bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Efficient sequential consistency via conflict ordering
Authors: Lin Changhui , Nagarajan Vijay , Gupta Rajiv , Rajaram Bharghava
Published: February 2019

Although the sequential consistency (SC) model is the most intuitive, processor designers often choose to support relaxed memory consistency models for higher performance. This is because SC implementations that match the performance of relaxed memory models require post-retirement speculation and its associated hardware costs. In this paper we propose an efficient approach for enforcing SC without requiring post-retirement speculation. While prior SC implementations guarantee SC by explicitly completing memory operations within a processor in program order, we guarantee SC by completing conflicting memory operations, within and across processors, in an order that is consistent with the program order. More specifically, we identify those conflicting memory operations whose ordering is critical for the maintenance of SC and explicitly order them. This allows us to safely (non-speculatively) complete memory operations past pending writes, thus reducing memory ordering stalls. Our experiments with SPLASH-2 programs show that SC can be achieved efficiently, with performance comparable to RMO (relaxed memory order).
Path-exploration lifting
Authors: Martignoni Lorenzo , McCamant Stephen , Poosankam Pongsin , Song Dawn , Maniatis Petros
Published: February 2019

Processor emulators are widely used to provide isolation and instrumentation of binary software. However they have proved difficult to implement correctly: processor specifications have many corner cases that are not exercised by common workloads. It is untenable to base other system security properties on the correctness of emulators that have received only ad-hoc testing. To obtain emulators that are worthy of the required trust, we propose a technique to explore a high-fidelity emulator with symbolic execution, and then lift those test cases to test a lower-fidelity emulator. The high-fidelity emulator serves as a proxy for the hardware specification, but we can also further validate by running the tests on real hardware. We implement our approach and apply it to generate about 610,000 test cases; for about 95% of the instructions we achieve complete path coverage. The tests reveal thousands of individual differences; we analyze those differences to shed light on a number of root causes, such as atomicity violations and missing security features.
An update-aware storage system for low-locality update-intensive workloads
Authors: Simha Dilip Nijagal , Lu Maohua , Chiueh Tzi-cker
Published: February 2019

Traditional storage systems provide a simple read/write interface, which is inadequate for
low-locality update-intensive
workloads because it limits the disk scheduling flexibility and results in inefficient use of buffer memory and raw disk bandwidth. This paper describes an
update-aware
disk access interface that allows applications to explicitly specify disk update requests and associate with such requests call-back functions that will be invoked when the requested disk blocks are brought into memory. Because call-back functions offer a
continuation
mechanism after retrieval of requested blocks, storage systems supporting this interface are given more flexibility in scheduling pending disk update requests. In particular, this interface enables a simple but effective technique called
Batching mOdifications with Sequential Commit
(BOSC), which greatly improves the sustained throughput of a storage system under low-locality update-intensive workloads. In addition, together with a space-efficient low-latency disk logging technique, BOSC is able to deliver the same durability guarantee as synchronous disk updates. Empirical measurements show that the random update throughput of a BOSC-based B+ tree is more than an order of magnitude higher than that of the same B+ tree implementation on a traditional storage system.
Providing safe, user space access to fast, solid state disks
Authors: Caulfield Adrian M. , Mollov Todor I. , Eisner Louis Alex , De Arup , Coburn Joel , Swanson Steven
Published: February 2019

Emerging fast, non-volatile memories (e.g., phase change memories, spin-torque MRAMs, and the memristor) reduce storage access latencies by an order of magnitude compared to state-of-the-art flash-based SSDs. This improved performance means that software overheads that had little impact on the performance of flash-based systems can present serious bottlenecks in systems that incorporate these new technologies. We describe a novel storage hardware and software architecture that nearly eliminates two sources of this overhead: Entering the kernel and performing file system permission checks. The new architecture provides a private, virtualized interface for each process and moves file system protection checks into hardware. As a result, applications can access file data without operating system intervention, eliminating OS and file system costs entirely for most accesses. We describe the support the system provides for fast permission checks in hardware, our approach to notifying applications when requests complete, and the small, easily portable changes required in the file system to support the new access model. Existing applications require no modification to use the new interface. We evaluate the performance of the system using a suite of microbenchmarks and database workloads and show that the new interface improves latency and bandwidth for 4 KB writes by 60% and 7.2x, respectively, OLTP database transaction throughput by up to 2.0x, and Berkeley-DB throughput by up to 5.7x. A streamlined asynchronous file IO interface built to fully utilize the new interface enables an additional 5.5x increase in throughput with 1 thread and 2.8x increase in efficiency for 512 B transfers.
Dual-specificity phosphatase 4 is upregulated during skeletal muscle atrophy and modulates extracellular signal-regulated kinase activity
Authors: Haddock Ashley N. , Labuzan Sydney A. , Haynes Amy E. , Hayes Caleb S. , Kakareka Karina M. , Waddell David S.
Published: February 2019

