bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on Adaptive Cruise Control Car-following Model Based on Dynamic Spacing in V2X Scenario
Authors: Li Youyuan , Piao Changhao
Published: April 2022

In the adaptive cruise control (ACC) car-following model, the constant spacing strategy cannot adapt to complex and variable deceleration and acceleration situations. When the preceding car decelerates or accelerates suddenly, considering the safety and adaptability, the desire spacing should be larger or smaller, so the desire spacing is not only related to the speed of the two cars, but also to the speed change of the preceding car. For this problem of the deficiency, which the desire spacing existed, an adaptive cruise control car-following model based on dynamic headway strategy is proposed in this paper. In order to achieve more realtime and more accurate information transmission, this paper uses the v2v communication in v2x environment to obtain the preceding car information. MATLAB/Simulink is used to simulation modelling for verification and analysis. The experimental results show that, under the same simulation conditions, the dynamic spacing strategy proposed in this paper have a larger desire spacing for safety when preceding car decelerates, and a smaller desire spacing for comfort and road dynamic utilization when preceding car accelerates. So, the dynamic spacing strategy proposed in this paper shows different improvement effects for different acceleration and deceleration conditions.
Research on Depth Image Tracking Based on Aerial Refueling
Authors: Zhang Shuyao , Qian Xianyun , Wang Jun , Fan Zhenkai
Published: April 2022

Aiming at the problem of the current aerial refueling docking which is difficult to accurately identify the floating cone sleeve in a complex environment, the Meanshift algorithm can efficiently track moving targets in the plane, there is not very good solution strategy for the pose measurement of the cone sleeve and the movement in the optical axis direction. The Time-Of-Flight (TOF) in the depth camera can directly collect depth images and grayscale images, providing the distance information displayed by a flat camera. By using the Meanshift algorithm to iterate in the three-dimensional space, the Kalman filter is added to achieve robustness to the tracking of moving targets, effectively solve the problem of occlusion of the target, and provide the coordinate position of the target. In the experiment, 600 frames of images are extracted for comparison. The effect of the TOF camera has higher accuracy and stability than that of the flat camera. It still has a stable tracking effect after using the props to cover the cone model, which is better than the traditional plane Meanshift algorithm.
Research on improved genetic simulated annealing algorithm for multi-UAV cooperative task allocation
Authors: Wang Yao , Shi Yongkang , Liu Yunhui
Published: April 2022

In order to solve the cooperative search problem of multiple unmanned aerial vehicles (multi-UAVs) in a large-scale area, we propose a genetic algorithm (GA) incorporating simulated annealing (SA) for solving the task region allocation problem among multi-UAVs on the premise that the large area is divided into several small areas. Firstly, we describe the problem to be solved, and regard the task areas allocation problem of multi-UAVs as a multiple traveling salesman problem (MTSP). And the objective function is established under the premise that the number of task areas to be searched by each UAV is balanced. Then, we improve the GA, using the advantages of the SA can jump out of the local optimal solution to optimize the new population of offspring generated by GA. Finally, the validity of the algorithm is verified by using the TSPLIB database, and the set MTSP problem is solved. Through a series of comparative experiments, the validity of GAISA and the superiority of solving the MTSP problem can be demonstrated.
Study on convolutional recurrent neural networks for speech enhancement in fiber-optic microphones
Authors: Peng Wenli , Zhen Shenglai , Chen Xin , Xiong Qianjing , Yu Benli
Published: April 2022

In this paper, several improved convolutional recurrent networks (CRN) are proposed, which can enhance the speech with non-additive distortion captured by fiber-optic microphones. Our preliminary study shows that the original CRN structure based on amplitude spectrum estimation is seriously distorted due to the loss of phase information. Therefore, we transform the network to run in time domain and gain 0.42 improvement on PESQ and 0.03 improvement on STOI. In addition, we integrate dilated convolution into CRN architecture, and adopt three different types of bottleneck modules, namely long short-term memory (LSTM), gated recurrent units (GRU) and dilated convolutions. The experimental results show that the model with dilated convolution in the encoder-decoder and the model with dilated convolution at bottleneck layer have the highest PESQ and STOI scores, respectively.
Continuous blood oxygen estimation using PPG based on VMD
Authors: Tang Youyuan , Li Min , Wei Zijian
Published: April 2022

Existing photoplethysmography(PPG) signal is extremely susceptible to interference from baseline drift, and the training interval of traditional algorithms is basically fixed between 80% and 100%, which leads to the low accuracy of blood oxygen detection, especially in patients with severe hypoxemia. Based on the PPG acquisition system developed by ourselves, we use moving average filtering and variable mode decomposition(VMD) to remove high-frequency and baseline drift interference, and use the 30%-100% SpO2 data interval of the Fluke ProSim8 vital signs simulator as the SpO2 algorithm guarantee. Finally, the paper proposed a continuous blood oxygen saturation measurement algorithm based on VMD. The final experimental results show that in the five types of patient data of the simulator, high-precision measurement can be ensured in the normal SpO2 range and in the low SpO2 or even ultra-low SpO2 range; at the same time, the sensitivity of the algorithm to SpO2 is better than that of the reference oximeter. The response speed is faster; finally, in the process of detecting simulated apnea, compared with the reference oximeter, the error of the blood oxygen saturation in the stable interval is ±1, the error of the lowest SpO2 is ±3, and the calculated consistency of the blood oxygen reduction duration reaches 89.10%.
An Accelerated Proximal Extragradient Method with Applications in Representative Selection
Authors: Fang Changjie , He Liangsong
Published: April 2022

