bluuebunny/crossref_metadata_2025 huggingface dataset:
Ion temperature profile importance in collisional sheath modelling
Authors: Mun J-H , Muraglia M , Agullo O , Arnas C , Couedel L
Published: December 2022

A plasma fluid model is being developed for the simulation of a direct current plasma discharge simulation including the sheath regions. The code uses a second order centered finite difference scheme and time integration is done by strong stability preserving third order Runge-Kutta method. The separation of scalar and vectorial quantities in two different grids gives stable results. After validation by comparison with theoretical ion sheath profiles, a one dimensional direct current argon discharge was simulated and compared to 1D3v particle-in-cell simulation results. It is shown that the inclusion of a non constant ion temperature profile is mandatory in fluid models in order to recover correct increase of ion velocity in sheaths and thus to simulate direct current (DC) discharges where collisions are not negligible in the sheaths.
Numerical Investigation of the Ion Cyclotron Resonance Heating (ICRH) Physics in DTT
Authors: Cardinali A. , Baiocchi B. , Castaldo C. , Bilato R. , Brambilla M. , Casiraghi I. , Ceccuzzi S. , Napoli F. , Ravera G. L. , Tuccillo A. A.
Published: December 2022

An extensive linear analysis of the ICRH propagation and absorption in DTT full heating scenario has been performed by means of three advanced numerical tools: DISEMAG, FELICE and TORIC. The numerical codes solve respectively the full dispersion relation in the complex domain of the wavenumber (DISEMAG) and the integro-differential equation that accounts for the correct evaluation of the ICRH power absorption in a slab plasma (FELICE) and in the tokamak equilibrium configuration (TORIC). Moreover, by incorporating the antenna conceptual design, as released by the engineering design team, in FELICE and TORIC, the power spectrum, radiated by the antenna (3 straps) and coupled to the plasma, has been evaluated in the case of 60 and 90 MHz (3He and H minority heating respectively). By extensively using the abovementioned suite of codes, and after establishing the plasma target (fixing tokamak dimensions, density, temperatures, plasma current, magnetic field, isotopic composition, etc.), and the antenna characteristics (number, dimension, pitch, and radial position of the straps, antenna size, etc.), the power absorption on the various species (electrons, majority and minority ions) has been calculated as function of the minority concentration, parallel wavenumber, frequency, harmonic resonant layer, etc.. Comparison between the codes DISEMAG and TORIC in evaluating the absorption on electrons and minority ions has also been performed and shows a good agreement of the results. A new ion heating scheme based on three ions mixture has also been proposed in DTT.
Time evolution and finite element representation of Phase Space Zonal Structures in ORB5
Authors: Bottino A. , Falessi M.V. , Hayward-Schneider T. , Biancalani A. , Briguglio S. , Hatzky R. , Lauber Ph. , Mishchenko A. , Poli E. , Rettino B. , Vannini F. , Wang X. , Zonca F.
Published: December 2022

Phase Space Zonal Structures (PSZSs), obtained by averaging out dependencies on angle-like variables in the energetic particle (EP) distribution function, play a fundamental role in regulating EP transport induced by Alfvén instabilities in burning plasmas, acting as a slowly varying nonlinear equilibrium state. Therefore, they are of great interest for the development of reduced models for the description of EP heat and particle transport on long time scales, comparable with the energy confinement time, for future burning plasma experiments. In this work, we propose an efficient finite element based projection of the time evolution of the PSZS, suited for global particle-in-cell (PIC) gyrokinetic (GK) codes. The resulting algorithm has been implemented in the global GK PIC code ORB5. PSZSs can not only be used for validating reduced models, but also as a diagnostic tool for characterizing the nonlinear interaction in phase space between Alfvén instabilities and EPs in global GK simulations.
A new network of electric field mills at the Pierre Auger Observatory
Authors: Büsken Max
Published: December 2022

The Pierre Auger Observatory is the largest ground-based experiment for the detection of ultra-high energy cosmic rays. In a hybrid approach, many detectors – including radio antennas – observe the extensive air showers induced by cosmic rays. As part of the AugerPrime upgrade, new antennas will be installed on each of the surface-detector stations covering a total area of around 3000 km2. This will allow us to study the mass composition of cosmic rays arriving with large inclination angles.

The radio emission of air showers is heavily influenced in the presence of strong atmospheric electric fields during thunderstorm conditions. In that case measured data are difficult to interpret and therefore the atmospheric electric field over the array has to be monitored. We present the design and status of a new network of electric field mills (EFM) that will be used to take on this task. We show how we plan to perform the measurements with an absolute calibration. In addition, the electric-field data will be useful for other studies related to atmospheric electricity.
Detecting Terrestrial Gamma-Ray Flashes with CubeSats: the scientific payload of the LIGHT-1 mission
Authors: Di Giovanni A , Arneodo F. , Alkindi L. , Benabderrahmane M. L. , Mannino M. , Oikonomou P. , Kalos S. , Torres R. , Franchi G. , Perillo L. , Conicella V.
Published: December 2022