Skeletal muscle atrophy results from disparate physiological conditions, including denervation, corticosteroid treatment, and aging. The purpose of this study was to describe and characterize the function of dual-specificity phosphatase 4 (Dusp4) in skeletal muscle after it was found to be induced in response to neurogenic atrophy. Quantitative PCR and Western blot analysis revealed that Dusp4 is expressed during myoblast proliferation but rapidly disappears as muscle cells differentiate. The Dusp4 regulatory region was cloned and found to contain a conserved E-box element that negatively regulates Dusp4 reporter gene activity in response to myogenic regulatory factor expression. In addition, the proximal 3′-untranslated region of Dusp4 acts in an inhibitory manner to repress reporter gene activity as muscle cells progress through the differentiation process. To determine potential function, Dusp4 was fused with green fluorescent protein, expressed in C2C12 cells, and found to localize to the nucleus of proliferating myoblasts. Furthermore, Dusp4 overexpression delayed C2C12 muscle cell differentiation and resulted in repression of a MAP kinase signaling pathway reporter gene. Ectopic expression of a Dusp4 dominant negative mutant blocked muscle cell differentiation and attenuated MAP kinase signaling by preferentially targeting the ERK1/2 branch, but not the p38 branch, of the MAP kinase signaling cascade in skeletal muscle cells. The findings presented in this study provide the first description of Dusp4 in skeletal muscle and suggest that Dusp4 may play an important role in the regulation of muscle cell differentiation by regulating MAP kinase signaling.
STF-62247 accumulates in lysosomes and blocks late stages of autophagy to selectively target von Hippel-Lindau-inactivated cells
Authors: Bouhamdani Nadia , Comeau Dominique , Cormier Kevin , Turcotte Sandra
Published: February 2019

Autophagy is a highly conserved, homeostatic process by which cytosolic components reach lysosomes for degradation. The roles played by different autophagic processes in cancer are complex and remain cancer type and stage dependent. Renal cell carcinoma (RCC) is the most common subtype of kidney cancer and is characterized by the inactivation of the von Hippel-Lindau (VHL) tumor suppressor. Our previous study identified a small compound, STF-62247, as an autophagy-modulating molecule causing selective cytotoxicity for VHL-inactivated cells. This present study investigates the effects of STF-62247 specifically on the macroautophagic flux to better characterize its mechanism of action in RCC. Our results clearly demonstrate that this compound is a potent blocker of late stages of autophagy. We show that inhibiting autophagy by CRISPR knockouts of autophagy-related genes rendered VHL-deficient cells insensitive to STF-62247, uncovering the importance of the autophagic pathway in STF-selective cell death. By exploiting the autofluorescence of STF-62247, we pinpointed its cellular localization to lysosomes. Finally, in response to prolonged STF treatments, we show that VHL-proficient cells are able to surmount the block in late stages of autophagy by restoring their lysosome numbers. Conversely, an increase in autophagic vesicles accompanied by a time-dependent decrease in lysosomes was observed in VHL-deficient cells. This is the first mechanistic study investigating STF-62447’s effects on the autophagic flux in RCC. Importantly, our study reclassifies STF-62247 as a blocker of later stages of autophagy and highlights the possibility of blocking this process through lysosome disruption in VHL-mutated RCCs.
The nephron-arterial network and its interactions
Authors: Marsh Donald J. , Postnov Dmitry D. , Sosnovtseva Olga V. , Holstein-Rathlou Niels-Henrik
Published: February 2019

Tubuloglomerular feedback and the myogenic mechanism form an ensemble in renal afferent arterioles that regulate single-nephron blood flow and glomerular filtration. Each mechanism generates a self-sustained oscillation, the mechanisms interact, and the oscillations synchronize. The synchronization generates a bimodal electrical signal in the arteriolar wall that propagates retrograde to a vascular node, where it meets similar electrical signals from other nephrons. Each signal carries information about the time-dependent behavior of the regulatory ensemble. The converging signals support synchronization of the nephrons participating in the information exchange, and the synchronization can lead to formation of nephron clusters. We review the experimental evidence and the theoretical implications of these interactions and consider additional interactions that can limit the size of nephron clusters. The architecture of the arterial tree figures prominently in these interactions.
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.
Application of Peroxide Curing Systems in Cross-Linking of Rubber Magnets Based on NBR and Barium Ferrite
Authors: Kruželák Ján , Kvasničáková Andrea , Medlenová Elena , Dosoudil Rastislav , Hudec Ivan
Published: February 2019

