bluuebunny/crossref_metadata_2025 huggingface dataset:
The Curse of physics
Authors: Futoran Ben
Published: November 2018

This is essentially how I start my class each year. As educators we know that the primary way to ensure content retention is to connect the information to the students’ lives in a relevant way. Thankfully, as physics teachers, we teach the subject that explains nearly every natural phenomenon in the world…and outside of the world, for that matter. We all know that physics is all around us, from the period of oscillation of my electric toothbrush, to the way that the constriction of our blood vessels affects our blood pressure and body temperature. The Curse of which I speak is seeing physics everywhere all the time. It is my desire that my students are permanently cursed in that there is no object, movie, or activity in which they do not clearly see the physics involved. It is therefore my goal, throughout the year, to bring to the foreground the inescapable prevalence of physics in my students’ lives.
Mechanism of large-scale flow reversals in turbulent thermal convection
Authors: Wang Yin , Lai Pik-Yin , Song Hao , Tong Penger
Published: November 2018

Rare massive eruption of thermal plumes causes random reversals of the large-scale flow in turbulent thermal convection.
A hierarchically patterned, bioinspired e-skin able to detect the direction of applied pressure for robotics
Authors: Boutry Clementine M. , Negre Marc , Jorda Mikael , Vardoulis Orestis , Chortos Alex , Khatib Oussama , Bao Zhenan
Published: November 2018

An e-skin that uses multiple levels of biologically inspired patterning is capable of discriminating both normal and tangential forces.
Long-term mechanical function and integration of an implanted tissue-engineered intervertebral disc
Authors: Gullbrand Sarah E. , Ashinsky Beth G. , Bonnevie Edward D. , Kim Dong Hwa , Engiles Julie B. , Smith Lachlan J. , Elliott Dawn M. , Schaer Thomas P. , Smith Harvey E. , Mauck Robert L.
Published: November 2018

Tissue-engineered intervertebral discs demonstrate long-term functional integration in rat and goat disc replacement models.
Randomised cross-over study of automated oxygen control for preterm infants receiving nasal high flow
Authors: Reynolds Peter R , Miller Thomas L , Volakis Leonithas I , Holland Nicky , Dungan George C , Roehr Charles Christoph , Ives Kevin
Published: November 2018

Objective

To evaluate a prototype automated controller (IntellO2) of the inspired fraction of oxygen (FiO2) in maintaining a target range of oxygen saturation (SpO2) in preterm babies receiving nasal high flow (HF) via the Vapotherm Precision Flow.

Design

Prospective two-centre order-randomised cross-over study.

Setting

Neonatal intensive care units.

Patients

Preterm infants receiving HF with FiO2 ≥25%.

Intervention

Automated versus manual control of FiO2 to maintain a target SpO2 range of 90%–95% (or 90%–100% if FiO2=21%).

Main outcome measures

The primary outcome measure was per cent of time spent within target SpO2 range. Secondary outcomes included the overall proportion and durations of SpO2 within specified hyperoxic and hypoxic ranges and the number of in-range episodes per hour.

Results

Data were analysed from 30 preterm infants with median (IQR) gestation at birth of 26 (24–27) weeks, study age of 29 (18–53) days and study weight 1080 (959–1443) g. The target SpO2 range was achieved 80% of the time on automated (IntellO2) control (IQR 70%–87%) compared with 49% under manual control (IQR 40%–57%; p<0.0001). There were fewer episodes of SpO2 below 80% lasting at least 60 s under automated control (0 (IQR 0–1.25)) compared with manual control (5 (IQR 2.75–14)). There were no differences in the number of episodes per hour of SpO2 above 98% (4.5 (IQR 1.8–8.5) vs 5.5 (IQR 1.9–14); p=0.572) between the study arms.

Conclusions

The IntellO2 automated oxygen controller maintained patients in the target SpO2 range significantly better than manual adjustments in preterm babies receiving HF.

Trial registration number

NCT02074774.
Stochastic modeling of kaolinite transport through a sand filter
Authors: Won Jongmuk , Burns Susan E.
Published: November 2018

Accurately modeling the transport of clay particles through coarse-grained porous media is essential to engineering applications ranging from filtration and drainage, groundwater flow modeling, to contaminant transport. However, predicting the retention and clogging behavior of clay particles within a coarse-grained soil matrix is extremely challenging because clay particles can aggregate and form clusters with a variety of fabrics depending on the prevailing geochemistry of the pore fluid (i.e., pH and ionic strength). The work performed in this study developed a stochastic model to investigate the uncertainty of clay particle transport in porous media using random sampling at a given grain-size distribution to account for inherent uncertainty of the size of clay clusters being transported. Results demonstrated that the model proposed in this work can evaluate upper and lower boundaries of retention profiles of clay particles in a sand medium at given mean and standard deviation of grain-size distributions. In addition, the deterministic approach (using median sizes of sand and clay particles in the simulation) underestimated the mass of retained particles at small size ratios of clay particle size/sand particle size when compared with the stochastic prediction, which would result in nonconservative design.
Thermodynamics of black holes with higher order corrected entropy
Authors: Shahzad M. Umair , Jawad Abdul
Published: November 2018

