bluuebunny/crossref_metadata_2025 huggingface dataset:
A Multilabel Fuzzy Relevance Clustering System for Malware Attack Attribution in the Edge Layer of Cyber-Physical Networks
Authors: Alaeiyan Mohammadhadi , Dehghantanha Ali , Dargahi Tooska , Conti Mauro , Parsa Saeed
Published: March 2020

The rapid increase in the number of malicious programs has made malware forensics a daunting task and caused users’ systems to become in danger. Timely identification of malware characteristics including its origin and the malware sample family would significantly limit the potential damage of malware. This is a more profound risk in Cyber-Physical Systems (CPSs), where a malware attack may cause significant physical damage to the infrastructure. Due to limited on-device available memory and processing power in CPS devices, most of the efforts for protecting CPS networks are focused on the edge layer, where the majority of security mechanisms are deployed.

Since the majority of advanced and sophisticated malware programs are combining features from different families, these malicious programs are not similar enough to any existing malware family and easily evade binary classifier detection. Therefore, in this article, we propose a novel multilabel fuzzy clustering system for malware attack attribution. Our system is deployed on the edge layer to provide insight into applicable malware threats to the CPS network. We leverage static analysis by utilizing Opcode frequencies as the feature space to classify malware families.

We observed that a multilabel classifier does not classify a part of samples. We named this problem the instance coverage problem. To overcome this problem, we developed an ensemble-based multilabel fuzzy classification method to suggest the relevance of a malware instance to the stricken families. This classifier identified samples of VirusShare, RansomwareTracker, and BIG2015 with an accuracy of 94.66%, 94.26%, and 97.56%, respectively.
Multi-scale Supervised Attentive Encoder-Decoder Network for Crowd Counting
Authors: Zhang Anran , Jiang Xiaolong , Zhang Baochang , Cao Xianbin
Published: March 2020

Crowd counting is a popular topic with widespread applications. Currently, the biggest challenge to crowd counting is large-scale variation in objects. In this article, we focus on overcoming this challenge by proposing a novel Attentive Encoder-Decoder Network (AEDN), which is supervised on multiple feature scales to conduct crowd counting via density estimation. This work has three main contributions. First, we augment the traditional encoder-decoder architecture with our proposed residual attention blocks, which, beyond skip-connected encoded features, further extend the decoded features with attentive features. AEDN is better at establishing long-range dependencies between the encoder and decoder, therefore promoting more effective fusion of multi-scale features for handling scale-variations. Second, we design a new KL-divergence-based distribution loss to supervise the scale-aware structural differences between two density maps, which complements the pixel-isolated MSE loss and better optimizes AEDN to generate high-quality density maps. Third, we adopt a multi-scale supervision scheme, such that multiple KL divergences and MSE losses are deployed at all decoding stages, providing more thorough supervisions for different feature scales. Extensive experimental results on four public datasets, including ShanghaiTech Part A, ShanghaiTech Part B, UCF-CC-50, and UCF-QNRF, reveal the superiority and efficacy of the proposed method, which outperforms most state-of-the-art competitors.
Multichannel Attention Refinement for Video Question Answering
Authors: Zhuang Yueting , Xu Dejing , Yan Xin , Cheng Wenzhuo , Zhao Zhou , Pu Shiliang , Xiao Jun
Published: March 2020

Video Question Answering (VideoQA) is the extension of image question answering (ImageQA) in the video domain. Methods are required to give the correct answer after analyzing the provided video and question in this task. Comparing to ImageQA, the most distinctive part is the media type. Both tasks require the understanding of visual media, but VideoQA is much more challenging, mainly because of the complexity and diversity of videos. Particularly, working with the video needs to model its inherent temporal structure and analyze the diverse information it contains. In this article, we propose to tackle the task from a multichannel perspective. Appearance, motion, and audio features are extracted from the video, and question-guided attentions are refined to generate the expressive clues that support the correct answer. We also incorporate the relevant text information acquired from Wikipedia as an attempt to extend the capability of the method. Experiments on TGIF-QA and ActivityNet-QA datasets show the advantages of our method compared to existing methods. We also demonstrate the effectiveness and interpretability of our method by analyzing the refined attention weights during the question-answering procedure.
Consensus Dynamics
Authors: Becchetti Luca , Clementi Andrea , Natale Emanuele
Published: March 2020

The term distributed system typically refers to a set of entities, called nodes, connected by point-topoint communication links. The set of nodes together with the set of links form a network, which is usually represented by a graph. The term ?system" is used to reflect the fact that nodes evolve over time, i.e., they change their internal states according to some local interaction-rule, which is applied in every time step (i.e. round).
Effect of Partial Cycling of NCA/Graphite Cylindrical Cells in Different SOC Intervals
Authors: Benavente-Araoz Fabian , Varini Maria , Lundblad Anders , Cabrera Saúl , Lindbergh Göran
Published: March 2020

