bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the influence about back side sand pile on the stability and deformation of the Pile foundation frame Seawall
Authors: Xiongwei Wu , Mingli Tang , Yongxin Yao
Published: February 2021

The article analyzes the influence about backwater side sand piling of a Pile-based frame Seawall along the east coast of Zhejiang on the stability and deformation. When sand is not piled on the backwater side of the Seawall, the overall safety factor of the Seawall is 1.619∼2.941, which meets the specifications and design requirements; when the backwater side is piled with sand or sand piling+vehicle driving, the overall safety factor of the Seawall is respectively 1.119∼1.617, 1.107∼1.599, and the safety factor of some working conditions is less than required 1.20, which does not meet the specifications and design requirements. According to the simulation results of the MIDAS finite element software, the settlement of the Seawall within 3 months of sand piling is 22.0mm, and the horizontal displacement is 7.9mm, indicating that the sand piling on the back side has a great influence on the deformation of the Seawall. The settlement and horizontal displacement of the Seawall are too large, resulting in a large reduction in the vertical and horizontal bearing capacity of the pile foundation, which has a huge impact on the overall stability and safe operation, severely disrupting the stress balance of the Seawall structure, and causing landslides on the water-facing side risk.
A review of surface properties enhancement of pavement concrete
Authors: Cheng Hu , Xingzhong Weng , Xiangcheng Yan
Published: February 2021

The surface properties of pavement concrete have great influence on the overall performance of pavement, so it is of great significance to study how to effectively strengthen the surface properties of pavement concrete. The surface properties of pavement concrete are mainly reflected in three aspects: abrasion resistance, frost resistance, and impact resistance. The ways to strengthen the surface properties of pavement concrete are mainly focused on surface fortifier, adding polymer mixture, fiber, and additive, improving the way of maintenance, improving construction technology and optimizing the basic components of concrete. These five ways have its advantages and disadvantages. To enhance the surface properties of concrete economically, effectively and comprehensively, the way that laying fiber mesh into cement mortar layer is put forward.
Research on creep characteristics of sand with different fine content
Authors: Taotao Mei , Deyong Wang , Xiaocong Liang
Published: February 2021

The storage yard in port terminal project is generally is formed by backfilling. If the backfill contains high content of fine particle, on the one hand, it will cause difficulty in foundation treatment, on the other hand, excessive settlement will occur during the operation period, which will affecting the normal operation of the project. In this paper, through experimental research on the creep settlement of sandy soils with different fine content, the relevant parameters of sandy soils with different fine-grained contents and different types of finegrained soils are obtained, and through the analysis and fitting of commonly used rheological element models, the settlement calculation parameters of sandy soil with different fine contents are obtained.
Performance and Application of Rapid Assembling Anti-blast Wall
Authors: Hongrui CAO , Zhigang ZHANG , Peng CHEN , lizi CAO , Zhuo CHEN
Published: February 2021

With too much emphasis being laid on the antiknock performance of the current anti- blast wall and its mobility thus ignored, in order to strengthen the temporary protective capability of battlefield, a kind of rapid assembling anti-blast wall is proposed, its structural form and assembly method are introduced. The antiknock ability and the durability performance of the anti-blast wall are fully analyzed with the latest application cases, its application in military and civil field are introduced. The application results indicate that the anti-blast wall shows flexible mobility in transportation and assembling, moreover exhibit high adaptive capability, as well as protective capability. So it possesses great value in further research and promotion, and strengthening the combination with other protective technologies is considered to be the future trend.
The effect of different MQL supply strategies into the cutting zone on the tool wear when turning of Ti-6Al-4V alloy
Authors: Lisowicz Joanna , Habrat Witold , Krupa Krzysztof , Janocha Piotr
Published: February 2021

Titanium alloys, especially Ti-6Al-4V alloy, are widely used in industry due to their good mechanical properties, such as high specific strength and excellent corrosion resistance. However, titanium alloys are also difficult-to-cut materials. Metalworking fluids are employed in the machining process to improve the machinability of titanium alloys. In recent years much attention has been paid to the use of the minimum quantity lubrication (MQL) techniques in the machining of the titanium alloys. In this study, the tool wear and its influence on the components of cutting forces have been investigated for different MQL supply strategies into the cutting zone - MQL via external nozzle and MQL via tool holder were investigated. The obtained results were compared with dry turning. It was concluded that the mechanism of tool wear is very similar for each cutting condition, however, it was also noted that the tool life is 28% and 68% longer for the MQL via external nozzle and MQL via tool holder, respectively, compared with the dry cutting conditions.
Improving the performance characteristics of human hip-joint implants by increasing the quality of processing and geometric accuracy of their spherical surfaces
Authors: Turmanidze Raul , Popkhadze Giorgi , Inasharidze Ketevan
Published: February 2021

