bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of the artificial sweeteners on glucose metabolism in healthy adults: a randomized, double-blinded, crossover clinical trial
Authors: Ahmad Samar Y. , Friel James K. , MacKay Dylan S.
Published: November 2019

This study aimed to determine the effect of pure forms of sucralose and aspartame, in doses reflective of common consumption, on glucose metabolism. Healthy participants consumed pure forms of a non-nutritive sweetener (NNS) that were mixed with water and standardized to doses of 14% (0.425 g) of the acceptable daily intake (ADI) for aspartame and 20% (0.136 g) of the ADI for sucralose every day for 2 weeks. Blood samples were collected and analyzed for glucose, insulin, active glucagon-like peptide-1 (GLP-1), and leptin. Seventeen participants (10 females and 7 males; age, 24 ± 6.8 years; body mass index, 22.9 ± 2.5 kg/m2) participated in the study. The total area under the curve values of glucose, insulin, active GLP-1 and leptin were similar for the aspartame and sucralose treatment groups compared with the baseline values in healthy participants. There was no change in insulin sensitivity after NNS treatment compared with the baseline values. These findings suggest that daily repeated consumption of pure sucralose or aspartame for 2 weeks had no effect on glucose metabolism among normoglycaemic adults. However, these results need to be tested in studies with longer durations.

Novelty Daily consumption of pure aspartame or sucralose for 2 weeks had no effect on glucose metabolism. Daily consumption of pure aspartame or sucralose for 2 weeks had no effect on insulin sensitivity among healthy adults.
Discrete element model (DEM) simulations of cone penetration test (CPT) measurements and soil classification
Authors: Khosravi A. , Martinez A. , DeJong J.T.
Published: November 2019

This paper presents a study on the simulation of cone penetration tests (CPTs) using the discrete element model (DEM) method. This study’s main objective is to investigate the effect of different modeling parameters and simulation configurations on the ability of three-dimensional DEM simulations to replicate realistic CPT tip resistance (qc) and friction sleeve shear stress (fs) measurements. The CPT tests were simulated in virtual calibration chambers (VCCs) containing particles calibrated to model the behavior of sand. The parameters investigated included the granular assembly properties, interparticle contact parameters, particle–probe interface characteristics, and simulation configuration. Results indicate that the interparticle contact parameters, boundary conditions, and void ratio have an important role in the tip resistance and friction sleeve measurements obtained from the simulations. Particle-level interactions such as particle displacements and rotations and interparticle contact forces were analyzed throughout to provide insight into the differences in measured CPT response. Interpretation of the qcand fsmeasurements using soil behavior type (SBT) charts for soil classification indicates that the simulated CPT response is representative of the response of coarse-grained soils measured during field soundings. Analysis of results within the SBT framework can provide insight into the influence of soil particle properties on CPT-based soil classification.
Plant minus air temperature corresponds to different responses to water stress in wheat, canola, and chickpea grown in the semiarid Canadian prairie
Authors: Angadi Sangu , Cutforth Herb , McConkey Brian
Published: November 2019

The difference between plant and air temperature (PT–AT) is a good indicator of water stress. PT–AT for chickpea was negatively correlated to water deficit and air temperature and positively correlated to wind; for wheat, PT–AT was positively correlated to water deficit, air temperature and solar energy; for canola, PT–AT was not correlated to the environment. Chickpea maintained positive turgor at the expense of water content and therefore more water was available for transpirational cooling. Wheat maintained water content at the expense of turgor and therefore there was little water available for transpirational cooling. For canola, PT–AT was affected by parameters other than environment.
Quantum thermodynamics in a static de Sitter space-time and initial state of the universe
Authors: Musmarra Juan Ignacio , Bellini Mauricio
Published: November 2019

Using Relativistic Quantum Geometry we study back-reaction effects of space-time inside the causal horizon of a static de Sitter metric, in order to make a quantum thermodynamical description of space-time. We found a finite number of discrete energy levels for a scalar field from a polynomial condition of the confluent hypergeometric functions expanded around $$r=0$$r=0. As in the previous work, we obtain that the uncertainty principle is valid for each energy level on sub-horizon scales of space-time. We found that temperature and entropy are dependent on the number of sub-states on each energy’s level and the Bekenstein–Hawking temperature of each energy level is recovered when the number of sub-states of a given level tends to infinity. We propose that the primordial state of the universe could be described by a de Sitter metric with Planck energy $$E_p=m_p\,c^2$$Ep=mpc2, and a B–H temperature: $$T_{BH}=\left( \frac{\hbar \,c}{2\pi \,l_p\,K_B}\right) $$TBH=ħc2πlpKB.
Viaggiu entropy and the generalized second law in a flat FLRW universe
Authors: Saha Subhajit
Published: November 2019