A quasi-realistic aging test of NCA/graphite lithium-ion 18650 cylindrical cells is performed during a long-term low c-rate cycling and using a new protocol for testing and studying the aging. This to emulate a characteristic charge/discharge profile of off-grid PV-battery systems. The cells were partially cycled at four different cut-off voltages and two state of charge ranges (ΔSOC) for 1000 and 700 cycles over 24 months. Differential voltage analysis shows that a combination of loss of active material (LAM) and loss of lithium inventory (LLI) are the causes of capacity loss. Cells cycled with high cut-off voltages and wide ΔSOC (20% to 95%) were severely affected by material degradation and electrode shift. High cut-off voltage and narrow ΔSOC (65% to 95%) caused greater electrode degradation but negligible cell unbalance. Cell impedance is observed to increase in both cells. Cells cycled with middle to low cut-off voltages and narrow ΔSOC (35%–65% and 20% to 50%) had comparable degradation rates to calendar-aged cells. Cycling NCA/graphite cells with low c-rate and high cut-off voltages will degrade the electrode in the same way high c-rate would do. However, low c-rate at low and middle cut-off voltages greatly decrease cell degradation compared to similar conditions at middle to high c-rate, therefore increasing battery lifetime.
Development of a New Procedure for Nail Penetration of Lithium-Ion Cells to Obtain Meaningful and Reproducible Results
Authors: Diekmann Jan , Doose Stefan , Weber Svenja , Münch Swantje , Haselrieder Wolfgang , Kwade Arno
Published: March 2020

Internal short circuit tests of Lithium-Ion Batteries (LIBs) are used to test battery safety behavior in a custom made battery cell stressing chamber. However, systematic investigations regarding the test setup and test procedure are rare. In our research commercially available pouch cells (5 Ah) are employed for the method development and validation of nail penetration tests including measurement of gaseous reaction products. The effects of the thermal insulation material, the nail material (conductive and non-conductive), the influence of the penetration depth and the nail velocity were examined. It was observed that low penetration velocities (1 mm s−1) in combination with a conductive nail and a nail motion control, which is based on monitoring the temporal evaluation of the cell voltage change, provide the most promising results in terms of reproducibility at low standard deviation. By applying this method, only the energy required for a Thermal Runaway (TR) is released, which makes it possible to determine a novel key value for the assessment of battery safety. Based on this, a proposal has been made for a nail penetration test method which would allow the results to be compared between different test facilities.
Differential activation of the human costal and crural diaphragm during voluntary and involuntary breaths
Authors: Nguyen D. A. T. , Amirjani N. , McCaughey E. J. , Gandevia S. C. , Butler J. E. , Hudson A. L.
Published: March 2020

Simultaneous electromyographic recordings from the human costal and crural diaphragm during voluntary augmented breathing and involuntary rebreathing show that the increase in inspiratory crural diaphragm activity was ~60% of the increase in costal diaphragm activity. However costal to crural diaphragm activation did not differ between the two tasks. The dissociation in the amplitude of activation of the costal and crural diaphragm becomes apparent only as the drive to breathe increases above tidal breathing.
Control Policy Mix in Measles Transmission Dynamics Using Vaccination, Therapy, and Treatment
Authors: Jaharuddin  , Bakhtiar Toni
Published: March 2020

This paper considers a deterministic model for the dynamics of measles transmission in a population divided into six classes with respect to the disease states: susceptible, vaccinated, exposed, infected, treated, and recovered. First, we investigate the dynamical properties of the SVEITR model such as its equilibrium points, their stability, and parameter sensitivity by applying constant controls. Criteria for determining the stability of disease-free and endemic equilibrium points are provided in terms of basic reproduction number. The model is then extended by incorporating vaccination, therapy, and treatment rates as time-dependent control variables representing the level of coverages. Application of Pontryagin’s maximum principle provides the necessary conditions that must be satisfied for the existence of optimal controls aiming at minimization of the number of exposed and infected individuals simultaneously with the control effort. Numerical simulations that were carried out using the backward sweep method and Runge–Kutta scheme suggest that optimal controls under moderate and high scenarios can effectively reduce the cases of measles. In particular, the moderate scenario that utilizes the existing coverage level of 86% for MCV1 and 69% for MCV2 can degrade the cost functional by 47% of the low scenario. Meanwhile, high scenario that takes the 2020 target of 96% as coverage only makes a slight difference in reducing the number of exposed and infected individuals.
Properties of Sn‐Ag‐Cu Solder Joints Prepared by Induction Heating
Authors: Drienovsky Marian , Palcut Marián , Priputen Pavol , Cuninková Eva , Bošák Ondrej , Kubliha Marián , Trnková Lýdia Rízeková
Published: March 2020

In the present work, one near‐eutectic and three hypoeutectic Sn‐Ag‐Cu alloys have been employed for soldering by induction heating. The alloys were produced by induction melting of high purity Ag, Cu, and Sn lumps. The melting behavior of the alloys was investigated by differential scanning calorimetry. The solder alloys were subsequently applied for soldering by conventional hot‐plate heating as well as induction heating and both soldering times and peak temperatures were recorded during soldering. Solder joints of two copper sheets were produced. The electrical resistance, tensile strength, and microstructure were analyzed on each soldered joint. The results indicate that the physical and mechanical properties of solder joints are determined by their chemical composition and soldering technology. Induction soldered joints not only have a slightly higher electrical resistivity but also higher mechanical strength, except of the 0.3 wt.% Ag hypoeutectic solder. The highest increase in ultimate tensile strength (28%) was observed for induction soldered joints with 1 wt.% Ag hypoeutectic solder. This effect is ascribed to the homogenous distribution of the intermetallic compounds within the eutectic in the alloy microstructure. The homogenous distribution is aided by rotation of liquid solder due to eddy currents and high‐frequency magnetic field generated during induction heating.
Two Cases of Pituitary Stalk Interruption Syndrome in Syrian Children
Authors: Alali Ibrahim , Saad Reem , Kabalan Younes
Published: March 2020