For analyzing the thermodynamical behavior of two well-known black holes, such as Reissner–Nordström – anti-de Sitter (RN-AdS) black hole with global monopole and f(R) black hole, we consider the higher order logarithmic corrected entropy. We develop various thermodynamical properties, such as entropy, specific heat, pressure, and Gibbs and Helmhotz free energies for both black holes in the presence of corrected entropy. A versatile study on the stability of black holes is made by using various frameworks, such as the ratio of heat capacities (γ), grand canonical and canonical ensembles, and phase transition in view of higher order logarithmic corrected entropy. It is observed that both black holes exhibit more stability (locally as well as globally) for growing values of cosmological constant and higher order correction terms.
Dynamics of Bianchi type-II anisotropic dark energy cosmological model in the presence of scalar-meson fields
Authors: Reddy D.R.K. , Aditya Y. , Naidu K. Dasu
Published: November 2018

Today dark energy cosmological models have become essential to explain the accelerated expansion of the universe. Motivated by this we investigate, in this paper, a dark energy model in the presence of massless scalar field in the framework of locally rotationally symmetric (LRS) Bianchi type-II space–time. To find a deterministic model of the universe we use the hybrid expansion law to solve Einstein’s field equations. We also use a relation between metric potential for this purpose. The dynamical cosmological parameters of the model are determined and their physical discussion is presented through graphical representation. It is observed that our model, being a scalar field model, varies in the quintessence region and exhibits a cosmic transition of the universe from early deceleration to late-time acceleration. This fact is in agreement with the observations of modern cosmology.
GPU-ACCELERATED FINITE ELEMENT MODELING OF BIO-HEAT CONDUCTION FOR SIMULATION OF THERMAL ABLATION
Authors: ZHANG JINAO , HILLS JEREMY , ZHONG YONGMIN , SHIRINZADEH BIJAN , SMITH JULIAN , GU CHENGFAN
Published: November 2018

Efficient simulation of heating processes in thermal ablation is of great importance for surgical simulation of thermal ablation procedures. This paper presents a Graphics Processing Unit (GPU) assisted finite element methodology for modeling and analysis of bio-heat transfer processes in the treatment of thermal ablation. The proposed methodology employs finite element method for discretization of the bio-heat equation, and the finite element modeling is implemented using the High-Level Shader Language of the Microsoft Direct3D 11. Simulations and comparison analyses are conducted, demonstrating computational performance improvement of up to 55.3 times using the proposed methodology.
COMBINED USE OF PARALLEL-PLATE COMPRESSION AND FINITE ELEMENT MODELING TO ANALYZE THE MECHANICAL PROPERTIES OF INTACT PORCINE LENS
Authors: WANG KEHAO , VENETSANOS DEMETRIOS T. , WANG JIAN , PIERSCIONEK BARBARA K.
Published: November 2018

The objective of this study is to explore the feasibility of a compression test for measuring mechanical properties of intact eye lenses using novel parallel plate compression equipment to compare the accuracy of implementing a classical Hertzian model and a newly proposed adjusted Hertzian model to calculate Young’s modulus from compression test results using finite element (FE) analysis. Parallel-plate compression tests were performed on porcine lenses. An axisymmetric FE model was developed to simulate the experimental process to evaluate the accuracy of using the classical Hertzian theory of contact mechanics as well as a newly proposed adjusted Hertzian theory model for calculating the equivalent Young’s modulus. By fitting the force-displacement relation obtained from FE simulations to both the classical and adjusted Hertzian theory model and comparing the calculated modulus to the input modulus of the FE model, the results demonstrated that the classical Hertzian theory model overestimated the Young’s modulus with a proportional error of over 10%. The adjusted Hertzian theory model produced results that are closer to original input values with error ratios all lower than 1.29%. Measurements of three porcine lenses from the parallel plate compression experiments were analyzed with resulting values of Young’s modulus of between 3.2[Formula: see text]kPa and 4.3[Formula: see text]kPa calculated. This study demonstrates that the adjusted Hertzian theory of contact mechanics can be applied in conjunction with the parallel-plate compression system to investigate the overall mechanical behavior of intact lenses.
ESTABLISHMENT AND APPLICATION OF LOWER LIMB FINITE ELEMENT MODEL BASED ON MUSCLE GROUPS
Authors: WANG MONAN , LI RONGPENG , JING JUNTONG
Published: November 2018

Living body or corpse could be replaced with the virtual human tissue model for biomechanical experimental study, which effectively avoids the non-reusability, great social controversy, huge costs and difficulty in extracting parameters, and finally, the accurate analysis results are obtained. Unlike the previous lower limb models, the finite element models of hip and thigh were established based on the concept of muscle group in this paper. The cortical bones of hip bone and femur were set as *MAT_PIECEWISE_LINEAR_ PLASTICITY. The material of cancellous bone was set as *MAT_ELASTIC_PLASTIC_ WITH_DAMAGE_FAILURE. The material of articular cartilage was set as *MAT_ISOTROPIC_ELASTIC. The materials of muscle and fat were set as *MAT_VISCOELASTIC. The accuracy of the finite element model was verified by dynamic three-point bending experiment of the thighs. Mechanical simulation was carried out to the stump-prosthetic socket and the comfort of socks by the established model. The simulation results were all between the upper and lower bounds of the experimental results in the dynamic three-point bending experiment of the thighs where the loads were separately applied to one-third of the distal end of thighs and the middle part of thighs. The simulation results of the stump-prosthetic socket example show that the optimal elastic modulus of silicone pad is 2.5[Formula: see text]MPa. Simulation results of socks comfort show that the distribution of stress and deformation of the anterior and posterior thighs is different when the human lower limbs are in stockings. The established simulation model meets the accuracy requirement and can replace the living body or corpse to carry out biomechanical experimental study. The finite element simulation results converge, and the time to complete a finite element calculation is less than or equal to 10[Formula: see text]min.
EFFECT OF A HIGH-FREQUENCY VIBRATION BOUNDARY ON RBC
Authors: YUN ZHONG , XIANG CHUANG , WANG LIANG
Published: November 2018