Proximal algorithms has the advantages of low iteration cost and fast convergence speed, and is a common method for dealing with sparse structures. In this paper, we present an accelerated proximal extra-gradient method for figuring out the representative selection problems. We proved the convergence of the algorithm we proposed. Moreover, we apply our method to solve representative selection problem. Numerical experiments illustrate the advantages of our method.
A hybrid model with dual channel feature processing for short-term photovoltaic power prediction
Authors: Yao Jing , Chen Yuanhao , Yang Siyuan , Wang Yuhui , Li Tao , Zhu Bo , Cheng Guanyin , Liu Xueqin
Published: April 2022

Adverse effects of random fluctuations and intermittent characteristics of solar irradiance usually hamper the proper operation of the photovoltaic power grid. It is therefore desirable to improve the accuracy of photovoltaic (PV) power prediction. In this work, PV forecasting is realized through a Bayesian optimized model which combines the long short-term memory and radial basis function neural network (BOA-LSTM-RBF). The hybrid model presents a dual channel feature processing by extracting the historical data of PV generation via long-short-term memory network (LSTM) and extracting the forecasted weather conditions via radial basis function neural network (RBF). Then the number of hidden layer neurons and the training batch size are simultaneously optimized by & the Bayesian optimization algorithm (BOA). The testing results of three stations demonstrate that, compared with other available models, the RMSE values of BOA-LSTM-RBF model decreased by 2% ∼ 17%, which has striking advantages in prediction precision and generalizability. More interestingly, high-precision PV power forecasting can be achieved even under dramatic weather changes.
Bi- level optimal configuration of hybrid energy storage for wind farms considering battery life
Authors: Wang Peng , Zhang Fuhua , Chen Qinghui
Published: April 2022

In the planning of hybrid energy storage in wind farms, considering the service life of the battery in the operation stage, a bi-level optimal configuration method of hybrid energy storage in wind farms considering the service life of the battery is proposed. The upper optimization model takes the optimal energy storage configuration cost as the goal, takes the configuration power and capacity of battery and supercapacitor as variables, and takes the configuration power and capacity of battery and supercapacitor satisfying their respective energy storage power instruction sequence as the constraint condition. The lower optimization model takes the maximum service life of the battery in the running stage as the goal, takes the power instruction sequence of the battery and the super-capacitor as variables, and takes the battery and supercapacitor power instruction sequence not exceeding the limit as the constraint condition. The upper optimization model is solved by the linear programming method, and the lower optimization model is solved by particle swarm optimization algorithm. Finally, the proposed method is compared with the energy storage configuration method based on frequency band demarcation. The results show that the proposed method can reduce the cost of energy storage configuration during planning and prolong the service life of the battery during operation.
Topology Optimization and Material Selection of Cooling Fin Structure in Submarine Data Center
Authors: Hao Guancheng , Jin Jianxiang , Zhong Chenghao
Published: April 2022

The optimization of fin heat dissipation structure has always been an interesting topic, and a good heat dissipation structure is conducive to the full function of electronic devices. In order to obtain the best heat dissipation structure, the COMSOL density penalty method and heat conduction model are adopted to study the topology optimization model of heat dissipation structure. On the basis of circular fins, the material types of fins are kept unchanged, and the optimized fins are obtained after topology optimization under various working conditions. The contact area and average temperature of the topological fin and circular fin are compared. The simulation results show that the topology fin has better heat dissipation performance when the heat source power and ambient temperature are similar. Compared with the circular fin profile, the contact length of the topological fin increases by 48%, and the average temperature is reduced by 14.7K. After obtaining the best heat dissipation structure, the entropy weight method is adopted to select the best heat dissipation material of heat dissipation fins and determine that the best heat dissipation material is lead.
Research on the Operation Specification of Arc Suppression and Resonance Elimination Device in Water Supply Distribution System
Authors: Shen Jie , Sun Jianwei , Wang Zheming , Zhao Wenbin , Miao Jing , Wu Yunfei
Published: April 2022

Arc suppression and resonance elimination device was used more and more widely in distribution power systems. The performance for limiting overvoltage and eliminating arc are better than arc suppression coil. But when the device not work properly,it would cause more great risk on the safe of the distribution network. It was analysed that an event of power failure of pair circuits distribution network installed with arc suppression and resonance elimination device. As an example, the simulation model was established with PSCAD software, and the working mechanism of the device was discussed. The overvoltage risk of the distribution system for water supply pump station was analysed. According to the analysing results, it is proposed that routine maintenance method and typical configuration of the device.
Study on layer system complementarity technology in Block N
Authors: Tang Yan
Published: April 2022

In view of the low permeability of oil reservoir, poor physical properties of crude oil, narrow strip development of channel sand, scattered development of plane sand body and serious heterogeneity in block n, there are some problems in water drive development, such as low well pattern control, low oil production rate, fast water cut rise rate and large production decline, the ideal stimulation effect can not be achieved by conventional measures, which restricts the potential of the block. In block n, 9 water injection wells and 16 production wells are selected to carry out layer series complementarity. Through the layer series complementarity of infill wells and basic well pattern, the well spacing is reduced, the injection production relationship of narrow sand body is improved, the water drive control degree and multidirectional connectivity ratio are improved, and the feasibility of improving the water drive development effect of block n is improved. In this paper, through the analysis of various remaining oil distribution types, the hole filling mode is optimized, so as to obtain better social and economic benefits.
A Novel Protection Scheme for Outgoing Line Fault of AC Transmission Line near the Inverter Station of AC/DC Hybrid Power Grid based on AC Filter Characteristics
Authors: Yang Lin , Wen Minghao , Chen Yu , Wang Xingzhu
Published: April 2022