Pituitary stalk interruption syndrome (PSIS) is an extremely rare cause of growth failure and delayed puberty. It can be diagnosed by magnetic resonance imaging (MRI) of the hypothalamus and pituitary gland, showing an ectopic or absent posterior pituitary, an absent or interrupted pituitary stalk, or small anterior pituitary, in combination with growth hormone or other pituitary hormone deficiencies. The exact etiology of PSIS is unknown. In this article, we describe two cases of PSIS in Syria which are, as far as we know, the first published cases.
Multiplicity Solutions for Integral Boundary Value Problem of Fractional Differential Systems
Authors: Song Shiying , Cui Yujun
Published: March 2020

This paper deals with the existence and multiplicity of solutions for the integral boundary value problem of fractional differential systems:D0+α1u1t=f1t,u1t,u2t,D0+α2u2t=f2t,u1t,u2t,u10=0, D0+β1u10=0, D0+γ1u11=∫01D0+γ1u1ηdA1η,u20=0, D0+β2u20=0, D0+γ2u21=∫01D0+γ2u2ηdA2η,, wherefi:0,1×0,∞×0,∞⟶0,∞is continuous andαi−2<βi≤2,αi−γi≥1,2<αi≤3,γi≥1i=1,2.D0+αis the standard Riemann–Liouville’s fractional derivative of order α. Our result is based on an extension of the Krasnosel’skiĭ’s fixed-point theorem due to Radu Precup and Jorge Rodriguez-Lopez in 2019. The main results are explained by the help of an example in the end of the article.
Acetylation and Evaluation of Taro Boloso-I Starch as Directly Compressible Excipient in Tablet Formulation
Authors: Getachew Afewerk , Yilma Zewdu , Abrha Solomon
Published: March 2020

Taro Boloso-I (TB1), a newly improved Colocasia esculenta variety, is a potential source of starch with high yield. However, to improve some limitations of the native starches (NS), such as flowability and compactibility, different physical and chemical starch modifications have been employed. Acetylation is one of the chemical modifications which improves the flow and compaction of the NS, which are prerequisite during direct compression (DC) of tablets. Hence, in this study, TB1 starch was acetylated using acetic anhydride and evaluated as an ideal excipient for direct compression. Starch acetates (SA) with a degree of substitution (DS) of 0.072 (SA1) and 0.695 (SA2) were produced and evaluated. FTIR spectra of the SAs were used to verify the acetylation of the NS. Powder flow evaluation parameters showed significant improvement in the flow properties of the NS following acetylation. In addition, the swelling power, solubility, and compactibility were also improved. Tensile strength (TS) of the tablets comprising SAs only, SA1 (41.40) and SA2 (63.43 Kg/cm2), was significantly higher than tablets made of the NS (31.96) and Starch 1500® (15.12 Kg/cm2). The SAs also showed lower sensitivity towards lubrication than the NS and Starch 1500® as lower lubricant sensitivity ratios were recorded. In addition, tablets comprising the SAs satisfactorily accommodated at least up to 50 % w/w paracetamol—compared to 30 % w/w by Starch 1500®—upon DC processing. The paracetamol tablets comprising SAs also complied with the United States Pharmacopeia specifications for disintegration and dissolution studies. Therefore, taking all the facts into consideration, the SAs could be potential DC excipients in tablet formulations.
Correlation between Taste Threshold Sensitivity and MMP-9, Salivary Secretion, Blood Pressure, and Blood Glucose Levels in Smoking and Nonsmoking Women
Authors: Tjahajawati Sri , Rafisa Anggun , Murniati Nani , Zubaedah Cucu
Published: March 2020

Cigarette smoking can cause taste receptors to increase the taste threshold value. Consequently, the consumption of sugar and salt will not be controlled, therefore causing systemic diseases such as hypertension and diabetes. Nicotine and tobacco in cigarettes can stimulate MMP-9 which plays vital physiological roles in normal tissue growth and repair processes. This study aimed to find the correlation between taste threshold sensitivity and MMP-9, salivary secretion, blood pressure, and blood glucose levels in smoking and nonsmoking women. This was a cross-sectional study consisting of young adult women aged 18–24 years. Subjects were divided into two groups: the nonsmoking and smoking groups. In the combined data of both groups, the sweet taste threshold was correlated with age (r = 0.308, p=0.008), blood glucose levels (r = 0.238, p=0.043), and MMP-9 (r = –0.297, p=0.011). The salt taste threshold was only correlated with systolic blood pressure in the smoking (r = 0.440, p=0.032) and combined data groups (r = 0.260, p=0.026). By using partial correlation, it was shown that the relationship between the salt taste threshold and systolic blood pressure was influenced by smoking habits. The sweet taste threshold in women was found to correlate with age, blood glucose levels, and MMP-9 levels. On the other hand, there was a significant relationship between the salt taste threshold in women with systolic blood pressure, which was the only correlation analyzed in sthis study that was found to be influenced by smoking. However, both sweet and salt taste thresholds were not statistically correlated with salivary secretion.
Integrating Security Requirements Engineering into MBSE: Profile and Guidelines
Authors: Mažeika D. , Butleris R.
Published: March 2020