Terrestrial Gamma-ray Flashes (TGFs) are a prompt, high energy, very intense natural emission of gamma rays from Earth’s atmosphere. Consisting of an upward sub-millisecond bursts of gamma rays (energy up to one hundred MeV), TGFs are mostly generated in powerful thunderstorms by lightnings. Given their production mechanism, several TGF counterparts can be detected too (mostly radio waves, electron beams and neutrons from photo-production). To investigate the X- and gamma-ray components, the ideal experiment is a space-borne instrument, operating at Low Earth Orbit (LEO) and featuring a fast detector response, possibly with spectral abilities. The CubeSat space mission LIGHT-1, launched in December 21st, 2021 and deployed from the International Space Station (ISS) on February 3rd, 2022, has been tailored around such physics requirements and it represents the technological demonstrator of possible larger missions to detect and localize TGF events. LIGHT-1 will help in making advancements in the TGF current knowledge: TGF occurring rates, average ignition altitude, production mechanism and effects on daily life on Earth are yet to be fully modeled and understood. In this paper the main characteristics of LIGHT-1 mission and the first preliminary flight data are reported.
Correcting MAGIC Telescope data taken under non-optimal atmospheric conditions with an elastic LIDAR
Authors: Schmuckermaier Felix , Gaug Markus , Fruck Christian , Hahn Alexander , Acciari Victor , Besenrieder Jürgen , Prester Dijana Dominis , Dorner Daniela , Fink David , Font Lluís , Mićanović Saša , Mirzoyan Razmik , Müller Dominik , Pavletić Lovro , Will Martin
Published: December 2022

The Major Atmospheric Gamma-ray Imaging Cherenkov (MAGIC) telescopes are a system of two Imaging Atmospheric Cherenkov Telescopes (IACTs). IACTs make calorimetric use of the Earth’s atmosphere, which allows them to reach large effective areas, but also makes them strongly dependent on the quality of the atmosphere at the time of the observations. Dust intrusions or clouds obscuring the observed Cherenkov light can then lead to a wrong reconstruction of the gamma-ray data. In order to mitigate this problem, the MPP group built and has been operating a single wavelength elastic LIDAR (LIght Detection And Ranging) system to perform real time ranged-resolved measurements of the aerosol transmission. This information is then used to quantify the quality of the telescope data, as well as to correct the data taken under suboptimal aerosol conditions. In this talk, the correction of atmospherically impaired IACT data will be described and the first systematic evaluation of the correction capabilities of the LIDAR system will be presented. The results describe the impact of the LIDAR corrections for a variety of atmospheric and observational conditions, and therefore contribute to a better understanding of the telescope’s performance and related systematic uncertainties.
Design, modeling, and characteristic analysis of an index finger exoskeleton for rehabilitation
Authors: Zhang Hanzhe
Published: December 2022

Since the rehabilitation hand exoskeleton robot is the current research hotspot, it can play a great role in patients’ hand rehabilitation and can replace the rehabilitation physician to treat the patient. Many of today’s rehabilitation hand exoskeleton robots can not achieve a good rehabilitation effect. In order to improve the treatment effect of the rehabilitation hand exoskeleton robot on patients and alleviate the pressure of insufficient human hands in China’s rehabilitation physicians, this paper, on the basis of analyzing the biological characteristics of the human hand, focuses on the functional analysis of the rehabilitation exoskeleton hand, the mechanical structure design of the exoskeleton hand, Kinematic analysis, Modeling and simulation to design an exoskeleton hand using a one-wheel-two way combining sliding guide rod and SEA tandem elastic drive to achieve the mechanism that can adjust the stretch according to the length of the finger and the rehabilitation force perpendicular for the purpose of the finger surface. A closed-loop structure is established to analyze the mechanism of plane motion of the structure and the coupling of the structure and the range of motion of the human hand. Through simulation analysis of the motion trajectory of the structure and the stability of the dynamic model analysis system based on the force source control method to establish a dynamic model of the tandem elastic drive, the results show that the DIP joint rotation angle is 16-73 degrees, the PIP joint rotation angle is 0-108 degrees, and the MP joint is 0-86 degrees, which is basically consistent with the human hand, and the series elastic drive should choose a smaller stiffness and larger damping to ensure the stability of the system.
A Rigid and Flexible Combined Finger Exoskeleton Design with Variable Curvature
Authors: Lan Zixuan
Published: December 2022

Some hand exoskeletons have been used in the rehabilitation treatment of paralyzed patients caused by stroke and cerebral apoplexy as a result of research into hand exoskeletons. However, how to make the patient more comfortable to use and how to make the exoskeleton more precise are still key issues that need to be studied. Aiming at the motion law and skeletal characteristics of the human hand, this paper proposes a soft exoskeleton machine for hand rehabilitation training that combines rigidity and flexibility. Using a simplified two-layer sliding spring mechanism, the device combines the comfort and fit of a flexible device with the accurate kinematics of a rigid device. The mechanism requires only one degree of freedom to drive the normal flexion and expansion of the three finger joints. By changing the section thickness of the spring sheet to change its section moment of inertia, the bending effect of the mechanism is optimized to better fit the bending characteristics of the finger joints. To simplify the simulation of the mechanism, the method of the pseudo-rigid-body model is used to target the spring leaf’s nonlinear deformation, to achieve intuitively understandable kinematics. Finally, the accuracy of the design is demonstrated through simulation and prototype models.
Design of Low-Power High-Speed Double-Tail Dynamic Comparator Based on Charge-Steering Concept
Authors: Zhang Zhe , Lei Qianqian , Zhao Erhu , Yang Yanfei , Feng Song
Published: December 2022