Rubber magnetic composites were prepared by incorporation of barium ferrite in constant amount—50 phr into acrylonitrile-butadiene rubber. Dicumyl peroxide as the curing agent was used for cross-linking of rubber magnets alone, or in combination with four different types of co-agents. The main aim was to examine the influence of curing system composition on magnetic and physical-mechanical properties of composites. The cross-link density and the structure of the formed cross-links were investigated too. The results demonstrated that the type and amount of the co-agent had significant influence on cross-link density, which was reflected in typical change of physical-mechanical properties. The tensile strength increased with increasing amount of co-agents, which can be attributed to the improvement of adhesion and compatibility on the interphase filler-rubber due to the presence of co-agents. Magnetic characteristics were found not to be influenced by the curing system composition. The application of peroxide curing systems consisting of organic peroxide and co-agents leads to the preparation of rubber magnets with not only good magnetic properties but also with improved physical-mechanical properties, which could broaden the sphere of their application uses.
Effects of Lightly Burnt MgO Expansive Agent on the Deformation and Microstructure of Reinforced Concrete Wall
Authors: Yu Lanqing , Deng Min , Mo Liwu , Liu Jinxin , Jiang Feifei
Published: February 2019

Compensation for shrinkages with three kinds of lightly burnt MgO expansive agent (LBMEA) is used in a reinforced concrete wall poured in the summer. Influences of the internal temperature history on the expansion of concrete and the microstructure of cement paste containing LBMEA were investigated. The results showed that LBMEA exhibited significant expansion around the end of the fall temperature stage; then, the expansion rate declined obviously, and concrete containing LBMEA with low hydration reactivity (140 s and 220 s) showed larger expansion than LBMEA with high hydration reactivity (60 s). Microstructural analysis indicated that brucite preferentially forms in the pores in cement paste containing LBMEA with high reactivity, but brucite mainly grows on the surface of the MgO particles in cement paste containing LBMEA with low reactivity during the early age. Paste containing LBMEA with low reactivity showed a larger volume of single brucite crystal than LBMEA with high reactivity, which further led to larger expansion in the latter than the former. The results revealed the expansion process of LBMEA and can help engineers select suitable LBMEA for application to actual engineering.
Combined Synchronization among Three Inconsistent Networks
Authors: Chai Yuan , Zhu Xiaojing , Cai Jingjing
Published: February 2019

A new type of network-combination synchronization is proposed between two drive networks, small-world and scale-free, and one response community network based on the model of multiple system combination. According to Lyapunov Stability Theorem, combined controllers are designed to control three disparate networks with different topological structures. A realistic combination model of multiple inhomogeneous networks and a universal controller are devised in the combination design. The paper is characterized by two parts of one response community network loaded from the combined signals of two drive networks. Numerical simulations are presented to show the full and partial control of the proposed method.
Safed Musli (Chlorophytum borivilianum L.) Callus-Mediated Biosynthesis of Silver Nanoparticles and Evaluation of their Antimicrobial Activity and Cytotoxicity against Human Colon Cancer Cells
Authors: Huang Fengchang , Long Yaxin , Liang Qingqing , Purushotham Boregowda , Swamy Mallappa Kumara , Duan Yongqing
Published: February 2019

With the advancement of nanobiotechnology, eco-friendly approaches of plant-mediated silver nanomaterial (AgNP) biosynthesis have become more attractive for biomedical applications. The present study is a report of biosynthesizing AgNPs using Chlorophytum borivilianum L. (Safed musli) callus extract as a novel source of reducing agent. AgNO3 solution challenged with the methanolic callus extract displayed a change in color from yellow to brown owing to the bioreduction reaction. Further, AgNPs were characterized by using UV–visible spectrophotometry, X-ray Diffraction (XRD), Atomic Force Microscopy (AFM), and Fourier Transform Infrared Spectroscopy (FTIR). UV–vis spectrum revealed the surface plasmon resonance property of AgNPs at around 450 nm. XRD pattern with typical peaks indicated the face-centered cubic nature of silver. AFM analysis confirmed the existence of spherical-shaped and well-dispersed AgNPs having an average size of 52.0 nm. Further, FTIR analysis confirmed the involvement of different phytoconstituents of the callus extract role in the process of bioreduction to form nanoparticles. The AgNPs were more efficient in inhibiting the tested pathogenic microbes, namely, Pseudomonas aeruginosa, Bacillus subtilis, Methicillin-resistant Escherichia coli, Staphylococcus aureus, and Candida albicans compared to callus extract. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay confirmed the cytotoxic property of AgNPs against human colon adenocarcinoma cell line (HT-29) in a dose-dependent manner. At higher concentrations of 500 μg/mL AgNPs, the cell viability was observed to be only 7% after 24 hours with IC50 value of 254 μg/mL. Therefore, these AgNPs clearly endorse the manifold potential to be used in various biomedical applications in the near future.
Molecular Patterns of MEFV Gene Mutations in Egyptian Patients with Familial Mediterranean Fever: A Retrospective Cohort Study
Authors: Mansour Amal R. , El-Shayeb Ayman , El Habachi Nihal , Khodair Mohamad A. , Elwazzan Doaa , Abdeen Nermeen , Said Marwa , Ebaid Riham , ElShahawy Noha , Seif Amr , Zaki Nadia
Published: February 2019