Our aim, in this paper, is to study the generalized second law by considering the dynamical apparent horizon to be endowed with the Hawking temperature and the Viaggiu entropy introduced in a pioneering work in 2014. We have devoted our attention to a flat FLRW universe filled with a perfect fluid having a constant equation of state [Formula: see text]. It is worthwhile to note that we have considered both forms of the Hawking temperature, the original one as well as the truncated version. The latter one is generally used during calculations, however, several arguments have been put forward against it. Our analysis yields a startling result. The Viaggiu entropy naturally forbids the phantom era. In other words, the Viaggiu entropy will never allow the EoS parameter to go beyond the Cosmological Constant. This result is in strong agreement with recent observations and we have deduced it purely by thermodynamic means. This is in striking contrast with the results obtained with the Bekenstein–Hawking formalism.
Surface-enhanced Raman scattering (SERS) by Ag nanoparticles on anodized TiO2−X nanotubes
Authors: Zhang Ting , Ye Junzhi , Arul Rakesh , Yang Tingxuan , Wang Yixuan , Yue Xiaoyu , Schaefer Marcel , Simpson Cather , Nieuwoudt Michél K. , Huang Saifang , Wei Shanghai , Gao Wei
Published: November 2019

In this work, Ag nanoparticles were deposited in the TiO[Formula: see text] nanotube films through magnetron sputtering to form Ag-TiO[Formula: see text] nanocomposite. Scanning electron microscopy (SEM) was used to study microstructure and surface morphology. Rhodamine B (RhB) was deposited on the surface of Ag-TiO[Formula: see text] substrate for Raman spectroscopy test. The size of Ag nanoparticles can be controlled by changing the magnetron sputtering time. The result indicated that sputtering for 30 s obtained the highest Raman enhancement.
A randomized incremental primal-dual method for decentralized consensus optimization
Authors: Chen Chenxi , Chen Yunmei , Ye Xiaojing
Published: November 2019

We consider a class of convex decentralized consensus optimization problems over connected multi-agent networks. Each agent in the network holds its local objective function privately, and can only communicate with its directly connected agents during the computation to find the minimizer of the sum of all objective functions. We propose a randomized incremental primal-dual method to solve this problem, where the dual variable over the network in each iteration is only updated at a randomly selected node, whereas the dual variables elsewhere remain the same as in the previous iteration. Thus, the communication only occurs in the neighborhood of the selected node in each iteration and hence can greatly reduce the chance of communication delay and failure in the standard fully synchronized consensus algorithms. We provide comprehensive convergence analysis including convergence rates of the primal residual and consensus error of the proposed algorithm, and conduct numerical experiments to show its performance using both uniform sampling and important sampling as node selection strategy.
Jointly low-rank and bisparse recovery: Questions and partial answers
Authors: Foucart Simon , Gribonval Rémi , Jacques Laurent , Rauhut Holger
Published: November 2019

We investigate the problem of recovering jointly [Formula: see text]-rank and [Formula: see text]-bisparse matrices from as few linear measurements as possible, considering arbitrary measurements as well as rank-one measurements. In both cases, we show that [Formula: see text] measurements make the recovery possible in theory, meaning via a nonpractical algorithm. In case of arbitrary measurements, we investigate the possibility of achieving practical recovery via an iterative-hard-thresholding algorithm when [Formula: see text] for some exponent [Formula: see text]. We show that this is feasible for [Formula: see text], and that the proposed analysis cannot cover the case [Formula: see text]. The precise value of the optimal exponent [Formula: see text] is the object of a question, raised but unresolved in this paper, about head projections for the jointly low-rank and bisparse structure. Some related questions are partially answered in passing. For rank-one measurements, we suggest on arcane grounds an iterative-hard-thresholding algorithm modified to exploit the nonstandard restricted isometry property obeyed by this type of measurements.
Generalized representer theorems in Banach spaces
Authors: Huang Liren , Liu Chunguang , Tan Lulin , Ye Qi
Published: November 2019

In this paper, we generalize the representer theorems in Banach spaces by the theory of nonsmooth analysis. The generalized representer theorems assure that the regularized learning models can be constructed by the nonconvex loss functions, the generalized training data, and the general Banach spaces which are nonreflexive, nonstrictly convex, and nonsmooth. Specially, the sparse representations of the regularized learning in 1-norm reproducing kernel Banach spaces are shown by the generalized representer theorems.
The Application of Homotopy Analysis Method to Determine the Thermal Response of Convective-Radiative Porous Fins with Temperature-Dependent Properties
Authors: Zargar Omid , Mollaghaee-Roozbahani Masoud , Bashirpour Mohammad , Baghani Mostafa
Published: November 2019

In this paper, the Homotopy Analysis Method (HAM) is utilized to investigate the thermal response of a circular convective-radiative porous fin having a rectangular cross-section. It is assumed that internal heat generation depends linearly on the temperature for the solid part of the porous fin, while temperature-dependent functions are used for thermal conductivity and convective terms. The thermal conductivity and convective coefficient of heat transfer are supposed to change respectively as a nonlinear hyperbolic and as a power-law function of the temperature all through the fin length. The function employed for the thermal conductivity can be applied for the thermal analysis if for example fins are made of semiconductor materials. Additionally, the general form of convective function enables us to account for the convection heat transfer in different processes. The heat transfer analysis in the porous media is conducted through passage velocity in Darcy’s model. HAM is utilized to study the effects of different pertinent parameters and nondimensional numbers on the described problem. The accuracy and convergence of HAM are validated with numerical methods (i.e., Runge–Kutta method) as well as other published works that reveal an excellent agreement.
Numerical Simulation of Vibration of Composite Pipelines Conveying Pulsating Fluid
Authors: Khudayarov B. A. , Komilova KH. M. , Turaev F. ZH.
Published: November 2019