In this thesis, a low-power dissipation high-speed double-tail dynamic comparator is designed. Based on the principles of charge-steering, a clock charge pump is used at the tail of the latch stage to replace the clock current source, which reduce the output swing and kick-back noise of the comparator. Meanwhile, digital logic is added to the pre-amplification stage to eliminate quiescent current and further reduce power consumption. Based on the SMIC 28nm CMOS process, the proposed comparator is simulated and verified. The results show that under the condition of 0.9V supply voltage and 1MHz sampling frequency, the power dissipation is 5.4μW, the delay is 245ps, and the offset voltage is 6.9mV. Compared with a high-speed comparator, under the premise of achieving the same performance, the power consumption is reduced by 69%.
Design of a Monitoring System for Power-consumption Devices Based on Modbus Protocol
Authors: Sun Jinhua , Lin Jiayuan , Meng Zhaorui
Published: December 2022

To better monitor the usage status of electric energy for production and living devices, the paper has put forward an electric energy monitoring system based on Modbus protocol, starting by analyzing the demand for monitoring and management of users’ electric energy. A three-layer structure has been used in the system, which consists of the sensing layer, control layer, and application layer. The lower computer of the sensing layer used the one-master-multi-slave mode to collect the power data of multiple devices in the bus in real time and transmits the voltage, current, power consumption, and other data of power-consumption devices to the host through the RS-485 interface, Modbus protocol, and GPRS network. Meanwhile, the lower computer interacts with the remote user monitoring terminal to realize the monitoring and management of power consumption data of the devices. The test has shown that the system can steadily monitor and manage the power consumption status of the devices in real time, and can be applied to energy saving, monitoring of power-consumption devices, property management, and other fields, which have good application prospects.
Machine Vision Product Appearance Defect Detection Based on Deep Learning
Authors: Wang Chengyan , Shi Weiping , Li Yuling
Published: December 2022

Due to the influence of objective environmental conditions in the image acquisition stage, the image quality of the existing methods is poor, which makes the effect of defect detection not ideal. In this paper, research on product appearance defect detection based on deep learning machine vision is proposed. A product appearance model is constructed by using a Gaussian mixture, and multiple sub-images with different sizes are used as the data support of the multi-scale expression of the Gaussian model to calculate the Gaussian difference features of the image. A Faster R-CNN network algorithm in deep learning is used to recognize defects. The multi-task mechanism is introduced in the setting of the loss function to realize the concurrent function of defect detection. The mean pooling and maximum pooling operations are introduced in the setting of the classification regression network to realize the comprehensive detection of target images. Judge whether that product has a defect according to the output result of the algorithm and the DOG characteristics of the image. The test results show that the accuracy of the designed method for various types of defect detection is more than 90. 00% and it has a high detection efficiency.
Space Manipulator Assembly Operation Technique based on Deep Residual Reinforcement Learning
Authors: Huang Kui , Liang Binyan , Quan Junyu , Luo Zhiwen , Jiang Shan
Published: December 2022

In recent years, there are more and more space complex operational tasks such as the maintenance and assembly of on-orbit aircraft. Traditional robot planning and control methods require precise dynamic models, which are difficult to accommodate to on-orbit assembly operations in extreme space environments. Typical space operation tasks, such as plug and pull operation, whose control strategy can be artificially designed. Being artificially designed by combining the output control strategy and deep reinforcement learning algorithm, which can simplify the training difficulty of deep reinforcement learning, making the learning process more efficient and training results better. In this paper, a deep Residual reinforcement learning algorithm combined with a heuristic control strategy is constructed to complete the space mechanical arm assembly operation training in a highly realistic simulation environment. Based on the experimental data, the Residual deep reinforcement-learning algorithm designed in this paper shows the performance of rapid convergence and can complete the on-orbit assembly operation task with a high probability.
Research on Static Test Verification Technology of the Connection Between APU and Fuselage of Civil Aircraft
Authors: Zhu Zhengyi
Published: December 2022

This paper studies the static strength verification of the connection between APU and fuselage of large civil aircraft, which provides a verification method for the airworthiness verification of the connection between APU and fuselage. Based on the internal force analysis results of APU finite element, this paper selects the static test load, completes the design from the theoretical load to the test load, designs a set of APU dummy loading device to introduce the load to complete the static test. The finite element analysis model is verified by the test results. The verified finite element analysis, limit load and limit load static strength test are used to show the airworthiness compliance of the static strength of the connection between APU and fuselage.
Study of COSPAS-SARSAT Beacon Device Used in Chinese Crewed Spaceflight
Authors: Ji Xue , He Ze Hua , Song Xing Xue , Ye Jian She , Zhang Bei Ming
Published: December 2022