The vibrations in blood pumps were often caused by high speed, suspension structure, viscoelastic implantation environment and other factors in practical application. Red blood cell (RBC) was modeled using a nonlinear spring network model. The immersed boundary-lattice Boltzmann method (IB-LBM) was used to investigate the impact of high-frequency vibration boundary on RBC. To confirm the RBC model, the simulation results of RBC stretching were compared with experimental results. We examined the force acting on RBC membrane nodes; moreover, we determined whether RBC energy was affected by different frequencies, amplitudes, and vibration models of the boundary. Furthermore, we examined whether RBC energy was affected by the distance between the top and bottom boundaries. The energy of RBCs in shear flow disturbed by the vibration boundary was also investigated. The results indicate that larger amplitude (Am), frequency (Fr), and opposite vibration velocity of top and bottom boundary produced a larger force that acted on RBC membrane nodes and larger energy changes in RBCs. The vibration boundary may cause turbulence and alter RBC energy. When the blood pump was designed and optimized, the vibration frequency and amplitude of the blood pump body and impeller should be reduced, the phase of the blood pump body and impeller vibration velocity should be close. To alleviate the free energy of RBCs and to reduce RBC injury in the blood pump, the distance between RBCs and the boundary should not be less than 20[Formula: see text][Formula: see text]m.
MOBILE ROBOT MOTOR BEARING FAULT DETECTION AND CLASSIFICATION ON DISCRETE WAVELET TRANSFORM AND LSTM NETWORK
Authors: LI SHIWEI , ZHAO YONGPING , DING MINGLI
Published: November 2018

The impact of motors breakdown and failures on mobile robot motor bearing is an important concern for robot industries. For this reason, predictive motor lifetime and bearing fault classification techniques are being investigated extensively as a method of decreasing motor downtime and enhancing mobile robot reliability. With increasing attention on neural network technologies, many researchers have carried out lots of the relevant experiments and analyses, very plentiful and important conclusions are obtained. In this article, a classification method based on discrete wavelet transform (DWT) and long short-term memory network (LSTM) a proposed to find and classify fault type of mobile robot permanent magnet synchronous motor (PMSM). First, a set of mobile robot motor vibration signal were collected by the sensors. Second, the obtained vibration signal is decomposed into six frequency bands by the DWT. Haar function is selected as the mother function in the processing. The energy of every frequency band was calculated as a classification feature. Thirdly, four classification features with high classification rate are obtained. The feature vector is used as input of the neural network, and the fault type is identified by LSTM classifier with deviation unit. From the results of the experiments provided in the paper, the method can detect the fault type accurately and it is feasible and effective under different motor speed.
Geology, geomorphology and geohazards on a section of the Betic coastline, southern Spain
Authors: Hearn G. J.
Published: November 2018

The geology of the Betic Cordillera has inspired national and international interest since the first half of the 19th century and structural and tectonic models continue to be refined. The coastal mountain ranges between Nerja and La Herradura expose rocks of the internal Betics that comprise predominantly sheared, folded and faulted schists, phyllites, quartzites and carbonates. Steep and complex terrain, adverse structure, highly disturbed rock masses, seasonally intense rainfall and coastal erosion create a challenging environment for infrastructure and urban development.
A century-long commitment to assessing artificial intelligence and its impact on society
Authors: Grosz Barbara J. , Stone Peter
Published: November 2018

A series of reports promises the general public a technologically accurate view of the state of AI and its societal implications.
Promoting common sense, reality, dependable engineering
Authors: Hoffmann Leah
Published: November 2018

Peter G. Neumann traces a lifetime devoted to identifying computing risks.
Roles of blood-brain barrier integrins and extracellular matrix in stroke
Authors: Edwards Danielle N. , Bix Gregory J.
Published: November 2018

Ischemicstroke is a leading cause of death and disability in the United States, but recent advances in treatments [i.e., endovascular thrombectomy and tissue plasminogen activator (t-PA)] that target the stroke-causing blood clot, while improving overall stroke mortality rates, have had much less of an impact on overall stroke morbidity. This may in part be attributed to the lack of therapeutics targeting reperfusion-induced injury after the blood clot has been removed, which, if left unchecked, can expand injury from its core into the surrounding at risk tissue (penumbra). This occurs in two phases of increased permeability of the blood-brain barrier, a physical barrier that under physiologic conditions regulates brain influx and efflux of substances and consists of tight junction forming endothelial cells (and transporter proteins), astrocytes, pericytes, extracellular matrix, and their integrin cellular receptors. During, embryonic development, maturity, and following stroke reperfusion, cerebral vasculature undergoes significant changes including changes in expression of integrins and degradation of surrounding extracellular matrix. Integrins, heterodimers with α and β subunits, and their extracellular matrix ligands, a collection of proteoglycans, glycoproteins, and collagens, have been modestly studied in the context of stroke compared with other diseases (e.g., cancer). In this review, we describe the effect that various integrins and extracellular matrix components have in embryonic brain development, and how this changes in both maturity and in the poststroke environment. Particular focus will be on how these changes in integrins and the extracellular matrix affect blood-brain barrier components and their potential as diagnostic and therapeutic targets for ischemic stroke.
Inhibitory effects of growth differentiation factor 11 on autophagy deficiency-induced dedifferentiation of arterial smooth muscle cells
Authors: Yuan Xinxu , Bhat Owais M. , Lohner Hannah , Li Ningjun , Zhang Yang , Li Pin-Lan
Published: November 2018