In view of the fact that the endo-prosthesis heads of human hip-joint are operated in extreme conditions, in respect of load, the selection of corresponding material and also increase of precision and quality of machining of spherical surfaces is rather topical task. In the submitted work are reviewed the problems connected with definition of the influence degree of orientation of the sapphire crystal on its workability during diamond grinding with a butt of the ring and elaboration of the perspective, original scheme of formation of the incomplete spherical surface, particularly, of the sapphire head of endo-prosthesis of the human hip-joint.
Axiomatic Design as an innovation framework
Authors: Cavique Miguel , Dodun Oana , Brown Christopher
Published: February 2021

Innovation can be defined as a set of processes for altering human activity, with economic or social relevance. Innovation has been the economic driver of several companies and countries. This article presents laws with preconditions for innovation, and it proposes a framework for innovation based on Axiomatic Design (AD) theory. There are three laws which set out necessary preconditions to initiate and maintain innovation. Research, financing, and companies that can carry out an innovation project, must be available for a project. AD can be a tool for innovation. Three main elements to AD are: Suh’s axioms, to maintain functional independence and minimize information content; a structure, domains and hierarchies in which solutions develop; and a process, decomposing from abstract to detailed components and physically integrating components into a complete solution. Suh’s axioms ensure that design solutions are adjustable, controllable, and robust. These are essential elements in innovation. Design matrices for functional–physical relationships select for independence, then information content is used to select the best solution. Design structures are completed by zigzagging between functional, physical, and process domains, creating the hierarchical decompositions of abstraction while applying Suh’s axioms at each level.
Modelling the dependence between regular reliefs ridges height and the ball burnishing regime’s parameters for 2024 aluminum alloy processed by using CNC-lathe machine
Authors: Slavov S D , Dimitrov D M
Published: February 2021

New approach for obtaining regular reliefs onto cylindrical and tapered surfaces, by using ball burnishing process, performed on CNC-lathe machine having C-axis installed, is presented. It allows to simplify the burnishing tool and to perform the burnishing operation on the same lathe machine as previous cutting operations. The equations for the points coordinates calculation of the needed complex ball tool trajectory are shown. For their approbation, and in order to obtain a stochastic model which established the relation between the ball burnishing regime parameters (deforming force F, and feedrate f) and resulting height (Rz) of regular reliefs cells boundary ridges, an experimental investigation is carried out, using 2024-T3 aluminum alloy, and the methodology of the rotatable experimental plans. The corresponding response surface of the model is given and discussed. Conclusions about the advantages and disadvantages of the approach are given, and also for the suitable application of the obtained stochastic model.
A study on casting of structural mesh-like metal parts
Authors: Vlagkoulis D , Vasileiou A , Vosniakos G-C
Published: February 2021

Mesh-like parts are employed in order to reduce weight of mechanical structures. This study focused on cylindrical shaped mesh-like spacers. First, the mesh shape was parametrically defined and mechanical strength and strain under specific combination of axial and shear loads were determined by numerical simulation. Manufacture of the best design was then investigated focusing on investment casting under both gravity and vacuum modes with a simple, yet uncommon, top feeding system. The best combination of casting mode and parameter values was determined by numerical simulation on commercially available dedicated software, considering solidification time and lack of defects as primary quality indices accompanied by an investigation of residual stress and deformation fields. To implement simulation-based decisions the part was investment-cast employing 3D printed dies for constructing the wax models.
A computational wall mechanics study of an ascending thoracic aortic aneurysm under hypertensive conditions
Authors: Manopoulos C , Raptis A , Krishan W , Mavratzas C , Drandakis M , Astraka S , Kouerinis I , Vaxevanidis N M
Published: February 2021

A wall mechanics study is performed on two human aortic models, reconstructed from computed tomography (CT) image data using the Materialise Mimics software. The first model represents a rare ascending thoracic aortic aneurysm (aTAA) case with an excessive aortic ballooning that has displaced the cardiac cavities, and the second one a normal case free of cardiovascular diseases. Special attention was paid for the reconstruction of realistic models that do not deviate from the original data. The study presents the workflow from medical imaging data to structural simulation with the use of various software, aiming to examine the stress state of a normal aorta and an aneurysmal one (both patient specific) under a range of systolic blood pressure loads. Using the FEBio software, the effective (Lagrange) strain and the effective stress (von Mises) distributions are calculated for assessing the risk of rupture or dissection of the aorta.
Paint removal from thermoplastic materials and its influence on the physical-mechanical properties for the recycling of the polymer
Authors: Sover A , Zink M. , Michalak M.
Published: February 2021