Vibration problems of pipelines made of composite materials conveying pulsating flow of gas and fluid are investigated in the paper. A dynamic model of motion of pipelines conveying pulsating fluid flow supported by a Hetenyi’s base is developed taking into account the viscosity properties of the structure material, axial forces, internal pressure and Winkler’s viscoelastic base. To describe the processes of viscoelastic material strain, the Boltzmann–Volterra integral model with weakly singular hereditary kernels is used. Using the Bubnov–Galerkin method, the problem is reduced to the study of a system of ordinary integro-differential equations (IDE). A computational algorithm is developed based on the elimination of the features of IDE with weakly singular kernels, followed by the use of quadrature formulas. The effect of rheological parameters of the pipeline material, flow rate and base parameters on the vibration of a viscoelastic pipeline conveying pulsating fluid is analyzed. The convergence analysis of the approximate solution of the Bubnov–Galerkin method is carried out. It was revealed that the viscosity parameters of the material and the pipeline base lead to a significant change in the critical flow rate. It was stated that an increase in excitation coefficient of pulsating flow and the parameter of internal pressure leads to a decrease in the critical flow rate. It is shown that an increase in the singularity parameter, the Winkler base parameter, the rigidity parameter of the continuous base layer and the Reynolds number increases the critical flow rate.
Productivity and efficiency analysis of Pakistani mutual funds using Malmquist index approach
Authors: Naz Farah , Khan Hafsa , Ahmad Muhammad Ishfaq , Rehman Ramiz Ur , Naseem Muhammad Akram
Published: November 2019

The key area of this research is to analyze the total factor productivity of mutual funds by using Data Envelopment Analysis (DEA) and also to identify the components which play a significant role in the growth of productivity. Malmquist productivity index approach is a nonparametric method that decomposes the index into components of productivity. The process of decomposition also helps in identifying the contribution of technology and efficiency in the growth of mutual funds in Pakistan. Empirical results suggest that efficiency growth in mutual funds is presenting the upward trend. The individual results of mutual funds showed the divergent trend. The component of pure efficiency change has a great influence on productivity growth except for all others components, and technical change has a smaller number of contributions in productivity growth.
Market efficiency in the emerging and frontier markets of the MENA countries
Authors: Derbali Abdelkader
Published: November 2019

Daily and weekly market index returns were analyzed to examine market efficiency in emerging and frontier markets in MENA region. Based on a set of tests, autocorrelation, runs, unit root and multiple variance report tests, over a period of 7 years, our results show mixed results for different indices. However, emerging and frontier market and yield series indicate the lack of market efficiency. We find that daily and weekly market index returns do not follow random markets. We can conclude that investors can obtain the flow of arbitrage profits due to the inefficiency of the market belonging to these countries.
Muscle2View, a CellProfiler pipeline for detection of the capillary-to-muscle fiber interface and high-content quantification of fiber type-specific histology
Authors: Sanz Gema , Martínez-Aranda Luis Manuel , Tesch Per A. , Fernandez-Gonzalo Rodrigo , Lundberg Tommy R.
Published: November 2019

Because manual immunohistochemical analysis of features such as skeletal muscle fiber typing, capillaries, myonuclei, and fiber size-related parameters is time consuming and prone to user subjectivity, automatic computational methods could allow for faster and more objective evaluation. Here, we developed Muscle2View, a free CellProfiler-based pipeline that integrates all key fiber-morphological variables, including the novel quantification of the capillary-to-fiber interface, in one single tool. Provided that the images are of sufficient quality and the settings are configured for the specific study, the pipeline allows for automatic and unsupervised analysis of fiber borders, myonuclei, capillaries, and morphometric parameters in a fiber type-specific manner from large batches of images in <10 min/tissue sample. The novel identification of the capillary-to-fiber interface allowed for the calculation of microvascular factors such as capillary contacts (CC), individual capillary-to-fiber ratio (C/Fi), and capillary-to-fiber perimeter exchange (CFPE) index. When comparing the Muscle2View pipeline to manual or semiautomatic analysis, overall the results revealed strong correlations. For several variables, however, there were differences (5–15%) between values computed by manual counting and Muscle2View, suggesting that the methods should not necessarily be used interchangeably. Collectively, we demonstrate that the Muscle2View pipeline can provide unbiased and high-content analysis of muscle cross-sectional immunohistochemistry images. In addition to the classical morphological measurements, the Muscle2View can identify the complex capillary-to-fiber network and myonuclear density in a fiber type-specific manner. This robust analysis is done in one single run within a user-friendly and flexible environment based on the free and widely used image software CellProfiler.