Growth differentiation factor (GDF)11 has been reported to reverse age-related cardiac hypertrophy in mice and cause youthful regeneration of cardiomyocytes. The present study attempted to test a hypothesis that GDF11 counteracts the pathologic dedifferentiation of mouse carotid arterial smooth muscle cells (CASMCs) due to deficient autophagy. By real-time RT-PCR and Western blot analysis, exogenously administrated GDF11 was found to promote CASMC differentiation with increased expression of various differentiation markers (α-smooth muscle actin, myogenin, myogenic differentiation, and myosin heavy chain) as well as decreased expression of dedifferentiation markers (vimentin and proliferating cell nuclear antigen). Upregulation of the GDF11 gene by trichostatin A (TSA) or CRISPR-cas9 activating plasmids also stimulated the differentiation of CASMCs. Either GDF11 or TSA treatment blocked 7-ketocholesterol-induced CASMC dedifferentiation and autophagosome accumulation as well as lysosome inhibitor bafilomycin-induced dedifferentiation and autophagosome accumulation. Moreover, in CASMCs from mice lacking the CD38 gene, an autophagy deficiency model in CASMCs, GDF11 also inhibited its phenotypic transition to dedifferentiation status. Correspondingly, TSA treatment was shown to decrease GDF11 expression and reverse CASMC dedifferentiation in the partial ligated carotid artery of mice. The inhibitory effects of TSA on dedifferentiation of CASMCs were accompanied by reduced autophagosome accumulation in the arterial wall, which was accompanied by attenuated neointima formation in partial ligated carotid arteries. We concluded that GDF11 promotes CASMC differentiation and prevents the phenotypic transition of these cells induced by autophagosome accumulation during different pathological stimulations, such as Western diet, lysosome function deficiency, and inflammation.

NEW & NOTEWORTHY The present study demonstrates that growth differentiation factor (GDF)11 promotes autophagy and subsequent differentiation in carotid arterial smooth muscle cells. Upregulation of GDF11 counteracts dedifferentiation under different pathological conditions. These findings provide novel insights into the regulatory role of GDF11 in the counteracting of sclerotic arterial diseases and also suggest that activation or induction of GDF11 may be a new therapeutic strategy for the treatment or prevention of these diseases.
Downregulation of GATA6 in mTOR-inhibited human aortic endothelial cells: effects on TNF-α-induced VCAM-1 expression and monocytic cell adhesion
Authors: Fan Xing , Chen Xiaolin , Feng Qi , Peng Kai , Wu Qianqian , Passerini Anthony G. , Simon Scott I. , Sun ChongXiu
Published: November 2018

Increased expression of vascular cell adhesion molecule 1 (VCAM-1) on the aortic endothelium is an early marker of atherogenesis, promoted in part by elevated levels of inflammatory cytokines such as TNF-α. Mammalian target of rapamycin (mTOR) is a ubiquitous signaling molecule that has been considered to contribute to diverse cellular processes through mTOR complex 1 (mTORC1) or complex 2 (mTORC2). This study aimed to elucidate the role of mTOR signaling in TNF-α-induced VCAM-1 expression by the arterial endothelium. Primary human aortic endothelial cells (HAECs) were treated with low-dose (0.1 ng/ml) TNF-α, and VCAM-1 expression was measured by real-time quantitative PCR, Western blot analysis, and flow cytometry. Inhibition of mTOR through siRNA-mediated depletion or treatment with chemical inhibitors rapamycin or torin 1 suppressed VCAM1 transcription, which translated to inhibition of VCAM-1 surface expression by HAECs and concomitant decreased adhesion of monocytes. A promoter luciferase assay and chromatin immunoprecipitation indicated that mTOR regulated VCAM1 transcription through a mechanism involving transcription factor GATA6. Activation of PKC-α and an increase in miR-200a-3p expression, caused by mTOR inhibition but not disruption of mTORC1 or mTORC2 singly or together, decreased TNF-α-induced GATA6 expression and its enrichment at the VCAM1 promoter. In conclusion, mTOR inhibition activates PKC-α independently of disruption of mTORC1 and/or mTORC2, which challenges the conventional wisdom regarding mTOR signaling. Moreover, mTOR signals through transcriptional and posttranscriptional mechanisms to elicit maximal cytokine-induced endothelial inflammation that precedes atherosclerosis.

