bluuebunny/crossref_metadata_2025 huggingface dataset:
KCNQ3 is the principal target of retigabine in CA1 and subicular excitatory neurons
Authors: Varghese Nissi , Lauritano Anna , Taglialatela Maurizio , Tzingounis Anastasios V.
Published: March 2021

Retigabine has risen to prominence as a first-in-class potassium channel opener approved by the Food and Drug Administration, with potential for treating multiple neurological disorders. Here, we demonstrate that KCNQ3 channels are the primary target of retigabine in excitatory neurons, as deleting these channels greatly diminishes the effect of retigabine in pyramidal neurons. Our data provide the first indication that retigabine controls neuronal firing properties primarily through KCNQ3 channels.
Bu Shen Yi Sui Capsule Alleviates Neuroinflammation and Demyelination by Promoting Microglia toward M2 Polarization, Which Correlates with Changes in miR‐124 and miR‐155 in Experimental Autoimmune Encephalomyelitis
Authors: Zha Zheng , Gao Yan-Fang , Ji Jing , Sun Ya-Qin , Li Jun-Ling , Qi Fang , Zhang Nan , Jin Liang-Yun , Xue Bing , Yang Tao , Fan Yong-Ping , Zhao Hui , Wang Lei
Published: March 2021

Background. Bu Shen Yi Sui capsule (BSYS) is a traditional Chinese medicine prescription that has shown antineuroinflammatory and neuroprotective effects in treating multiple sclerosis (MS) and its animal model of experimental autoimmune encephalomyelitis (EAE). Microglia play an important role in neuroinflammation. The M1 phenotype of microglia is involved in the proinflammatory process of the disease, while the M2 phenotype plays an anti‐inflammatory role. Promoting the polarization of microglia to M2 in MS/EAE is a promising therapeutic strategy. This study is aimed at exploring the effects of BSYS on microglial polarization in mice with EAE. Methods. The EAE model was established by the intraperitoneal injection of pertussis toxin and subcutaneous injection of myelin oligodendrocyte glycoprotein (MOG)35-55 in C57BL/6J mice. The mice were treated with BSYS (3.02 g/kg), FTY720 (0.3 mg/kg), or distilled water by intragastric administration. H&E and LFB staining, transmission electron microscopy, qRT‐PCR, immunofluorescence, ELISA, fluorescence in situ hybridization, and western blotting were used to detect the histological changes in myelin, microglial M1/M2 polarization markers, and the expression of key genes involved in EAE. Results and Conclusions. BSYS treatment of EAE mice increased the body weight, decreased the clinical score, and reduced demyelination induced by inflammatory infiltration. BSYS also inhibited the mRNA expression of M1 microglial markers while increasing the mRNA level of M2 markers. Additionally, BSYS led to a marked decrease in the ratio of M1 microglia (iNOS+/Iba1+) and an obvious increase in the number of M2 microglia (Arg1+/Iba1+). In the EAE mouse model, miR‐124 expression was decreased, and miR‐155 expression was increased, while BSYS treatment significantly reversed this effect and modulated the levels of C/EBP α, PU.1, and SOCS1 (target genes of miR‐124 and miR‐155). Therefore, the neuroprotective effect of BSYS against MS/EAE was related to promoting microglia toward M2 polarization, which may be correlated with changes in miR‐124 and miR‐155 in vivo.
Spontaneous Free Peritoneal Perforation of an Infected Pancreatic Fluid Collection Managed with Laparoscopic Drainage and Necrosectomy
Authors: Kanchana W. G. P. , Dharmapala A. D. , Dassanayake B. K. , Wasala W. M. A. S. B. , Galketiya K. B.
Published: March 2021

Introduction. Free peritoneal perforation of pancreatic fluid collections is extremely rare and only few case reports exist in the literature. Many of these patients undergo emergency exploratory laparotomy due to sepsis and haemodynamic instability requiring sepsis control. The use of laparoscopic techniques in this circumstance is limited by the haemodynamic stability of the patient and the technical challenges. But effective laparoscopic management is associated with less morbidity to the patient. Case Presentation. A 28-year-old patient presented with worsening generalized abdominal pain with increased inflammatory markers. She required persistent inotropic support despite adequate fluid resuscitation. She had transient acute renal impairment and acute respiratory distress, which improved with noninvasive support. CECT (contrast-enhanced computed tomography) showed an infected pancreatic fluid collection with peritoneal free fluid. Aspiration of pelvic collection showed purulent fluid. Based on these clinical and imaging findings, she was diagnosed with a free peritoneal perforation of an infected pancreatic fluid collection. She underwent a laparoscopic drainage and necrosectomy of the infected pancreatic collection and peritoneal washout. She had a gradual recovery. All inotropes were omitted on the second day following surgery. She was sent to the ward from the ICU (intensive care unit) on the 4th postoperative day. Conclusion. The laparoscopic approach is a viable option in managing ruptured pancreatic fluid collections when patient and technical factors are supportive. It reduces surgical morbidity, thereby reducing the overall strain on physiological reserves. When opted for laparoscopic drainage, the procedure must be guided by imaging findings. Multidisciplinary participation is critical in the overall management.
On Decomposition Formulas Related to the Gaussian Hypergeometric Functions in Three Variables
Authors: Hasanov Anvar , Younis Jihad , Aydi Hassen
Published: March 2021