Laser technology offers many advantages when removing paint (coating) layers from different substrates such as metals, plastics or ceramics. Sensitive carriers with a low melting point like thermoplastic materials can easily be thermally damaged or destroyed using this technology. This paper analyses the quality of the thermoplastic material after removing the thermoset layers from its surface by laser and aims to identify the changes of the most important properties of the polymeric material. The physical-mechanical properties of thermoplastic materials which were coated were investigated before as well as after the removal of the coating layers and compared with parts which were not coated. The focus was on melt flow rate, impact strength, and tensile stress as well as strain. The results show that even a small amount of the paint (coating) can change the behaviour of the thermoplastic material and thus has an impact on further processing. Moreover, it was found that removing the thermoset coating from the thermoplastic material leads to a considerable improvement of its physical-mechanical properties and consequently also extends the possibilities of recycling (reuse) of this polymeric material.
Structural aspects and chemical analyses on cutting process of metallic-ceramic materials
Authors: Lutcanu M , Istrate B , Coteata M , Chicet D L , Ionita I , Paraschiv C , Stirbu I , Badarau G , Cimpoesu N
Published: February 2021

Preliminary results on the behaviour of metallo-ceramic system during the cutting process were presented. The ceramic layer was obtained, after sandblasting of the substrate, through air plasma spraying with thicknesses of 30 μm on a steel substrate. Layers are chemically homogeneous, without cracks, pores or crevices. The thin layer (30 μm) present discontinuities with uncovered surfaces were the substrate is near in contact with the environment. Cutting process was realized on marking fiber laser equipment (Boron), of 30 watts’ maximum power and wave length of 1064 nm. There were obtained two different grooves on the test pieces with the following parameters: laser double pass at speed of 500 mm/sec, pulsed laser of 20KHz frequency and the beam power was set at 50% (around 15W) for the first groove) and at 80% (around 24W for the second groove). Structural, morphological and chemical evaluation of the cutting kerf was realized using scanning electron microscopy (SEM, Vega Tescan LMHII, SE detector, 30 kV, 15.5 mm WD) and energy dispersive spectroscopy (EDS, Bruker X-flash) using automatic/element list mode, Point, Mapping and Line features. This analysis highlighted the type of defects along the cut, respectively the phenomena occurring at the ceramic - metal interface.
Investigation of the occurrence and development of fatigue cracks after corrosion of welded samples of ferritic - austenitic steel
Authors: Georgiev Georgi , Argirov Yaroslav , Mechkarova Tatyana , Spasova Daniela , Stoyanova Aneliya
Published: February 2021

The article treats the occurrence and development of fatigue cracks in welded samples of ferritic - austenitic steel, which were previously subjected to corrosion. For the purposes of the study, two groups of sheet steel samples were prepared: the first group were reference parts, and the second group of samples were welded and then exposed to a corrosive environment. Corrosion tests were performed by immersing the samples in an acidic solution of (HCl, HNO3 and NaCl). Both groups of samples were tested with specially developed vibrating equipment for high cycle fatigue (106 - 107 cycles). The durability of SAF 2507 steel is estimated by the number of cycles until a crack is obtained at a certain alternating load. The damaged surfaces were examined by microstructural analysis to trace the shape and development of the crack in the structure of ferro-austenitic steel SAF 2507 after its welding and corrosion.
Reliability model of freight bogie damper based on real field data
Authors: Spiroiu M A
Published: February 2021

In the present paper is estimated the reliability probabilistic model of the dry friction damper of the freight bogie Y25. The analysis is made on the basis of real field data, observed in actual operations of freight wagons. The theoretical probability distributions used to model the reliability are exponential and Weibull. The Weibull reliability models are estimated according to the Regression Method and to the Maximum Likelihood Method.
Software application for uniform quantitative evaluation of social economy projects
Authors: Florea B , Marcu D , Ioana A , Semenescu A , Solea R , Iacob G , Niculescu F
Published: February 2021

The qualitative impact calculation for the implementation of a social economy project can be done using dedicated computing software. In this paper we have defined PQS which is an application on JAVA support that allows use irrespective of the existing support platform on the computer. The created application has the advantage that it can run both on computers and on other devices (tablets, phones, etc.). The input data are represented by the values assumed and realized in the project and are stored in a MySQL database.
Geometric stability of stepped shafts by ribbing its surface
Authors: Drachev O I , Gorshkov B M , Samokhina N S
Published: February 2021

The article discusses the technology of manufacturing low-stiff long multistage shafts made of stainless steels. A feature of this technology is the cutting of annular cooling fins on the entire surface of the shaft blank during machining and their use in thermal operations and further to finishing turning. To implement the technology, self-centering steady rests with double rollers were used during machining.
The cyber-production mechanization control
Authors: Gurjanov A V , Babenkov V I , Zharinov I O , Kosarevskaia S A
Published: February 2021

This article pays your attention to the cyber-production mechanized equipment control problem. There is a scheme proposed of automatic cyber-production segment control, mechanized technological aggregates and multi-chain manipulation systems. The control system is made in a multi-loop mode with a sensor measuring part to correct production automatics functionality errors. Within the technological aggregates there is a physical processes regulation loop in the machine working volume and one for the assembly units being manufactured material tide. There is a control loop in the manipulation system to move the rail chassis base movement and positioning loop of force and momentum regulation with a multi-chain grip. To control the cyber-production segment mechanization they propose a global loop to engage in the company virtual environment the equipment reference models and digital model (twin) of the product being manufactured.
Combustion of lean fuel mixtures with subcritical streamer microwave discharge
Authors: Bulat P V , Esakov I I , Grachev L P , Volkov K N
Published: February 2021