NEW & NOTEWORTHY Here, we developed a freely available CellProfiler-based pipeline termed Muscle2View, which provides unbiased, high-content analysis of muscle cross-sectional immunohistochemistry images. In addition to fiber typing, myonuclei counting, and the quantification of fiber type-specific morphological measurements, the Muscle2View pipeline can identify the complex capillary-to-fiber network from a batch of images within minutes. Thus, the Muscle2View is a viable tool for researchers aiming to quantify immunohistochemical variables from skeletal muscle biopsies.
Fiber typing human skeletal muscle with fluorescent immunohistochemistry
Authors: Murach Kevin A. , Dungan Cory M. , Kosmac Kate , Voigt Thomas B. , Tourville Timothy W. , Miller Mark S. , Bamman Marcas M. , Peterson Charlotte A. , Toth Michael J.
Published: November 2019

Skeletal muscle myosin heavy chain (MyHC) fiber type composition is a critical determinant of overall muscle function and health. Various approaches interrogate fiber type at the single cell, but the two most commonly utilized are single-muscle fiber sodium dodecyl sulfate-polyacrylamide gel electrophoresis (smfSDS-PAGE) and fluorescent immunohistochemistry (IHC). Although smfSDS-PAGE is generally considered the “gold standard,” IHC is more commonly used because of its time-effectiveness and relative ease. Unfortunately, there is lingering inconsistency on how best to accurately and quickly determine fiber type via IHC and an overall misunderstanding regarding pure fiber type proportions, specifically the abundance of fibers exclusively expressing highly glycolytic MyHC IIX in humans. We therefore 1) present information and data showing the low abundance of pure MyHC IIX muscle fibers in healthy human skeletal muscle and 2) leverage this information to provide straightforward protocols that are informed by human biology and employ inexpensive, easily attainable antibodies for the accurate determination of fiber type.
Dual-Sense Circular Polarization Antenna Based on Reconfigurable Orthogonal Network
Authors: Sun Mingyu , Zhang Zhe , An Kang , Wang Xianghui , Jiang Yuezhi , Chen Aixin
Published: November 2019

A novel circular polarization (CP) reconfigurable microstrip antenna is presented. The CP reconfigurable antenna is divided into three layers, composed of an annular radiating patch, ring slot, and reconfigurable orthogonal network (RON). The designed antenna is fed by dual vertical branches at the output port of the RON. By adjusting the bias voltage of the PIN switch loaded on the reconfigurable orthogonal network, the output phase can be changed, which means that the polarization direction of CP antenna is switchable. Simulation results show that the proposed feeding network provides constant phase difference and lower insertion loss for both states in the operating frequency band, thereby achieving good match and axial ratio characteristics either LHCP or RHCP state. Measured results show that the proposed antenna exhibits operational bandwidth of 1.2% with axial ratio below 3 dB and return loss above 10 dB in both polarized states. Good agreement between simulated and measured results is obtained.
Apoptotic Effects of Xanthium strumarium via PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma
Authors: Kim Juyoung , Jung Kyung Hee , Ryu Hyung Won , Kim Doo-Young , Oh Sei-Ryang , Hong Soon-Sun
Published: November 2019

Xanthium strumarium (XS) has been traditionally used as a medicinal herb for treating inflammatory diseases, such as appendicitis, chronic bronchitis, rheumatism, and rhinitis. In this study, we yielded ethanol extracts from XS and investigated whether they could inhibit the progression of hepatocellular carcinoma (HCC) and its underlying mechanism. The XS-5 and XS-6 extracts dose-dependently inhibited the growth and proliferation in HCC cell lines. The apoptotic effects of them were observed via increased levels of cleaved caspase-3 and cleaved PARP, as well as elevated numbers of terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling- (TUNEL-) positive apoptotic cells. They also decreased XIAP and Mcl-1 expression via loss of mitochondrial membrane potential. Additionally, they inhibited the invasion and migration of HCC cells. In an ex vivo model, the extracts significantly inhibited tumor cell growth and induced apoptosis by increasing the expression of the cleaved caspase-3. A mechanistic study revealed that they effectively suppressed PI3K/AKT/mTOR signaling pathways in HCC cells. Taken together, our findings demonstrate that they could efficiently not only induce apoptosis but also inhibit cell growth, migration, and invasion of human HCC cells by blocking the PI3K/AKT/mTOR pathway. We suggest XS-5 and XS-6 as novel natural anti-HCC agents.
Synthesis of Some New Barbituric and Thiobarbituric Acids Bearing 1,2,4-Triazine Moiety and Their Related Systems as Herbicidal Agents
Authors: Al-Romaizan Abeer N.
Published: November 2019

In search for highly bioactive barbituric and thiobarbituric acid derivatives, some new barbituric and thiobarbituric acids bearing 1,2,4-triazine moiety and their related systems (5–13) have been obtained from the addition of isocyanate and isothiocyanate to 3-amino-5,6-diphenyl-1,2,4-triazine (1) followed by ring closure reactions with diethyl malonate. Also, chemical reactivities of the related systems were obtained from the condensation of barbituric and thiobarbituric acid derivatives with aromatic aldehyde and/or fluoroacylation reactions. The structure of all the products was deduced from both elemental analysis and spectral data (IR, 1H NMR, 13C NMR, and MS). The herbicidal activity was also evaluated for the products.
A Study of the Impact Resistance of Rubber Concrete at Low Temperatures (−30°C)
Authors: Xue Gang , Liu Jia-xiang , Cao Mei-ling
Published: November 2019

In the present study, the impact resistance of rubber concrete at low temperatures (−30°C) was examined. The initial and ultimate crack impact times and the ductility indexes were evaluated. This study’s specimens were prepared by adding two different sizes of rubber particles (20 mesh and 50 mesh) in different ratios (0%, 5%, 10%, 15%, and 20%) at both 25°C and −30°C. The concrete specimens were evaluated using a drop hammer weight test method. The results showed that the initial and ultimate crack impact times and ductility indexes of the rubber concrete specimens had decreased at −30°C. Also, the decrease amplitudes were determined to be lower than those of the reference concrete specimens. Consideration was given in this study to the large variations in the impact values, and a two‐parameter Weibull distribution method was adopted in order to analyze the obtained experimental data. The results had demonstrated that the impact times of the rubber concrete specimens could be described using the two‐parameter Weibull distribution method results.
Solitary Colorectal Cancer Metastasis to the Pancreas
Authors: Karageorgou M. , Myoteri D. , Kotsis T. , Polymeneas G. , Bournakis E. , Dellaportas D.
Published: November 2019