In this paper, by using certain inverse pairs of symbolic operators introduced by Choi and Hasanov in 2011, we establish several decomposition formulas associated with the Gaussian triple hypergeometric functions. Some transformation formulas for these functions have also been obtained.
Intelligent Coordination Distribution of the Whole Supply Chain Based on the Internet of Things
Authors: Cui Hongxiu
Published: March 2021

In this paper, through the intelligent research of the whole process of logistics and distribution with the Internet of Things supply chain, we study how to improve the development of the cold chain, reduce the loss in circulation, improve the social and economic benefits, and carry out intelligent information collection, monitoring, management, and information tracing of the whole cold chain. This paper analyzes and empirically studies the impact of key technologies of the Internet of Things in cold chain coordination from the perspective of building an intelligent cold chain coordination system with the Internet of Things technology. This paper analyzes the current situation of cold chain logistics and the impact that the application of IoT technology will have, explains that IoT technology can improve the intelligence level of the cold chain, and then introduces the application of intelligent cold chain logistics under IoT orientation, combining the process of cold chain logistics with the three‐layer architecture of IoT technology. By extracting the key technologies of IoT perception layer, network layer, and intelligence layer, the intelligent cold chain coordination system based on IoT technology is constructed, and then, the correctness of the system is verified, to have some reference and evaluation for the cold chain construction. The system was then verified to have some reference and guidance significance for the construction and evaluation of the cold chain. The results of this paper are more accurate and more efficient.
Effect of Joint Density on Rockburst Proneness of the Elastic‐Brittle‐Plastic Rock Mass
Authors: Pan Jiliang , Ren Fenhua , Cai Meifeng
Published: March 2021

The prediction of rockburst proneness is the basis of preventing and controlling rockburst disasters in rock engineering. Based on energy theory and damage mechanics, the quantitative functional relationship between joint density and energy density was derived. Then, the theoretical results were verified by numerical simulation and uniaxial compression test, and the effect of joint density on rockburst proneness of the elastic‐brittle‐plastic rock mass was discussed. The results show that the relationship between the joint density and the dissipated energy index of the jointed rock mass is a logarithmic function. With the same total input energy, the higher the joint density, the more the damage dissipation energy. Even in the case of high joint density, the rock mass still has limited resistance to external failure. Under the same joint density, the strength of parallel jointed rock mass is better than that of the cross‐jointed rock mass, and the parallel jointed rock mass can accumulate more elastic strain energy and has higher rockburst proneness. The joint density is closely related to the ability of the rock mass to store high strain energy. The higher the joint density is, the weaker the ability to accumulate the elastic strain energy of rock mass is and the lower the rockburst proneness is. It is helpful to predict rockburst proneness by investigating and studying the properties of geological discontinuities. The research results have some theoretical and engineering guiding significance for the prediction of rockburst proneness of the jointed rock mass.
Association between Sleep Duration, Physical Activity, and Mental Health Disorders: A Secondary Analysis of the National Survey of Children’s Health 2017‐2018
Authors: Xiang Shiting , Dong Jie , Li Xun , Li Liping
Published: March 2021

Background. The purpose of this article was to examine the association of sleep duration and physical activity and their interactions on mental health disorders in American children aged 6‐17 years. Methods. Data were analyzed from the combined 2017‐2018 National Survey of Children’s health. Ultimately, a total of 36370 children aged 6‐17 years were selected as the samples. Weighted logistic regression models were used to estimate odds ratios and 95% confidence intervals. Results. Insufficient sleep duration was associated with an increased risk for current anxiety, depression, and behavior/conduct problems (odds ratio = 1.449, 1.991, 1.375; 95% confidence interval: 1.313‐1.702, 1.648‐2.406, 1.162‐1.627). Insufficient physical activity was associated with an increased risk for current anxiety (odds ratio = 1.448; 95% confidence interval: 1.230‐1.706) and depression (odds ratio = 1.743; 95% confidence interval: 1.304‐2.329). In addition, additive interactions between sleep duration and physical activity were observed on current anxiety and depression. Conclusions. Insufficient sleep duration and insufficient physical activity in children were associated with mental health disorders. There is a synergistic interaction effect between insufficient sleep duration and insufficient physical activity on current anxiety and current depression.
Preprosthetic Management of “Flabby Ridge” on Edentulous Patient
Authors: Mizouri Amani , Tayari Oumaima , Mahfoudhi AlaEddine , Bouguezzi Adel , Jaouadi Jamila
Published: March 2021

For edentulous patients, the integrity of the osteomucosal-bearing surface is a significant factor for the balance of the future removable prosthesis. The supporting tissues are influenced by several factors. Physiological bone resorption, senescence, and changes caused by systemic diseases and polypharmacy lead to modifications in these tissues. Similarly, trauma caused by an ill-fitted prosthesis influences the degree of bone resorption and the development of hyperplastic tissue. The etiology of bone resorption is multifactorial and complex, with continuous individual variations that are often unexplained. Although, no study has been able to establish the importance of the different factors in relation to each other, it is often reported that chronic excessive mechanical pressure in relation to occlusal constraints is responsible for the appearance of local resorption’s areas. The aim of this work is to present, through three clinical cases, the various factors involved in the alteration of the osteomucous-bearing surface and eventually, possible therapeutic attitude to deal with.
Effect of Rotation Speed and Flow Rate on Slip Factor in a Centrifugal Pump
Authors: Chen Bo , Song Baolin , Tu Bicheng , Zhang Yiming , Li Xiaojun , Li Zhigang , Zhu Zuchao
Published: March 2021