Compared with traditional AC power grid, the fault characteristics of the AC/DC hybrid power grid are more complex and variable. Hence there is a problem of incorrect action for the fault detection elements used in traditional AC power grid which comes up when an outgoing line fault occurs on the AC transmission line in the vicinity of the inverter station. To distinguish the fault direction under the aforementioned situation, a directional protection scheme based on the characteristics of the AC filter is proposed in this paper. Considering the information can be measured by AC line relay, a method for estimating the current provided by the AC filter is given during an outgoing line fault. According to the difference of current characteristics between forward and reverse fault, the fault direction can be judged based on waveform similarity among the currents provided by the AC filter and measured by the AC line relay. Finally, a simulation model is built on the PSCAD/EMTDC platform for extensive performance evaluation. The reliability and effectiveness of the protection scheme are verified under different cases.
Recent Advances on Distributed Dispatching and Control Algorithms in Virtual Power Plant
Authors: Liu Hong , Li Zhiwei , Liu Pengde , Cheng Qing , Ji Yajuan , Qu Jiping
Published: April 2022

In recent years, the concept of Virtual Power Plant (VPP) is becoming more and more popular due to its capability of aggregating Distributed Energy Resources (DERs) and exploring its potential of providing flexibility to the existing power grid. Distributed algorithms have several potential advantages over centralized approaches, such as sharing limited amounts of information, performing parallel computations, and having strong robustness. In this context, this paper surveys the literature of distributed algorithms regarding VPP applications. Firstly, we established the VPP framework and operation control modes. Secondly, the basic distributed algorithms were given. Then, this paper studied distributed algorithms in VPP for economic dispatch, bidding optimization, autonomous control strategy within VPP, coordinated control strategy among muti-VPP, and interactive control strategy with grid side. Finally, the key issues and research potential were analyzed.
Research on the Access Capacity of Power System to Electric Vehicles Under Battery Swapping Modes
Authors: Cheng Jinmin , Xu Chao , Wang Weiyuan , Liu Boliang , Dou Fei , Gao Yifan , Xu Yiqing
Published: April 2022

In view of the access capacity of the power system to electric vehicles, not only whether the power generation side can meet the load demand of electric vehicles shall be considered, but also the changes in voltage quality, capacity of lines and transformers, short-circuit current after electric vehicles accessed shall be comprehensively taken into account. Considering the electric vehicles supplement energy by swapping batteries, in a multi-objective optimization method, through the service capacity analysis of charging stations and combined with economic indicators, an improved particle swarm optimization algorithm with mutation operator was applied, and a calculation method for maximum number of electric vehicles in power system was proposed. Finally, simulation for the power system of a certain district was performed, the maximum electric vehicle capacity that can be accessed to the power system was calculated, and the corresponding site selection of centralized charging stations and charging & battery swapping stations were given.
Test and simulation of primary frequency regulation of 600MW sub-critical thermal power units with wide load operation
Authors: Zhang Chunlei , Zhu Longfei , Yu Dahai , Si Paiyou , Liu Shuangbai , Mei Long , Zhao Ting , Zhang Jing , Zhang Tao , Hu Yuou
Published: April 2022

To reveal the performance of primary frequency regulation of the 600MW sub-critical thermal power units in a wide load range and accurately simulate the process, the primary frequency regulation performance of a 600MW sub-critical thermal power unit was studied with a wide load ranging from 20% to 90% under rated conditions. The model of steam turbine in BPA was modified in consideration of steam pressure and the valve throttling effect. The primary frequency regulation performance of the unit was simulated with the modified model. The research results show that the primary frequency regulation performance of the thermal power unit is poor at low load and the results of simulation with the modified model are highly consistent with the tested data due to consideration of steam pressure and valve throttling effect, meaning that the model can be used to simulate the primary frequency regulation of the thermal power unit with wide load operation accurately.
Coupling optimization model of hydropower station power dispatching based on complex dispatching constraints and cascade joint commissioning
Authors: Xie Liang , Zhang Feng
Published: April 2022

In order to increase the average power generation of a hydropower station and reduce its water consumption, this paper proposes a hydropower dispatching coupling optimization model based on complex dispatch constraints and cascade-connected dispatching. The power generation water consumption and the remaining load of the power grid are used as the objective function to construct a power dispatch coupling optimization model. After all the constraints are met to solve the objective function, the improved genetic algorithm and the coupling constraint adjustment strategy are combined to form a hybrid search method to realize the genetic operation. The strategy is improved to complete the optimization of power dispatch. The experimental results show that the above model can effectively realize the optimization of power dispatch and increase the average power generation of hydropower stations. It is hoped that the model can reasonably optimize the power dispatch during the flood season and the dry season, thereby effectively reducing the water consumption of the cascade and increasing the power generation of the cascade.
Research on the Method of Improving the Current-carrying Capacity of Power Cable
Authors: Tang Jipeng , Fang Xiangyang , Luo Xiqun , Qin Tao , Yang Tao , Ma Congzhi , Zhang Yong
Published: April 2022