Introduction. Secondary pancreatic metastasis from other solid organ malignancy is rare and accounts for less than 2% of all pancreatic tumors. The aim of this study is to highlight that colorectal metastatic disease in the pancreas could be in selected cases an indication for surgery rather than for palliative chemotherapy. Case Presentation. We present a case of a 62-year-old Caucasian female with a history of rectal adenocarcinoma. Four years ago, the patient underwent low anterior resection of the rectosigmoid, post neoadjuvant chemoradiotherapy, with adjuvant chemotherapy. During her follow-up, imaging examinations revealed a lesion in the pancreatic neck with features indicating primary pancreatic cancer. Near-total distal pancreatectomy with en bloc splenectomy was performed. Histopathology revealed metastatic disease compatible with colorectal adenocarcinoma as the primary cancer. Second-line chemotherapy was decided from the institutional tumor board. The patient remains disease free one year later. Conclusion. Pancreatic lesions in patients with a history of extrapancreatic malignancy should raise suspicions of metastatic disease. Surgical intervention is a legitimate treatment option for these pancreatic lesions, since they represent solitary disease deposits and of course in the context of multidisciplinary meeting decisions, and after proper and extensive staging investigations.
Ticagrelor-Induced Prolongation of the QTc Interval
Authors: Ray Avik , Najmi Ahmad , Khandelwal Gaurav , Sadasivam Balakrishnan
Published: November 2019

Background. Ticagrelor has been accepted as a class I antiplatelet agent in patients undergoing percutaneous coronary angioplasty (PTCA). There have been cases reported on ticagrelor being associated with various cardiac conduction defects. But there is no evidence of QTc prolongation associated with the drug as of yet. Case Presentation. A 64-year-old male who underwent PTCA was given ticagrelor. A baseline electrocardiogram (ECG) showed a QTc of 402 ms. He returned after 1.5 months with complaints of shortness of breath. An ECG revealed a prolonged QTc of 468 ms. Ticagrelor was discontinued in view of ticagrelor-induced dyspnea and the patient was started on clopidogrel. The other medications were kept unchanged. The patient returned after a month without any complaints. A follow-up ECG showed a reduced QTc of 425 ms. Conclusion. We present a case of ticagrelor-induced QTc prolongation. To our knowledge, this is the first case to be reported on the same. The Naranjo algorithm for causality assessment gave a total score of 6 indicating that the adverse drug reaction falls under the probable category.
Persistent Necrotizing Mediastinitis after Dental Extraction
Authors: de Figueiredo Eugênia Leal , Aires Carolina Chaves Gama , Neres Bruno José Carvalho Macêdo , de Araújo Bruna Luna , de Arruda José Alcides Almeida , de Holanda Vasconcellos Ricardo José
Published: November 2019

Mediastinitis is a rare, progressive, and destructive infectious process due to cervical or odontogenic infections, which, if not diagnosed early, may lead to several complications, including airway involvement and even an imminent risk of death. Herein, we report an unusual case of a 37-year-old male with a bilateral submandibular hard swelling after the left third molar extraction. After surgical intervention with submandibular drainage and antibiotic therapy, the infection persisted without explanation, since the patient was not hypertensive, did not have diabetes mellitus or sexually transmitted infections such as HIV or syphilis, and did not smoke or drink alcoholic beverages. A thoracic surgeon then intervened, treating the mediastinitis surgically by drainage, thus obtaining a significant improvement of the patient’s health. Mediastinitis is a serious condition. Clinicians and maxillofacial surgeons should be alert to make an immediate diagnosis and select the appropriate treatment in order to prevent worsening of the patient’s clinical condition.
Fault Diagnosis of High‐Speed Train Bogie Based on Synchrony Group Convolutions
Authors: Wu Yunpu , Jin Weidong , Ren Junxiao , Sun Zhang
Published: November 2019

Health monitoring and fault diagnosis of a high‐speed train is an important research area in guaranteeing the safe and long‐term operation of the high‐speed railway. For a multichannel health monitoring system, a major technical challenge is to extract information from different channels with divergence patterns as a result of distinct types and layout of sensors. To this end, this paper proposes a novel group convolutional network based on synchrony information. The proposed method is able to gather signals with similar patterns and process these channels with specific groups of neurons while simultaneously assigning signals with significant difference to different groups. In this approach, the feature can be extracted more effectively and the performance can be improved, owing to the sharing of filters for similar patterns. The effectiveness of the method is validated on high‐speed train fault dataset. Experiments show that the proposed model performs better than normal convolutions and normal group convolutions on this task, which achieves an accuracy of 98.27% (σ = 1.73) with good computational efficiency.
Nine Hole Peg Test and Transcranial Magnetic Stimulation: Useful to Evaluate Dexterity of the Hand and Disease Progression in Amyotrophic Lateral Sclerosis
Authors: Czell David , Neuwirth Christoph , Weber Markus , Sartoretti-Schefer Sabine , Gutzeit Andreas , Reischauer Carolin
Published: November 2019