This work analyzes the causes of the slip phenomenon in the impeller on the basis of the internal flow mechanism. Detailed optical measurements of the flow inside the rotation passages of a five‐bladed centrifugal pump impeller are obtained through particle image velocimetry (PIV). On the basis of experimental data, the deviation coefficient of slip velocity is proposed and then revised according to the slip factor calculation formula of Stechkin. Results show that, at the same rotation speed, the slip factor increases with the flow rate and reaches the maximum value at 1.0 QBEP flow rate. At different rotation speeds, the slip factor increases with the rotation speed and shows a relatively large variation range. Moreover, a revised slip factor formula is proposed. The modified model is suitable for the correction of slip factor at part‐load flow rates and serves as a guide for the hydraulic performance design and prediction of centrifugal pumps.
Mucosal Epithelial Jak Kinases in Health and Diseases
Authors: Kumar Narendra , Kuang Longxiang , Villa Ryan , Kumar Priyam , Mishra Jayshree
Published: March 2021

Janus kinases (Jaks) are a family of nonreceptor tyrosine kinase that include four different members, viz., Jak1, Jak2, Jak3, and Tyk2. Jaks play critical roles in immune cells functions; however, recent studies suggest they also play essential roles in nonimmune cell physiology. This review highlights the significance of epithelial Jaks in understanding the molecular basis of some of the diseases through regulation of epithelial-mesenchymal transition, cell survival, cell growth, development, and differentiation. Growth factors and cytokines produced by the cells of hematopoietic origin use Jak kinases for signal transduction in both immune and nonimmune cells. Among Jaks, Jak3 is widely expressed in both immune cells and in intestinal epithelial cells (IECs) of both humans and mice. Mutations that abrogate Jak3 functions cause an autosomal severe combined immunodeficiency disease (SCID) while activating Jak3 mutations lead to the development of hematologic and epithelial cancers. A selective Jak3 inhibitor CP-690550 (Xeljanz) approved by the FDA for certain chronic inflammatory conditions demonstrates immunosuppressive activity in rheumatoid arthritis, psoriasis, and organ transplant rejection. Here, we also focus on the consequences of Jak3-directed drugs on adverse effects in light of recent discoveries in mucosal epithelial functions of Jak3 with some information on other Jaks. Lastly, we brief on structural implications of Jak3 domains beyond the immune cells. As information about the roles of Jak3 in gastrointestinal functions and associated diseases are only just emerging, in the review, we summarize its implications in gastrointestinal wound repair, inflammatory bowel disease, obesity-associated metabolic syndrome, and epithelial cancers. Lastly, we shed lights on identifying potential novel targets in developing therapeutic interventions of diseases associated with dysfunctional IEC.
Discussion on the Rehabilitation of Stroke Hemiplegia Based on Interdisciplinary Combination of Medicine and Engineering
Authors: Sun Xiaowei , Xu Ke , Shi Yuqing , Li Hongtao , Li Ruobing , Yang Siyu , Jin Hong , Feng Chuwen , Li Baitao , Xing Chunyue , Qu Yuanyuan , Wang Qingyong , Chen Yinghua , Yang Tiansong
Published: March 2021

Interdisciplinary combinations of medicine and engineering are part of the strategic plan of many universities aiming to be world-class institutions. One area in which these interactions have been prominent is rehabilitation of stroke hemiplegia. This article reviews advances in the last five years of stroke hemiplegia rehabilitation via interdisciplinary combination of medicine and engineering. Examples of these technologies include VR, RT, mHealth, BCI, tDCS, rTMS, and TCM rehabilitation. In this article, we will summarize the latest research in these areas and discuss the advantages and disadvantages of each to examine the frontiers of interdisciplinary medicine and engineering advances.
Development of TOPSIS Technique under Pythagorean Fuzzy Hypersoft Environment Based on Correlation Coefficient and Its Application towards the Selection of Antivirus Mask in COVID‐19 Pandemic
Authors: Zulqarnain Rana Muhammad , Siddique Imran , Jarad Fahd , Ali Rifaqat , Abdeljawad Thabet
Published: March 2021

The correlation coefficient between two variables plays an important role in statistics. Also, the accuracy of relevance assessment depends on information from a set of discourses. The data collected from numerous statistical studies are full of exceptions. The Pythagorean fuzzy hypersoft set (PFHSS) is a parameterized family that deals with the subattributes of the parameters and an appropriate extension of the Pythagorean fuzzy soft set. It is also the generalization of the intuitionistic fuzzy hypersoft set (IFHSS), which is used to accurately assess insufficiency, anxiety, and uncertainties in decision‐making. The PFHSS can accommodate more uncertainties compared to the IFHSS, and it is the most substantial methodology to describe fuzzy information in the decision‐making process. The core objective of the this study is to develop the notion and features of the correlation coefficient and the weighted correlation coefficient for PFHSS and to introduce the aggregation operators such as Pythagorean fuzzy hypersoft weighted average (PFHSWA) and Pythagorean fuzzy hypersoft weighted geometric (PFHSWG) operators under the PFHSS scenario. A prioritization technique for order preference by similarity to the ideal solution (TOPSIS) under PFHSS based on correlation coefficients and weighted correlation coefficients is presented. Through the developed methodology, a technique for solving multiattribute group decision‐making (MAGDM) problem is planned. Also, the importance of the developed methodology and its application in indicating multipurpose antivirus mask throughout the COVID‐19 pandemic period is presented. A brief comparative analysis is described with the advantages, effectiveness, and flexibility of numerous existing studies that demonstrate the effectiveness of the proposed method.
Design of Planar Microstrip Ultrawideband Circularly Polarized Antenna Loaded by Annular-Ring Slot
Authors: Ma Zhong-Hua , Chen Jia-Xiang , Chen Peng , Jiang Yan Feng
Published: March 2021