Background. Familial Mediterranean Fever (FMF) is a hereditary autosomal recessive disease which is mainly seen in the Turks, Armenians, Arabs, and Jews. It is characterized by recurrent episodes of fever, polyserositis, and rash. MEFV gene, encoding pyrin protein, is located on the short arm of chromosome 16. FMF is associated with a broad mutational spectrum in this gene. Certain mutations are more common in particular ethnic groups. To date, different mutations of MEFV were observed in studies carried out in different regions worldwide. However, most of these studies did not extensively investigate the Egyptian population, in spite of the high prevalence of FMF in this geographical region. Aim. To identify the frequency of MEFV gene mutations among the patients who presented with FMF like symptoms and, to characterize the different genetic mutations and their association with increased Amyloid A among Egyptian patients. Methods. FMF Strip Assay (Vienna Lab Diagnostics, Vienna, Austria) was used. This test is based on reverse hybridization of biotinylated PCR products on immobilized oligonucleotides for mutations and controls in a parallel array of allele-specific oligonucleotides. Results. Among the 1387 patients presenting with signs and symptoms suggestive of FMF, 793 (57.2%) were of undefined mutations, whereas 594 had MEFV gene mutations. 363 patients (26.2%) were heterozygous mutants, 175 patients (12.6%) were compound heterozygous mutants, and 56 patients (4%) were homozygous mutants. The most commonly encountered gene mutations in heterozygous and homozygous groups were E148Q (38.6%), M694I (18.1%), and V726A (15.8%). The most commonly encountered gene mutations in the compound heterozygous groups were E148Q+M694I observed in 20.6% of the patients, followed by M694I+V726A and M6801+V726A found in 18.9% and 11.4 %, respectively. The most commonly encountered gene mutation associated with abdominal pain, fever, and high serum Amyloid A was E148Q allele (37.5%). Conclusions. Unlike all previous publications, E148Q allele was found to be the most frequent in the studied patients. Moreover, this allele was associated with increased Amyloid A. 793 patients were free of the 12 studied Mediterranean mutations, which implies the necessity to perform future sequencing studies to reveal other mutations.
Effects of Habitat Types on Macroinvertebrates Assemblages Structure: Case Study of Sun Island Bund Wetland
Authors: Khudhair Nagam , Yan Cai , Liu Manhong , Yu Hongxian
Published: February 2019

Sun Island Bund Wetland (SIBW) is a river floodplain wetland located at the south part of Heilongjiang Province in Northeast China. An investigation of the influence of habitat type on macroinvertebrates assemblages structure was conducted in July 2016. Nine (9) sampling sites were selected based on sediment type, water condition, and aquatic vegetation type. Macroinvertebrates attributes including density, biomass, and four diversity indices (Simpson diversity index, Margalef richness index, Shannon-Weiner index, and Pielou evenness index) were assessed. A total of 53 taxa were collected during the study period, with the highest density dominated being from aquatic insects and gastropods.Bellamya purificataandExopalaemon annandaleiwere the most dominant among all the species. The results showed that the assemblages structure of macroinvertebrates in different habitats was significantly different. Also, the results with PCA showed that the higher values of invertebrates density, biomass, diversity indices, and species richness had a greater association with the habitat types of silt-humus sediment, closed lentic area, and submerged-flouting-emergent vegetation.
Functional Connectivity Pattern Analysis Underlying Neural Oscillation Synchronization during Deception
Authors: Liu Peng , Shen Hongkui , Ji Shumei
Published: February 2019

To characterize system cognitive processes during deception, event-related coherence was computed to investigate the functional connectivity among brain regions underlying neural oscillation synchronization. In this study, 15 participants were randomly assigned to honesty or deception groups and were instructed to tell the truth or lie when facing certain stimuli. Meanwhile, event-related potential signals were recorded using a 64-channel electroencephalography cap. Event-related coherence was computed separately in four frequency bands (delta (1-3.5 Hz), theta (4-7 Hz), alpha (8-13 Hz), and beta (14-30 HZ)) for the long-range intrahemispheric electrode pairs (F3P3, F4P4, F3T7, F4T8, F3O1, and F4O2). The results indicated that deceptive responses elicited greater connectivities in the frontoparietal and frontotemporal networks than in the frontooccipital network. Furthermore, the deception group displayed lower values of coherence in the frontoparietal electrode pairs in the alpha and beta bands than the honesty group. In particular, increased coherence in the delta and theta bands on specific left frontoparietal electrode pairs was observed. Additionally, the deception group exhibited higher values of coherence in the delta band and lower values of coherence in the beta band on the frontotemporal electrode pairs than did the honesty group. These data indicated that the active cognitive processes during deception include changes in ensemble activities between the frontal and parietal/temporal regions.
Robust Stabilization of Discrete‐Time Switched Periodic Systems with Time Delays
Authors: Dong Yali , Hao Jing , Yao Yonghong , Wang Huimin
Published: February 2019

