bluuebunny/crossref_metadata_2025 huggingface dataset:
Optic atrophy–associated TMEM126A is an assembly factor for the ND4-module of mitochondrial complex I
Authors: Formosa Luke E. , Reljic Boris , Sharpe Alice J. , Hock Daniella H. , Muellner-Wong Linden , Stroud David A. , Ryan Michael T.
Published: April 2021

Significance

Mitochondria are critical organelles that play a central role in energy conversion in cells. Mutations in genes encoding mitochondrial proteins can lead to disease. Here, we discover that the optic atrophy–associated mitochondrial disease gene TMEM126A plays a role in the assembly of the first enzyme of the respiratory chain, complex I. Critically, we show that TMEM126A interacts in a complex with newly synthesized ND4, a highly hydrophobic subunit of complex I that is encoded by mitochondrial DNA. Our findings expand the molecular machinery required to build complex I from its constituent subunits and elucidates the function of a gene mutated in mitochondrial disease.
Atomistic investigation of surface characteristics and electronic features at high-purity FeSi(110) presenting interfacial metallicity
Authors: Yang Biao , Uphoff Martin , Zhang Yi-Qi , Reichert Joachim , Seitsonen Ari Paavo , Bauer Andreas , Pfleiderer Christian , Barth Johannes V.
Published: April 2021

Significance

Iron silicide (FeSi) provides multiple fascinating features whereby intriguing functional properties bearing significant application prospects were recognized. FeSi is understood notably as a correlated
d
-electron narrow-gap semiconductor and a putative Kondo insulator, hosting unconventional quasiparticles. Recently, metallic surface conduction channels were identified at cryogenic conditions and suggested to play a key role in the resistivity of high-quality single-crystalline specimens. Motivated by these findings, we prepared and closely examined a FeSi(110) surface with atomistically defined termination and topography. In the low-temperature regime, where surface metallicity emerges, the electronic band gap undergoes a subtle evolution. The pertaining key features, asymmetrization of the gap shape and formation of in-gap states, underscore the similarity of FeSi to unequivocal topological Kondo insulator materials.
A pocket-factor–triggered conformational switch in the hepatitis B virus capsid
Authors: Lecoq Lauriane , Wang Shishan , Dujardin Marie , Zimmermann Peter , Schuster Leonard , Fogeron Marie-Laure , Briday Mathilde , Schledorn Maarten , Wiegand Thomas , Cole Laura , Montserret Roland , Bressanelli Stéphane , Meier Beat H. , Nassal Michael , Böckmann Anja
Published: April 2021

Significance

Viral hepatitis causes more deaths than tuberculosis and HIV-1 infection. Most cases are due to chronic infection with hepatitis B virus (HBV), which afflicts >250 million people. Current therapies are rarely curative, and new approaches are needed. Here, we report the discovery (by nuclear magnetic resonance) of a small molecule binder in the hydrophobic pocket in the HBV capsid. This structural element is, in an unknown manner, central in capsid envelopment. Binding of the pocket factor induces a distinct, stable conformation in the capsid, as expected for a signaling switch. This brings not only a new molecular view on the mechanism underlying capsid envelopment, but it also opens a rationale for its inhibition.
Caveolar peroxynitrite formation impairs endothelial TRPV4 channels and elevates pulmonary arterial pressure in pulmonary hypertension
Authors: Daneva Zdravka , Marziano Corina , Ottolini Matteo , Chen Yen-Lin , Baker Thomas M. , Kuppusamy Maniselvan , Zhang Aimee , Ta Huy Q. , Reagan Claire E. , Mihalek Andrew D. , Kasetti Ramesh B. , Shen Yuanjun , Isakson Brant E. , Minshall Richard D. , Zode Gulab S. , Goncharova Elena A. , Laubach Victor E. , Sonkusare Swapnil K.
Published: April 2021

Significance

Pulmonary hypertension (PH) is a serious disorder with a mortality rate of 40% over 5 y after diagnosis. Endothelial dysfunction is a major contributor to increased pulmonary arterial pressure (PAP) in PH. Here, we provide evidence that endothelial cell caveolin-1–TRPV4 channel signaling lowers resting PAP. Moreover, an impairment of endothelial caveolin-1–TRPV4 channel signaling elevates PAP in PH. In PH, there is an up-regulation of NOX1 and iNOS enzymes in endothelial cells, which increases peroxynitrite levels. Peroxynitrite, in turn, targets endothelial caveolin-1 and lowers endothelial caveolin-1–TRPV4 channel signaling. Finally, decreasing peroxynitrite levels rescues endothelial caveolin-1–TRPV4 channel signaling and lowers PAP in PH.
Smart and sustainable agriculture through weather and climate informatics and multi-scale modelling.
Authors: Prashant Goswami Prashant Goswami , Rao E. V. S. P.
Published: April 2021