A sub-critical microwave discharge is used to achieve a stable ignition and combustion of lean air-fuel mixtures in a long tube. The microwave discharge is burnt at the presence of initiator with the quasi-optical microwave beam. The resonance way of initiation of a microwave discharge is more effective compared to traditional plasma-assisted ways of ignition and stabilization of combustion. The experimental observations show that ignition and combustion of a lean air and propane mixture in a long tube is achieved at low ignition limit with fuel/air ratio lower than 0.55. The results obtained are useful for design of new and improvement of the existing plasma-assisted technologies in aviation industry.
Simulation of the effect of secondary Doppler modulation for air targets with a turbojet engine
Authors: Gribanov P V , Kuznetcov V A , Menshikh N A , Andrianov D Y , Kokov R R , Baranchuk N A
Published: February 2021

The paper analyzes various approaches to modeling the effect of secondary Doppler modulation for turbojet engines. The issue of studying the conditions for the appearance of the effect of secondary Doppler modulation of the sounding signal of onboard radar stations for the further formation of the base of standards for the detection and recognition of air targets with reduced radar signature is considered. The results of modeling this effect based on ray approximation in the MATLAB environment are presented using the example of the situation of reflection of an electromagnetic wave from the blades of the first stage of a low-pressure compressor of a hypothetical turbojet engine. The stages of modeling the process of propagation of an electromagnetic wave from a radar station to a target and back, as well as “collecting” rays in the receiver antenna and forming a reflected signal with subsequent spectral analysis are described.
Automated installation for pipelines brazing in protective environments using induction heating
Authors: Murygin A V , Tynchenko V S , Kurashkin S O , Bocharova O A , Seregin Yu N , Bocharov A N
Published: February 2021

The article presents an automated installation for pipelines brazing in protective environments using the induction heating method. The types of pipe connections are considered, and the use of boxes to ensure the formation of a protective environment in the process of induction soldering is proposed. A diagram of a projected automated installation for induction brazing of pipelines in protective media, as well as its main technical characteristics are given. Using the proposed installation, soldering of welding of prototypes was carried out, the results of which are presented in the article.
Qualitative analysis relations
Authors: V Ya Tsvetkov
Published: February 2021

The object of this paper is to introduce relationship models into qualitative analysis to simplify this analysis. The article proposes a set of relations based on the predicate calculus. The concept of “quality relations” is introduced. The relations content is revealed: proportionality, complementarity, connectedness, opposition and dichotomy. Single, double and triple predicates are used. It is shown a qualitative difference between oppositional and dichotomous relations. The principles of qualitative analysis are described. The presence of two directions in the qualitative analysis is shown: social and intellectual. It is shown that qualitative relations are the basis for qualitative analysis and finding cause-and-effect relations. Methods of carrying out qualitative analysis are shown: discrete values, qualitative values, ambiguous values, qualitative process simulation.
Online information service for training in Industry 4.0 technologies
Authors: Gurjanov A V , Zakoldaev D A , Zharinov I O , Zharinov O O
Published: February 2021

A new element of the information service in the field of technical training of specialists for Industry 4.0 is an online platform that implements distance forms of e-learning for specialists. An online learning service is an interactive transdisciplinary infrastructure that accumulates knowledge in demand by the intellectual industry. The information potential of the online learning service allows students to create curricula based on an arbitrary sequence of studying theoretical disciplines. The designer of professional courses ensures the structuring of content and its presentation to the listener in informational forms that cause maximum involvement of students in the disciplines studied. The online training information service contains methods and scenarios based on generally recognized world practices and adapting the trajectories of individual training of specialists to modern industry requirements. A scheme of an online information service for training technical specialists for Industry 4.0 based on network technologies of interaction between the listener and educational content is proposed. It is shown that online training services form an informational competitive environment that integrates the resources of private business, state educational institutions, scientific, industrial and academic communities.
Automated systems for main oil pipelines diagnostics and control
Authors: Ospanov Ye A , Moldasheva Zh Zh , Toleuov T Zh , Shuteyeva G S , Demyanenko A I , Seidaliyev A A
Published: February 2021

The issues of diagnostics of the technological objects operation of the main oil pipeline and control of their operation modes using automated systems are investigated. The systems and methods for diagnostics and determination of oil leakage from main oil pipelines are studied. A method for remote detection of oil leakage from main oil pipelines is described. SCADA systems that allow monitoring changes in all pumping technological parameters in real mode are described. The mathematical formulation of the problem of controlling the operating modes of technological objects of the main oil pipeline in the conditions of indistinctness of some part of the initial information is formalized and obtained. Based on the modification of the idea of the principle of the main criterion, a heuristic method for the effective solution of the obtained fuzzy problem has been developed.
A combined heat and power (CHP) plant consisting of a microturbine and a Stirling engine
Authors: Antipov Y A , Smirnov S V , Oshchepkov P P , Khalife H S
Published: February 2021