Objective. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with involvement of the upper and lower motor neurons. Since the loss of fine motor skills is one of the earliest signs of ALS, the hypothesis was tested if the nine hole PEG test (NHPT) and transcranial magnet stimulation (TMS) with resting-motor threshold (RMT) could be useful in monitoring disease progression. Methods. We examined 28 ALS patients and 27 age-matched healthy controls. ALS patients and healthy controls underwent the nine hole peg test (NHPT) and TMS with RMT. Measurements in patients were repeated after three and six months. Results. At baseline, the median NHPT durations were 1,4-fold longer (p<0.001), and TMS scores showed a significant 0.8-fold smaller score in ALS patients compared with healthy controls (p<0.001). The comparison of three and six months versus baseline revealed significant differences for NHPT durations and ALSFRS-R in patients, whereas TMS scores did not significantly differ in the patients. Conclusion. NHPT seems to be a good tool to evaluate dexterity of the hand and the progression of the disease in ALS patients. TMS RMT to the hand muscles seems to be poorly qualified to evaluate the dexterity of the hand function and the course of the disease.
Overexpression of Inducible Nitric Oxide Synthase in Allergic and Nonallergic Nasal Polyp
Authors: Sadek Ahmed Adel , Abdelwahab Soha , Eid Safaa Yehia , Almaimani Riyad A. , Althubiti Mohammad A. , El-Readi Mahmoud Zaki
Published: November 2019

Sinonasal polyps are very common benign lesions of the nasal mucosa. Most of nasal polyps (NP) are idiopathic, and the pathophysiology of this disease is still incompletely understood. Nitric oxide (NO) is a reactive molecule generated by nitric oxide synthase (NOS). NO has been identified as an important mediator in airway function and pathogenesis of several respiratory system diseases. Histological and genetical expression of iNOS was detected to evaluate the role of NO in the pathogenesis of allergic (ANP) and nonallergic nasal polyps (NANP). Forty patients with nasal polyps (20 allergic and 20 nonallergic) were identified by history, clinical examination, and investigation. NPs were obtained from the middle turbinate (MT) during concha bullosa surgery. Twenty normal MT nasal tissues were taken as the control from patients undergoing concha bullosa surgery, without any evidence of allergy or inflammation. A nasal polyp specimen from each patient was subjected for immune-histochemical study followed by histological examination to detect the expression of iNOS. RT-PCR was used to evaluate the iNOS gene expression in isolated tissues. The expression of iNOS in both epithelial and stromal layers was greater in NP than in MT tissues. The ANP group showed more iNOS expression than those of the NANP group. The relative mRNA levels of iNOS gene were significantly higher in ANP (2.5-fold) compared to the normal (1.02-fold, P<0.001) and NANP (1.5-fold, P<0.01) groups. NP exhibited a significantly high expression of iNOS at both histological and genetical levels. NO might be an essential factor in the life history of NP. Further studies in a larger sample size are required to explain the probable mechanisms of NO in pathogenesis of NP.
An Improved Spatial Difference Smoothing Method Based on Multistage Wiener Filtering
Authors: Gong Jian , Guo Yiduo , Wan Qun
Published: November 2019

In order to solve the angle estimation problem of coherent sources in the colored background noise, an improved forward and backward spatial difference smoothing algorithm is proposed by combining the improved spatial smoothing algorithm with the spatial difference algorithm. By the algorithm we can not only decoherent the coherent source but also suppress the influence of the color noise. In order to further reduce the computational complexity of the IFBSDS algorithm, an improved forward and backward spatial difference smoothing algorithm based on Wiener filtering is also proposed. Thus, the eigenvalue decomposition operation of subspace class algorithm can be avoided, and at the same time, the same performance with the IFBSDS algorithm can be obtained, which is more consistent with the real demand of MIMO radar signal real‐time processing.
HIF-1-miR-219-SMC4 Regulatory Pathway Promoting Proliferation and Migration of HCC under Hypoxic Condition
Authors: Chen Yang , Huang Fei , Deng liang , Yuan Xiaowei , Tao Qiang , Wang Tielong , Li Dong , Fan Youwen , Peng Quanzhou , Tang Di
Published: November 2019

This paper aims to investigate the function of structural maintenance of chromosome 4 (SMC4) in the progression of hepatocellular carcinoma (HCC) under hypoxic condition. In this study, we found that suppression of SMC4 could inhibit proliferation and migration of HCC cells through inducing G1 phase arrest and affecting process of epithelial-mesenchymal transition (EMT) under hypoxic condition. Moreover, we demonstrated that SMC4 was transcriptionally regulated by hypoxia-inducible factor-1 (HIF-1) under hypoxic condition. As SMC has been shown to be a target gene of miR-219, we observed that miR-219 was downregulated under hypoxic condition and suppression of HIF-1a could lead to the upregulation of miR-219. We also proved that miR-219 could affect the proliferation and migration of HCC cells under hypoxic condition. In conclusion, our study demonstrated a novel HIF-1-miR-219-SMC4 regulatory pathway under hypoxic condition in HCC cells.
The Effect of Package Structure on the Light Extraction Efficiency of Near-Ultraviolet LED
Authors: Bing-qian Li
Published: November 2019