Positioning and carrying out search and rescue as soon as possible after a spacecraft is forced to land or crash is a key issue in the field of the Global Human Spaceflight Program. To promptly obtain an emergency location in the event of an unplanned landing, the Search and Rescue Satellite System (COSPAS-SARSAT) has been widely used in Global Human Spaceflight Program. Due to the currently widely used distress beacon landing crash activation, the spacecraft often lost the chance to survive at that time. Therefore, the Search and Rescue Satellite System regards the Emergency Locator Transmitter for In-Flight Distress Tracking (ELT-DT) alike device as the main research direction of technology. This paper introduces the application of COSPAS-SARSAT in global human spaceflight programs, the operation performance of the ELT-DT, the operation of the custom ELT alike device on the re-entry module and the prospects of the application.
Forecasting and analysis of PM2.5 concentration in Hainan Province based on LSTM Neural Networks
Authors: Hu Shuning , Liu Bing , Wang Jizhen , Zhang Youchao
Published: December 2022

The change of PM2.5 concentration not only reflects the change of air quality level, but also affects human life and health. However, because the PM2.5 change is caused by wide-ranging factors and the occurrence mechanism is complex, it is difficult to build a stable forecasting model with general physical methods. This study builds three different LSTM models to forecast the PM2.5 concentration of Hainan Province from 2019 to 2021. Model 1 is a fully connected neural network, which is also the base model. Model 2 is a single unit LSTM model. Model 3 is a multi-LSTM layer model. The conclusion indicate that the multi-layer LSTM model has the best forecasting precison for PM2.5 concentration, and the single unit LSTM model quite the opposite. The length of the time series has certain influence on the precision of PM2.5 forecasted by LSTM models, suggesting that a suitable time series length should be selected when building LSTM models.
Intrusion Detection System for Internet of Vehicles Based on Ensemble Learning and CNN
Authors: Luo Anlun
Published: December 2022

With the combination of network and automotive technology, more and more modern cars are controlled based on electronic control units (ECUs). And multiple ECUs in modern cars are interconnected and cooperate through the in-vehicle network. But such in-vehicle networks do not consider potential security issues, which might lead to property damage and life threat. An intrusion Detection System (IDS) is a method to detect anomalies and warn about network intrusions. In this study, an IDS model based on Convolutional Neural Networks (CNNs) and ensemble learning is proposed. Meanwhile, to further improve the capability of the proposed IDS model, the structure of some CNN basic models is modified. Finally, the proposed model is validated on a representative standard Internet of Vehicles (IoV) dataset Car-Hacking Dataset. In the experiment, the proposed model achieves 100% accuracy and fl-score, and the detection time is from 1.0ms to 2.8ms, which demonstrates that the proposed IDS model detects the effectiveness of network intrusions.
An effective algorithm for offshore air temperature prediction with LSTM neural network and wavelet decomposition and reconstruction
Authors: Wang Longfei , Song Miaomiao , Liu Shixuan , Wang Bo , Chen Shizhe , Hu Tong , Hu Wei
Published: December 2022

Offshore air temperature is an important parameter in marine scientific research. The change of offshore air as an indicator of the marine ecological environment is not only related to the growth of offshore organisms but also affects the development of the marine economy. Effective prediction of offshore air temperature is significant. The prediction model of offshore air temperature data is established by using wavelet decomposition and reconstruction algorithm combined with long short-term memory neural network (LSTM). We use the wavelet decomposition to decompose the offshore air temperature data of the ocean station into the overview signal and the detail signal, and the decomposed signal is reconstructed by a single branch to obtain the reconstructed signal. Then, input the reconstructed signals into LSTM model to predict the future offshore temperature. Finally, through the experiments, the proposed model is verified that has more advantages than the prediction effect of the LSTM offshore air temperature prediction model based on seasonal-trend decomposition procedure based on seasonal trend loss (STL) decomposition and the traditional LSTM prediction model. The proposed model has better prediction accuracy for offshore air temperature, and the prediction model can achieve effective prediction of the offshore air temperature.
On the formation of lines in quantum phase space
Authors: Steuernagel Ole , Yang Popo , Lee Ray-Kuang
Published: December 2022

We theoretically study the formation of lines in phase space using Wigner’s distribution

W
.

In trapped quantum systems such lines form generically, crisscrossing phase space and they can have astonishing extent, reaching across the entire state. In classical systems this does not happen. We show that the formation of such straight line patterns is due to the formation of ‘randomized comb-states’. We establish their stability to perturbations, and that they are tied to coherences in configuration space. We additionally identify generic higher-order ‘eye’ patterns in phase space which occur less often since they arise from more specific symmetric comb-states; we show that the perturbation of eye patterns through their randomization tends to deform them into lines. Lines in phase space should give rise to large probability peaks in measurements.
Beyond crystal balls: multimodal prediction of early recovery of consciousness
Authors: Claassen Jan
Published: December 2022