A miniaturized planar microstrip circularly polarized ultrawideband (UWB) antenna loaded by annular-ring slot is proposed and implemented in the paper. With the annular-ring slot loaded in the radiating patch of the antenna, the side of the radiating patch is connected by the asymmetric inverted L-shaped microstrip. At the same time, a quarter of a circle is cut off from the radiating patch. The above designed structure shows improvements on the operating frequency band and realization of the circular polarization radiation. A tapered microstrip is placed between the feed line and the radiating patch to achieve the slow-changing impedance transformation. The results of simulation and measurement demonstrate that the 3 dB axial ratio (AR) fractional bandwidth of the antenna structure achieves 21.25%. The peak gain within the 3 dB axial ratio bandwidth fluctuates between 3.74 and 4.59 dBi. The antenna shows good impedance matching in the ultrawideband range. With the compact structure of the UWB antenna, it has potential application in various wireless communication devices.
Study on the Creep Constitutive Model of a Sandstone Rock under the Water‐Rock Interaction
Authors: Luo Zuosen , Zhu Zuoxiang , Li Jianlin , Wang Lehua , Jiang Qiao , Zhang Jingyu , Assefa Eleyas , Deng Huafeng
Published: March 2021

With the continuous construction of large‐scale geotechnical engineering, more and more attention has been paid to the long‐term stability of rock mass engineering, especially the problem of rock creep under the influence of water. Combined with the author’s previous research on the triaxial creep characteristics of sandstone under water‐rock interaction, a nonlinear creep constitutive model was established to capture the degradation behavior of a sandstone rock due to cyclic wetting and drying of the reservoir water. Due to the limitations of the visco‐elastoplastic model, a thorough modification was done to account the effect of the water‐rock interaction on the mechanical degradation of the sandstone rock. Finally, the predicted results were proved to be in a good agreement with the experimental results. Moreover, the strong correlations between the predicted results and the experimental results show the effectiveness of the modified model to scrutinize the nonlinear creep behavior of sandstone rock. Relevant research results have important theoretical significance for the accurate prediction and effective control of the long‐term stability of rock mass engineering under the influence of water‐rock interaction.
Bioactive Substances, Heavy Metals, and Antioxidant Activity in Whole Fruit, Peel, and Pulp of Citrus Fruits
Authors: Czech Anna , Malik Agnieszka , Sosnowska Bożena , Domaradzki Piotr
Published: March 2021

The use of whole citrus fruits in the food industry means that the valuable peel is used, but this may raise palatability or health concerns among consumers. The content of sugars, dietary fibre, redox compounds, lead, and cadmium was compared in citrus fruits (orange; pomelo; mandarin; lemon; key lime; and red, yellow, and green grapefruit). The pulp of all fruits contained significantly less fibre, tannins, and phenolic compounds than the peel. Whole citrus fruits had significantly lower content of sugars and higher content of dietary fibre and phenolic compounds, including ferulic acid, than their pulps. Whole grapefruits had higher concentrations of ascorbic acid. Whole lemons, limes, and mandarins had higher antioxidant potential than their pulp, due to their higher content of ascorbic acid, tannins, and phenolic compounds. Lead and cadmium content in whole fruits, while higher than in the pulps, was well below the acceptable daily intake.
The Innovative Use of Ureter Catheter in the Surgery of Obstructive Uropathy
Authors: Zhan Xiangcheng , Liu Ding , Wang Guangchun , Zhang Haimin , Kadier Aimaitiaji , Yao Xudong , Xu Yunfei
Published: March 2021

Purpose. Relieving obstruction and protecting renal function are the main therapeutic purposes of obstructive uropathy which often involve surgical treatment, and the ureter catheter is one of the surgical instruments commonly used in surgery. We aimed to explore the innovative use of a ureter catheter in the surgery of obstructive uropathy. Methods. We used a ureteral catheter to innovate the surgical procedure of the most common causes of obstructive uropathy: ureteral calculi and stricture, establishing an internal circulation system (ICS), proposing a three-step dilatation method, and reviewing their effects on patients. Furthermore, we introduced a simple real-time intrapelvic pressure measurement device to monitor intrarenal pressure during operation. Results. Postoperative laboratory examination showed that blood CRP, leukocyte neutrophil level, changes in the hemoglobin, urine occult blood, and positive rate of urine culture in the ICS group are significantly lower than those in the control group, corresponding to a lower incidence of bleeding and infection-related complications clinically. A three-month follow-up revealed 1/3 rate of ureteral stricture in the ICS group comparing to the control. We applied the three-step dilatation in patients with severe stenosis in which the balloon could not pass; the overall effective rate was 90.9%. The pressure of the renal pelvis was displayed on the monitor in real time. The surgeon could estimate the degree of filling of the renal pelvis and adjust the intake volume through the data. Conclusion. The innovative application of ureteral catheters in the operation of obstructive uropathy can realize the real-time monitor of intraoperative renal pelvis pressure, reduce the incidence of lithotripsy postoperative complications, and expand the indications of balloon dilatation in ureteral stricture, which has certain clinical significance.
Flocculation Settling Characteristics of Ultra‐Fine Iron Tailings with Rich Gypsum
Authors: Deng Daiqiang , Cao Guodong
Published: March 2021

