during object manipulation in uncertain grasp situations
Authors: Schneider Thomas Rudolf , Buckingham Gavin , Hermsdörfer Joachim 
Published: February 2019

Predicting instead of only reacting to the properties of objects we grasp is crucial to dexterous object manipulation. Although we normally plan our grasps according to well-learned associations, we rely on implicit sensorimotor memories when we learn to interact with novel or ambiguous objects. However, little is known about the influence of sensorimotor predictions on subsequent perception and action. Here, young and elderly subjects repeatedly lifted an object in which the center of mass (CoM) was randomly varied between trials straight upward with the aim of preventing object tilts. After each lift, subjects indicated the location of the perceived CoM and reported how heavy the object felt. Surprisingly, we found that sensorimotor torque memories eventually causing initial lifting errors had substantial effects on the perception of torques, weight, and the torque planning for the next lift. Whereas subjects tended to partly retain their previous erroneous sensorimotor memories (instead of solely relying on the previously encountered torque for the upcoming motor plan), they perceived encountered torques to be stronger when they erroneously predicted them. Additionally, we found that torque prediction errors, as well as the actual torques, made the object feel heavier. By contrast, perception did not influence upcoming motor control. There were no major differences observed between the age groups. The sensorimotor impact on torque perception can be explained by internal feedforward prediction highlighting task-relevant errors, while the partial retention and adaptation of sensorimotor torque memories is reconciled with the trial-to-trial learning rule for motor adaptation. NEW & NOTEWORTHY The current study is the first to demonstrate in an object manipulation task in uncertainty that errors in the sensorimotor prediction of torques influence the perception of both torques and weight, whereas sensorimotor torque memories are partly retained and partly adapted to planning errors. Our results provide novel insights into the predictive mechanisms underpinning the common everyday task of object manipulation and further support theories about the predictive modulation of perception established in other neuroscientific disciplines.
ACE: A Workbench Using Evolutionary Genetic Algorithms for Analyzing Association in TCGA
Authors: Gilmore Alan R. , Alderdice Matthew , Savage Kienan I. , O'Reilly Paul G. , Roddy Aideen C. , Dunne Philip D. , Lawler Mark , McDade Simon S. , Waugh David J. , McArt Darragh G. 
Published: February 2019

AbstractModern methods of acquiring molecular data have improved rapidly in recent years, making it easier for researchers to collect large volumes of information. However, this has increased the challenge of recognizing interesting patterns within the data. Atlas Correlation Explorer (ACE) is a user-friendly workbench for seeking associations between attributes in The Cancer Genome Atlas (TCGA) database. It allows any combination of clinical and genomic data streams to be searched using an evolutionary algorithm approach. To showcase ACE, we assessed which RNA sequencing transcripts were associated with estrogen receptor (ESR1) in the TCGA breast cancer cohort. The analysis revealed already well-established associations with XBP1 and FOXA1, but also identified a strong association with CT62, a potential immunotherapeutic target with few previous associations with breast cancer. In conclusion, ACE can produce results for very large searches in a short time and will serve as an increasingly useful tool for biomarker discovery in the big data era.Significance:ACE uses an evolutionary algorithm approach to perform large searches for associations between any combinations of data in the TCGA database.
NRF2 Activation in Cancer: From DNA to Protein
Authors: Cloer Erica W. , Goldfarb Dennis , Schrank Travis P. , Weissman Bernard E. , Major Michael B. 
Published: February 2019

Abstract
The Cancer Genome Atlas catalogued alterations in the Kelch-like ECH-associated protein 1 and nuclear factor erythroid 2–related factor 2 (NRF2) signaling pathway in 6.3% of patient samples across 226 studies, with significant enrichment in lung and upper airway cancers. These alterations constitutively activate NRF2-dependent gene transcription to promote many of the cancer hallmarks, including cellular resistance to oxidative stress, xenobiotic efflux, proliferation, and metabolic reprogramming. Almost universally, NRF2 activity strongly associates with poor patient prognosis and chemo- and radioresistance. Yet to date, FDA-approved drugs targeting NRF2 activity in cancer have not been realized. Here, we review various mechanisms that contribute to NRF2 activation in cancer, organized around the central dogma of molecular biology (i) at the DNA level with genomic and epigenetic alterations, (ii) at the RNA level including differential mRNA splicing and stability, and (iii) at the protein level comprising altered posttranslational modifications and protein–protein interactions. Ultimately, defining and understanding the mechanisms responsible for NRF2 activation in cancer may lead to novel targets for therapeutic intervention.
Enterovirus Persistence in Cardiac Cells of Patients With Idiopathic Dilated Cardiomyopathy Is Linked to 5’ Terminal Genomic RNA-Deleted Viral Populations With Viral-Encoded Proteinase Activities
Authors: Bouin Alexis , Gretteau Paul-Antoine , Wehbe Michel , Renois Fanny , N’Guyen Yohan , Lévêque Nicolas , Vu Michelle N. , Tracy Steven , Chapman Nora M. , Bruneval Patrick , Fornes Paul , Semler Bert L. , Andreoletti Laurent 
Published: February 2019