This scientific commentary refers to ‘Multimodal prediction of residual consciousness in the intensive care unit: the CONNECT-ME study’ by Amiri et al. (https://doi.org/10.1093/brain/awac335).
Gene amplification mutations originate prior to selective stress in Acinetobacter baylyi
Authors: Herrmann Jennifer A , Koprowska Agata , Winters Tesa J , Villanueva Nancy , Nikityuk Victoria D , Pek Feini , Reis Elizabeth M , Dominguez Constancia Z , Davis Daniel , McPherson Eric , Rocco Staci R , Recendez Cynthia , Difuntorum Shyla M , Faeth Kelly , Lopez Mario D , Awwad Habeeba M , Ghobashy Rola A , Cappiello Lauren , Neidle Ellen L , Quiñones-Soto Semarhy , Reams Andrew B
Published: December 2022

The controversial theory of adaptive amplification states gene amplification mutations are induced by selective environments where they are enriched due to the stress caused by growth restriction on unadapted cells. We tested this theory with three independent assays using an Acinetobacter baylyi model system that exclusively selects for cat gene amplification mutants. Our results demonstrate all cat gene amplification mutant colonies arise through a multistep process. While the late steps occur during selection exposure, these mutants derive from low-level amplification mutant cells that form before growth-inhibiting selection is imposed. During selection, these partial mutants undergo multiple secondary steps generating higher amplification over several days to multiple weeks to eventually form visible high-copy amplification colonies. Based on these findings, amplification in this Acinetobacter system can be explained by a natural selection process that does not require a stress response. These findings have fundamental implications to understanding the role of growth-limiting selective environments on cancer development. We suggest duplication mutations encompassing growth factor genes may serve as new genomic biomarkers to facilitate early cancer detection and treatment, before high-copy amplification is attained.
Environmental Interaction of Resolved Human Cytomegalovirus Infection With Crohn’s Disease Location
Authors: Shih Terri , Yusung Susy , Gonsky Rivkah , Dutra-Clarke Rhiannon , Ziring David , Rabizadeh Shervin , Kugathasan Subra , Denson Lee A , Li Dalin , Braun Jonathan
Published: December 2022

Lay Summary

Active cytomegalovirus (CMV) infection complicates management of inflammatory bowel disease, but the relationship of resolved CMV infection to Crohn’s disease (CD) behavior or localization is unknown. This article reports a striking risk (9-fold) of Crohn’s disease localization to the colon with prior CMV infection. It also reports imputed mucosal cellular composition, HLA class 1, and KIR gene variants that delimit prior observations regarding HLA and KIR associations with Crohn’s disease risk and behavior.
The Power of Keratinous Matrices (Head Hair, Body Hair and Nail Clippings) Analysis in a Case of Death Involving Anabolic Agents
Authors: Gheddar Laurie , Blanchot Adeline , Ameline Alice , Arbouche Nadia , Raul Jean-Sébastien , Kintz Pascal
Published: December 2022

A 29-year-old man with no previous medical history was found dead at home. Anabolic products (tablets and oily solutions) and syringes were found at the scene. The man was known to train regularly at a fitness club and to use anabolic drugs. Following an unremarkable autopsy with normal histology, toxicological analyses were requested by the local prosecutor to provide further information. Blood, head hair (5 cm, black), body hair (axillary and leg) and toe and finger nail clippings were submitted to liquid and gas chromatography coupled to tandem mass spectrometry (LC and GC–MS-MS) methods to test for anabolic steroids. Blood tested positive for testosterone (4 ng/mL), boldenone (26 ng/mL), stanozolol (3 ng/mL) and trenbolone (<1 ng/mL). Segmental head hair tests (2 × 2.5 cm) revealed a repeated consumption of testosterone (65–72 pg/mg), testosterone propionate (930–691 pg/mg), testosterone isocaproate (79 pg/mg to <5 pg/mg), nandrolone decanoate (202–64 pg/mg), boldenone (16 pg/mg), stanozolol (575–670 pg/mg), trenbolone (4 pg/mg–not detected), drostanolone (112–30 pg/mg), drostanolone enanthate (26–5 pg/mg) and drostanolone propionate (15–4 pg/mg). In addition to the substances identified in head hair, testosterone decanoate, testosterone cypionate and nandrolone were identified in both body hair and nails. The experts concluded that the manner of death can be listed as toxic due to massive repetitive use of anabolic steroids during the previous months. For anabolic agents, blood does not seem to be the best matrix to document a fatal intoxication. Indeed, these products are toxics when abused long term and are known to cause cardiac, hepatic and renal diseases. When compared to blood, hair and nails have a much larger window of detection. Therefore, keratinous matrices seem to be the best approach to test for anabolic steroids when a sudden death is observed in the context of possible abuse of steroids.
Network Topology Can Explain Differences in Pleiotropy Between Cis- and Trans-regulatory Mutations
Authors: Vande Zande Pétra , Wittkopp Patricia J
Published: December 2022