This paper studies the problems of robust stability and robust stabilization for discrete‐time switched periodic systems with time‐varying delays and parameter uncertainty. We obtain the novel sufficient conditions to ensure the switched system is robustly asymptotically stable in terms of linear matrix inequalities. To obtain these conditions, we utilize a descriptor system method and introduce a switched Lyapunov‐Krasovskii functional. The robust stability results are then extended to solve problems of robust stabilization via periodic state feedback. Novel sufficient conditions are established to ensure that the uncertain switched periodic system is robustly asymptotically stabilizable. Finally, we give two numerical examples to illustrate the effectiveness of our method.
Coordinating Real-Time Serial Cooperative Work by Cuing the Order in the Case of Theatrical Performance Practice
Authors: Sasaki Kosuke , Inoue Tomoo
Published: February 2019

Our goal is to facilitate real-time serial cooperative work. In real-time serial cooperative work, the order of subtasks is important because a failure of the order leads to a failure of the whole task. So, coordinating the order of workers’ subtasks is necessary to smoothly accomplish the tasks. In this paper, we propose a method that uses vibration to present the action order and coordinate the orders. We conducted a user study to verify the effectiveness of the method in theatrical performance practice, which was an example of real-time serial cooperative work. As a result, order coordination reduced mistakes in the order of speech and action and in the contents of lines and action. This result suggests that order coordination can improve real-time serial cooperative work.
Influence of Flaw Inclination Angle on Unloading Responses of Brittle Rock in Deep Underground
Authors: Chen Zhenghong , Li Xibing , Weng Lei , Wang Shaofeng , Dong Longjun
Published: February 2019

Excavation unloading is a primary stress condition for engineering rock mass in deep underground. Based on the unloading stress condition during the excavation operation, this paper employed a distinct element method (DEM) to simulate the unloading responses of intact and preflawed rock specimens. The simulation results revealed that the unloading failure strength, unloading damage thresholds, and cracking characteristics were largely dependent on the inclination angle α of the preflaws. With the increase in the flaw inclination angle, the unloading failure strength of a preflawed specimen exhibited a sigmoidal curve increasing trend, and it decreased by 5.5%-20% compared to the unloading failure strength of an intact specimen. Based on the crack accumulation in specimens, three damage thresholds were identified under unloading condition and two damage thresholds σci and σdi were found to be increased with the increase in the flaw inclination angle. Furthermore, when the flaw inclination angle was smaller, cracks were initiated around the preflaws, and there were obvious axial splitting cracks in the failure modes of preflawed specimens, while axial splitting cracks were few in the preflawed specimen with a larger flaw inclination angle and none in the intact specimen. These unloading responses indicate that inducing preflaws can reliably reduce the unloading failure strength and promote the cracking process of hard rock during an excavation unloading process. Moreover, inducing preflaws with a smaller inclination angle (e.g., vertical to the unloading direction) will be more helpful for the unloading failure and rock cracking during an excavation unloading process.
Safety and Efficacy of Triple Antithrombotic Therapy with Dabigatran versus Vitamin K Antagonist in Atrial Fibrillation Patients: A Pilot Study
Authors: Russo Vincenzo , Rago Anna , Proietti Riccardo , Attena Emilio , Rainone Carmen , Crisci Mario , Papa Andrea Antonio , Calabrò Paolo , D’Onofrio Antonio , Golino Paolo , Nigro Gerardo
Published: February 2019