Most agricultural processes, from choice of crops to sowing schedule to harvest management, depend on a number of weather variables; shifts in the weather regimes due to climate change determine crop variability at regional levels. Thus, advance and accurate information on weather variables, and their quantitative relations to the crop processes (agro-weather informatics) as well as quantification of role of climate conditions in agricultural processes (agro-climate informatics) can play critical to enabling roles in sustainable and smart (optimal in terms of planning, resource utilization and adaptability) agriculture. In particular, agro-weather-climate informatics have scopes and challenges including but beyond those in agriculture or weather informatics in isolation. This review examines principles and the scope of applications of weather and climate informatics in some of the key areas of agriculture such as crop choice, irrigation, energy management and long-term sustainability. While a serious bottleneck in application of forecast-based agro-advisories is low reliability of the forecasts, methodology combining optimization of forecast model, assimilation of data, multi-scale modelling and design of evaluation strategy for specific farm advisories is possible, so that the forecasts are risk-free and yet useful in spite of their errors. We provide a brief overview of weather and climate forecasting at different scales and the general methodology used; this is followed by an overview of status of these applications at different timescales such as daily, seasonal and beyond for a variety of issues such as precision agriculture and pro-active control of crop diseases. The roles of high-performance computing and multi-platform observations, including remote sensing, are outlined. This is followed by our conclusions and perspectives.
More is less: Partisan ideology, changes of government, and policy integration reforms in the UK
Authors: Maggetti Martino , Trein Philipp
Published: April 2021

Researchers have argued that political parties in government matter for policy integration reforms, but the way they do so remains somewhat undetermined. In this paper, we contribute to this literature by tackling two interrelated open questions: How does the presence of different political parties in government, which rely on policy programs on opposite sides of the ideological spectrum, shape the intensity of policy integration reforms? To what extent do changes in governing political parties affect the political motivation of policy integration reforms and thereby influence the goals and means of these reforms? To explore these questions, we examine a case where institutional capacity is generally favorable to such reforms. Specifically, we compare policy integration reforms in the UK under the New Labor government (1997–2010) with those passed by the Conservative governments (1979–1996), and by the coalition government of Conservatives and Liberal Democrats (2010–2014). We find that political parties’ policy positions, and respectively, their political motivations, decisively shape the intensity of policy integration reforms, as well as their substantial goals and means. Furthermore, our results imply that changes in governing parties increase the overall frequency but can reduce the coherence of reform programs over time. These results point to a paradox for the governance of problems through policy integration, whereby the presence of high institutional capacity as provided by a majoritarian system can have negative long-term consequences for policies aiming to solve complex problems.
Chaotic ultrasound generation using a nonlinear piezoelectric microtransducer
Authors: Defoort Martial , Rufer Libor , Basrour Skandar
Published: April 2021

We report on a piezoelectric micromachined ultrasonic transducer (PMUT) driven in a nonlinear regime, generating chaotic amplitude modulated ultrasonic waves. At large enough drives, the PMUT enters in the Duffing regime which opens a hysteresis with two available states. By modulating the frequency of the driving signal, the system may switch between both states, and selecting the appropriate modulation frequency enables to enter in the chaotic regime. The chaos is then imprinted as a modulation of the PMUT’s amplitude. We characterize this regime in the three accessible domains: electrical, mechanical and acoustic, and demonstrate they are fully correlated. We then focus on the generated acoustic signals and demonstrate that the chaotic modulation propagates according to the PMUT’s linear regime. Remarkably, the detected acoustic waves are strongly correlated to the on-chip piezoelectric measurements, regardless of the acoustic beam profile. The frequency spectrum of the chaotic modulation spreads around the ultrasonic carrier, mimicking a noise modulated carrier signal. We exploit this property for jamming applications where the chaotic PMUT is used to mask surrounding acoustic waves. Unlike most jamming applications, our approach does not require driving signals with a broad frequency spectrum, the noisy pattern arising directly from the structure’s dynamics. Using two PMUTs, one in the linear and the other in the nonlinear regime, we realize a proof-of-concept where the ultrasound generated by the first PMUT is drowned out by the chaotic PMUT signal. We demonstrate that the carrier frequency of the jamming PMUT does not need to match perfectly the one of the linear PMUT. This chaos generation is generic and could be adapted to any PMUT, and thanks to the rich frequency spectrum of the chaotic modulation, the frequency of the signal to jam does not need to be precisely known.
Influence of gas flow turbulence scale on heat exchange intensity in a long smooth pipe
Authors: Nevolin A M , Osipov L E , Plotnikov L V
Published: April 2021