A mutation's degree of pleiotropy (i.e., the number of traits it alters) is predicted to impact the probability of the mutation being detrimental to fitness. For mutations that impact gene expression, mutations acting in cis have been hypothesized to generally be less pleiotropic than mutations affecting the same gene's expression in trans, suggesting that cis-regulatory mutations should be less deleterious and more likely to fix over evolutionary time. Here, we use expression and fitness data from Saccharomyces cerevisiae gene deletion strains to test these hypotheses. By treating deletion of each gene as a cis-regulatory mutation affecting its own expression and deletions of other genes affecting expression of this focal gene as trans-regulatory mutations, we find that cis-acting mutations do indeed tend to be less pleiotropic than trans-acting mutations affecting expression of the same gene. This pattern was observed for the vast majority of genes in the data set and could be explained by the topology of the regulatory network controlling gene expression. Comparing the fitness of cis- and trans-acting mutations affecting expression of the same gene also confirmed that trans-acting deletions tend to be more deleterious. These findings provide strong support for pleiotropy playing a role in the preferential fixation of cis-regulatory alleles over evolutionary time.
Unscheduled epigenetic modifications cause genome instability and sterility through aberrant R-loops following starvation
Authors: Sun Bing , Sherrin McLean , Roy Richard
Published: December 2022

During starvation, organisms modify both gene expression and metabolism to adjust to the energy stress. We previously reported that Caenorhabditis elegans lacing AMP-activated protein kinase (AMPK) exhibit transgenerational reproductive defects associated with abnormally elevated trimethylated histone H3 at lysine 4 (H3K4me3) levels in the germ line following recovery from acute starvation. Here, we show that these H3K4me3 marks are significantly increased at promoters, driving aberrant transcription elongation resulting in the accumulation of R-loops in starved AMPK mutants. DNA-RNA immunoprecipitation followed by high-throughput sequencing (DRIP-seq) analysis demonstrated that a significant proportion of the genome was affected by R-loop formation. This was most pronounced in the promoter–transcription start site regions of genes, in which the chromatin was modified by H3K4me3. Like H3K4me3, the R-loops were also found to be heritable, likely contributing to the transgenerational reproductive defects typical of these mutants following starvation. Strikingly, AMPK mutant germ lines show considerably more RAD-51 (the RecA recombinase) foci at sites of R-loop formation, potentially sequestering them from their roles at meiotic breaks or at sites of induced DNA damage. Our study reveals a previously unforeseen role of AMPK in maintaining genome stability following starvation. The downstream effects of R-loops on DNA damage sensitivity and germline stem cell integrity may account for inappropriate epigenetic modification that occurs in numerous human disorders, including various cancers.
Disclosing the molecular basis of salinity priming in olive trees using proteogenomic model discovery
Authors: Skodra Christina , Michailidis Michail , Moysiadis Theodoros , Stamatakis George , Ganopoulou Maria , Adamakis Ioannis-Dimosthenis S , Angelis Lefteris , Ganopoulos Ioannis , Tanou Georgia , Samiotaki Martina , Bazakos Christos , Molassiotis Athanassios
Published: December 2022

Plant responses to salinity are becoming increasingly understood, however, salt priming mechanisms remain unclear, especially in perennial fruit trees. Herein, we showed that low-salt pre-exposure primes olive (Olea europaea) plants against high salinity stress. We then performed a proteogenomic study to characterize priming responses in olive roots and leaves. Integration of transcriptomic and proteomic data along with metabolic data revealed robust salinity changes that exhibit distinct or overlapping patterns in olive tissues, among which we focused on sugar regulation. Using the multi-crossed -omics data set, we showed that major differences between primed and nonprimed tissues are mainly associated with hormone signaling and defense-related interactions. We identified multiple genes and proteins, including known and putative regulators, that reported significant proteomic and transcriptomic changes between primed and nonprimed plants. Evidence also supported the notion that protein post-translational modifications, notably phosphorylations, carbonylations and S-nitrosylations, promote salt priming. The proteome and transcriptome abundance atlas uncovered alterations between mRNA and protein quantities within tissues and salinity conditions. Proteogenomic-driven causal model discovery also unveiled key interaction networks involved in salt priming. Data generated in this study are important resources for understanding salt priming in olive tree and facilitating proteogenomic research in plant physiology.
Can the Area Under the Curve/Trough Level Ratio Be Used to Optimize Tacrolimus Individual Dose Adjustment?
Authors: Woillard Jean-Baptiste , Monchaud Caroline , Saint-Marcoux Franck , Labriffe Marc , Marquet Pierre
Published: December 2022

Background.

The aim of this work was to evaluate, in a large data set of renal transplant recipients, the intraindividual variability of the area under the curve (AUC)/predose concentration (C0) ratio in comparison with that of AUC, C0, AUC/dose, and C0/dose.

Methods.

Patients with at least 2 tacrolimus AUC estimation requests were extracted from the Immunosuppressant Bayesian dose Adjustment website, and relative variations between 2 consecutive visits for the different metrics were calculated and compared.

Results.

Data from 1325 patients on tacrolimus (3827 measured C0 and estimated AUC) showed that the lowest mean relative variation between 2 consecutives visits was for the AUC/C0 ratio (95% confidence interval [CI] relative fold change = –43% to 44% for AUC/C0; 95% CI, –77% to 72% for AUC; 95% CI, –82% to 98% for AUC/dose; 95% CI, –81% to 80% for C0 and 95% CI, –94% to 117% for C0/dose. The correlation between 2 consecutive requests, whether close or far apart, was also best for the AUC/C0 ratio (r = 0.33 and r = 0.34, respectively) in comparison with C0 (r = 0.21 and r = 0.22, respectively) and AUC (r = 0.19 and 0.28, respectively). Regression analysis between AUC0-24 and C0 showed that for some patients, the usual C0 targets translated into some very unusual AUC values. As the AUC/C0 ratio is quite stable during large periods, individualized C0 targets can be derived from the AUC targets, and an algorithm that estimates the individualized C0 was developed for situations in which prior AUC estimates are available or not.