Background. Combination of dual antiplatelet (DAPT) and oral anticoagulation therapy is required to decrease cardioembolic stroke and stent thrombosis risk in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS). We compared the safety and efficacy of dabigatran etexilate with vitamin K antagonist (VKA), in combination with DAPT (aspirin plus clopidogrel) treatment in AF patients who underwent percutaneous coronary intervention (PCI) with stenting for ACS. Methods. Consecutive nonvalvular AF patients who received twice-daily dabigatran 110 mg (n = 389) or VKA (n = 510) and DAPT were included. Primary endpoints were major bleeding (safety) and the composite of ischemic stroke, systemic embolism, and myocardial infarction (efficacy). The secondary efficacy endpoint was hospitalization for cardiovascular disease. Results. After propensity score matching, comparative treatment groups comprised 175 dabigatran recipients and 175 VKA recipients. The cumulative incidence of major bleeding was lower in the dabigatran group (2.3%) compared with the VKA group (10.3%) with a hazard ratio (HR) of 4.81 [95% confidence interval (CI) 1.6–14.2, p < 0.005]. The cumulative incidence of thromboembolic events with dabigatran was slightly higher (8.0%) than with VKA (6.85%), but not statistically significantly so (0.8, 0.39–1.8; p = 0.6). Cumulative incidence of hospitalization for cardiovascular disease was lower with dabigatran (10.3%) compared with VKA (20.6%) treatment (2.2, 1.25–3.8; p < 0.006). Conclusion. Dabigatran at the dose used for stroke prevention appears safer than VKA and maintains a similar efficacy profile, when used with DAPT, in AF patients who have undergone PCI with stenting for ACS.
NLRP3 Inflammasome Is Involved in Calcium-Sensing Receptor-Induced Aortic Remodeling in SHRs
Authors: Zhang Xin , Hong Siting , Qi Shuhan , Liu Wenxiu , Zhang Xiaohui , Shi Zhiyu , Chen Wenjia , Zhao Meng , Yin Xinhua
Published: February 2019

Increasing evidence suggests that the NLRP3 (nucleotide oligomerization domain-like receptor family, pyrin domain containing 3) inflammasome participates in cardiovascular diseases. However, its role and activation mechanism during hypertension remains unclear. In this study, we tested the role and mechanism of calcium-sensing receptor (CaSR) in NLRP3 inflammasome activation during hypertension. We observed that the expressions of CaSR and NLRP3 were increased in spontaneous hypertensive rats (SHRs) along with aortic fibrosis. In vascular smooth muscle cells (VSMCs), the activation of NLRP3 inflammasome associated with CaSR and collagen synthesis was induced by angiotensin II (Ang II). Furthermore, inhibition of CaSR and NLRP3 inflammasome attenuated proinflammatory cytokine release, suggesting that CaSR-mediated activation of the NLRP3 inflammasome may be a therapeutic target in aortic dysfunction and vascular inflammatory lesions.
Bioactive Characteristics and Storage of Salt Mixtures Seasoned with Powdered Cereal Sprouts
Authors: Šaponjac Vesna Tumbas , Ćetković Gordana , Čanadanović-Brunet Jasna , Mandić Anamarija , Šeregelj Vanja , Vulić Jelena , Stajčić Sladjana
Published: February 2019

Sprouting is a process that can improve nutritional and beneficial properties of seeds. This work studies the design of the new healthier product salt seasoned with freeze-dried powdered cereal sprouts. The cereal sprouts mixture (SM), including barley sprouts (BS), oat sprouts (OS), and wheat sprouts (WS), was optimized in terms of total phenolic content (TPh) and antioxidant capacity (AC). The sprouts mixture with optimal features (OSM), composed of 92.9% BS, 0% OS, and 7.1% WS, had 482.82 mg GAE/100 g of polyphenols and 797.97 µmol TE/100 g antioxidant capacity. HPLC analysis showed that the most abundant phenolic compound in OMS was gallic acid (94.27 mg/100 g). OSM was mixed with salt in different ratios (1 : 1, 1 : 2, and 1 : 3) and stored in transparent and amber bottles for six months. Colour, TPh, and AC retention of seasoned salts and OSM was significantly better (p<0.05) preserved in amber bottles during storage, protected from light. The sprout content was in correlation with TPh and AC retention and colour change. These results suggest that cereal sprouts can be used as a safe ingredient for food products such as seasoned salt, adding value to the basic daily diet with no changes in dietary habits.
Monitoring the Interannual Spatiotemporal Changes in the Land Surface Thermal Environment in Both Urban and Rural Regions from 2003 to 2013 in China Based on Remote Sensing
Authors: Li Yuanzheng , Wang Lan , Zhang Liping , Wang Qing
Published: February 2019