Modern industrial development of governments is largely determined by the condition of the power industry. Nowadays, the energy policy of governments is focused on the improvement of highly efficient combined heat and power (CHP) plants, to conserve fossil fuels and achieve higher output power. The application of gas turbines and heat recovery systems is considered a promising method of increasing the overall efficiency of the power plant. In this article, a microturbine was considered as the prime mover in a CHP plant, while the exhaust gases were used to power a Stirling engine, and consequently generating additional power and heat, increasing the overall efficiency of the power plant. Also, the advantages and disadvantages of the Stirling engine were briefly discussed. Moreover, two general configuration schemes and a calculation method of the CHP plant have been developed. Finally, the results of utilizing the exhaust gases of a microturbine and a Stirling engine were presented.
Application of the PLP-01M microwave laboratory system using control samples to assess the accuracy of the results of studies of cadmium content
Authors: Maksimiuk N N , Rebezov M B , Tretyak L N , Varivoda A A , Artyukhova S I , Tolstoguzova T T
Published: February 2021

This paper considers and analyzes the results of examining samples for cadmium content by determining them on a Kvant-2AT atomic absorption spectrometer, taking into account the use of the PLP-01M microwave laboratory system and during sample preparation in accordance with GOST 26929 “Raw materials and food products. Sample preparation. Mineralization to determine the content of toxic elements”. The PLP-01M microwave laboratory system uses a fundamentally new method of sample preparation. The decomposition was carried out in a closed system - sealed fluoroplastic vessels under the influence of high temperature, pressure and microwave field. The microwave field in the working chamber of the furnace was created by a special generator-magnetron. Based on the results of the assessment of the operational control of the measurement procedure using samples for cadmium control during the implementation of the PLP-01M microwave laboratory system in the laboratory, the analysis procedure was recognized as satisfactory.
Certification of diamond HPHT-plates for their use as substrates for CVD-synthesis
Authors: Martynova T V , Polushin N I , Laptev A I , Maslov A L , Markova I Y
Published: February 2021

Incoming control of substates and gases is very important part of technological chain. The properties of diamond layer on substrates with different misorientation angles may differ considerably, therefore, determining the deviation of diamond growth plane (100) from the direction [100] is important. Also, in order to select diamond substrates that are most suitable for synthesis of pure quality crystal, it is required to determine the content of impurities in them and the roughness of their surface. In this research, HPHT-plates of one lot were examined using Fourier transform infrared spectrometry, high-resolution diffractometry and scanning probe microscopy in order to classify them according to the studied parameters. Further the classified diamond substrates were used to synthesize diamond layers. Ardis 300 was used for deposition of monocrystalline diamond; synthesis was carried out from a methane-hydrogen plasma with 3% methane at a temperature of 1100 °C, a pressure of 26.7 kPa and a power of 3800 W. The studies have shown that certification of diamond HPHT-plates allows to select substrates for the synthesis of pure quality monocrystalline diamonds.
Identification and distinct regulation of three di/tripeptide transporters in Aspergillus oryzae
Authors: Tanaka Mizuki , Ito Keisuke , Matsuura Tomomi , Kawarasaki Yasuaki , Gomi Katsuya
Published: February 2021

The uptake of di/tripeptides is mediated by the proton-dependent oligopeptide transporter (POT) family. In this study, 3 POT family transporters, designated PotA, PotB, and PotC were identified in Aspergillus oryzae. Growth comparison of deletion mutants of these transporter genes suggested that PotB and PotC are responsible for di/tripeptide uptake. PotA, which had the highest sequence similarity to yeast POT (Ptr2), contributed little to the uptake. Nitrogen starvation induced potB and potC expression, but not potA expression. When 3 dipeptides were provided as nitrogen sources, the expression profiles of these genes were different. PrtR, a transcription factor that regulates proteolytic genes, was involved in regulation of potA and potB but not in potC expression. Only potC expression levels were dramatically reduced by disruption of ubrA, an orthologue of yeast ubiquitin ligase UBR1 responsible for PTR2 expression. Expression of individual POT genes is apparently controlled by different regulatory mechanisms.
Heterogeneity-aware and communication-efficient distributed statistical inference
Authors: Duan Rui , Ning Yang , Chen Yong
Published: February 2021