Because of the uniqueness of geological mineralization, tailings obtained from Chenchao Iron Mine have low SiO2 content of only 27.80%. Content of Al2O3 and MgO is 13.31% and CaSO4 is 22.09%. The fineness modulus of the ores is large enough for convenient mineral separation, thus resulting in 16.03% −5 μm particles and 27.76% −10 μm particles in the tailings, respectively. The average particle size is only 69.36 μm; it belongs to the category of very fine tailings. The natural sedimentation of tailings is extremely slow due to the comprehensive effects of their physical and chemical properties. Hence, sedimentation tests using four types of flocculating agents are conducted to accelerate the sedimentation of the tailings of Chenchao Iron Mine. Compared with natural sedimentation, the flocculating sedimentation is considerably quicker. Among the four flocculants, the sedimentation of sample using the special BASF flocculant is the fastest. When the tailings of 1 ton add this flocculant of 20 g, the maximum settling concentration reaches 60.98% after 40 min and its special gravity is 1.577 g/cm3, thus it fulfills future requirements of filling technologies. As the largest iron mine in the mid‐southern region of China, Chenchao Iron Mine must turn to filling mining. This study can provide technological support for goaf management and environment‐friendly treatment of solid waste in the Yangtze River basin, which plays important roles in ecological protection.
A Closed-Form Solution for Estimating the Accuracy of Circular Feature’ Pose for Object 2D-3D Pose Estimation System
Authors: Li Cui , Chen Derong , Gong Jiulu , Wu Yangyu
Published: March 2021

Many objects in the real world have circular feature. In general, circular feature’s pose is represented by 5-DoF (degree of freedom) vector

ξ
=

X
,
Y
,
Z
,
α
,
β

T

. It is a difficult task to measure the accuracy of circular feature’s pose in each direction and the correlation between each direction. This paper proposes a closed-form solution for estimating the accuracy of pose transformation of circular feature. The covariance matrix of

ξ

is used to measure the accuracy of the pose. The relationship between the pose of the circular feature of 3D object and the 2D points is analyzed to yield an implicit function, and then Gauss–Newton theorem is employed to compute the partial derivatives of the function with respect to such point, and after that the covariance matrix is computed from both the 2D points and the extraction error. In addition, the method utilizes the covariance matrix of 5-DoF circular feature’s pose variables to optimize the pose estimator. Based on pose covariance, minimize the mean square error (Min-MSE) metric is introduced to guide good 2D imaging point selection, and the total amount of noise introduced into the pose estimator can be reduced. This work provides an accuracy method for object 2D-3D pose estimation using circular feature. At last, the effectiveness of the method for estimating the accuracy is validated based on both random data sets and synthetic images. Various synthetic image sequences are illustrated to show the performance and advantages of the proposed pose optimization method for estimating circular feature’s pose.
A Novel Coverage Optimization Strategy Based on Grey Wolf Algorithm Optimized by Simulated Annealing for Wireless Sensor Networks
Authors: Zhang Yong , Cao Li , Yue Yinggao , Cai Yong , Hang Bo
Published: March 2021

The coverage optimization problem of wireless sensor network has become one of the hot topics in the current field. Through the research on the problem of coverage optimization, the coverage of the network can be improved, the distribution redundancy of the sensor nodes can be reduced, the energy consumption can be reduced, and the network life cycle can be prolonged, thereby ensuring the stability of the entire network. In this paper, a novel grey wolf algorithm optimized by simulated annealing is proposed according to the problem that the sensor nodes have high aggregation degree and low coverage rate when they are deployed randomly. Firstly, the mathematical model of the coverage optimization of wireless sensor networks is established. Secondly, in the process of grey wolf optimization algorithm, the simulated annealing algorithm is embedded into the grey wolf after the siege behavior ends and before the grey wolf is updated to enhance the global optimization ability of the grey wolf algorithm and at the same time improve the convergence rate of the grey wolf algorithm. Simulation experiments show that the improved grey wolf algorithm optimized by simulated annealing is applied to the coverage optimization of wireless sensor networks. It has better effect than particle swarm optimization algorithm and standard grey wolf optimization algorithm, has faster optimization speed, improves the coverage of the network, reduces the energy consumption of the nodes, and prolongs the network life cycle.
Indirect Determination Approach of Blast‐Induced Ground Vibration Based on a Hybrid SSA‐Optimized GP‐Based Technique
Authors: Jiang Zhaoxin , Xu Hongyan , Chen Hui , Gao Bei , Jia Shijie , Yu Zhi , Zhou Jian
Published: March 2021