It is known that the initial level of gas flow turbulence has a noticeable effect on the development and structure of the boundary layer and on the intensity of heat transfer, respectively. Many scientists have evaluated the influence of the flow turbulence number on the level of heat transfer for various applications, among them Dyban E.P., Kestin J., Simonich JC, Isomoto K., Dreitser G.A., Terekhov V.I., MacMullin R. and etc. In all cases, the turbulence of the flow led to the intensification of heat transfer. However, insufficient attention is paid to studies of the effect of turbulence on the heat transfer of flows in pipes. The studies were carried out on the basis of numerical modeling of gas dynamics and heat transfer of stationary flows based on the CFD method. The results of numerical modeling to assess the influence of the turbulence scale of gas flows on heat transfer in a long smooth pipe are presented in the article. It has been established that a growth in the heat transfer coefficient by about 3% occurs with an increase in the turbulence scale from 10 to 30% with a Reynolds number equal to 250,000.
The effect of surface structures on evaporation and free convection in evaporating sessile drops
Authors: Morozov V S
Published: April 2021

The effect of various surface structures of the AlMg6 aluminum-magnesium alloy on the evaporation rate and convection in a sessile droplet was experimentally studied. Structures on the surface were created using laser exposure. The evaporation of water droplets on heated structured surfaces was compared with a smooth wall. The wall temperature Tw = 68 °C. The data obtained for the evaporation rate without taking into account the diameter of the droplet base for a structured hydrophilic surface is 11-13% higher than for a smooth surface. The difference between structured hydrophilic and hydrophobic surfaces was 4-6%. The strongest effect of convection enhancement was observed for a structured hydrophobic surface.
Measurements of the gas composition in the flame during evaporating diesel fuel combustion with steam injection
Authors: Kopyev E P , Mukhina M A , Sadkin I S
Published: April 2021

This paper presents a study of the effect of superheated water steam on the combustion of liquid hydrocarbons such as diesel fuel. An experimental study of the content of intermediate components of the combustion process along the axis of flame symmetry inside the burner and in the external torch was carried out using a vaporizing burner with a forced superheated water steam supply to the area of incomplete oxidation of liquid hydrocarbon fuel. The values of oxygen, carbon monoxide, hydrogen, hydrocarbons, and carbon dioxide content were also obtained. It is shown that the content of flame intermediate components of the burner depends on operating parameters such as the steam flow rate or heated air flow rate and the type of the supplied substance.
Optical diagnostics of the temperature field of a hydrogen-air flame
Authors: Zolotukhina O S , Arbuzov V A , Arbuzov E V , Dubnishchev Yu N , Lukashov V V
Published: April 2021

A method for multi-wave optical diagnostics of phase structure and temperature fields in an axisymmetric hydrogen-air flame is discussed. An algorithm for numerical simulation of Hilbert images of phase fields reconstructed from radial temperature profiles and molar concentrations of combustion products using the Abel transform is developed and experimentally justified.
Dynamics of a soluble surfactant and evolution of daughterly concentration tongue in a Hele-Shaw cell
Authors: Demin V A , Petukhov M I
Published: April 2021

The origin and evolution of a concentration tongue, which is generated in the volume of a fluid due to the non-uniform desorption of a soluble surfactant, is investigated theoretically by the method of direct numerical simulation. Initially, a film of the soluble surfactant is located on the surface of the fluid that fills up the thin vertical rectangular slot (Hele – Shaw cell), heated non-uniformly from above. The intensity of desorption into the volume is determined by the compression of the film, caused by the Marangoni force, acting along the up boundary in opposite direction to the tangential component of temperature gradient. The dynamics of concentration tongue depends on the intensity of a creeping convective flow, which is produced in the volume jointly by the Archimedean and thermocapillary forces. The spatial motion of the fluid and the process of an admixture exchange between the surface and the volume in the Hele – Shaw cell are carried out in the plane of wide vertical boundaries of the cavity. This permits to simulate numerically and clearly visualize behaviour of the contaminants in multifarious fluid systems.
Maximum heat fluxes and features of heat transfer mechanisms with boiling during jet impingement cooling of electronics
Authors: Pukhovoy M V , Kunts K A , Spesivtsev S E , Kabov O A
Published: April 2021