In multicentre research, individual-level data are often protected against sharing across sites. To overcome the barrier of data sharing, many distributed algorithms, which only require sharing aggregated information, have been developed. The existing distributed algorithms usually assume the data are homogeneously distributed across sites. This assumption ignores the important fact that the data collected at different sites may come from various subpopulations and environments, which can lead to heterogeneity in the distribution of the data. Ignoring the heterogeneity may lead to erroneous statistical inference. We propose distributed algorithms which account for the heterogeneous distributions by allowing site-specific nuisance parameters. The proposed methods extend the surrogate likelihood approach (Wang et al. 2017; Jordan et al. 2018) to the heterogeneous setting by applying a novel density ratio tilting method to the efficient score function. The proposed algorithms maintain the same communication cost as existing communication-efficient algorithms. We establish a nonasymptotic risk bound for the proposed distributed estimator and its limiting distribution in the two-index asymptotic setting, which allows both sample size per site and the number of sites to go to infinity. In addition, we show that the asymptotic variance of the estimator attains the Cramér–Rao lower bound when the number of sites is smaller in rate than the sample size at each site. Finally, we use simulation studies and a real data application to demonstrate the validity and feasibility of the proposed methods.
Intravenous Artesunate for the Treatment of Severe Imported Malaria: Implementation, Efficacy, and Safety in 1391 Patients
Authors: Roussel Camille , Ndour Papa Alioune , Kendjo Eric , Larréché Sébastien , Taieb Aida , Henry Benoît , Lebrun-Vignes Bénédicte , Chambrion Charlotte , Argy Nicolas , Houzé Sandrine , Mouri Oussama , Courtin David , Angoulvant Adela , Delacour Hervé , Gay Frédérick , Siriez Jean-Yves , Danis Martin , Bruneel Fabrice , Bouchaud Olivier , Caumes Eric , Piarroux Renaud , Thellier Marc , Jauréguiberry Stéphane , Buffet Pierre ,   the FRench Artesunate Working Group
Published: February 2021

Background

Intravenous artesunate is the World Health Organization–recommended first-line treatment for severe malaria worldwide, but it is still not fully licensed in Europe. Observational studies documenting its safety and efficacy in imported malaria are thus essential.

Methods

We prospectively collected clinical and epidemiological features of 1391 artesunate-treated patients among 110 participant centers during the first 7 years (2011–2017) of a national program implemented by the French Drug Agency.

Results

Artesunate became the most frequent treatment for severe malaria in France, rising from 9.9% in 2011 to 71.4% in 2017. Mortality was estimated at 4.1%. Treatment failure was recorded in 27 patients, but mutations in the Kelch-13 gene were not observed. Main reported adverse events (AEs) were anemia (136 cases), cardiac events (24, including 20 episodes of conduction disorders and/or arrhythmia), and liver enzyme elevation (23). Mortality and AEs were similar in the general population and in people with human immunodeficiency virus, who were overweight, or were pregnant, but the only pregnant woman treated in the first trimester experimented a hemorrhagic miscarriage. The incidence of post-artesunate–delayed hemolysis (PADH) was 42.8% when specifically assessed in a 98-patient subgroup, but was not associated with fatal outcomes or sequelae. PADH was twice as frequent in patients of European compared with African origin.

Conclusions

Artesunate was rapidly deployed and displayed a robust clinical benefit in patients with severe imported malaria, despite a high frequency of mild to moderate PADH. Further explorations in the context of importation should assess outcomes during the first trimester of pregnancy and collect rare but potentially severe cardiac AEs.
Mastery of everyday life and social support needs in older vulnerable women with myocardial infarction and their relatives: a qualitative study
Authors: Pedersen Maria , Støier Louise , Egerod Ingrid , Overgaard Dorthe
Published: February 2021

Aims

The Danish public healthcare system provides a comprehensive cardiac rehabilitation (CR) programme, but attendance rates are low among older vulnerable women. Effective interventions enabling increased CR attendance are warranted. Knowledge about everyday life and social support needs is crucial to the development of effective CR interventions in this group. To explore mastery of everyday life and social support needs in older, vulnerable women with myocardial infarction (MI) and their relatives.

Methods and results

A qualitative explorative design using semi-structured individual or dyadic interviews with patients (n = 21) and their relatives (n = 13) and applying thematic analysis. Five themes captured mastery of everyday life and social support needs. ‘The Big Picture’ suggesting that comorbidities dwarfed the impact of MI. ‘Blaming the Doctor’ illustrated issues of distrust and treatment delay. ‘Rehabilitation Barriers’ explained why these vulnerable patients failed to participate in CR. ‘Caregiver Concerns’ described relatives dual roles as supporters and supported. ‘Finding their Way’ indicated how patients were assisted by peer support to negotiate the trajectory.

Conclusion

The study offers a basis for the development of CR interventions customized to this group of patients. Interventions should target patients with multimorbidity, low motivation for lifestyle changes, and transportation issues. Peer support is suggested for this group of patients where relatives are also apt to be vulnerable.
The Phenotype of mes-2, mes-3, mes-4 and mes-6, Maternal-Effect Genes Required for Survival of the Germline in Caenorhabditis elegans, Is Sensitive to Chromosome Dosage
Authors: Garvin Carol , Holdeman Richard , Strome Susan
Published: February 2021