Model-Based System Engineering (MBSE) provides a number of ways on how to create, validate, and verify the complex system design; unfortunately, the inherent security aspects are addressed neither by the SysML language that is the main MBSE enabler nor by popular MBSE methods. Although there are many common points between MBSE and security requirements engineering, the key advantages of MBSE (such as managed complexity, reduced risk and cost, and improved communication across a multidisciplinary team) have not been exploited enough. This paper reviews security requirements engineering processes and modeling methods and standards and provides the MBSE security profile as well, which is formalized with the UML 2.5 profiling capability. The new UML-based security profile conforms to the ISO/IEC 27001 information security standard. In addition to the MBSE security profile, this paper also presents the security profile application use case and the feasibility study of current status for security and systems engineering processes.
Residual Stress and Microstructure Characterization of 34CrMo4 Steel Modified by Shot Peening
Authors: Li Kejian , Wu Xu , Chen Liping , Chen Dengming , Zhu Gungjun , Shen Qian , Yoon Jae Hong
Published: March 2020

34CrMo4 steel is widely used for drill stem in oil exploration, because of its excellent properties, such as favorable hardenability, shock absorption, less tendency of temper brittleness, and eminent wear resistance. In this study, the main works are residual stress test and microstructure characterization of 34CrMo4 steel upon various shot peening treatments. The residual stress distribution with effect depth was studied upon the shot peening. Face-to-face paste sample preparation method is required for continuous observation for microstructure evolution of shot-peened specimen from the treat surface to matrix. Grain refinement, lath structure, and precipitates are clearly observed in the gradient deformation layer.
Too Real to Be Virtual: Autonomic and EEG Responses to Extreme Stress Scenarios in Virtual Reality
Authors: Fadeev Kirill A. , Smirnov Alexey S. , Zhigalova Olga P. , Bazhina Polina S. , Tumialis Alexey V. , Golokhvast Kirill S.
Published: March 2020

The evolution of virtual reality (VR) technologies requires setting boundaries of its use. In this study, 3 female participants were experiencing VR scenarios with stressful content and their activity of the autonomic nervous system and EEG were recorded. It has been discovered that virtual reality can evoke acute stress reactions accompanied by activation of the sympathetic nervous system and a decrease in the activity of the parasympathetic nervous system. The high-stress response is accompanied by a decrease in the power of the EEG, and, on the contrary, the activation of the avoidance reaction is accompanied by an increase in the power of the EEG alpha waves. Therefore, the use of stressful VR content can cause high emotional stress to a user and restrictions should be considered.
The Culture of Herbal Preparations Among Pregnant Women: A Remedy or a Suicide Potion? A Case Report and Mini Review
Authors: Ossei P. P. S. , Appiah-Kubi A. , Ankobea-Kokroe F. , Owusu-Asubonteng G. , Ayibor W. G. , Aninkora O. K. , Taylor J. , Fenteng E. A. , Agyemang-Duah E. , Agagli B. M. , Niako N.
Published: March 2020

In general, use of herbal remedies and preparations is on the ascendency in recent times among the general population and especially in young pregnant women, and this may be very dangerous due to adverse effects and interactions with drugs. A survey by the World Health Organization revealed that 70–80% of the world population resort to nonconventional medicines especially, herbal medicines in their primary healthcare. A lot of work has been done on the positive effects of herbs on the human body but very few publications on the potential side effects of consuming crude herbal preparations especially among pregnant women or the awareness of the medical team of this problem. Herbal remedies may come with many adverse effects and potentially serious interactions with some conventional medications. However, little is known about the dangers associated with consumption of herbal remedies by pregnant patients. Herbal medicines like their orthodox counterparts act through some mechanisms to bring about their curative effects in the body, and this usually goes out of order when these remedies interact with chemical drugs as a result of a combination of both by the victims. This is a case study to review the use of herbal medicine products among pregnant women, especially adolescent girls for abortive purposes, and also attempts to discuss some of the dangers associated with the use of herbal medicinal products together with conventional drugs during pregnancy.
Deflection Calculation Based on SDOF Method for Axially Loaded Concrete-Filled Steel Tubular Members Subjected to Lateral Impact
Authors: Wang Luming , Liu Yanhui , Song Jiahuan , Zhao Shichun , Wang Zhe , Zeng Yue , Feng Xingyu
Published: March 2020