The inadvertent current carrying capacity of power cable is bound to be affected by many factors, such as air temperature, ground temperature, backfill sand, soil covering depth, grounding mode, soil thermal resistance coefficient, number of circuits, ventilation design, laying mode, groundwater, metal sheath circulation, layout mode, solar radiation, surrounding heat source . This paper analyzes the common factors in the work, and expounds the mode of flow promotion through the analysis and numerical calculation of power cable ampacity. It also compares the effects of the two methods, hoping to provide new ideas for the follow-up research on related issues.
Operation control and capacity configuration optimization of CCHP system based on high temperature phase change heat storage
Authors: Xu GuiZhi , Ma MeiXiu , Hu Xiao , Chen Mengdong , Yao Wenzhuo , Zhang Kang , Lv Hongkun , Ding Liwei
Published: April 2022

The existing regional integrated energy system with thermal storage electric boiler as the main body cannot solve the cooling problem. In this paper, LiBr refrigerators were added on its basis to realize an energy supply mode that integrates heating and cooling. Established a multi-party win-win mechanism to ensure the minimum risk and obtain the maximum benefit. The results shown that the power grid load reduction ratios in winter and summer were 39% and 31%, respectively. When the subsidy price was 0.1CNY/kWh, the spending gap between sensitive and insensitive users reached 40%. A case of 100 office buildings in Beijing shown that the optimal capacity of phase change heat storage was 80MWh.
Development of a direct-sampling RF receiver for precision beam charge measurements in the MOLLER experiment
Authors: Mei Y. , Li S. , Arrington J. , Camilleri J. , Cuda A. , Egelhoff J. , Kolomensky Yu.G. , Sichtermann E.P.
Published: April 2022

We have developed and tested a direct-sampling RF receiver
capable of measuring the amplitude of a 1497 MHz sinusoidal beam
signal in 0.5 ms integration windows with a relative uncertainty of
better than 10 parts per million. The receiver is intended for
measuring signals from beam current monitoring cavities on the
beamline of the Continuous Electron Beam Accelerator Facility
(CEBAF) at Jefferson Lab. The beam signal strength, frequency, and
integration window fulfill the thus far unmet requirements of the
upcoming MOLLER experiment to measure the beam charge for different
helicity states.
Afforestation affects rain-on-snow climatology over Norway
Authors: Mooney P A , Lee H
Published: April 2022

Rain-on-snow (ROS) events are most commonly found in sub-polar and alpine climates where they pose a considerable threat to society and nature. While the relationship between ROS frequency and large-scale climate features have been identified, little is known about the role of localised factors, such as land cover, in ROS frequency. Importantly, the impact of future land cover changes, such as afforestation, on ROS frequency is also unknown. In this study, we use gridded observational products and kilometer-scale regional climate simulations to investigate the comparative roles of forests and open spaces in ROS frequency, and to identify the impact of afforestation on ROS frequency. The seNorge gridded observational products generally show that evergreen forests have a higher ROS frequency than open spaces despite the large discrepancies in land cover between different datasets. The observed behaviour was well simulated by a regional climate model, albeit with a more pronounced difference between ROS frequency in forests and open spaces. Model-based results show that future changes in ROS frequency are larger in evergreen forests than in open spaces, and afforestation will increase the frequency of ROS events. Our results demonstrate the relationship between land cover and ROS frequency, and highlight the need to include unique features of the local climate system, such as ROS events, in studies on climate and land use land cover change. Importantly, our study shows that afforestation policies in sub-polar and alpine regions should carefully consider the impacts of such policies on ROS frequency and the downstream consequences for society and nature.
Winding number statistics of a parametric chiral unitary random matrix ensemble*
Authors: Braun Petr , Hahn Nico , Waltner Daniel , Gat Omri , Guhr Thomas
Published: April 2022

The winding number is a concept in complex analysis which has, in the presence of chiral symmetry, a physics interpretation as the topological index belonging to gapped phases of fermions. We study statistical properties of this topological quantity. To this end, we set up a random matrix model for a chiral unitary system with a parametric dependence. We analytically calculate the discrete probability distribution of the winding numbers, as well as the parametric correlations functions of the winding number density. Moreover, we address aspects of universality for the two-point function of the winding number density by identifying a proper unfolding procedure. We conjecture the unfolded two-point function to be universal.
Higher connectivity of the Morse complex
Authors: Scoville Nicholas , Zaremsky Matthew
Published: April 2022

The Morse complex

M

(
Δ
)

\mathcal {M}(\Delta )

of a finite simplicial complex

Δ
\Delta

is the complex of all gradient vector fields on

Δ
\Delta

. In this paper we study higher connectivity properties of

M

(
Δ
)

\mathcal {M}(\Delta )

. For example, we prove that

M

(
Δ
)

\mathcal {M}(\Delta )

gets arbitrarily highly connected as the maximum degree of a vertex of

Δ
\Delta

goes to

∞
\infty

, and for

Δ
\Delta

a graph additionally as the number of edges goes to

∞
\infty

. We also classify precisely when

M

(
Δ
)

\mathcal {M}(\Delta )

is connected or simply connected. Our main tool is Bestvina–Brady Morse theory, applied to a “generalized Morse complex.”
Segre-degenerate points form a semianalytic set
Authors: Lebl Jiří
Published: April 2022