Conclusions.

In this study, we confirmed in a large data set that the AUC/C0 ratio yields low intraindividual variability, whereas C0 shows the largest, and we propose to calculate individualized C0 targets based on this ratio.
High-resolution app data reveal sustained increases in recreational fishing effort in Europe during and after COVID-19 lockdowns
Authors: Audzijonyte Asta , Mateos-González Fernando , Dainys Justas , Gundelund Casper , Skov Christian , DeWeber J. Tyrell , Venturelli Paul , Vienožinskis Vincentas , Smith Carl
Published: December 2022

It is manifest that COVID-19 lockdowns extensively impacted human interactions with natural ecosystems. One example is recreational fishing, an activity which involves nearly 1 in 10 people in developed countries. Fishing licence sales and direct observations at popular angling locations suggest that recreational fishing effort increased substantially during lockdowns. However, the extent and duration of this increase remain largely unknown due to a lack of objective data. We used four years (2018 to 2021) of anonymous, high-resolution data from a personal fish-finder device to explore the impact of COVID-19 lockdowns on recreational fishing effort in four European countries (Lithuania, the Czech Republic, Denmark, and Germany). We show that device use and, by extension, angling effort increased 1.2-3.8 fold during March-May 2020 and remained elevated even at the end of 2021 in all countries except Denmark. Fishing during the first lockdown also became more frequent during weekdays. Statistical models with the full set of fixed (weekdays, lockdown, population) and random (season, year, administrative unit) factors typically explained 50-70% of the variation, suggesting that device use and angling effort were relatively consistent and predictable through space and time. Our study demonstrates that recreational fishing behaviour can change substantially and rapidly in response to societal shifts, with profound ecological, human well-being and economic implications. We also show the potential of angler devices and smartphone applications to supply data for high-resolution fishing effort analysis and encourage more extensive science and industry collaborations to take advantage of this information.

Significance statement

Recreational fishing is a popular and widespread activity with ecological, social and economic impacts, though problematic to assess and manage due to a paucity of information regarding effort and catch. Here, we use high-resolution data from a personal angler sonar device to show how the COVID-19 pandemic changed angler behaviour and fishing effort across Europe. We demonstrate that angling effort doubled and remained higher at the end of 2021 than before the first lockdowns. Such rapid and profound changes could have significant consequences for aquatic ecosystems, possibly requiring new management approaches. We encourage the adoption of novel data from angler devices, citizen science, and more active science-industry collaborations to improve recreational fishing assessment and management.
ROTACs leverage signaling-incompetent R-spondin for targeted protein degradation
Authors: Sun Rui , Lee Hyeyoon , Niehrs Christof
Published: December 2022

Proteolysis-targeting chimeras (PROTACs) are an emerging technology for therapeutic intervention but options to target cell surface proteins and receptors remain limited. Here we introduce ROTACs, bispecific WNT- and BMP signaling-disabled R-spondin (RSPO) chimeras, which leverage the specificity of these stem cell growth factors for ZNRF3/RNF43 E3 transmembrane ligases, to target degradation of transmembrane proteins. As proof of concept, we targeted the immune checkpoint protein programmed death ligand 1 (PD-L1), a prominent cancer therapeutic target, with a bispecific RSPO2 chimera, R2PD1. The R2PD1 chimeric protein bound PD-L1 and at picomolar concentration induced its lysosomal degradation. In three melanoma cell lines, R2PD1 induced between 50-90% PD-L1 protein degradation. PD-L1 degradation was strictly dependent on ZNRF3/RNF43. We conclude that signaling-disabled ROTACs represent a novel strategy to target cell surface proteins for degradation.
From whole genome to probiotic candidates: a study of potentialLactobacillusstrain selection for vaginitis treatment
Authors: Lyu Jinli , Gao Mengyu , Zhao Shaowei , Liu Xinyang , Zhao Xinlong , Zou Yuanqiang , Zhong Yiyi , Ge Lan , Zhang Haifeng , Xiao Liang , Zhang Xiaowei
Published: December 2022