The accurate determination of blast‐induced ground vibration has an important significance in protecting human activities and the surrounding environment. For evaluating the peak particle velocity resulting from the quarry blast, a robust artificial intelligence system combined with the salp swarm algorithm (SSA) and Gaussian process (GP) was proposed, and the SSA was used to find the optimal hyperparameters of the GP here. In this regard, 88 datasets with 9 variables including the ratio of bench height to burden (H/B) and the ratio of spacing to burden (S/B) were selected as the input variables, while peak particle velocity (PPV) was measured. Then, an ANN model, an SVR model, a GP model, an SSA‐GP model, and three empirical models were established, and the predictive performance was evaluated by using the root‐mean‐square error (RMSE), determination coefficient (R2), value account for (VAF), Akaike Information Criterion (AIC), Schwarz Bayesian Criterion (SBC), and the run time. After comparing, it is found that the proposed SSA‐GP yielded a superior performance and the ratio of bench height to burden (H/B) was the most sensitive variable.
Numerical and Experimental Research on the Effect of Platform Heave Motion on Vortex‐Induced Vibration of Deep Sea Top‐Tensioned Riser
Authors: Zhang Jie , Zeng Ying , Tang Yougang , Guo Wenyun , Wang Zhenkui
Published: March 2021

The prediction and control of vortex‐induced vibration (VIV) is one of the key problems for riser design. The effect of platform heave motion on VIV of deep sea top‐tensioned riser (TTR) is presented by means of numerical simulation and experiment in this research. First, the heave motion was modeled as a parametric excitation, and the governing equation of VIV of riser considering the parametric excitation was established. Then, the dynamic response of TTR was calculated numerically by the finite difference method based on the Van der Pol wake‐oscillator model. Finally, a validation experiment was carried out at the towing tank of Tianjin university. The results show that the VIV response at the bottom of riser is significantly increased due to the platform heave motion, especially in the situation of low current velocity. The larger amplitude and the higher frequency of the platform heave motion with the greater influence are generated on VIV of TTR. In particular, the value of 0.5 times, 1 time, or other multiples of the platform heave frequency will be included in the vibration frequency component of TTR when the platform heave amplitude is large and the frequency is high.
Hypersonic Vehicle Aerodynamic Optimization Using Field Metamodel-Enhanced Sequential Approximate Optimization
Authors: Wang Wenjie , Wu Zeping , Wang Donghui , Yang Jiawei , Wang Pengyu , Zhang Weihua
Published: March 2021

Hypersonic vehicle has gained increasing attention due to its high cruise speed and long voyage. In this paper, an enhanced Sequential Approximate Optimization method is proposed for aerodynamic optimization of a hypersonic vehicle. In this method, a constrained design of experiment method is adopted to generate the initial sampling set with adequate number of feasible points. A field metamodel is proposed to surrogate the aerodynamic parameters distributions in the flow field obtained by the aerodynamic simulation. A hybrid metamodel combing radial basis functions and polynomial chaos expansion is applied to construct the field metamodel with good approximate performance. A robust mesh morphing scheme based on radial basis functions is developed to generate high-quality meshes for the sequential optimization scheme. The hypersonic vehicle aerodynamic optimization problem is performed using the proposed optimization framework and satisfactory results are obtained with limited computational budgets. Results show that the proposed field metamodel-enhanced Sequential Approximate Optimization method possesses powerful optimization performance and promising prospects in the field of hypersonic vehicle optimization design.
Augmented Reality-Assisted Pancreaticoduodenectomy with Superior Mesenteric Vein Resection and Reconstruction
Authors: Tang Rui , Yang Wei , Hou Yucheng , Yu Lihan , Wu Guangdong , Tong Xuan , Yan Jun , Lu Qian
Published: March 2021

Introduction. Pancreaticoduodenectomy (PD) with superior mesenteric vein (SMV) reconstruction are often required to achieve complete (R0) resection for pancreatic head cancer (PHC) with tumor invasion of the SMV. Augmented reality (AR) technology can be used to assist in determining the extent of SMV involvement by superimposing virtual 3-dimensional (3D) images of the pancreas and regional vasculature on the surgical field. Materials and Methods. Three patients with PHC and tumor invasion of the SMV underwent AR-assisted PD with SMV resection and reconstruction following preoperative computed tomography scanning. Preoperative imaging data were used to reconstruct 3D images of anatomical structures, including the tumor, portal vein (PV), SMV, and splenic vein (SV). Using AR software installed on a smart phone, the reconstructed 3D images were superimposed on the surgical field as viewed in a smart phone display to provide intermittent navigational assistance to the surgeon in identifying the boundaries of PHC tumor invasion for resection of the vessels involved. Result. All patients successfully completed the operation. Intraoperative AR applications displayed virtual images of the pancreas, SMV, bile duct, common hepatic artery (CHA), and superior mesenteric artery (SMA). Two patients required end-to-end anastomosis for reconstruction of the SMV. One patient required allogenic vascular bypass to reconstruct the SMV-PV juncture with concomitant reconstruction of the SV-SMV confluence by end-to-side anastomosis of the SV and bypass vessel. Postoperative pathology confirmed R0 resections for all patients. Conclusion. AR navigation technology based on preoperative CT image data can assist surgeons performing PD with SMV resection and reconstruction.
Chromatin Accessibility Identifies Regulatory Elements Predictive of Gene Expression and Disease Outcome in Multiple Myeloma
Authors: Barwick Benjamin G. , Gupta Vikas A. , Matulis Shannon M. , Patton Jonathan C. , Powell Doris R. , Gu Yanyan , Jaye David L. , Conneely Karen N. , Lin Yin C. , Hofmeister Craig C. , Nooka Ajay K. , Keats Jonathan J. , Lonial Sagar , Vertino Paula M. , Boise Lawrence H.
Published: March 2021

Purpose:

Multiple myeloma is a malignancy of plasma cells. Extensive genetic and transcriptional characterization of myeloma has identified subtypes with prognostic and therapeutic implications. In contrast, relatively little is known about the myeloma epigenome.