NEW & NOTEWORTHY Both mammalian target of rapamycin (mTOR) complex 1 (mTORC1) and mTORC2 contribute to PKC-α activation in the human aortic endothelium. Inhibition of mTOR is not equivalent to disruption of mTORC1 and/or mTORC2 in affecting human aortic endothelial cell signaling. Specifically, inhibition of mTOR causes PKC-α activation and miR-200a-3p upregulation, which independently suppresses TNF-α-induced transcription factor GATA6 expression and subsequently inhibits VCAM-1 expression and monocytic cell adhesion onto the aortic endothelium.
Dopamine modulates excitatory transmission to orexin neurons in a receptor subtype-specific manner
Authors: Linehan Victoria , Rowe Todd M. , Hirasawa Michiru
Published: November 2018

Dopamine (DA) can promote or inhibit consummatory and reward-related behaviors by activating different receptor subtypes in the lateral hypothalamus and perifornical area (LH/PF). Because orexin neurons are involved in reward and localized in the LH/PF, DA may modulate these neurons to influence reward-related behaviors. To determine the cellular mechanism underlying dopaminergic modulation of orexin neurons, the effect of DA on excitatory transmission to these neurons was investigated using in vitro electrophysiology on rat brain slices. We found that low concentrations (0.1–1 µM) of DA increased evoked excitatory postsynaptic current amplitude while decreasing paired-pulse ratio. In contrast, high concentrations (10–100 µM) of DA did the opposite. The excitatory effect of low DA was blocked by the D1 receptor antagonist SCH-23390, whereas the inhibitory effect of high DA was blocked by the D2 receptor antagonist sulpiride. These results indicate distinct roles of D1 and D2 receptors in bidirectional presynaptic modulation of excitatory transmission. DA had stronger effects on isolated synaptic activity than repetitive ones, suggesting that sensitivity to dopaminergic modulation depends on the level of network activity. In orexin neurons from high-fat diet-fed rats, a high concentration of DA was less effective in suppressing repetitive synaptic activity compared with chow controls. Therefore, in diet-induced obesity, intense synaptic inputs may preferentially reach orexin neurons while intermittent signals are inhibited by high DA levels. In summary, our study provides a cellular mechanism by which DA may exert opposite behavioral effects in the LH/PF through bidirectional modulation of orexin neurons via different DA receptors.
Tracking autonomic balance using an open-loop model of the arterial baroreflex
Authors: Birjiniuk Jonathan , Heldt Thomas
Published: November 2018

Blood pressure control is vital for maintaining adequate perfusion of the brain and other organs in the body across varying physiological demands, and the arterial baroreceptor reflex (baroreflex) is the major short-term blood pressure control loop mediated by the autonomic nervous system (ANS). Accurate quantitative models of the baroreflex would provide physiological insight and could allow for real-time tracking of ANS activity in clinical settings. In this work, we formulate a causal, parametric beat-to-beat model, relating systolic blood pressure (input) to heart rate (output). Model structure and parameterization are explicitly based on prior physiological insights of the response dynamics of the sympathetic and parasympathetic branches of the ANS. We analyze the model’s ability to track changes in autonomic balance using data from 14 nonsmoking adult males, without any history of cardiopulmonary disease, subject to both pharmacological blockade and postural changes. Our results show that the model parameters faithfully track expected changes in autonomic balance resulting from changing posture ( P < 0.01) and sympathetic blockade ( P < 0.05), and in many cases, the model parameters are more sensitive to changes in autonomic activity and balance than autonomic indices derived from the power spectral density of heart rate variability. Overall, the contributions of this work further the goal of obtaining real-time quantitative assessment of the ANS.
Glucagon and insulin secretion, insulin clearance, and fasting glucose in GIP receptor and GLP-1 receptor knockout mice
Authors: Tura Andrea , Pacini Giovanni , Yamada Yuchiro , Seino Yutaka , Ahrén Bo
Published: November 2018

It is not known whether GIP receptor and GLP-1 receptor knockout (KO) mice have perturbations in glucagon secretion or insulin clearance, and studies on impact on fasting glycemia have previously been inconsistent in these mice. We therefore studied glucagon secretion after oral whey protein (60 mg) and intravenous arginine (6.25 mg), insulin clearance after intravenous glucose (0.35 g/kg) and fasting glucose, insulin, and glucagon levels after standardized 5-h fasting in female GIP receptor and GLP-1 receptor KO mice and their wild-type (WT) littermates. Compared with WT controls, GIP receptor KO mice had normal glucagon responses to oral protein and intravenous arginine, except for an enhanced 1-min response to arginine, whereas glucagon levels after oral protein and intravenous arginine were enhanced in GLP-1 receptor KO mice. Furthermore, the intravenous glucose test revealed normal insulin clearance in both GIP receptor and GLP-1 receptor KO mice, whereas β-cell glucose sensitivity was enhanced in GIP receptor KO mice and reduced in GLP-1 receptor KO mice. Finally, GIP receptor KO mice had reduced fasting glucose (6.7 ± 0.1, n = 56, vs. 7.4 ± 0.1 mmol/l, n = 59, P = 0.001), whereas GLP-1 receptor KO mice had increased fasting glucose (9.1 ± 0.2, n = 44, vs. 7.7 ± 0.1 mmol/l, n = 41, P < 0.001). We therefore suggest that GIP has a limited role for glucagon secretion in mice, whereas GLP-1 is of importance for glucagon regulation, that GIP and GLP-1 are of importance for the regulation of β-cell function beyond their role as incretin hormones, and that they are both of importance for fasting glucose.
Curcumin improves exercise performance of mice with coronary artery ligation-induced HFrEF: Nrf2 and antioxidant mechanisms in skeletal muscle
Authors: Wafi Ahmed M. , Hong Juan , Rudebush Tara L. , Yu Li , Hackfort Bryan , Wang Hanjun , Schultz Harold D. , Zucker Irving H. , Gao Lie
Published: November 2018