Background:
Group B enteroviruses are common causes of acute myocarditis, which can be a precursor of chronic myocarditis and dilated cardiomyopathy, leading causes of heart transplantation. To date, the specific viral functions involved in the development of dilated cardiomyopathy remain unclear.

Methods:
Total RNA from cardiac tissue of patients with dilated cardiomyopathy was extracted, and sequences corresponding to the 5’ termini of enterovirus RNAs were identified. After next-generation RNA sequencing, viral cDNA clones mimicking the enterovirus RNA sequences found in patient tissues were generated in vitro, and their replication and impact on host cell functions were assessed on primary human cardiac cells in culture.

Results:
Major enterovirus B populations characterized by 5’ terminal genomic RNA deletions ranging from 17 to 50 nucleotides were identified either alone or associated with low proportions of intact 5’ genomic termini. In situ hybridization and immunohistological assays detected these persistent genomes in clusters of cardiomyocytes. Transfection of viral RNA into primary human cardiomyocytes demonstrated that deleted forms of genomic RNAs displayed early replication activities in the absence of detectable viral plaque formation, whereas mixed deleted and complete forms generated particles capable of inducing cytopathic effects at levels distinct from those observed with full-length forms alone. Moreover, deleted or full-length and mixed forms of viral RNA were capable of directing translation and production of proteolytically active viral proteinase 2A in human cardiomyocytes.

Conclusions:
We demonstrate that persistent viral forms are composed of B-type enteroviruses harboring a 5’ terminal deletion in their genomic RNAs and that these viruses alone or associated with full-length populations of helper RNAs could impair cardiomyocyte functions by the proteolytic activity of viral proteinase 2A in cases of unexplained dilated cardiomyopathy. These results provide a better understanding of the molecular mechanisms that underlie the persistence of EV forms in human cardiac tissues and should stimulate the development of new therapeutic strategies based on specific inhibitors of the coxsackievirus B proteinase 2A activity for acute and chronic cardiac infections.
Cardiac Sympathetic Denervation Suppresses Atrial Fibrillation and Blood Pressure in a Chronic Intermittent Hypoxia Rat Model of Obstructive Sleep Apnea
Authors: Yang Xuechao , Zhang Linfei , Liu Huan , Shao Yongfeng , Zhang Shijiang 
Published: February 2019

Background

Chronic intermittent hypoxia (
CIH
) is a distinct pathological mechanism of obstructive sleep apnea (
OSA
), which is recognized as an independent risk factor for cardiovascular diseases. The aims of this study were to ascertain whether
CIH
induces atrial fibrillation (
AF
), to determine whether cardiac sympathetic denervation (
CSD
) can prevent it and suppress blood pressure, and to explore the potential molecular mechanisms involved.

Methods and Results

Sixty Sprague‐Dawley male rats were randomly divided into 4 groups: sham,
CSD
,
CIH
,
CIH
+
CSD
. The rats were exposed either to
CIH
8 hours daily or normoxia for 6 weeks. Cardiac pathology and structure were analyzed by hematoxylin and eosin staining and echocardiogram. ECG, blood pressure, body weight, and blood gas were recorded. Connexin 43 and tyrosine hydroxylase were detected by western blot, immunohistochemistry, and immunofluorescence.
CIH
induced atrial remodeling, and increased
AF
inducibility.
CSD
treatment reduced postapneic blood pressure rises and
AF
susceptibility, which could attenuate
CIH
‐associated structural atrial arrhythmogenic remodeling. In addition,
CIH
‐induced sympathetic nerve hyperinnervation and
CSD
treatment reduced sympathetic innervation, which may affect
CIH
‐induced
AF
‐associated sympathovagal imbalance. Connexin 43 was specifically downregulated in
CIH
, whereas
CSD
treatment increased its expression.