Experimental Design:

CD138+CD38+ myeloma cells were isolated from fresh bone marrow aspirate or the same aspirate after freezing for 1–6 months. Gene expression and chromatin accessibility were compared between fresh and frozen samples by RNA sequencing (RNA-seq) and assay for transpose accessible chromatin sequencing (ATAC-seq). Chromatin accessible regions were used to identify regulatory RNA expression in more than 700 samples from newly diagnosed patients in the Multiple Myeloma Research Foundation CoMMpass trial (NCT01454297).

Results:

Gene expression and chromatin accessibility of cryopreserved myeloma recapitulated that of freshly isolated samples. ATAC-seq performed on a series of biobanked specimens identified thousands of chromatin accessible regions with hundreds being highly coordinated with gene expression. More than 4,700 of these chromatin accessible regions were transcribed in newly diagnosed myelomas from the CoMMpass trial. Regulatory element activity alone recapitulated myeloma gene expression subtypes, and in particular myeloma subtypes with immunoglobulin heavy chain translocations were defined by transcription of distal regulatory elements. Moreover, enhancer activity predicted oncogene expression implicating gene regulatory mechanisms in aggressive myeloma.

Conclusions:

These data demonstrate the feasibility of using biobanked specimens for retrospective studies of the myeloma epigenome and illustrate the unique enhancer landscapes of myeloma subtypes that are coupled to gene expression and disease progression.
Kinetic Characterization of ASXL1/2-Mediated Allosteric Regulation of the BAP1 Deubiquitinase
Authors: Peng Hongzhuang , Cassel Joel , McCracken Daniel S. , Prokop Jeremy W. , Sementino Eleonora , Cheung Mitchell , Collop Paul R. , Polo Alexander , Joshi Surbhi , Mandell Jacob P. , Ayyanathan Kasirajan , Hinds David , Malkowicz S. Bruce , Harbour J. William , Bowcock Anne M. , Salvino Joseph , Kennedy Eileen J. , Testa Joseph R. , Rauscher Frank J.
Published: March 2021

BAP1 is an ubiquitin hydrolase whose deubiquitinase activity is mediated by polycomb group-like protein ASXL2. Cancer-related BAP1 mutations/deletions lead to loss-of-function by targeting the catalytic ubiquitin C-terminal hydrolase (UCH) or UCH37-like domain (ULD) domains of BAP1, and the latter disrupts binding to ASXL2, an obligate partner for BAP1 enzymatic activity. However, the biochemical and biophysical properties of domains involved in forming the enzymatically active complex are unknown. Here, we report the molecular dynamics, kinetics, and stoichiometry of these interactions. We demonstrate that interactions between BAP1 and ASXL2 are direct, specific, and stable to biochemical and biophysical manipulations as detected by isothermal titration calorimetry (ITC), GST association, and optical biosensor assays. Association of the ASXL2-AB box greatly stimulates BAP1 activity. A stable ternary complex is formed, comprised of the BAP1-UCH, BAP1-ULD, and ASXL2-AB domains. Stoichiometric analysis revealed that one molecule of the ULD domain directly interacts with one molecule of the AB box. Real-time kinetic analysis of the ULD/AB protein complex to the BAP1-UCH domain, based on surface plasmon resonance, indicated that formation of the ULD/AB complex with the UCH domain is a single-step event with fast association and slow dissociation rates. In vitro experiments validated in cells that the ASXL-AB box directly regulates BAP1 activity.

Implications:

Collectively, these data elucidate molecular interactions between specific protein domains regulating BAP1 deubiquitinase activity, thus establishing a foundation for small-molecule approaches to reactivate latent wild-type BAP1 catalytic activity in BAP1-mutant cancers.
Schisandrin Restores the Amyloid β-Induced Impairments on Mitochondrial Function, Energy Metabolism, Biogenesis, and Dynamics in Rat Primary Hippocampal Neurons
Authors: Piao Zhongyuan , Song Lin , Yao Lifen , Zhang Limei , Lu Yichan
Published: March 2021