The near-ultraviolet high-power LED, with five package structures, is designed and fabricated. The efficiency of electric conversion to light (EECL) of various package structures is measured, and the EECL is used to characterize the light extraction efficiency (LEE) of the package structure. By analyzing the Fresnel loss (FNL) and total inner reflection loss (TIRL) of light at different interfaces, the experimental results are explained qualitatively. When approximate spherical lens is used, filling silica gel between chip and lens can improve the LEE. The EECL of the device can reach 66.84%, which is higher than that of bare chip by 55.10%. In planar packaging, the EECL of the device is lower than that of the bare chip, whether or not it is filled with silica gel. After filling with silica gel, a new TIRL is produced at the final interface of the device, and the EECL of the device is even lower, which is only 37.14%. The experimental results show that when the LED chip adopts graphic substrate and surface microstructure to improve the LEE, the traditional coating of silica gel (or epoxy) and other materials on the chip surface may not improve the LEE of the device. If the introduction of the silica gel layer leads to a new total inner reflection interface, it will result in a significant decrease in LEE of the device. When a layer, such as silica gel, does not result in a new total reflection interface, the FNL and TIRL of the chip surface can be effectively reduced, and the LEE of the LED device can be improved.
Targeting CD39 in Cancer Reveals an Extracellular ATP- and Inflammasome-Driven Tumor Immunity
Authors: Li Xian-Yang , Moesta Achim K. , Xiao Christos , Nakamura Kyohei , Casey Mika , Zhang Haiyan , Madore Jason , Lepletier Ailin , Aguilera Amelia Roman , Sundarrajan Ashmitha , Jacoberger-Foissac Celia , Wong Clifford , dela Cruz Tracy , Welch Megan , Lerner Alana G. , Spatola Bradley N. , Soros Vanessa B. , Corbin John , Anderson Ana C. , Effern Maike , Hölzel Michael , Robson Simon C. , Johnston Rebecca L. , Waddell Nicola , Smith Corey , Bald Tobias , Geetha Nishamol , Beers Courtney , Teng Michele W. L. , Smyth Mark J.
Published: November 2019

We explored the mechanism of action of CD39 antibodies that inhibit ectoenzyme CD39 conversion of extracellular ATP (eATP) to AMP and thus potentially augment eATP–P2-mediated proinflammatory responses. Using syngeneic and humanized tumor models, we contrast the potency and mechanism of anti-CD39 mAbs with other agents targeting the adenosinergic pathway. We demonstrate the critical importance of an eATP–P2X7–ASC–NALP3-inflammasome–IL18 pathway in the antitumor activity mediated by CD39 enzyme blockade, rather than simply reducing adenosine as mechanism of action. Efficacy of anti-CD39 activity was underpinned by CD39 and P2X7 coexpression on intratumor myeloid subsets, an early signature of macrophage depletion, and active IL18 release that facilitated the significant expansion of intratumor effector T cells. More importantly, anti-CD39 facilitated infiltration into T cell–poor tumors and rescued anti–PD-1 resistance. Anti-human CD39 enhanced human T-cell proliferation and Th1 cytokine production and suppressed human B-cell lymphoma in the context of autologous Epstein–Barr virus–specific T-cell transfer.

Significance:

Overall, these data describe a potent and novel mechanism of action of antibodies that block mouse or human CD39, triggering an eATP–P2X7–inflammasome–IL18 axis that reduces intratumor macrophage number, enhances intratumor T-cell effector function, overcomes anti–PD-1 resistance, and potentially enhances the efficacy of adoptive T-cell transfer.

This article is highlighted in the In This Issue feature, p. 1631
Single-Cell RNA Sequencing Reveals Stromal Evolution into LRRC15+ Myofibroblasts as a Determinant of Patient Response to Cancer Immunotherapy
Authors: Dominguez Claudia X. , Müller Sören , Keerthivasan Shilpa , Koeppen Hartmut , Hung Jeffrey , Gierke Sarah , Breart Beatrice , Foreman Oded , Bainbridge Travis W. , Castiglioni Alessandra , Senbabaoglu Yasin , Modrusan Zora , Liang Yuxin , Junttila Melissa R. , Klijn Christiaan , Bourgon Richard , Turley Shannon J.
Published: November 2019

With only a fraction of patients responding to cancer immunotherapy, a better understanding of the entire tumor microenvironment is needed. Using single-cell transcriptomics, we chart the fibroblastic landscape during pancreatic ductal adenocarcinoma (PDAC) progression in animal models. We identify a population of carcinoma-associated fibroblasts (CAF) that are programmed by TGFβ and express the leucine-rich repeat containing 15 (LRRC15) protein. These LRRC15+ CAFs surround tumor islets and are absent from normal pancreatic tissue. The presence of LRRC15+ CAFs in human patients was confirmed in >80,000 single cells from 22 patients with PDAC as well as by using IHC on samples from 70 patients. Furthermore, immunotherapy clinical trials comprising more than 600 patients across six cancer types revealed elevated levels of the LRRC15+ CAF signature correlated with poor response to anti–PD-L1 therapy. This work has important implications for targeting nonimmune elements of the tumor microenvironment to boost responses of patients with cancer to immune checkpoint blockade therapy.