The thermal environment is closely related to human well-being. Diurnal and seasonal variations in surface urban heat islands (SUHIs) have been extensively studied. Nevertheless, interannual changes in SUHIs as well as in land surface temperatures (LSTs) in cities and their corresponding villages remain poorly understood, particularly using data from several continuous years to analyse change rates and corresponding significance levels. Using Aqua/Terra moderate resolution imaging spectroradiometer (MODIS) data for 2003–2013, we explored not only the interannual changes in annual and seasonal mean LSTs in rural and urban regions which were identified based on modified criteria, but also the SUHI intensities (SUHIIs) for these cities. The results showed that most of LSTs and SUHIIs did not change significantly (p≥0.05). Their changes exhibited clear spatiotemporal agglomeration and variation laws. The rural region LST change rates, which exhibited significant changes, were generally highest in the summer, with most of values of 0.1–0.5°C (yr−1) during the daytime across China, except for the Xinjiang autonomous regions, and 0.1–0.2°C (yr−1) during the night-time. The rates were lowest in the winter, with most of values of −0.4 to −0.1°C (yr−1). The rates of daytime SUHIIs with significant changes were generally highest in the summer, with most of values of 0.1–0.3°C (yr−1), and lowest in the winter, even with most of values of −0.4 to −0.1°C (yr−1) in northern central China. During the night-time, most of rates were 0.0–0.1°C (yr−1). In China, most of the changes in the surface thermal environment were harmful to humans at both large national and local urban scales. The changes could lower thermal comfort levels, harm human health, affect human reproduction rates and lives, and increase the energy consumed for refrigeration or heating, thereby increase emissions of greenhouse gases.
Inhibition of HDAC3 Ameliorates Cerebral Ischemia Reperfusion Injury in Diabetic Mice In Vivo and In Vitro
Authors: Zhao Bo , Yuan Quan , Hou Jia-bao , Xia Zhong-yuan , Zhan Li-ying , Li Mei , Jiang Meng , Gao Wen-wei , Liu Lian
Published: February 2019

Background. A substantial increase in histone deacetylase 3 (HDAC3) expression is implicated in the pathological process of diabetes and stroke. However, it is unclear whether HDAC3 plays an important role in diabetes complicated with stroke. We aimed to explore the role and the potential mechanisms of HDAC3 in cerebral ischemia/reperfusion (I/R) injury in diabetic state.Methods. Diabetic mice were subjected to 1 h ischemia, followed by 24 h reperfusion. PC12 cells were exposed to high glucose for 24 h, followed by 3 h of hypoxia and 6 h of reoxygenation (H/R). Diabetic mice received RGFP966 (the specific HDAC3 inhibitor) or vehicle 30 minutes before the middle cerebral artery occlusion (MCAO), and high glucose-incubated PC12 cells were pretreated with RGFP966 or vehicle 6 h before H/R.Results. HDAC3 inhibition reduced the cerebral infarct volume, ameliorated pathological changes, improved the cell viability and cytotoxicity, alleviated apoptosis, attenuated oxidative stress, and enhanced autophagy in cerebral I/R injury model in diabetic state in vivo and in vitro. Furthermore, we found that the expression of HDAC3 was remarkably amplified, and the Bmal1 expression was notably decreased in diabetic mice with cerebral I/R, whereas this phenomenon was obviously reversed by RGFP966 pretreatment.Conclusions. These results suggested that the HDAC3 was involved in the pathological process of the complex disease of diabetic stroke. Suppression of HDAC3 exerted protective effects against cerebral I/R injury in diabetic state in vivo and in vitro via the modulation of oxidative stress, apoptosis, and autophagy, which might be mediated by the upregulation of Bmal1.
BuShenKangShuai Tablet Alleviates Hepatic Steatosis via Improving Liver Adiponectin Resistance in ApoE-/- Mice
Authors: Pang Shu-chao , Wang Shuo , Chen Mei-ling , Zhang Jun-ping , Wang Yuan-yuan , Jia Hui-yun , Bi Li-yuan , Wang Hui
Published: February 2019

BuShenKangShuai tablet (BSKS) is a Chinese herbal compound, which has been used to treat nonalcoholic fatty liver disease and cardiovascular diseases in clinic for over four decades. This study intends to explore whether BSKS administration can alleviates hepatic steatosis via improving liver adiponectin resistance in ApoE-/- mice. ApoE-/- mice were fed with western-type diet for 6 weeks and then were administrated with BSKS or atorvastatin for 6 weeks by gavage, and then blood and liver were collected for analysis. The results showed that BSKS attenuated hepatic steatosis, decreased blood lipids, and increased the serum level of adiponectin. We also found that adiponectin resistance in the liver was improved by BSKS, while the expression of TLR4 and NF-κB p65 was inhibited, followed by the suppression of proinflammatory mediators of TNF-α. Our data provided evidence that BSKS was able to alleviate hepatic steatosis in vivo. The underlying mechanism of BSKS was focused on improving liver adiponectin resistance, thereby regulating dyslipidemia and inhibiting inflammatory signaling pathway.
Development of a Dietary Factor Assessment Tool for Evaluating Associations between Visceral Fat Accumulation and Major Nutrients in Japanese Adults
Authors: Takase Hideto , Sakane Naoki , Morimoto Toshihisa , Uchida Takanobu , Mori Kenta , Katashima Mitsuhiro , Katsuragi Yoshihisa
Published: February 2019