Conclusions

These results suggested
CIH
induces atrial remodeling, increases
AF
inducibility, results in sympathetic nerve hyperinnervation, and decreases connexin 43 expression, but
CSD
treatment reduces
AF
susceptibility, postapneic blood pressure increase, sympathetic innervation, and the alteration of Cx43, which may be a key point in the genesis of
CIH
‐induced
AF
.
Axial Muscle Size as a Strong Predictor of Death in Subjects With and Without Heart Failure
Authors: Kumar Anupam , Ansari Bilal A. , Kim Jessica , Suri Arpita , Gaddam Sowmya , Yenigalla Sowjanya , Vanjarapu Jagan M. , Selvaraj Senthil , Tamvada Dheera , Lee Jonathan , Akers Scott R. , Chirinos Julio A. 
Published: February 2019

Background

The impact of skeletal muscle size, quantified using simple noninvasive images routinely obtained during cardiac magnetic resonance imaging studies on mortality in the heart failure (
HF
) population is currently unknown.

Methods and Results

We prospectively enrolled 567 subjects without
HF
(n=364), with
HF
with reduced ejection fraction (n=111), or with HF with preserved ejection fraction (n=92), who underwent a cardiac magnetic resonance imaging. Skeletal muscle cross‐sectional area was assessed with manual tracing of major thoracic muscle groups on axial chest magnetic resonance images. Factor analysis was used to identify a latent factor underlying the shared variability in thoracic muscle cross‐sectional area. Cox regression was used to assess the relationship between these measurements and all‐cause mortality (median follow up, 36.4 months). A higher overall thoracic muscle area factor assessed with principal component analysis was independently associated with lower mortality (standardized hazard ratio, 0.51;
P
<0.0001). The thoracic muscle area factor was predictive of death in subjects with
HF
with preserved ejection fraction,
HF
with reduced ejection fraction, and those without
HF
. Among all muscle groups, the pectoralis major cross‐sectional area was the most representative of overall muscle area and was also the most robust predictor of death. A higher pectoralis major cross‐sectional area predicted a lower mortality (standardized hazard ratio, 0.49;
P
<0.0001), which persisted after adjustment for various confounders (standardized hazard ratio, 0.55;
P
=0.0017).

Conclusions

Axial muscle size, and in particular smaller size of the pectoralis major, is independently associated with higher risk of mortality in patients with and without
HF
. Further work should clarify the role of muscle wasting as a therapeutic target in patients with
HF
.
Comorbid Conditions Explain the Association Between Posttraumatic Stress Disorder and Incident Cardiovascular Disease
Authors: Scherrer Jeffrey F. , Salas Joanne , Cohen Beth E. , Schnurr Paula P. , Schneider F. David , Chard Kathleen M. , Tuerk Peter , Friedman Matthew J. , Norman Sonya B. , van den Berk‐Clark Carissa , Lustman Patrick J. 
Published: February 2019

Background

Posttraumatic stress disorder (
PTSD
) is associated with risk of cardiovascular disease (
CVD
). Biopsychosocial factors associated with
PTSD
likely account for some or all of this association. We determined whether 1, or a combination of comorbid conditions explained the association between
PTSD
and incident
CVD
.

Methods and Results

Eligible patients used 1 of 5 Veterans Health Affairs medical centers distributed across the United States. Data were obtained from electronic health records. At index date, 2519 Veterans Health Affairs (
VA
) patients, 30 to 70 years of age, had
PTSD
diagnoses and 1659 did not. Patients had no
CVD
diagnoses for 12 months before index date. Patients could enter the cohort between 2008 and 2012 with follow‐up until 2015. Age‐adjusted Cox proportional hazard models were computed before and after adjusting for comorbidities. Patients were middle aged (mean=50.1 years,
SD
±11.0), mostly male (87.0%), and 60% were white. The age‐adjusted association between
PTSD
and incident
CVD
was significant (hazard ratio=1.41; 95%
CI
: 1.21–1.63). After adjustment for metabolic conditions, the association between
PTSD
and incident
CVD
was attenuated but remained significant (hazard ratio=1.23; 95%
CI
: 1.06–1.44). After additional adjustment for smoking, sleep disorder, substance use disorder, anxiety disorders, and depression,
PTSD
was not associated with incident
CVD
(hazard ratio=0.96; 95%
CI
: 0.81–1.15).

Conclusions

PTSD
is not an independent risk factor for
CVD
. Physical and psychiatric conditions and smoking that co‐occur with
PTSD
explain why this patient population has an increased risk of
CVD
. Careful monitoring may limit exposure to
CVD
risk factors and subsequent incident
CVD
.