Axial force has a great influence on the dynamic behavior and the impact resistance of concrete-filled steel tubular (CFST) members. Based on numerical simulation and theoretical analysis, the impact response and deflection calculation method for axially loaded CFST members subjected to lateral impact are investigated in this paper. The nonlinear numerical model of an axially loaded CFST member considering the strain rate effects has been established, and the simulation accuracy has been validated by comparing with existing test results. The contrastive investigation is carried out to illustrate the influence of axial load on the variation pattern of impact force for CFST members under various structural and impact parameters, and its result indicates that the impact force-time histories for CFST members with different axial loads are mainly characterized by rectangular pulse and triangular pulse. Moreover, a simplified calculation method considering the effect of axial force is proposed based on the equivalent single degree of freedom (SDOF) method, devoted to predicting the deflection of axially loaded CFST members subjected to lateral impact. The comparisons with the numerical simulation prove that the deflection calculation method has a reasonable accuracy; thus, the proposed method can be utilized in the damage assessment and anti-impact design for CFST members subjected to lateral impact and axial load.
Reaction Control System Optimization for Maneuverable Reentry Vehicles Based on Particle Swarm Optimization
Authors: Gui Hang , Sun Ruisheng , Chen Wei , Zhu Bin
Published: March 2020

This paper presents a new parametric optimization design to solve a class of reaction control system (RCS) problem with discrete switching state, flexible working time, and finite-energy control for maneuverable reentry vehicles. Based on basic particle swarm optimization (PSO) method, an exponentially decreasing inertia weight function is introduced to improve convergence performance of the PSO algorithm. Considering the PSO algorithm spends long calculation time, a suboptimal control and guidance scheme is developed for online practical design. By tuning the control parameters, we try to acquire efficacy as close as possible to that of the PSO-based solution which provides a reference. Finally, comparative simulations are conducted to verify the proposed optimization approach. The results indicate that the proposed optimization and control algorithm has good performance for such RCS of maneuverable reentry vehicles.
Anticontrol of a Fractional-Order Chaotic System and Its Application in Color Image Encryption
Authors: Niu Yujun , Sun Xuming , Zhang Cheng , Liu Hongjun
Published: March 2020

This paper investigates the anticontrol of the fractional-order chaotic system. The necessary condition of the anticontrol of the fractional-order chaotic system is proposed, and based on this necessary condition, a 3D fractional-order chaotic system is driven to two new 4D fractional-order hyperchaotic systems, respectively, without changing the parameters and fractional order. Hyperchaotic properties of these new fractional dynamic systems are confirmed by Lyapunov exponents and bifurcation diagrams. Furthermore, a color image encryption algorithm is designed based on these fractional hyperchaotic systems. The effectiveness of their application in image encryption is verified.
Option Pricing Based on Modified Advection-Dispersion Equation: Stochastic Representation and Applications
Authors: Lv Longjin , Wang Luna
Published: March 2020

In this paper, we first investigate the stochastic representation of the modified advection-dispersion equation, which is proved to be a subordinated stochastic process. Taking advantage of this result, we get the analytical solution and mean square displacement for the equation. Then, applying the subordinated Brownian motion into the option pricing problem, we obtain the closed-form pricing formula for the European option, when the underlying of the option contract is supposed to be driven by the subordinated geometric Brownian motion. At last, we compare the obtained option pricing models with the classical Black–Scholes ones.
Effect of Alternate Corrosion and Fatigue on Fatigue Crack Growth Characterization of 2024-T4 Aluminum Alloy
Authors: Zhang Tianyu , He Yuting , Li Changfan , Zhang Teng , Zhang Sheng
Published: March 2020

To investigate the effect of alternate corrosion and fatigue on fatigue crack growth characterization of 2024-T4 aluminum alloy, the pure fatigue test, “corrosion + fatigue” test (commonly known as pre-corrosion fatigue), and the “fatigue + corrosion + fatigue” alternating test of single-sided notched specimen of 2024-T4 aluminum alloy were carried out. The fatigue crack life of alternate corrosion and fatigue is longer than that of the pre-corrosion fatigue when the corrosion time is the same. And the more the times of alternating, the longer the crack growth life will be. This is mainly because the fatigue crack growth rate will change suddenly, which will have a certain hysteresis effect on the fatigue crack growth. The corrosion and fracture morphology characteristics of the alternate test were examined by scanning electron microscopy (SEM), and the composition of corrosion products was examined by the energy dispersion spectrum (EDS). The prediction model of fatigue crack growth rate considering the alternating hysteresis effect of corrosion and fatigue based on the Paris formula was established, and the parameters and precision of the model were calculated and verified. The results show that the model has certain engineering application value.
Protective Effect of Hydroxysafflor Yellow A on Nephropathy by Attenuating Oxidative Stress and Inhibiting Apoptosis in Induced Type 2 Diabetes in Rat
Authors: Lee Maosheng , Zhao Hengxia , Liu Xuemei , Liu Deliang , Chen Jianping , Li Zengying , Chu Shufang , Kou Xinhui , Liao Si , Deng Yuxiu , Li Huilin , Xie Weidong
Published: March 2020