The needs of microelectronics for heat removal are growing and have already exceeded the value of 1 kW/cm2. To assess the ability of jet impingement cooling to meet the growing requirements, a review of experimental studies was conducted. The review demonstrated both the lack of progress in increasing critical heat flux value over the past 30 years, and the fact that this technique is still considered effective and promising. The review showed that the movement to intensify heat transfer is in the same direction as in other promising cooling technologies. It is noted that the most productive heat transfer occurs in the region of the thinnest liquid film spreading from a free impingement liquid jet. New fundamental studies are discussed that note the significance of heat transfer values in a very thin liquid film, and this is important for the development of cooling technologies. Problems are formulated for the required detailed studies of highly dynamic processes in the boiling region of an ultrafine liquid film at the micro level, aimed at intensifying heat transfer.
Dependence of the temperature fields of a thin vertical wall on the intensity of the oncoming flow of a heated liquid
Authors: Mikhaylov A V , Grishkov V A , Berdnikov V S
Published: April 2021

The processes of the development of free convection of ethanol in the regimes of heating the vertical wall of a rectangular cavity are experimentally investigated. The hydrodynamics in the cavity and the dependence of the temperature field on the opposite thin vertical wall are studied. Non-stationary temperature fields on a thin wall were measured with a thermal imager. The experiments were carried out at different densities of heat fluxes on the heater and at a discrete set of heights of the liquid layers.
Plasma-chemical synthesis of zinc oxide nanotubes
Authors: Timerkaev B A , Felsinger V S , Kaleeva A A , Erlingayte E A , Uktamov J A , Nuriddinov H S
Published: April 2021

This research presents the results of the synthesis of zinc oxide nanotubes in electric arc plasma. The diameters of these nanotubes are about 120-150 nm, and the length is about several micrometers. Individual nanotubes can reach up to 1 mm. As electron microscopic studies have shown, zinc oxide nanotubes are a “matryoshka”: they are strung on a carbon nanotube. Firstly, a broken carbon nanotube with a diameter of about 30 nm is formed, and then a zinc oxide nanotube grows on it. Moreover, there is no contact between these nanotubes.
Synthesis of silicon spherical nanostructures in argon plasma
Authors: Timerkaev B A , Feltsinger V S , Gevorgian R K , Shaikhattorov R P , Kaleeva A A
Published: April 2021

The paper presents the results of the synthesis of silicon nanospheres (silicon fullerenes) in argon plasma. During the experiment, silicon atoms were evaporated from the surface of a single crystal using a plasma jet. Silicon atoms were entrained by the flow of argon plasma and, as the plasma cooled, formed in the form of spherical structures several atomic layers thick or in the form of silicon nanotubes. The diameters of silicon nanospheres range from 50 nm to 15 microns, and silicon nanotubes - from 40 to 100 nm.
Synthesis of silicon carbide in arc discharge in fuel oil
Authors: Timerkaev B A , Felzinger V S , Akhmetvaleeva A , Zainutdinova D A , Zalyalieva A A , Dautov G Y , Abramova D A
Published: April 2021

In this work, an experimental physical setup is proposed and a method for the synthesis of silicon carbide in an electric arc drowned into the thickness of hydrocarbon raw materials is described. Silicon carbide and carbon nanotubes were found in the deposits at the cathode. The resulting sample was analyzed using an optical microscope. And also confirmed the hardness of silicon carbide.
Formation of a powerful flow of steam-water plasma in a gas discharge with an aqueous solution cathode
Authors: Tazmeev G K , Tazmeev K K
Published: April 2021

A powerful flow of steam-water plasma was created using a gas discharge with a aqueous solution cathode. For this purpose, plasma generators with a power in the range of 25-40 kW were developed and created. The problems of choosing the composition of an aqueous solution and its concentration were solved. The energy characteristics of plasma generators were investigated. It is shown that the thermal protection of the walls of discharge chamber can be carried out by supplying gas to the interelectrode gap.
Synthesis of nanodiamonds and carbon nanotubes in siliconargon arc
Authors: Timerkaev B A , Shaikhattarov R R , Gevorgyan R K , Ibragimov I S , Akhmetvaleeva A R
Published: April 2021