A hallmark of chronic heart failure (HF) with low ejection fraction (HFrEF) is exercise intolerance. We hypothesized that reduced expression of nuclear factor E2-related factor 2 (Nrf2) in skeletal muscle contributes to impaired exercise performance. We further hypothesized that curcumin, a Nrf2 activator, would preserve or increase exercise capacity in HF. Experiments were carried out in mice with coronary artery ligation-induced HFrEF. Curcumin was deliveried by a subcutaneous osmotic minipump at a dose of 50 mg·kg−1·day−1 for 8 weeks. In vivo, in situ, and in vitro experiments were employed to evaluate exercise capacity, muscle function, and molecular mechanisms. We found that: 1) the maximal speed, running distance to exhaustion, and limb grip force were significantly lower in HFrEF mice compared with sham. Curcumin-treated HF mice displayed enhanced exercise performance compared with vehicle-treated HF mice; 2) both soleus (Sol) and extensor digitorum longus (EDL) muscles of HFrEF mice exhibited reduced force and rapid fatigue, which were ameliorated by curcumin; and 3) protein expression of Nrf2, hemeoxygenase-1, SOD2, myogenin, and MyoD were significantly lower, but total ubiquitinated proteins, MURF1, and atrogen-1 were higher in Sol and EDL of HFrEF compared with sham mice, whereas these alterations in Nrf2 signaling and antioxidant defenses in HFrEF were attenuated by curcumin, which had no effect on cardiac function per se in mice with severe HFrEF. These data suggest that impaired Nrf2 signaling intrinsic to skeletal muscle contributes to exercise intolerance in HFrEF. Skeletal muscle Nrf2 should be considered as a novel therapeutic target in severe HF.

NEW & NOTEWORTHY These studies suggest that impaired nuclear factor E2-related factor 2 (Nrf2) signaling is a critical mechanism underlying the enhanced oxidative stress in skeletal muscle in heart failure with low ejection fraction (HFrEF). Curcumin prevents the decline in running performance in HFrEF mice by upregulating antioxidant defenses in skeletal muscle, likely mediated by activating Nrf2 signaling. These findings suggest a novel therapeutic target for the improvement of exercise capacity and quality of life in HFrEF patients.
Colocalization of distinct NMDA receptor subtypes at excitatory synapses in the entorhinal cortex
Authors: Beesley Stephen , Sullenberger Thomas , Pilli Jyotsna , Abbasi Saad , Gunjan Akash , Kumar Sanjay S.
Published: November 2018

The subunit composition of N-methyl-d-aspartate receptors (NMDARs) at synaptic inputs onto a neuron can either vary or be uniform depending on the type of neuron and/or brain region. Excitatory pyramidal neurons in the frontal and somatosensory cortices (L5), for example, show pathway-specific differences in NMDAR subunit composition in contrast with the entorhinal cortex (L3), where we now show colocalization of NMDARs with distinct subunit compositions at individual synaptic inputs onto these neurons. Subunit composition was deduced electrophysiologically based on alterations of current-voltage relationship ( I–V) profiles, amplitudes, and decay kinetics of minimally evoked, pharmacologically isolated, NMDAR-mediated excitatory postsynaptic currents by known subunit-preferring antagonists. The I–Vs were outwardly rectifying in a majority of neurons assayed (~80%), indicating expression of GluN1/GluN2/GluN3-containing triheteromeric NMDARs ( t-NMDARs) and of the conventional type, reversing close to 0 mV with prominent regions of negative slope, in the rest of the neurons sampled (~20%), indicating expression of GluN1/GluN2-containing diheteromeric NMDARs ( d-NMDARs). Blocking t-NMDARs in neurons with outwardly rectifying I–Vs pharmacologically unmasked d-NMDARs, with all responses antagonized using D-AP5. Coimmunoprecipitation assays of membrane-bound protein complexes isolated from the medial entorhinal area using subunit-selective antibodies corroborated stoichiometry and together suggested the coexpression of t- and d-NMDARs at these synapses. Colocalization of functionally distinct NMDAR subtypes at individual synaptic inputs likely enhances the repertoire of pyramidal neurons for information processing and plasticity within the entorhinal cortex.

NEW & NOTEWORTHY The subunit composition of a N-methyl-d-aspartate (NMDA) receptor, which dictates most aspects of its function, can vary between neurons in different brain regions and/or between synaptic inputs onto single neurons. Here we demonstrate colocalization of tri- and diheteromeric-NMDA receptors at the same/single synaptic input onto excitatory neurons in the entorhinal cortex. Synaptic colocalization of distinct NMDAR subtypes might endow entorhinal cortical neurons with the ability to encode distinct patterns of neuronal activity through single synapses.
Analysis and Optimal Control Intervention Strategies of a Waterborne Disease Model: A Realistic Case Study
Authors: Collins Obiora Cornelius , Duffy Kevin Jan
Published: November 2018