We prove that the set of Segre-degenerate points of a real-analytic subvariety

X
X

in

C

n

{\mathbb {C}}^n

is a closed semianalytic set. It is a subvariety if

X
X

is coherent. More precisely, the set of points where the germ of the Segre variety is of dimension

k
k

or greater is a closed semianalytic set in general, and for a coherent

X
X

, it is a real-analytic subvariety of

X
X

. For a hypersurface

X
X

in

C

n

{\mathbb {C}}^n

, the set of Segre-degenerate points,

X

[
n
]

X_{[n]}

, is a semianalytic set of dimension at most

2
n
−
4

2n-4

. If

X
X

is coherent, then

X

[
n
]

X_{[n]}

is a complex subvariety of (complex) dimension

n
−
2

n-2

. Example hypersurfaces are given showing that

X

[
n
]

X_{[n]}

need not be a subvariety and that it also need not be complex;

X

[
n
]

X_{[n]}

can, for instance, be a real line.
Boost-RS: boosted embeddings for recommender systems and its application to enzyme–substrate interaction prediction
Authors: Li Xinmeng , Liu Li-Ping , Hassoun Soha
Published: April 2022

Motivation

Despite experimental and curation efforts, the extent of enzyme promiscuity on substrates continues to be largely unexplored and under documented. Providing computational tools for the exploration of the enzyme–substrate interaction space can expedite experimentation and benefit applications such as constructing synthesis pathways for novel biomolecules, identifying products of metabolism on ingested compounds, and elucidating xenobiotic metabolism. Recommender systems (RS), which are currently unexplored for the enzyme–substrate interaction prediction problem, can be utilized to provide enzyme recommendations for substrates, and vice versa. The performance of Collaborative-Filtering (CF) RSs; however, hinges on the quality of embedding vectors of users and items (enzymes and substrates in our case). Importantly, enhancing CF embeddings with heterogeneous auxiliary data, specially relational data (e.g. hierarchical, pairwise or groupings), remains a challenge.

Results

We propose an innovative general RS framework, termed Boost-RS that enhances RS performance by ‘boosting’ embedding vectors through auxiliary data. Specifically, Boost-RS is trained and dynamically tuned on multiple relevant auxiliary learning tasks Boost-RS utilizes contrastive learning tasks to exploit relational data. To show the efficacy of Boost-RS for the enzyme–substrate prediction interaction problem, we apply the Boost-RS framework to several baseline CF models. We show that each of our auxiliary tasks boosts learning of the embedding vectors, and that contrastive learning using Boost-RS outperforms attribute concatenation and multi-label learning. We also show that Boost-RS outperforms similarity-based models. Ablation studies and visualization of learned representations highlight the importance of using contrastive learning on some of the auxiliary data in boosting the embedding vectors.

Availability and implementation

A Python implementation for Boost-RS is provided at https://github.com/HassounLab/Boost-RS. The enzyme-substrate interaction data is available from the KEGG database (https://www.genome.jp/kegg/).
Data integration: exploiting ratios of parameter estimates from a reduced external model
Authors: Taylor Jeremy M G , Choi Kyuseong , Han Peisong
Published: April 2022

We consider the situation of estimating the parameters in a generalized linear prediction model, from an internal dataset, where the outcome variable $Y$ is binary and there are two sets of covariates, $X$ and $Z$. We have information from an external study that provides parameter estimates for a generalized linear model of $Y$ on $X$. We propose a method that makes limited assumptions about the similarity of the distributions in the two study populations. The method involves orthogonalizing the $Z$ variables and then borrowing information about the ratio of the coefficients from the external model. The method is justified based on a new result relating the parameters in a generalized linear model to the parameters in a generalized linear model with omitted covariates. The method is applicable if the regression coefficients in the $Y$ given $X$ model are similar in the two populations, up to an unknown scalar constant. This type of transportability between populations is something that can be checked from the available data. The asymptotic variance of the proposed method is derived. The method is evaluated in a simulation study and shown to gain efficiency compared to simple analysis of the internal dataset, and is robust compared to an alternative method of incorporating external information.
Repurposing ibudilast to mitigate Alzheimer’s disease by targeting inflammation
Authors: Oliveros Giovanni , Wallace Charles H , Chaudry Osama , Liu Qiao , Qiu Yue , Xie Lei , Rockwell Patricia , Figueiredo-Pereira Maria E , Serrano Peter A
Published: April 2022

Alzheimer’s disease is a multifactorial disease that exhibits cognitive deficits, neuronal loss, amyloid plaques, neurofibrillary tangles and neuroinflammation in the brain. Hence, a multi-target drug would improve treatment efficacy. We applied a new multi-scale predictive modelling framework that integrates machine learning with biophysics and systems pharmacology to screen drugs for Alzheimer’s disease using patients’ tissue samples. Our predictive modelling framework identified ibudilast as a drug with repurposing potential to treat Alzheimer’s disease. Ibudilast is a multi-target drug, as it is a phosphodiesterase inhibitor and toll-like receptor 4 (TLR4) antagonist. In addition, we predict that ibudilast inhibits off-target kinases (e.g. IRAK1 and GSG2). In Japan and other Asian countries, ibudilast is approved for treating asthma and stroke due to its anti-inflammatory potential.