This paper presents the results of the synthesis of nanodiamonds and carbon nanotubes in silicon-argon plasma. At a pressure of 500 Torr in the plasma reactor, carbon atoms evaporated from the surface of the graphite anode of the electric arc. The peculiarity of the graphite anode was that small pieces of silicon were embedded on the surface of the anode. As a result of the experiment, nanodiamonds and carbon nanotubes were formed on the surface of the graphite cathode. The linear dimensions of nanodiamonds range from 10 to 50 nm. The diameters of carbon nanotubes range from 4 nm to 20 nm, and their length is from 100 to 2 microns.
Structural Design Optimization of the Top Beam of a Propeller Processing Machine Tool Using FEA Analysis
Authors: Zheng Wei , Huang Xiaoqing , Liu Shihao
Published: April 2021

Aiming to reduce the weight under its rigidity and strength restrictions of a propeller processing machine tool, structural design optimization of the top beam of the machine tool is carried out using FEA analysis approach. Based on static and modal analysis, both the thickness and the width of the rib are optimized and light-weighted, followed FEA analysis results demonstrate that although the maximum stress and deformation of the optimized structure go up slightly, but are still allowable. After optimization, the weight of the top beam is reduced by approximately 8.03% and the dynamic characteristics of the top beam are also enhanced, which is beneficial to the noise reduction of the machine tool.
Stress and Deformation Analysis of Oil-Free Air Scroll Compressor
Authors: Ullah Hanif , Bin Peng , Bocko Jozef , Pengcheng Zhang , Yubo Zhang
Published: April 2021

This paper examined the deformation and the distribution of von-mises stress on the fixed and orbiting scroll. The stress and deformation of the scroll plate has been achieved under thermal load, structural load and thermo-static load. The full process of compression is achieved by the meshing operation of the moving and fixed scroll during the compression process of the scroll compressor. In this process, the teeth of the scrolls are mainly subjected to the combined effect of temperature and gas force resulting in stress and deformation. The performance of the scroll compressor can be affected by the high stress and deformation of the scroll, so it is important to research the scrolls under different field conditions. In this paper we presented the scrolls specification and deformation of oil-free scroll compressor. This study will enable the researcher and designers to improve the workability of the scroll compressor, resulting in a good performance prototype.
Analysis Method for the Mass Center of Low Earth Orbit Remote Sensing in Orbit
Authors: Jinghao Xu , Wenjing Ding , Lei Zhang , Zhilong Zhang
Published: April 2021

A real-time method for estimating the mass center of low earth orbit (LEO) remote sensing satellite in orbit is introduced in this paper. LEO remote sensing satellite requires highly on calculating the position of its mass center, due to the need of precise orbit determination and attitude control. This article offers an analysis method for the factors that play a leading role in the change of the centroid of satellite in orbit, which are the consuming of satellite fuel, the circulation of satellite-to-ground data transmission antenna and rotation of solar arrays. The parameters for calculating the centroid of LEO remote sensing satellite are defined, and a formula for computing the position of the satellite mass center in orbit is proposed.
Numerical analysis of the effect of underpass construction on an existing bridge foundation
Authors: Elgamal Ahmed
Published: April 2021

Micropiles are used effectively in many ground improvement applications, such as increasing soil bearing capacity, reducing the settlement of existing foundations, strengthening existing foundations, and reducing lateral soil movement due to arching. In this research, the micropiles, a geotechnical supposed solution, have applied to maximize the benefit for all the mentioned features. The frictional resistance between the surface of micropiles and the surrounding soil is considered. Besides, the effect of the micropiles network is considered as a possible means for improvement. We have examined a case study in which micropiles of400 mm diameter and 13.00 m length were used to improve the bearing capacity of soil underlies the existing bridge foundations, reduce their settlement, and decrease the side-support system’s deformation. The models created for this study were used to simulate the proposed geotechnical solution.
Thickness-dependent gap energies in thin layers of Hf Te5
Authors: Belke C , Locmelis S , Thole L , Schmidt H , Behrens P , Haug R J
Published: April 2021