Mutations in mes-2, mes-3, mes-4, and mes-6 result in maternal-effect sterility: hermaphrodite offspring of mes/mes mothers are sterile because of underproliferation and death of the germ cells, as well as an absence of gametes. Mutant germ cells do not undergo programmed cell death, but instead undergo a necrotic-type death, and their general poor health apparently prevents surviving germ cells from forming gametes. Male offspring of mes mothers display a significantly less severe germline phenotype than their hermaphrodite siblings, and males are often fertile. This differential response of hermaphrodite and male offspring to the absence of mes+ product is a result of their different X chromosome compositions; regardless of their sexual phenotype, XX worms display a more severe germline phenotype than XO worms, and XXX worms display the most severe phenotype. The sensitivity of the mutant phenotype to chromosome dosage, along with the similarity of two MES proteins to chromatin-associated regulators of gene expression in Drosophila, suggest that the essential role of the mes genes is in control of gene expression in the germline. An additional, nonessential role of the mes genes in the soma is suggested by the surprising finding that mutations in the mes genes, like mutations in dosage compensation genes, feminize animals whose male sexual identity is somewhat ambiguous. We hypothesize that the mes genes encode maternally supplied regulators of chromatin structure and gene expression in the germline and perhaps in somatic cells of the early embryo, and that at least some of their targets are on the X chromosomes.
Characterization of the Germinal and Somatic Activity of the Arabidopsis Transposable Element Tag1
Authors: Liu Dong , Crawford Nigel M
Published: February 2021

Tag1 is an autonomous transposon of Arabidopsis thaliana. The excision behavior of Tag1 during reproductive and vegetative development was examined using CaMV 35S-Tag1-GUS constructs. Germinal reversion frequencies varied from 0 to 27% and correlated with Tag1 copy number. Southern blot and somatic sector analyses indicated that each revertant was derived from an independent excision event, and approximately 75% of the revertants had new Tag1 insertions. Revertants were obtained with similar frequencies from the male and female parents. In flowers, small somatic sectors were observed in siliques, carpels, petals and sepals while stemlike organs (filaments and pedicels) had larger sectors. No sectors encompassing entire flowers or inflorescences were observed, however, indicating that excision occurs late in flower development and rarely in inflorescence meristems. Late excision was also observed during vegetative development with 99.8% of leaves showing small sectors encompassing no more than 20 cells. Roots and cotyledons, however, showed larger sectors that included entire lateral roots and cotyledons. These results indicate that Tag1 can excise in the embryo and all the organs of the plant with the timing of excision being restricted to late stages of vegetative and reproductive development in the shoot.
Genetic Variation Within and Among Populations of Arabidopsis thaliana
Authors: Bergelson Joy , Stahl Eli , Dudek Scott , Kreitman Martin
Published: February 2021

We investigated levels of nucleotide polymorphism within and among populations of the highly self-fertilizing Brassicaceous species, Arabidopsis thaliana. Four-cutter RFLP data were collected at one mitochondrial and three nuclear loci from 115 isolines representing 11 worldwide population collections, as well as from seven commonly used ecotypes. The collections include multiple populations from North America and Eurasia, as well as two pairs of collections from locally proximate sites, and thus allow a hierarchical geographic analysis of polymorphism. We found no variation at the mitochondrial locus Nad5 and very low levels of intrapopulation nucleotide diversity at Adh, Dhs1, and Gpa1. Interpopulation nucleotide diversity was also consistently low among the loci, averaging 0.0014. gst, a measure of population differentiation, was estimated to be 0.643. Interestingly, we found no association between geographical distance between populations and genetic distance. Most haplotypes have a worldwide distribution, suggesting a recent expansion of the species or long-distance gene flow. The low level of polymorphism found in this study is consistent with theoretical models of neutral mutations and background selection in highly self-fertilizing species.
The lacI Gene as a Target for Mutation in Transgenic Rodents and Escherichia coli
Authors: de Boer Johan G , Glickman Barry W
Published: February 2021

The lacI gene has been used extensively for the recovery and analysis of mutations in bacteria with various DNA repair backgrounds and after exposure to a wide variety of mutagens. This has resulted in a large database of information on mutational mechanisms and specificity of many mutagens, as well as the effect of DNA repair background on mutagenicity. Most importantly, knowledge about the mutational sensitivity of the lacI gene is now available, yielding information about mutable nucleotides. This popularity and available knowledge resulted in the use of the lacI gene in transgenic rodents for the study of mutagenesis in mammals, where it resides in ~40 repeated copies. As the number of sequenced mutations recovered from these animals increases, we are able to analyze the sites at which mutations have been recovered in great detail and to compare the recovered sites between bacteria and transgenic animals. The nucleotides that code for the DNA-binding domain are nearly saturated with base substitutions. Even after determining the sequences of ~10,000 mutations recovered from the animals, however, new sites and new changes are still being recovered. In addition, we compare the nature of deletion mutations between bacteria and animals. Based on the nature of deletions in the animals, we conclude that each deletion occurs in a single copy of the gene.
Signatures of Population Expansion in Microsatellite Repeat Data
Authors: Kimmel Marek , Chakraborty Ranajit , King J Patrick , Bamshad Michael , Watkins W Scott , Jorde Lynn B
Published: February 2021