Based on these previous studies and on our predictions, we tested for the first time the efficacy of ibudilast in Fisher transgenic 344-AD rats. This transgenic rat model is unique as it exhibits hippocampal-dependent spatial learning and memory deficits and Alzheimer’s disease pathology, including hippocampal amyloid plaques, tau paired-helical filaments, neuronal loss and microgliosis, in a progressive age-dependent manner that mimics the pathology observed in Alzheimer’s disease patients. Following long-term treatment with ibudilast, transgenic rats were evaluated at 11 months of age for spatial memory performance and Alzheimer’s disease pathology.

We demonstrate that ibudilast-treatment of transgenic rats mitigated hippocampal-dependent spatial memory deficits, as well as hippocampal (hilar subregion) amyloid plaque and tau paired-helical filament load, and microgliosis compared to untreated transgenic rat. Neuronal density analysed across all hippocampal regions was similar in ibudilast-treated transgenic compared to untreated transgenic rats. Interestingly, RNA sequencing analysis of hippocampal tissue showed that ibudilast-treatment affects gene expression levels of the TLR and ubiquitin-proteasome pathways differentially in male and female transgenic rats. Based on the TLR4 signalling pathway, our RNA sequencing data suggest that ibudilast-treatment inhibits IRAK1 activity by increasing expression of its negative regulator IRAK3, and/or by altering TRAF6 and other TLR-related ubiquitin ligase and conjugase levels.

Our results support that ibudilast can serve as a repurposed drug that targets multiple pathways including TLR signalling and the ubiquitin/proteasome pathway to reduce cognitive deficits and pathology relevant to Alzheimer’s disease.
Genomic Insights Into the Mechanism of Carbapenem Resistance Dissemination in Enterobacterales From a Tertiary Public Heath Setting in South Asia
Authors: Farzana Refath , Jones Lim S , Rahman Md Anisur , Sands Kirsty , van Tonder Andries J , Portal Edward , Criollo Jose Munoz , Parkhill Julian , Guest Martyn F , Watkins W John , Pervin Monira , Boostrom Ian , Hassan Brekhna , Mathias Jordan , Kalam Md Abul , Walsh Timothy R
Published: April 2022

10.6% patients were CRE positive. Only 27% patients were prescribed at least 1 antibiotic to which infecting pathogen was susceptible. Burn and ICU admission and antibiotics exposures facilitate CRE acquisition. Escherichia coli ST167 was the dominant CRE clone.

Background

Given the high prevalence of multidrug resistance (MDR) across South Asian (SA) hospitals, we documented the epidemiology of carbapenem-resistant Enterobacterales (CRE) infections at Dhaka Medical College Hospital between October 2016 and September 2017.

Methods

We enrolled patients and collected epidemiology and outcome data. All Enterobacterales were characterized phenotypically and by whole-genome sequencing. Risk assessment for the patients with CRE was performed compared with patients with carbapenem-susceptible Enterobacterales (CSE).

Results

10.6% of all 1831 patients with a clinical specimen collected had CRE. In-hospital 30-day mortality was significantly higher with CRE [50/180 (27.8%)] than CSE [42/312 (13.5%)] (P = .001); however, for bloodstream infections, this was nonsignificant. Of 643 Enterobacterales isolated, 210 were CRE; blaNDM was present in 180 isolates, blaOXA-232 in 26, blaOXA-181 in 24, and blaKPC-2 in 5. Despite this, ceftriaxone was the most commonly prescribed empirical antibiotic and only 27% of patients were prescribed at least 1 antibiotic to which their infecting pathogen was susceptible. Significant risk factors for CRE isolation included burns unit and intensive care unit admission, and prior exposure to levofloxacin, amikacin, clindamycin, and meropenem. Escherichia coli ST167 was the dominant CRE clone. Clustering suggested clonal transmission of Klebsiella pneumoniae ST15 and the MDR hypervirulent clone, ST23. The major trajectories involved in horizontal gene transfer were IncFII and IncX3, IS26, and Tn3.

Conclusions

This is the largest study from an SA public hospital combining outcome, microbiology, and genomics. The findings indicate the urgent implementation of targeted diagnostics, appropriate antibiotic use, and infection-control interventions in SA public institutions.
Comparative Effectiveness of mRNA and Inactivated Whole-Virus Vaccines Against Coronavirus Disease 2019 Infection and Severe Disease in Singapore
Authors: Premikha M , Chiew Calvin J , Wei Wycliffe E , Leo Yee Sin , Ong Benjamin , Lye David Chien , Lee Vernon J , Tan Kelvin Bryan
Published: April 2022

Compared with individuals vaccinated with Pfizer-BioNTech/Comirnaty, recipients of Sinovac-CoronaVac and Sinopharm were 2.37 (95% CI, 2.29–2.46) and 1.62 (95% CI, 1.43–1.85) times more likely to be infected with coronavirus disease 19, respectively, while individuals vaccinated with Moderna were 0.42 (95% CI, 0.25–0.70) times less likely to develop severe disease.
Prevention of Typhoid by Vi Conjugate Vaccine and Achievable Improvements in Household Water, Sanitation, and Hygiene: Evidence From a Cluster-Randomized Trial in Dhaka, Bangladesh
Authors: Tadesse Birkneh Tilahun , Khanam Farhana , Ahmmed Faisal , Im Justin , Islam Md Taufiqul , Kim Deok Ryun , Kang Sophie S Y , Liu Xinxue , Chowdhury Fahima , Ahmed Tasnuva , Binte Aziz Asma , Hoque Masuma , Park Juyeon , Pak Gideok , Zaman Khalequ , Khan Ashraful Islam , Pollard Andrew J , Kim Jerome H , Marks Florian , Qadri Firdausi , Clemens John D
Published: April 2022

Background

Typhoid fever contributes to approximately 135 000 deaths annually. Achievable improvements in household water, sanitation, and hygiene (WASH) combined with vaccination using typhoid conjugate vaccines (TCVs) may be an effective preventive strategy. However, little is known about how improved WASH and vaccination interact to lower the risk of typhoid.