Hafnium pentatelluride (Hf Te5) is a layered two-dimensional material with various exotic properties. It is thought to be a topological insulator. Whereas bulk Hf Te5 has a small band gap, single layers are predicted to be a quantum spin hall insulator with a large band gap. Here we measured band gap energies for samples with varying thicknesses and found a clear increase of gap energies for the thinner samples. With decreasing thickness an increase of the measured band gap energies from 40 to 304 meV is observed.
Daily Motivational Text Messages to Promote Physical Activity in University Students: Results From a Microrandomized Trial
Authors: Figueroa Caroline A , Deliu Nina , Chakraborty Bibhas , Modiri Arghavan , Xu Jing , Aggarwal Jai , Jay Williams Joseph , Lyles Courtney , Aguilera Adrian
Published: April 2021

Background

Low physical activity is an important risk factor for common physical and mental disorders. Physical activity interventions delivered via smartphones can help users maintain and increase physical activity, but outcomes have been mixed.

Purpose

Here we assessed the effects of sending daily motivational and feedback text messages in a microrandomized clinical trial on changes in physical activity from one day to the next in a student population.

Methods

We included 93 participants who used a physical activity app, “DIAMANTE” for a period of 6 weeks. Every day, their phone pedometer passively tracked participants’ steps. They were microrandomized to receive different types of motivational messages, based on a cognitive-behavioral framework, and feedback on their steps. We used generalized estimation equation models to test the effectiveness of feedback and motivational messages on changes in steps from one day to the next.

Results

Sending any versus no text message initially resulted in an increase in daily steps (729 steps, p = .012), but this effect decreased over time. A multivariate analysis evaluating each text message category separately showed that the initial positive effect was driven by the motivational messages though the effect was small and trend-wise significant (717 steps; p = .083), but not the feedback messages (−276 steps, p = .4).

Conclusion

Sending motivational physical activity text messages based on a cognitive-behavioral framework may have a positive effect on increasing steps, but this decreases with time. Further work is needed to examine using personalization and contextualization to improve the efficacy of text-messaging interventions on physical activity outcomes.

ClinicalTrials.gov Identifier

NCT04440553.
Is point-of-care testing feasible and safe in care homes in England? An exploratory usability and accuracy evaluation of a point-of-care polymerase chain reaction test for SARS-CoV-2
Authors: Micocci Massimo , Gordon Adam L , Seo Mikyung Kelly , Allen A Joy , Davies Kerrie , Lasserson Dan , Thompson Carl , Spilsbury Karen , Akrill Cyd , Heath Ros , Astle Anita , Sharpe Claire , Perera Rafael , Hayward Gail , Buckle Peter
Published: April 2021

Introduction

Reliable rapid testing for COVID-19 is needed in care homes to reduce the risk of outbreaks and enable timely care. This study aimed to examine the usability and test performance of a point of care polymerase chain reaction (PCR) test for detection of SARS-CoV-2 (POCKITTM Central) in care homes.

Methods

POCKITTM Central was evaluated in a purposeful sample of four UK care homes. Test agreement with laboratory real-time PCR and usability and used errors were assessed.

Results

No significant usability-related hazards emerged, and the sources of error identified were found to be amendable with minor changes in training or test workflow. POCKITTM Central has acceptable sensitivity and specificity based on RT-PCR as the reference standard, especially for symptomatic cases.

Asymptomatic specimens showed 83.3% (95% confidence interval (CI): 35.9–99.6%) positive agreement and 98.7% negative agreement (95% CI: 96.2–99.7%), with overall prevalence and bias-adjusted kappa (PABAK) of 0.965 (95% CI: 0.932– 0.999). Symptomatic specimens showed 100% (95% CI: 2.5–100%) positive agreement and 100% negative agreement (95% CI: 85.8–100%), with overall PABAK of 1.

Recommendations are provided to mitigate the frequency of occurrence of the residual use errors observed. Integration pathways were discussed to identify opportunities and limitations of adopting POCKIT™ Central for screening and diagnostic testing purposes.