Vaginitis is a syndrome characterized by not only the invasion of pathogens, but also the lack ofLactobacillus.Lactobacillussupplementation emerged as an innovative therapy for vaginitis which targeted the vaginal microbiota in recent years. However, limited live biotherapeutic products were explicitly marketed for this. The aim of our study is to characterize the potentialLactobacilluscandidates for enhancing the treatment of vaginitis. Initially, 98Lactobacillusisolates with whole genome were selected into the candidate pool. The genomic pathways involved in the biosynthesis of probiotic metabolites, adhering ability and acid/bile resistance, as well as sequences of antibiotic resistance genes, plasmids, transposons, viruses, and prophages were annotated. A scoring model was then established based on genomic analysis for ranking the performance of the strains, and the top-performing ones were applied toin vitrotests for sub-screening. As a result, two candidates were selected, and their probiotic abilities were verified with three reference strains.L. crispatusLG55-27 andL. gasseriTM13-16 presented outstanding ability to produce D-lactate and adhere to human vaginal epithelial cells. They also showed higher antimicrobial activity againstGardnerella vaginalis, Escherichia coli, Candida albicans, Staphylococcus aureusandPseudomonas aeruginosathan control ones. Their acid/bile-resistant ability suggested the potential of oral supplementation. Strain LG55-27 and TM13-16 also display improved effects on pH changes, and the production of inflammation cytokines in BV model rats. This study provided a probiotic dosage recommendation for vaginitis treatment by demonstrating an effective probiotic screening pipeline based on genome sequences,in vitrotests andin vivoBV model experiment.
Rates and spectra of de novo structural mutations inChlamydomonas reinhardtii
Authors: López-Cortegano Eugenio , Craig Rory J. , Chebib Jobran , Balogun Eniolaye J. , Keightley Peter D.
Published: December 2022

Genetic variation originates from several types of spontaneous mutation, including single-nucleotide substitutions, short insertions and deletions (indels), and larger structural changes. Structural mutations (SMs) drive genome evolution and are thought to play major roles in evolutionary adaptation, speciation, and genetic disease, including cancers. Sequencing of mutation accumulation (MA) lines has provided estimates of rates and spectra of single-nucleotide and indel mutations in many species, yet the rate of new SMs is largely unknown. Here, we use long-read sequencing to determine the full mutation spectrum in MA lines derived from two strains (CC-1952 and CC-2931) of the green algaChlamydomonas reinhardtii. The SM rate is highly variable between strains and between MA lines, and SMs represent a substantial proportion of all mutations in both strains (CC-1952 6%; CC-2931 12%). The SM spectra differ considerably between the two strains, with almost all inversions and translocations occurring in CC-2931 MA lines. This variation is associated with heterogeneity in the number and type of active transposable elements (TEs), which comprise major proportions of SMs in both strains (CC-1952 22%; CC-2931 38%). In CC-2931, a Crypton and a previously undescribed type of DNA element have caused 71% of chromosomal rearrangements, whereas in CC-1952, aDualenLINE is associated with 87% of duplications. Other SMs, notably large duplications in CC-2931, are likely products of various double-strand break repair pathways. Our results show that diverse types of SMs occur at substantial rates, and support prominent roles for SMs and TEs in evolution.
Clients’ digitalization, audit firms’ digital expertise, and audit quality: evidence from China
Authors: Rahman Md Jahidur , Ziru Ao
Published: December 2022

Purpose

This study aims to examine whether clients’ degree of digitalization and audit firms’ expertise in information technology (IT) influence audit quality (AQ).

Design/methodology/approach

Data of Chinese A-share firms listed on the primary board of the Shanghai and Shenzhen stock exchanges from 2011 to 2019 are taken as the sample. All the data are obtained from the China Stock Market and Accounting Research. Clients’ digitalization is determined using the keywords “AI technology,” “blockchain,” “cloud computing,” “big data technology” and “digital technology.” Auditor firm’s digital expertise is determined by the proportion of higher IT expertise. As the proxy for AQ, this study uses audit fees, given that its quantum reflects the effort auditors expend that in turn affects the AQ.

Findings

A fixed-effect regression model shows that clients with high digitalization attain AQ. This study also finds a significant and positive coefficient of audit fees, indicating that AQ is high in the same situation if an audit firm’s IT is mature and developed. Furthermore, results confirm the moderating effect of clients’ digitalization and auditors’ expertise and on AQ. Auditors’ expertise in IT mitigates the audit risk and increase AQ.

Originality/value

Findings can enhance AQ and corporate governance literature by clarifying how external audits must evolve through digitalization and incorporating newly developed digital tools such as big data, analytics, artificial intelligence and robotic process automation. This study also provides important insights regarding how the development of new digital tools allow the audit profession to perform as a corporate governance mechanism.
Deal or No Deal: comparing individual and group choices in a risky context
Authors: Morone Andrea , Santorsola Marco , Tiranzoni Paola
Published: December 2022

Purpose

The authors believe that comparing individuals to groups' decision making is crucial provided that many important choices in society are made by groups, i.e. committees, governing bodies, juries, business partners and families. This study aims to discuss the aforementioned topic.

Design/methodology/approach

The authors analyze risky decision making in the context of the television game show Deal or No Deal – Italian edition. Specifically, the authors scrutinize and compare individual (standard “Deal or No Deal” edition) and group (special edition) choices in the risky choice context provided by programe.

Findings

After analyzing contestant's behavior in the standard edition episodes plus a special edition the authors calculate a risk index observing that no statically significant difference is present between individuals' and groups' actions.

Originality/value

In the “Deal or No Deal” special edition contestant were groups of two strangers. It is not uncommon to have couples playing on TV, however the individuals usually know each other well and have relationships in real life. The special edition therefore provides a unique setting (absent to best of the authors’ knowledge in the literature) for investigation and could offer real-world insight. Indeed, in many instances the authors have to contract/make decisions with people the authors do not know/know very little (i.e. occasional business partners, representative at other companies/institutions, insurance/finance advisors, new work colleagues, etc.).