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus, and its prevalence has been increasing all over the world, which is also the leading cause of end-stage renal failure. Hydroxysafflor yellow A (HSYA) is the main active chemical component of Carthamus tinctorius L., and it is commonly used in patients with cardiovascular and cerebrovascular diseases in China. The aim of this study was to investigate the renal protective effects and molecular mechanisms of HSYA on high-fat diet (HFD) and streptozotocin- (STZ-) induced DN in rats. The DN rats were treated with HSYA for eight weeks. We assessed creatinine (CR), urea nitrogen (UN), glomerular volume, podocyte number, renal inflammation, oxidative stress, and cells apoptosis markers after HSYA treatment. The number of apoptotic cells was measured by the TUNEL assay, and apoptosis-related proteins BAX, caspase-3, and BCL-2 in the renal tissue were analyzed by western blot. The treatment with HSYA significantly decreased fasting blood glucose, CR, UN, and blood lipid profile, including triglyceride and total and low-density lipoprotein cholesterol, even though it did not change the rats’ body weights. The western blot results indicated that HSYA reversed the upregulation of BAX and caspase-3 and significantly increased BCL-2 in renal tissue. Moreover, the levels of TNF-α and the inflammatory products, including free fatty acids (FFA) and lactic dehydrogenase (LDH) in the HSYA group, were significantly decreased. For the oxidative stress marker, the superoxide dismutase (SOD) markedly increased in the HSYA treatment group, while the malondialdehyde (MDA) in the serum and kidney tissue evidently decreased. In conclusion, HSYA treatment preserved kidney function in diabetic nephropathy in the HFD- and STZ-induced rats. The potential mechanism of renal protective effect of HSYA might be through inhibiting oxidative stress, reducing inflammatory reaction, and attenuating renal cell apoptosis. Our studies present a promising use for Hydroxysafflor yellow A in the treatment of type 2 diabetes mellitus.
Jiawei Xianglian Decoction (JWXLD), a Traditional Chinese Medicine (TCM), Alleviates CPT‐11‐Induced Diarrhea in Mice
Authors: Lu Jinhua , Lin Zechen , Huang Siyu , Shen Yiwei , Jiang Jing , Lin Shengyou
Published: March 2020

Irinotecan (CPT‐11) is used for therapy of various cancers. However, it has several serious adverse reactions such as diarrhea which is caused by SN‐38, the active form of CPT‐11. This study aimed to evaluate the effectiveness of Jiawei xianglian decoction (JWXLD), which has been widely used for the treatment of diarrhea in China. In this study, a mouse model with delayed diarrhea was generated by CPT‐11. Real‐time PCR and enzyme‐linked immunosorbent assay (ELISA) were performed to explore intestinal microflora and inflammatory cytokine. Hematoxylin and eosin (H&E) staining was used to analyze tissue morphology. We found that 0.12, 0.23, and 0.46 g JWXLD significantly reduced the severity of CPT‐11‐induced diarrhea. The levels of Lactobacillus (Lacto) and Bifidobacterium (Bifid) were significantly downregulated by CPT‐11, and these effects can be reversed by JWXLD treatment. Furthermore, JWXLD was observed to decrease the activity of β‐glucuronidase (β‐GD). Histopathological data showed that CPT‐11 induced severe intestinal mucosal injury, which was characterized as grade 6, and JWXLD significantly alleviated the injury. In addition, CPT‐11 increased the productions of tumor necrosis factor‐alpha (TNF‐α), tumor necrosis factor‐beta (TNF‐β), interleukin‐6 (IL‐6), and interleukin‐1 (IL‐1), but decreased interleukin‐15 (IL‐15), interleukin‐7 (IL‐7), and uridine diphosphate‐glucuronosyltransferase 1A1 (UGT1A1). In conclusion, JWXLD can counteract these effects caused by CPT‐11 treatment. JWXLD could alleviate CPT‐11‐induced diarrhea.
Tunnel Back Analysis Based on Differential Evolution Using Stress and Displacement
Authors: An Joon-Sang , Kang Kyung-Nam , Choi Ju-Young , Sung Won-Suh , Suy Vathna , Song Ki-Il
Published: March 2020

The stability of tunnels has mainly been evaluated based on displacement. Because displacement due to the excavation process is significant, back analysis of the structure and ground can be performed easily. Recently, the length of a segment‐lined tunnel driven by the mechanized tunneling method is increasing. Because the internal displacement of a segment‐lined tunnel is trivial, it is difficult to analyze the stability of segment‐lined tunnels using the conventional method. This paper proposes a back analysis method using stress and displacement information for a segment‐lined tunnel. A differential evolution algorithm was adopted for tunnel back analysis. Back analysis based on the differential evolution algorithm using stress and displacement was established and performed using the finite difference code, FLAC3D, and built‐in FISH language. Detailed flowcharts of back analysis based on DEA using both monitored displacement stresses were also suggested. As a preliminary study, the target variables of the back analysis adopted in this study were the elastic modulus, cohesion, and friction angle of the ground. The back analysis based on the monitored displacement is useful when the displacement is significant due to excavation. However, the conventional displacement‐based back analysis is unsuitable for a segment‐lined tunnel after construction because of its trivial internal displacement since the average error is greater than 32% and the evolutionary calculation is finalized due to the maximum iteration criteria. The average error obtained from the proposed back analysis algorithm using both stress and displacement ranged within approximately 6–8%. This also confirms that the proposed back analysis algorithm is suitable for a segment‐lined tunnel.
A Novel Methodology for Estimating the Capacity and Level of Service for the New Mega Elliptical Roundabout Intersection
Authors: Mohamed Ahmed I. Z. , Ci Yusheng , Tan Yiqiu
Published: March 2020