Conclusions

Point-of-care PCR testing in care homes can be considered with appropriate preparatory steps and safeguards. Further diagnostic accuracy evaluations and in-service evaluation studies should be conducted, if the test is to be implemented more widely, to build greater certainty on this initial exploratory analysis.
Body mass dynamics of migratory nightjars are explained by individual turnover and fueling
Authors: Hidalgo-Rodríguez Paula , Sáez-Gómez Pedro , Blas Julio , Hedenström Anders , Camacho Carlos
Published: April 2021

Body mass is a commonly used indicator of the energy stores of migratory animals and there is considerable evidence that it is a critical determinant of migration decisions and outcomes. Mean population mass often increases during the post-breeding period in most migratory species. Usually, this increase is interpreted as the result of fuel accumulation for migration based on the assumption that mean population mass mirrors mean individual mass. However, an empirical test of this assumption is lacking, and it is unknown whether the general increase in mean population mass is entirely the result of within-individual mass gain, or if it rather reflects a change in the nature of individuals in the population (mass-dependent turnover). We investigated changes in body mass during the post-fledging period of a migratory bird, the Red-necked Nightjar (Caprimulgus ruficollis), and combined longitudinal and cross-sectional data collected over 9 years to disentangle the relative contribution of individual-level (mass gain) and population-level (selective appearance and disappearance) processes. We found that the average body mass of fully-developed juveniles increased as the season progressed and that both individual mass gain and the selective disappearance of lighter individuals contributed to this increase. Contrary to the general expectations for migrants, the turnover of individuals contributed 3.5 times more to the seasonal increase in average body mass than individual mass gain. On a practical note, this differential contribution implied a discrepancy of over 40% between the time-average rates of mass gain (fuel deposition rates) estimated from population-level and individual-level data. Our study calls for caution in the use of population-level changes in body mass to make inferences about individual fuel deposition rates and, more generally, indicates that longitudinal and cross-sectional approaches need to be combined to uncover phenotype-time correlations in natural populations.
Point-of-care testing technologies for the home in chronic kidney disease: a narrative review
Authors: Bodington Richard , Kassianides Xenophon , Bhandari Sunil
Published: April 2021

Point-of-care testing (POCT) performed by the patient at home, paired with eHealth technologies, offers a wealth of opportunities to develop individualized, empowering clinical pathways. The non-dialysis-dependent chronic kidney disease (CKD) patient who is at risk of or may already be suffering from a number of the associated complications of CKD represents an ideal patient group for the development of such initiatives. The current coronavirus disease 2019 pandemic and drive towards shielding vulnerable individuals have further highlighted the need for home testing pathways. In this narrative review we outline the evidence supporting remote patient management and the various technologies in use in the POCT setting. We then review the devices currently available for use in the home by patients in five key areas of renal medicine: anaemia, biochemical, blood pressure (BP), anticoagulation and diabetes monitoring. Currently there are few devices and little evidence to support the use of home POCT in CKD. While home testing in BP, anticoagulation and diabetes monitoring is relatively well developed, the fields of anaemia and biochemical POCT are still in their infancy. However, patients’ attitudes towards eHealth and home POCT are consistently positive and physicians also find this care highly acceptable. The regulatory and translational challenges involved in the development of new home-based care pathways are significant. Pragmatic and adaptable trials of a hybrid effectiveness–implementation design, as well as continued technological POCT device advancement, are required to deliver these innovative new pathways that our patients desire and deserve.
Exploring efficient linear mixed models to detect quantitative trait locus-by-environment interactions
Authors: Yamamoto Eiji , Matsunaga Hiroshi
Published: April 2021

Genotype-by-environment (G × E) interactions are important for understanding genotype–phenotype relationships. To date, various statistical models have been proposed to account for G × E effects, especially in genomic selection (GS) studies. Generally, GS does not focus on the detection of each quantitative trait locus (QTL), while the genome-wide association study (GWAS) was designed for QTL detection. G × E modeling methods in GS can be included as covariates in GWAS using unified linear mixed models (LMMs). However, the efficacy of G × E modeling methods in GS studies has not been evaluated for GWAS. In this study, we performed a comprehensive comparison of LMMs that integrate the G × E modeling methods to detect both QTL and QTL-by-environment (Q × E) interaction effects. Model efficacy was evaluated using simulation experiments. For the fixed effect terms representing Q × E effects, simultaneous scoring of specific and nonspecific environmental effects was recommended because of the higher recall and improved genomic inflation factor value. For random effects, it was necessary to account for both G × E and genotype-by-trial (G × T) effects to control genomic inflation factor value. Thus, the recommended LMM includes fixed QTL effect terms that simultaneously score specific and nonspecific environmental effects and random effects accounting for both G × E and G × T. The LMM was applied to real tomato phenotype data obtained from two different cropping seasons. We detected not only QTLs with persistent effects across the cropping seasons but also QTLs with Q × E effects. The optimal LMM identified in this study successfully detected more QTLs with Q × E effects.
Population scale nucleic acid delivery toCaenorhabditis elegansvia electroporation
Authors: Khodakova Anastasia S , Vilchis Daniela Vidal , Blackburn Dana , Amanor Ferdinand , Samuel Buck S
Published: April 2021