Significance:

This study describes the single-cell landscape of CAFs in pancreatic cancer during in vivo tumor evolution. A TGFβ-driven, LRRC15+ CAF lineage is associated with poor outcome in immunotherapy trial data comprising multiple solid-tumor entities and represents a target for combinatorial therapy.

This article is highlighted in the In This Issue feature, p. 161
Evolving Treatment Paradigms for Pancreatic Cancer
Authors: Abbassi Rami , Schmid Roland M.
Published: November 2019

Background: Pancreatic adenocarcinoma is an extremely aggressive tumor which is supposed to become the second deadliest malignancy in 2030. For a long time the possibilities to treat this complex disease were very limited. Summary: In the last years the development of new chemotherapeutic regimens has led to a better outcome in the ad­juvant, neoadjuvant, and palliative setting. Furthermore, progress in sequencing technologies has enabled a detailed investigation of the genetic alterations, mutational burden, expression pattern, and stroma composition in pancreatic cancer and led to the identification of subtypes of this disease. Messages: This analysis will increase our understanding of tumor heterogeneity and hopefully translate into new potential targets, biomarkers, and the development of individual therapeutic approaches in the future.
The Gut Microbiome in Inflammatory Bowel Diseases: Diagnostic and Therapeutic Implications
Authors: Aden Konrad , Reindl Wolfgang
Published: November 2019

The incidence of chronic inflammatory bowel diseases (IBD) is rising worldwide, and the interaction between the mucosal immune system and the intestinal microbiota is crucial for the understanding of these diseases. Due to new technologies, the data published on the intestinal microbiota has increased rapidly in the recent years. While many findings are descriptive, reporting associations between disease and microbial populations, recent advancement in technology made it possible to ask and answer more functional questions and to elucidate complex interactions between the intestinal microbiota and the mucosal immune system. In addition, first trials influenced the intestinal microbiota with the intention to treat IBD. This review summarizes aspects of the physiological function as well as the inflammation-induced changes of the gut microbiota and the association between the gut microbiota and pathogenesis in IBD. In addition, diagnostic and therapeutic options for treating IBD are reviewed.
S-Nitrosylation of Plastin-3 Exacerbates Thoracic Aortic Dissection Formation via Endothelial Barrier Dysfunction
Authors: Pan Lihong , Lin Zhe , Tang Xin , Tian Jiaxin , Zheng Qiao , Jing Jin , Xie Liping , Chen Hongshan , Lu Qiulun , Wang Hong , Li Qingguo , Han Yi , Ji Yong
Published: November 2019

Objective:

Thoracic aortic dissection (TAD) is a fatal disease that leads to aortic rupture and sudden death. However, little is known about the effect and molecular mechanism of S-nitrosylation (SNO) modifications in TAD formation.

Approach and Results:

SNO levels were higher in aortic tissues from TAD patients than in those from healthy controls, and PLS3 (plastin-3) SNO was identified by liquid chromatography-tandem mass spectrometry analysis. Furthermore, tail vein administration of endothelial-specific adeno-associated viruses of mutant PLS3-C566A (denitrosylated form) suppressed the development of TAD in mice, but the wild-type PLS3 (S-nitrosylated form) virus did not. Mechanistically, Ang II (angiotensin II)–induced PLS3 SNO enhanced the association of PLS3 with both plectin and cofilin via an iNOS (inducible nitric oxide synthase)-dependent pathway in endothelial cells. The formation of PLS3/plectin/cofilin complex promoted cell migration and tube formation but weakened adherens junction formation in Ang II–treated endothelial cells. Interestingly, denitrosylated form of PLS3 partially mitigated Ang II–induced PLS3/plectin/cofilin complex formation and cell junction disruption. Additionally, the inhibition of iNOS attenuated PLS3 SNO and the association of PLS3 with plectin and cofilin, thereby modulating endothelial barrier function.

Conclusions:

Our data indicate that protein SNO modification in endothelial cells modulates the progression of aortic aneurysm and dissection. The iNOS-mediated SNO of PLS3 at the Cys566 site promoted its interaction with cofilin and plectin, thus contributing to endothelial barrier disruption and pathological angiogenesis in TAD.
Subclinical and Device-Detected Atrial Fibrillation: Pondering the Knowledge Gap: A Scientific Statement From the American Heart Association
Authors: Noseworthy Peter A. , Kaufman Elizabeth S. , Chen Lin Y. , Chung Mina K. , Elkind Mitchell S.V. , Joglar José A. , Leal Miguel A. , McCabe Pamela J. , Pokorney Sean D. , Yao Xiaoxi ,   On behalf of the American Heart Association Council on Clinical Cardiology Electrocardiography and Arrhythmias Committee; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and Stroke Council
Published: November 2019

The widespread use of cardiac implantable electronic devices and wearable monitors has led to the detection of subclinical atrial fibrillation in a substantial proportion of patients. There is evidence that these asymptomatic arrhythmias are associated with increased risk of stroke. Thus, detection of subclinical atrial fibrillation may offer an opportunity to reduce stroke risk by initiating anticoagulation. However, it is unknown whether long-term anticoagulation is warranted and in what populations. This scientific statement explores the existing data on the prevalence, clinical significance, and management of subclinical atrial fibrillation and identifies current gaps in knowledge and areas of controversy and consensus.