To examine the signature of population expansion on genetic variability at microsatellite loci, we consider a population that evolves according to the time-continuous Moran model, with growing population size and mutations that follow a general asymmetric stepwise mutation model. We present calculations of expected allele-size variance and homozygosity at a locus in such a model for several variants of growth, including stepwise, exponential, and logistic growth. These calculations in particular prove that population bottleneck followed by growth in size causes an imbalance between allele size variance and heterozygosity, characterized by the variance being transiently higher than expected under equilibrium conditions. This effect is, in a sense, analogous to that demonstrated before for the infinite allele model, where the number of alleles transiently increases after a stepwise growth of population. We analyze a set of data on tetranucleotide repeats that reveals the imbalance expected under the assumption of bottleneck followed by population growth in two out of three major racial groups. The imbalance is strongest in Asians, intermediate in Europeans, and absent in Africans. This finding is consistent with previous findings by others concerning the population expansion of modern humans, with the bottleneck event being most ancient in Africans, most recent in Asians, and intermediate in Europeans. Nevertheless, the imbalance index alone cannot reliably estimate the time of initiation of population expansion.
Chromosome 14 Contains Determinants That Regulate Susceptibility to Theiler's Virus–Induced Demyelination in the Mouse
Authors: Bureau J-F , Drescher K M , Pease L R , Vikoren T , Delcroix M , Zoecklein L , Brahic M , Rodriguez M
Published: February 2021

Theiler's murine encephalomyelitis virus causes a chronic demyelinating disease in susceptible strains of mice that is similar to human multiple sclerosis. Several nonmajor histocompatibility complex–linked genes have been implicated as determinants of susceptibility or resistance to either demyelination or virus persistence. In this study, we used linkage analysis of major histocompatibility complex identical H-2d (DBA/2J × B10.D2) F2 intercross mice to identify loci associated with susceptibility to virus-induced demyelinating disease. In a 20-cM region on chromosome 14, we identified four markers, D14Mit54, D14Mit60, D14Mit61, and D14Mit90 that are significantly associated with demyelination. Because two peaks were identified, one near D14Mit54 and one near D14Mit90, it is possible that two loci in this region are involved in controlling demyelination.
Estimating Within-Locus Nonadditive Coefficient and Discriminating Dominance Versus Overdominance as the Genetic Cause of Heterosis
Authors: Deng Hong-Wen
Published: February 2021

Testing (over)dominance as the genetic cause of heterosis and estimating the (over)dominance coefficient (h) are related. Using simulations, we investigate the statistical properties of Mukai's approach, which is intended to estimate the average (h¯) of hi across loci by regression of outcrossed progeny on the sum of the two corresponding homozygous parents. A new approach for estimating h¯ is also developed, utilizing data on families formed by multiple selfed genotypes from each outcrossed parent, thus not requiring constructing homozygotes. Assuming constant mutation effects, h can be estimated accurately by both approaches under dominance. When rare alleles have low frequencies at any polymorphic locus, Mukai's approach can estimate h accurately under over(under)dominance. Therefore, the (over)dominance hypothesis for heterosis can be tested by estimating h, under either dominance or overdominance at all genomic loci. However, this is invalid with more plausible mixed dominance and overdominance at different loci. Estimating the variance of hi across loci is also investigated. In self-compatible outcrossing populations with mutations of variable effects and lethals, our new approach is better than Mukai's, not only because of not requiring homozygotes but also because of the better statistical performance reflected by the smaller mean square errors of the estimates.
A DNA Methyltransferase Homolog With a Chromodomain Exists in Multiple Polymorphic Forms in Arabidopsis
Authors: Henikoff Steven , Comai Luca
Published: February 2021

Chromodomains are thought to mediate protein-protein interactions between chromatin components. We have detected a chromodomain embedded within the catalytic region of a predicted Arabidopsis DNA methyltransferase that is diverged from other eukaryotic enzymes. The 791 residue “chromomethylase” (CMT1) is encoded by a floral transcript that is spliced from 20 exons and is present at only ~1/10−7 of total mRNA. Genomic sequencing reveals an ancient haplotype split at CMT1 between Col-0 + Metz and the other ecotypes examined. In the Col-0 + Metz haplotype, alternative mRNA processing at intron 13 truncates the coding region. In Ler, RLD, and No-0, similar truncation is caused by insertion of an intact retrotransposon, Evelknievel, which is present as a single copy in Ler and RLD and is currently methylated and inactive. Evelknievel is found at this site on a single branch that connects the Ler, RLD, and No-0 ecotypes but is absent from the genomes of all other ecotypes examined. A stop codon within exon 6 of the Metz ecotype confirms that CMT1 is nonessential. Nevertheless, comparison to CMT1 of Cardaminopsis arenosa, an outcrossing relative, indicates conservation for DNA methyltransferase function. We discuss how allelic diversity of CMT1 may reflect loosened selective constraints in a self-fertilizing species such as Arabidopsis thaliana.