Background and Objectives. The increased prevalence of metabolic syndrome necessitates the establishment of tools for evaluating dietary factors associated with visceral fat accumulation and preventing visceral fat obesity. Here, we aimed to develop a dietary factor assessment tool for evaluating visceral fat accumulation. Methods. We conducted a dietary habit questionnaire survey and visceral fat measurement by bioelectrical impedance analysis in 11,438 adults (Survey 1) and a dietary habit questionnaire survey and dietary assessment based on 3-day meal records in 579 adults (Survey 2). Dietary habit factors were identified by factor analysis with varimax rotation, and their relationship with visceral fat accumulation and major nutrients were analyzed. Results. Factor analysis of the dietary habit questionnaire revealed the following five main dietary factors: “Appetite (15 questions),” “Healthy food choice (5 questions),” “Sedentary behavior (6 questions),” “Calorie restriction (5 questions),” and “Irregular mealtime (4 questions).” “Appetite” correlated positively with visceral fat accumulation and energy intake mainly from carbohydrate. “Healthy food choice” correlated negatively with visceral fat accumulation and positively with the protein/fat ratio, dietary fiber/carbohydrate ratio, and N-3 fatty acid/fat ratio. Dietary guidance to modify excess energy intake and increase nutritional balance might be effective toward preventing visceral fat accumulation. Conclusions. The dietary factor assessment tool developed in this study can be used to diagnose problems related to dietary habits and provide guidance for dietary modifications aimed at preventing visceral fat accumulation.
Survival and Behavior of Encapsulated Probiotics (Lactobacillus plantarum) in Calcium-Alginate-Soy Protein Isolate-Based Hydrogel Beads in Different Processing Conditions (pH and Temperature) and in Pasteurized Mango Juice
Authors: Praepanitchai Ong-Ard , Noomhorm Athapol , Anal Anil Kumar
Published: February 2019

Hybrid alginate-soy protein isolate-based hydrogel beads were prepared and evaluated to enhance the survival of the encapsulated probiotics (Lactobacillus plantarum) during heat processing to incorporate in mango juice. The solutions of sodium alginate-soy protein isolate (SA-SPI) with probiotic cells were dropped into the gelation bath containing calcium chloride (3% w/v) solution to develop various types of hydrogel beads. The level of survival of probiotics in encapsulated beads under acidic conditions (pH 2, 3, and 6.5) and bile salt (0.5 and 1.0% w/v) was evaluated. The survival of the encapsulated probiotics to thermal processing was evaluated by treating the beads in saline solution (0.9% w/v) at 30, 50, 63, and 72°C. The encapsulated probiotic bacteria were found alive even after treatment at 72°C for 90 s. Most of the free cells did not survive at the temperature higher than 50°C and very low pH (pH 2 and 3). The survival of probiotic cells was found higher with the hybrid hydrogel beads containing alginate and soy protein isolate (1:8 w/w). Furthermore, mango juice fortified with encapsulated L. plantarum in hydrogel beads was subjected to thermal pasteurization at 72°C for 90 s.
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

Modern 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

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.
Kinetics of Hepatic Volume Evolution and Architectural Changes after Major Resection in a Porcine Model
Authors: Bekheit Mohamed , Bucur Petru O. , Audebert Chloe , Miquelestorena-Standley Elodie , Vignon-Clementel Irene , Vibert Eric
Published: February 2019

Background: The hepatic volume gain following resection is essential for clinical recovery. Previous studies have focused on cellular regeneration. This study aims to explore the rate of hepatic regeneration of the porcine liver following major resection, highlighting estimates of the early microarchitectural changes that occur during the cellular regeneration. Methods: Nineteen large white pigs had 75% resection with serial measurements of the hepatic volume, density, blood flow, and architectural changes. Results: The growth rate initially was 45% per day, then rapidly decreased and was accompanied by a similar pattern of hepatic fat deposition. The architectural changes showed a significant increase in the Ki67 expression (p < 0.0001) in the days following resection with a peak on the 2nd day and nearly normalized on day 7. The expression of CD31 increased significantly on the 2nd and 3rd days compared to the pre-resection samples (p = 0.03). Hepatic artery flow per liver volume remained at baseline ranges during regeneration. Portal flow per liver volume increased after liver resection (p < 0.001), was still elevated on the 1st postoperative day, then decreased. Correlations were significantly negative between the hepatic volume increase on day 3 and the hepatic oxygen consumption and the net lactate production at the end of the procedure (r = –0.82, p = 0.01, and r = –0.70, p = 0.03). Conclusion: The volume increase in the first days – a fast process – is not explained by cellular proliferation alone. The liver/body weight ratio is back to 50% of the preoperative value after 3 days to close to 100% volume regain on days 10–15.