A mathematical model is formulated that captures the essential dynamics of waterborne disease transmission under the assumption of a homogeneously mixed population. The important mathematical features of the model are determined and analysed. The model is extended by introducing control intervention strategies such as vaccination, treatment, and water purification. Mathematical analyses of the control model are used to determine the possible benefits of these control intervention strategies. Optimal control theory is utilized to determine how to reduce the spread of a disease with minimum cost. The model is validated using a cholera outbreak in Haiti.
Tetramethylpyrazine and Paeoniflorin Inhibit Oxidized LDL‐Induced Angiogenesis in Human Umbilical Vein Endothelial Cells via VEGF and Notch Pathways
Authors: Yuan Rong , Shi Weili , Xin Qiqi , Yang Binrui , Hoi Maggie Puiman , Lee Simon Mingyuan , Cong Weihong , Chen Keji
Published: November 2018

Atherosclerotic plaque angiogenesis is key factor in plaque instability and vulnerability, and low concentrations of oxidized low density lipoprotein (ox‐LDL) promote the in vitro angiogenesis of endothelial cells and play an important role in plaque angiogenesis. Ligusticum chuanxiong Hort. and Radix Paeoniae Rubra herb pair in Chinese medicine obtains the optimum therapeutic efficacy in atherosclerosis, and their major active ingredients tetramethylpyrazine (TMP) and paeoniflorin (PF) are reported to alleviate atherosclerosis. The aim of this study was to investigate the effects of TMP and PF on ox‐LDL‐induced angiogenesis and the underlying mechanism. Human umbilical vein endothelial cells (HUVECs) were incubated with ox‐LDL and were then treated with TMP, PF, or a combination of TMP and PF. Cell proliferation, migration, tube formation, and the expression of angiogenesis‐related proteins were measured. Synergism was evaluated using the combination index in cell proliferation. We found that TMP and PF attenuated the in vitro angiogenesis in ox‐LDL‐induced HUVECs. In addition, the combination of TMP and PF not only inhibited the ox‐LDL‐induced expression of CD31, vascular endothelial growth factor (VEGF), and VEGF receptor 2 (VEGFR2) but also decreased the ox‐LDL‐induced expression of Notch1, Jagged1, and Hes1. In summary, the combination of TMP and PF suppresses ox‐LDL‐induced angiogenesis in HUVECs by inhibiting both the VEGF/VEGFR2 and the Jagged1/Notch1 signaling pathways, which might contribute to the stability of plaques in atherosclerosis.
An SDN-Based Approach to Ward Off LAN Attacks
Authors: Rietz René , Cwalinski Radoslaw , König Hartmut , Brinner Andreas
Published: November 2018

The detection of attacks on large administrative network domains is nowadays generally accomplished centrally by analyzing the data traffic on the uplink to the Internet. The first phase of an infection is usually difficult to observe. Often attackers use e-mail attachments or external media, such as USB sticks, hardware with preinstalled malware, or contaminated mobile devices to infect target systems. In such scenarios, the initial infection cannot be blocked at the network level. The lateral movement of attack programs (exploits) through internal networks and the exfiltration of data, however, which are the main purpose of targeted attacks, run always over the network. Security measures against such internal network attacks require a comprehensive monitoring concept that spans the entire network to its edge. Especially for preventive measures, this means providing a security concept for local area networks (LANs). In this paper, we propose based on an analysis of typical LAN-based attacks an approach for preventing these attacks for both IPv4 and IPv6 networks. It applies the software-defined networking (SDN) paradigm for centralizing the related network decisions in a central authority—the SDN controller—that manages all network connections and hence the associated data flows.
Prevalence and Risk Factors of ACO (Asthma-COPD Overlap) in Aboriginal People
Authors: Koleade Adetola , Farrell Jamie , Mugford Gerald , Gao Zhiwei
Published: November 2018

Background and Objective. Aboriginal peoples are at a higher risk of many chronic respiratory diseases compared to the general Canadian population. Patients with asthma-COPD overlap (ACO), a disease newly described in 2015, are associated with frequent exacerbations, rapid decline in lung function, poor quality of life, high mortality, and disproportionate utilization of health-care resources than patients with asthma and COPD alone. The objective was to investigate the prevalence and risk factors of ACO in Aboriginal peoples.Methods. Data from the 2012 Aboriginal Peoples Survey (APS) were used for this study. The ACO definition was based on the respondent giving positive responses to both of the following questions“Do you/Does (name) have Asthma diagnosed by a health professional?”and“Do you/Does (name) have chronic bronchitis, emphysema or chronic pulmonary obstructive disease or COPD diagnosed by a health professional?” Results. Aboriginal peoples older than 45 years, women, widowed, separated, or divorced, having a total personal income below $20,000 were associated with a significant risk of ACO. Residing in Ontario, being a daily smoker, living in a rented dwelling, dwelling in need of major repairs, having diabetes, and working more than 40 hrs a week were also significantly associated with increased risk of ACO.Conclusion. The results from this study will provide information to aid the development of prevention and intervention strategies for Aboriginal communities.
Drug‐Repositioning Approach for the Discovery of Anti‐Influenza Virus Activity of Japanese Herbal (Kampo) Medicines In Vitro: Potent High Activity of Daio‐Kanzo‐To
Authors: Watanabe Ken
Published: November 2018