Methods

A total of 61 654 urban Bangladeshi children aged 9 months to <16 years, residing in 150 clusters with a baseline population of 205 760 residents, were randomized 1:1 by cluster to Vi-tetanus toxoid TCV or Japanese encephalitis (JE) vaccine. Surveillance for blood culture–confirmed typhoid fever was conducted over 2 years. Existing household WASH status was assessed at baseline as Better or Not Better using previously validated criteria. The reduction in typhoid risk among all residents associated with living in TCV clusters, Better WASH households, or both was evaluated using mixed-effects Poisson regression models.

Results

The adjusted reduced risk of typhoid among all residents living in the clusters assigned to TCV was 55% (95% confidence interval [CI], 43%–65%; P < .001), and that of living in Better WASH households, regardless of cluster, was 37% (95% CI, 24%–48%; P < .001). The highest risk of typhoid was observed in persons living in households with Not Better WASH in the JE clusters. In comparison with these persons, those living in households with Better WASH in the TCV clusters had an adjusted reduced risk of 71% (95% CI, 59%–80%; P < .001).

Conclusions

Implementation of TCV programs combined with achievable and culturally acceptable household WASH practices were independently associated with a significant reduction in typhoid risk.

Clinical Trials Registration

ISRCTN11643110.
Cut peony industry: the first 30 years of research and new horizons
Authors: Kamenetsky-Goldstein Rina , Yu Xiaonan
Published: April 2022

Herbaceous peony is an ancient medicinal and ornamental crop, cultivated in China and Japan for thousands of years. Numerous varieties of different colors are popular garden plants in different continents and countries. In recent decades, peony has gained a new reputation as cut flowers. Only in Europe, in 30 years, trade in cut peony stems has increased 50 fold. Today, more than 25 countries produce cut peony flowers, with primary markets in Europe, Asia and the USA. This short review summarizes the contribution of research in plant physiology to the development of new technologies of peony production and flowering advancement. Despite the popularity of cut peonies, several factors still restrict their production: complicated flowering physiology, challenges in mass propagation, and postharvest handling. Further research of biochemical and molecular mechanisms, as well as breeding of new cultivars will promote the development of the peony industry and facilitate the creation of a Global Peony Chain for the successful marketing of this beautiful flower.
CRISPR/Cas9-targeted mutagenesis ofSlCMT4causes changes in plant architecture and reproductive organs in tomato
Authors: Guo Xuhu , Zhao Jianguo , Chen Zhiwen , Qiao Jun , Zhang Yongfang , Shen Hong , Hu Zongli
Published: April 2022

DNA methylation participates widely in the regulation of gene expression in plants. To date, the regulation and function of DNA methylation is still unknown in tomato plants. Here, we generated SlCMT4 mutants using the CRISPR-Cas9 gene editing system. We observed severe developmental defects in CRISPR-Cas9-mediated SlCMT4 mutants, including small and thick leaves, increased lateral buds, defective stamens and pistils, small fruit size with reduced setting rate, and defective seed development. The alterations at hormonal levels (IAA, tZR, strigol) were consistent with the multibranching phenotype in SlCMT4 mutant plants. CRISPR-Cas9-mediated knockout of SlCMT4 induced the expression of two pollen-specific genes (PMEI and PRALF) that suppressed the development of pollen wall and pollen tube elongation, which is responsible for irregular and defective pollen. The small-sized fruit phenotype is probably associated with upregulated expression of the IMA gene and reduced seeds in the mutant lines. Furthermore, we performed whole-genome bisulfite sequencing (WGBS) of fruits and found that SlCMT4 knockout reduced genome-wide cytosine methylation. A reduction of methylation was also observed in a 2-kp region of the IMA and LOXB promoters in the SlCMT4-mutant fruits, indicating that the hypermethylation status of the CHH context is critical for the inhibition of IMA and LOXB promoter activity. Our results show that SlCMT4 is required for normal development of tomato vegetative and reproductive organs. This study illuminates the function of SlCMT4 and sheds light on the molecular regulatory mechanism of tomato plant architecture and fruit development and ripening.
Atherogenicity of low-density lipoproteins after switching from a protease inhibitor to dolutegravir: a substudy of the NEAT022 study
Authors: Saumoy Maria , Sánchez-Quesada Jose Luís , Assoumou Lambert , Gatell José Maria , González-Cordón Ana , Guaraldi Giovanni , Domingo Pere , Giacomelli Andrea , Connault Jérôme , Katlama Christine , Masiá Mar , Ordónez-Llanos Jordi , Pozniak Anton , Martínez Esteban , Podzamczer Daniel
Published: April 2022

Background

The aim of this study was to investigate whether switching from a ritonavir-boosted PI-based regimen to a dolutegravir-based regimen improved the atherogenic properties of LDL particles in patients with HIV.