Introduction: Schisandrin which is derived from Schisandra chinensis has shown multiple pharmacological effects on various diseases including Alzheimer’s disease (AD). It is demonstrated that mitochondrial dysfunction plays an essential role in the pathogenesis of neurodegenerative disorders. Objective: Our study aims to investigate the effects of schisandrin on mitochondrial functions and metabolisms in primary hippocampal neurons. Methods: In our study, rat primary hippocampal neurons were isolated and treated with indicated dose of amyloid β1–42 (Aβ1–42) oligomer to establish a cell model of AD in vitro. Schisandrin (2 μg/mL) was further subjected to test its effects on mitochondrial function, energy metabolism, mitochondrial biogenesis, and dynamics in the Aβ1–42 oligomer-treated neurons. Results and Conclusions: Our findings indicated that schisandrin significantly alleviated the Aβ1–42 oligomer-induced loss of mitochondrial membrane potential and impaired cytochrome c oxidase activity. Additionally, the opening of mitochondrial permeability transition pore and release of cytochrome c were highly restricted with schisandrin treatment. Alterations in cell viability, ATP production, citrate synthase activity, and the expressions of glycolysis-related enzymes demonstrated the relief of defective energy metabolism in Aβ-treated neurons after the treatment of schisandrin. For mitochondrial biogenesis, elevated expression of peroxisome proliferator-activated receptor γ coactivator along with promoted mitochondrial mass was found in schisandrin-treated cells. The imbalance in the cycle of fusion and fission was also remarkably restored by schisandrin. In summary, this study provides novel mechanisms for the protective effect of schisandrin on mitochondria-related functions.
Long QT Syndrome
KCNH2
Variant Induces hERG1a/1b Subunit Imbalance in Patient-Specific Induced Pluripotent Stem Cell–Derived Cardiomyocytes
Authors: Feng Li , Zhang Jianhua , Lee ChangHwan , Kim Gina , Liu Fang , Petersen Andrew J. , Lim Evi , Anderson Corey L. , Orland Kate M. , Robertson Gail A. , Eckhardt Lee L. , January Craig T. , Kamp Timothy J.
Published: March 2021

Background:

Inherited long QT syndrome type 2 results from variants in the
KCNH2
gene encoding the human Ether-à-go-go related gene 1 (hERG1) potassium channel. Two main isoforms, hERG1a and hERG1b, assemble to form tetrameric channel. The N-terminal PAS (Per/Arnt/Sim) domain, present only on hERG1a subunits, is a hotspot for pathogenic variants, but it is unknown whether PAS domain variants impact hERG1b expression to contribute to the long QT syndrome type 2 phenotype. We aimed to use patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to investigate the pathogenesis of the hERG1a PAS domain variant hERG1-H70R.

Methods:

Human iPSCs were derived from a patient with long QT syndrome type 2 carrying the PAS domain variant hERG1-H70R. CRISPR/Cas9 gene editing produced isogenic control iPSC lines. Differentiated iPSC-CMs were evaluated for their electrophysiology,
hERG1a/1b
mRNA expression, and hERG1a/1b protein expression.

Results:

Action potentials from single hERG1-H70R iPSC-CMs were prolonged relative to controls, and voltage clamp studies showed an underlying decrease in I
Kr
with accelerated deactivation. In hERG1-H70R iPSC-CMs, transcription of
hERG1a
and
hERG1b
mRNA was unchanged compared with controls based on nascent nuclear transcript analysis, but
hERG1b
mRNA was significantly increased as was the ratio of
hERG1b
/
hERG1a
in mRNA complexes, suggesting posttranscriptional changes. Expression of complex glycosylated hERG1a in hERG1-H70R iPSC-CMs was reduced due to impaired protein trafficking, whereas the expression of the complex glycosylated form of hERG1b was unchanged.

Conclusions:

Patient-specific hERG1-H70R iPSC-CMs reveal a newly appreciated mechanism of pathogenesis of the long QT syndrome type 2 phenotype due to both impaired trafficking of hERG1a and maintained expression of hERG1b that produces subunit imbalance and reduced I
Kr
with accelerated deactivation.

Graphic Abstract:

A
graphic abstract
is available for this article.
Mid-Term Outcomes Following Percutaneous Pulmonary Valve Implantation Using the “Folded Melody Valve” Technique
Authors: Jalal Zakaria , Valdeolmillos Estíbaliz , Malekzadeh-Milani Sophie , Eicken Andreas , Georgiev Stanimir , Hofbeck Michael , Sieverding Ludger , Gewillig Marc , Ovaert Caroline , Bouvaist Helene , Pillois Xavier , Thambo Jean-Benoit , Boudjemline Younes
Published: March 2021

Background:

The folded valve is a manual shortening of the Melody device, which has been validated as a valuable therapeutic option for the management of dysfunctional right ventricular outflow tracts needing a short valved stent. In this article, we aimed to evaluate, in a multicenter cohort, the mid-term outcomes of patients in whom a percutaneous pulmonary valve implantation was performed using the folded valve technique.

Methods:

A 2012 to 2018 retrospective multicenter study was performed in 7 European institutions. All patients who benefit from percutaneous pulmonary valve implantation with a folded Melody valve were included.

Results:

A total of 49 patients (median age, 19 years [range 4–56], 63% male) were included. The primary percutaneous pulmonary valve implantation indication was right ventricular outflow tract stenosis (n=19; 39%), patched native right ventricular outflow tracts were the most common substrate (n=15; 31%). The folded technique was mostly used in short right ventricular outflow tracts (n=28; 57%). Procedural success was 100%. After a median follow-up of 28 months (range, 4–80), folded Melody valve function was comparable to the immediate postimplantation period (mean transvalvular peak velocity=2.6±0.6 versus 2.4±0.6 m/s,
P
>0.1; only 2 patients had mild pulmonary regurgitation). Incidence rate of valve-related reinterventions was 2.1% per person per year (95% CI, 0.1%–3.9%). The probability of survival without valve-related reinterventions at 36 months was 90% (95% CI, 76%–100%).

Conclusions:

The folded Melody valve is a safe technique with favorable mid-term outcomes up to 6.5 years after implantation, comparable with the usual Melody valve implantation procedure. Complications and reinterventions rates were low, making this technique relevant in selected patients.