Mega elliptical roundabout is a new intersection on rural multilane highways. This intersection was developed in a previous paper using simulation data, and the authors found that it is better than interchange (full cloverleaf) in most scenarios of traffic flow. Basically, there are no guidelines or procedures for designing mega elliptical roundabout in AASHTO Green Book, Federal Highway Administration guides, and Highway Capacity Manual. Thus, the purpose of this study is to analyze the traffic operation performance and propose a methodology for calculating the capacity of mega elliptical roundabout and also the level of service by gap acceptance theory. Moreover, this research studied the influence of different values of truck ratios and also different values of a major highway speed on geometric design and traffic operation performance for mega elliptical roundabout. To validate the thoroughness of the proposed methodology, VISSIM simulations were conducted. This research will assist practitioners in determining the appropriate geometric design, assessing mega elliptical roundabout intersections, and making comparisons with other alternatives.
Early-Stage Diabetic Neuropathy Reduces Foot Strength and Intrinsic but Not Extrinsic Foot Muscle Size
Authors: Henderson Adrienne D. , Johnson A. Wayne , Rasmussen Lindsey G. , Peine Weston P. , Symons Sydney H. , Scoresby Kade A. , Ridge Sarah T. , Bruening Dustin A.
Published: March 2020

Background. Tracking progression of diabetic peripheral polyneuropathy (DPN) is usually focused on sensory nerves and subjective testing methods. Recent studies have suggested that distal muscle atrophy may precede sensation loss. Methods to objectively measure distal muscle size and strength are needed to help understand how neuropathy affects muscle function. Purpose. To evaluate individual intrinsic and extrinsic foot muscle sizes and functional foot strength in participants with DPN. Methods. Thirty individuals participated in this cross-sectional study (15 DPN and 15 matched controls). Sizes of 10 separate muscles of the lower leg and foot were measured using ultrasound imaging. Functional foot strength was also quantified using custom great toe and lateral toe flexion tests along with a doming test. Muscle size and strength metrics were compared between groups using ANOVAs and paired t-tests (α=0.05). Correlations between strength and relevant muscle sizes were also evaluated. Results. The sizes of all four intrinsic foot muscles were smaller in individuals with DPN (p≤0.03), while only one (toe extensor) of the six extrinsic muscles was smaller (p<0.01). Great toe flexion (p=0.03) and lateral toe flexion (p<0.01) strengths were decreased between groups and showed moderate to strong correlations (0.43≤r≤0.80) with several corresponding intrinsic muscle sizes. The doming strength test did not show any difference between groups and was moderately correlated with one muscle size (r=0.59). Conclusion. Diabetic peripheral polyneuropathy affects intrinsic muscles before extrinsics. Ultrasound imaging of individual muscles and functional toe flexion tests can be used clinically to monitor DPN progression and foot function. Participants need to be trained in the doming test before a relationship can be established between this test and DPN foot function. Future studies should include muscle quality measurements to better understand characteristics of affected muscles.
CHK1 Inhibition Is Synthetically Lethal with Loss of B-Family DNA Polymerase Function in Human Lung and Colorectal Cancer Cells
Authors: Rogers Rebecca F. , Walton Michael I. , Cherry Daniel L. , Collins Ian , Clarke Paul A. , Garrett Michelle D. , Workman Paul
Published: March 2020

Checkpoint kinase 1 (CHK1) is a key mediator of the DNA damage response that regulates cell-cycle progression, DNA damage repair, and DNA replication. Small-molecule CHK1 inhibitors sensitize cancer cells to genotoxic agents and have shown single-agent preclinical activity in cancers with high levels of replication stress. However, the underlying genetic determinants of CHK1 inhibitor sensitivity remain unclear. We used the developmental clinical drug SRA737 in an unbiased large-scale siRNA screen to identify novel mediators of CHK1 inhibitor sensitivity and uncover potential combination therapies and biomarkers for patient selection. We identified subunits of the B-family of DNA polymerases (POLA1, POLE, and POLE2) whose silencing sensitized the human A549 non–small cell lung cancer (NSCLC) and SW620 colorectal cancer cell lines to SRA737. B-family polymerases were validated using multiple siRNAs in a panel of NSCLC and colorectal cancer cell lines. Replication stress, DNA damage, and apoptosis were increased in human cancer cells following depletion of the B-family DNA polymerases combined with SRA737 treatment. Moreover, pharmacologic blockade of B-family DNA polymerases using aphidicolin or CD437 combined with CHK1 inhibitors led to synergistic inhibition of cancer cell proliferation. Furthermore, low levels of POLA1, POLE, and POLE2 protein expression in NSCLC and colorectal cancer cells correlated with single-agent CHK1 inhibitor sensitivity and may constitute biomarkers of this phenotype. These findings provide a potential basis for combining CHK1 and B-family polymerase inhibitors in cancer therapy.