Methods

This was a substudy of the NEAT022 study (ClinicalTrials.gov NCT02098837). Adults with HIV with a Framingham score >10% or aged >50 years and being treated with a stable boosted PI-based regimen were randomized to either switch to dolutegravir or continue with boosted PI. At baseline and Week 48, we assessed atherogenic LDL properties: LDL particle size and phenotype (A, intermediate, B), oxidized LDL (ox-LDL) and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity.

Results

Eighty-six participants (dolutegravir 44; PI 42) were included. Participants had a median (IQR) age of 54 (51–57) years and 79.1% were male. In the dolutegravir arm, after 48 weeks, we observed: (1) an increase in LDL size [median 1.65 Å (IQR −0.60 to 4.20); P = 0.007], correlated with the decrease in triglyceride concentration [Spearman correlation = −0.352 (P = 0.001)], with a corresponding decrease of subjects with atherogenic LDL phenotype B (36.4% to 20.5%; P = 0.039); (2) a decrease in Lp-PLA2 activity [median 1.39 μmol/min/mL (IQR −2.3 to 0.54); P = 0.002]; and (3) a decrease in ox-LDL [median 14 U/L (IQR −102 to 13); P = 0.006]. In the PI arm, none of these favourable lipid modifications was observed.

Conclusions

Forty-eight weeks after switching from a PI-based to a dolutegravir-based regimen, patients with Framingham score >10% or aged >50 years showed improvement of several atherogenic lipid features, including LDL particle phenotype, ox-LDL and Lp-PLA2.
68 Late Gestational Nutrient Restriction Decreases Blood Flow to the Mammary Gland in Lactating Primiparous Beef Females
Authors: Redifer Colby A , Wichman Lindsey G , Meyer Allison M
Published: April 2022

To determine the effects of late gestational nutrient restriction on mammary blood flow during lactation, fall-calving Hereford-SimAngus heifers (single-sired; BW: 451 ± 28 [SD] kg; BCS: 5.4 ± 0.7) bred to a single sire were individually-fed 100% (control; CON; n = 10) or 70% (NR; n = 13) of NASEM net energy and metabolizable protein requirements for maintenance, pregnancy, and growth from d 160 of gestation to calving. Post-calving, all females were individually fed chopped tall fescue hay supplemented to meet lactational nutrient requirements in Calan gates. Transrectal color Doppler ultrasonography of both external pudendal arteries was conducted every 21 d from d 23 to 107 of lactation. Total mammary blood flow was calculated and hemodynamics from both sides averaged. Data were analyzed with fixed effects of nutritional plane, day of lactation, and their interaction, using repeated measures. Calving date and calf sex (if P < 0.25) were fixed effects, and Doppler angle of insonation was included in the model for flow-related variables. We have previously reported that CON cows had greater (P ≤ 0.003) BW, BCS, and backfat from calving to d 147 of lactation, and NR cows had 15% less (P < 0.04) milk yield. External pudendal artery pulsatility index tended to be greater (P = 0.06) and resistance index, peak systolic velocity, and cross-sectional area were greater (P ≤ 0.04) in CON cows. Heart rate was greater (P = 0.008), yet mammary blood flow was 19% less (P = 0.004) in NR cows. Mammary blood flow/cow BW and blood flow/milk yield were not affected (P ≥ 0.13) by nutritional plane. All hemodynamic variables were affected by day (P ≤ 0.04) except resistance index (P = 0.11). In summary, late gestational nutrient restriction decreased mammary blood flow similarly to the reduction observed in milk yield.
77 Determination of Cellutein and Betagro Mode of Action within Porcine Satellite Cell Cultures
Authors: Vaughn Mathew A , Gonzalez John M
Published: April 2022

The objective of the study was to evaluate the efficacy of celluTEIN and betaGRO to influence porcine myogenesis in vitro. Satellite cells (N = 3 piglets) were plated on ECL-coated 12-well plates at a density of 5,000 cells/cm2. Cells were grown to confluence in growth media containing 10% fetal bovine serum, 100 U penicillin/mL, 100 µg of strepmycin/mL, and 20 µg of gentamicin/mL in high glucose DMEM for 72 hours. Cells were treated with 1 of 4 treatments: 2% fetal bovine serum, 100 U penicillan/mL, 100 µg of strepmycin/mL, and 20 µg of gentamicin/mL (CON), CON+5 ng/mL recombinant IGF-1 (IGF-1), CON+10 mg/mL betaGRO (BG), CON+10 mg/mL celluTEIN (CT). For myotube width assays, FBS was reduced to 2% when cells were confluent for 96 hours, at which time treatments above were applied with or without 20 µM rapamycin. Fusion capacity (FC) and myotube width (MW) were determined from 5 representative photomicrographs and experiments were repeated 3×. There were treatment effects for FC and MW. Cells treated with CT and BG had greater FC and MW than the other treatments (( P < 0.05), but did not differ from each other (P > 0.05). Cells treated with IGF-1 had greater FC and MW than CON cells (( P < 0.05). There was a Treatment×Rapamycin interaction (( P < 0.05). Without rapamycin, CON myotubes had smaller diameters than other treatments (( P < 0.05), BG and CT myotubes were greater than IGF-1 (( P < 0.05), but were not different (P > 0.10) from each other. Though there was a statistical difference between treatments when rapamycin was added (P < 0.05), treatment differences did not reflect a difference that can be translated out of the satellite cell model. These data illustrate that celluTEIN and betaGRO stimulate porcine satellite cell differentiation and growth through mechanistic target of rapamycin signaling.