Influenza virus infections are a serious public health concern throughout the world. Emergence of viral resistance to the currently approved anti‐influenza drugs warrants the development of new antiviral agents. Japanese herbal medicines called Kampo are very commonly used as prescription medication in Japan, and Mao‐to is known to be effective against influenza that is caused by oseltamivir‐resistant viruses. However, influenza‐related death occurs mainly among the elderly, and for patients with hypertension and diabetes, Mao‐to may cause these diseases to worsen. Therefore, the exploration of more potent and safe Kampo medicines may be a good strategy for developing new influenza medicines. Here cell‐based screening of anti‐influenza virus activity for 42 approved Kampo medicines was performed using the drug‐repositioning approach. As a result, four Kampo medicines were selected as potent anti‐influenza agents against the A/WSN/33 strain. It was found that Daio‐kanzo‐to [50% inhibitory concentration (IC50) = 10.5 μg/mL; 50% cytotoxic concentration (CC50) = 71.6 μg/mL; selective index = 6.8] is more effective than Mao‐to. Daio‐kanzo‐to and its constituent Japanese Pharmacopoeia (JP) Rhubarb were also effective against H3N2 and H1N1 subtypes of influenza viruses, including oseltamivir‐insensitive‐2009 pandemic clinical isolates. These data suggest the potential application of Daio‐kanzo‐to for influenza treatment.
Molecular Antimicrobial Resistance ofNeisseria gonorrhoeaein a Moroccan Area
Authors: Karim Safae , Bouchikhi Chahrazed , Banani Abdelaziz , El Fatemi Hinde , Souho Tiatou , Erraghay Sanaa , Bennani Bahia
Published: November 2018

Objectives. To identify the prevalence and the types ofNeisseria gonorrhoeae(NG) resistance plasmids-mediated penicillin (PPNG) and tetracycline (TRNG), the ciprofloxacin resistance (CRNG), and related risk factors of each types of resistance.Methods. The beta-lactamase-producing plasmid types (Africa, Asia, and Toronto),tetMtetracycline resistance plasmid types (America and Dutch), and the determination of the Ser-91 mutation of GyrA were detected by specifics PCRs on 149 diagnosed NG positives samples followed byHinf1digestion fortetMandgyrAmutation.Results. 135 (90.1%) samples showed a profile of molecular resistance to at least one antibiotic with predominance of ciprofloxacin resistance. In fact, 36 (24.2%) and 69 (46.3%) cases harbored PPNG and TRNG, respectively, and 116 (77.9%) cases showed the mutation Ser-91 of GyrA (CRNG). From a total of 36 PPNG isolates, the Toronto, Asian, and Toronto/Asian types were detected in 13 (36.1%), 10 (27.8%), and 13 (36.1%) cases, respectively, whereas the African type was not detected. In addition, the American type of TRNG was detected in 92.8% (64/69) of cases, while the Dutch type was detected in 7.2% (5/69) of cases. The association of demographics and clinical variables with NG resistance to ciprofloxacin, penicillin, and tetracycline was studied and the risk factors have been determined.Conclusion. Resistance to penicillin, tetracycline, and ciprofloxacin among NG samples positives remained at high levels in Morocco as determined by molecular profile. So, the use of molecular tools for NG antimicrobial resistance detection can help in the management and spread limitation of this infection.
Acupuncture for Primary Dysmenorrhea: An Overview of Systematic Reviews
Authors: Zhang Furong , Sun Mingsheng , Han Shanshan , Shen Xiaoyu , Luo Yanan , Zhong Dongling , Zhou Xiujuan , Liang Fanrong , Jin Rongjiang
Published: November 2018

Objectives. As current evidence of the effectiveness on acupuncture for primary dysmenorrhea (PD) is inconsistent, we aimed to critically appraise the evidence from relevant systematic reviews (SRs). Methods. SRs of randomized controlled trials (RCTs) concerning acupuncture and PD were searched in four databases. The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) and latest Assessment of Multiple Systematic Reviews 2 (AMSTAR2) checklists were used to assess reporting characteristics and methodological quality, respectively. Results. The literature search yielded 38 potential records, of which five met the inclusion criteria. The total average (SD) for PRISMA was 20.60 (1.14) out of 27. All five SRs have more than one critical weakness in AMSTAR2, so their methodological qualities were considered as critically low. The most frequent problems included nonregistration of study protocol, absence of a list of excluded studies, and unclear acknowledgment of conflicts of interests. The three studies of higher methodological quality reported positive results in pain relief. Conclusion. The reporting and methodological quality of systematic reviews and meta‐analysis studies were suboptimal, which demands further improvement. More efforts are needed to improve validity of systematic reviews and RCTs in this area.
A New Weighting Scheme in Weighted Markov Model for Predicting the Probability of Drought Episodes
Authors: Ali Zulfiqar , Hussain Ijaz , Faisal Muhammad , Almanjahie Ibrahim M. , Ismail Muhammad , Ahmad Maqsood , Ahmad Ishfaq
Published: November 2018

Drought is a complex stochastic natural hazard caused by prolonged shortage of rainfall. Several environmental factors are involved in determining drought classes at the specific monitoring station. Therefore, efficient sequence processing techniques are required to explore and predict the periodic information about the various episodes of drought classes. In this study, we proposed a new weighting scheme to predict the probability of various drought classes under Weighted Markov Chain (WMC) model. We provide a standardized scheme of weights for ordinal sequences of drought classifications by normalizing squared weighted Cohen Kappa. Illustrations of the proposed scheme are given by including temporal ordinal data on drought classes determined by the standardized precipitation temperature index (SPTI). Experimental results show that the proposed weighting scheme for WMC model is sufficiently flexible to address actual changes in drought classifications by restructuring the transient behavior of a Markov chain. In summary, this paper proposes a new weighting scheme to improve the accuracy of the WMC, specifically in the field of hydrology.