Significance:

These findings demonstrate how the therapeutic benefit of CHK1 inhibitors may potentially be enhanced and could have implications for patient selection and future development of new combination therapies.
Molecular Mechanisms of Hair Growth and Regeneration: Current Understanding and Novel Paradigms
Authors: Houschyar Khosrow Siamak , Borrelli Mimi R. , Tapking Christian , Popp Daniel , Puladi Behrus , Ooms Mark , Chelliah Malcolm P. , Rein Susanne , Pförringer Dominik , Thor Dominik , Reumuth Georg , Wallner Christoph , Branski Ludwik K. , Siemers Frank , Grieb Gerrit , Lehnhardt Marcus , Yazdi Amir S. , Maan Zeshaan N. , Duscher Dominik
Published: March 2020

Hair is a defining feature of mammals and has critical functions, including protection, production of sebum, apocrine sweat and pheromones, social and sexual interactions, thermoregulation, and provision of stem cells for skin homeostasis, regeneration, and repair. The hair follicle (HF) is considered a “mini-organ,” consisting of intricate and well-organized structures which originate from HF stem and progenitor cells. Dermal papilla cells are the main components of the mesenchymal compartments in the hair bulb and are instrumental in generating signals to regulate the behavior of neighboring epithelial cells during the hair cycle. Mesenchymal-epithelial interactions within the dermal papilla niche drive HF embryonic development as well as the postnatal hair growth and regeneration cycle. This review summarizes the current understanding of HF development, repair, and regeneration, with special focus on cell signaling pathways governing these processes. In particular, we discuss emerging paradigms of molecular signaling governing the dermal papilla-epithelial cellular interactions during hair growth and maintenance and the recent progress made towards tissue engineering of human hair follicles.
Ease of Hydrodissection during Phacoemulsification: A Comparison between Patients with and Those without Exfoliation Syndrome
Authors: Sorkou Konstantina N. , Tsinopoulos Ioannis T. , Tsaousis Konstantinos T. , Karamitsos Athanasios , Meditskou Soultana , Ziakas Nikolaos , Manthou Maria Eleni
Published: March 2020

Background: Exfoliation syndrome (XFS), which is associated with increased surgical complications during phacoemulsification, has a relatively high incidence in Greece. Multiannual surgical experience in XFS patients has led to the clinical observation that hydrodissection occurs more easily in XFS patients. Objective: To compare the ease of hydrodissection between cataract patients with and those without XFS. Methods: One hundred and fifteen patients with senile cataract were included in the study. Forty-two of them had XFS. All patients underwent uneventful phacoemulsification by the same surgeon. For hydrodissection, three 1-mL insulin syringes were filled with 0.5 mL balanced salt solution (BSS). Sequentially, each one was quickly and continuously injected underneath the 3, 6, and 9 o’clock positions of the anterior lens capsule. If lens mobilization was achieved with this procedure, hydrodissection was characterized as “easy.” Results: The two groups were matched for age, gender, the biomicroscopic type of cataract, and the presence of diabetes mellitus. Glaucoma occurred more often among the XFS patients (p = 0.002). In 39 of the 42 exfoliation patients (92.8%), “easy” hydrodissection was recorded. In the control group, the corresponding number was 47 out of 73 (64.3%). The two groups differed significantly (p = 0.001). Conclusions: Hydrodissection was more easily performed on the XFS patients than on the controls. This finding could be related to the extensive ultrastructural subepithelial alterations of the anterior lens capsule in XFS, as recently described in electron microscopy studies. We suggest that less BSS can be used for hydrodissection in XFS patients during phacoemulsification.
Pharmacological Silencing of MicroRNA-152 Prevents Pressure Overload–Induced Heart Failure
Authors: LaRocca Thomas J. , Seeger Timon , Prado Maricela , Perea-Gil Isaac , Neofytou Evgenios , Mecham Brigham H. , Ameen Mohamed , Chang Alex Chia Yu , Pandey Gaurav , Wu Joseph C. , Karakikes Ioannis
Published: March 2020

Background:

MicroRNAs are small, noncoding RNAs that play a key role in gene expression. Accumulating evidence suggests that aberrant microRNA expression contributes to the heart failure (HF) phenotype; however, the underlying molecular mechanisms are not well understood. A better understanding of the mechanisms of action of microRNAs could potentially lead to targeted therapies that could halt the progression or even reverse HF.

Methods and Results:

We found that microRNA-152 (miR-152) expression was upregulated in the failing human heart and experimental animal models of HF. Transgenic mice with cardiomyocyte-specific miR-152 overexpression developed systolic dysfunction (mean difference, −38.74% [95% CI, −45.73% to −31.74%];
P
<0.001) and dilated cardiomyopathy. At the cellular level, miR-152 overexpression perturbed mitochondrial ultrastructure and dysregulated key genes involved in cardiomyocyte metabolism and inflammation. Mechanistically, we identified Glrx5 (glutaredoxin 5), a critical regulator of mitochondrial iron homeostasis and iron-sulfur cluster synthesis, as a direct miR-152 target. Finally, a proof-of-concept of the therapeutic efficacy of targeting miR-152 in vivo was obtained by utilizing a locked nucleic acid–based inhibitor of miR-152 (LNA 152) in a murine model of HF subjected to transverse aortic constriction. We demonstrated that animals treated with LNA–152 (n=10) showed preservation of systolic function when compared with locked nucleic acid–control treated animals (n=9; mean difference, 18.25% [95% CI, 25.10% to 11.39%];
P
<0.001).

Conclusions:

The upregulation of miR-152 expression in the failing myocardium contributes to HF pathophysiology. Preclinical evidence suggests that miR-152 inhibition preserves cardiac function in a model of pressure overload–induced HF. These findings offer new insights into the pathophysiology of HF and point to miR-152-Glrx5 axis as a potential novel therapeutic target.