The free-living nematode Caenorhabditis elegans remains one of the most robust and flexible genetic systems for interrogating the complexities of animal biology. Targeted genetic manipulations, such as RNA interference (RNAi), CRISPR/Cas9- or array-based transgenesis, all depend on initial delivery of nucleic acids. Delivery of dsRNA by feeding can be effective, but the expression in Escherichia coli is not conducive to experiments intended to remain sterile or with defined microbial communities. Soaking-based delivery requires prolonged exposure of animals to high-material concentrations without a food source and is of limited throughput. Last, microinjection of individual animals can precisely deliver materials to animals’ germlines, but is limited by the need to target and inject each animal one-by-one. Thus, we sought to address some of these challenges in nucleic acid delivery by developing a population-scale delivery method. We demonstrate efficient electroporation-mediated delivery of dsRNA throughout the worm and effective RNAi-based silencing, including in the germline. Finally, we show that guide RNA delivered by electroporation can be utilized by transgenic Cas9 expressing worms for population-scale genetic targeting. Together, these methods expand the scale and scope of genetic methodologies that can be applied to the C. elegans system.
Comparing the Effects of Two Cardiovascular Health Factors on Working Memory Capacity in Healthy Aging: Separate and Combined Effects of Arterial Elasticity and Physical Fitness
Authors: Qin Shuo , Basak Chandramallika
Published: April 2021

Objectives

Arterial elasticity and physical fitness are 2 important cardiovascular health factors that influence cognition in older adults. Working memory capacity (WMC), a core component underlying cognitive aging across many cognitive domains, may be affected by individual differences in cardiovascular health in older adults. This study aims to identify in older adults: (a) separate and combined effects of these 2 cardiovascular health factors on WMC and (b) which of the 2 factors is more critical in influencing WMC.

Methods

WMC in 89 healthy older adults was assessed by 2 complex span tasks. Arterial elasticity was assessed by pulse pressure (PsP). Physical fitness was measured by an established proxy of VO2 max (MET). Effects of PsP and MET on WMC were evaluated via step-wise regressions.

Results

After controlling for age, sex, and education, PsP and MET were separately predictive of WMC in older adults. Together, the combined effect of PsP and MET was more predictive of WMC than fitness alone, but not more than PsP alone. Mediation analysis indicates that the relationship between MET and WMC was completely mediated by PsP.

Discussion

This study innovatively demonstrates that though arterial elasticity and physical fitness separately predict WMC, the former completely mediates the relationship between fitness and WMC. This suggests that biologically based cardiovascular health factors like arterial elasticity are crucial individual difference variables that should be measured and monitored in cognitive aging studies as well as in physical interventions that are designed to improve cognition in healthy aging.
Childhood Respiratory Outpatient Visits Correlate With Socioeconomic Status and Drive Geographic Patterns in Antibiotic Prescribing
Authors: Kissler Stephen M , Klevens R Monina , Barnett Michael L , Grad Yonatan H
Published: April 2021

Background

Reducing geographic disparities in antibiotic prescribing is a central public health priority to combat antibiotic resistance, but drivers of this variation have been unclear.

Methods

We measured how variation in outpatient visit rates (observed disease) and antibiotic prescribing rates per visit (prescribing practices) contributed to geographic variation in per capita antibiotic prescribing in Massachusetts residents younger than 65 years between 2011 and 2015.

Results

Of the difference in per capita antibiotic prescribing between high- and low-prescribing census tracts in Massachusetts, 45.2% was attributable to variation in outpatient visit rates, while 25.8% was explained by prescribing practices. Outpatient visits for sinusitis, pharyngitis, and suppurative otitis media accounted for 30.3% of the gap in prescribing, with most of the variation in visit rates concentrated in children younger than 10 years. Outpatient visits for these conditions were less frequent in census tracts with high social deprivation index.

Conclusions

Interventions aimed at reducing geographic disparities in antibiotic prescribing should target the drivers of outpatient visits for respiratory illness and should account for possible underutilization of health services in areas with the lowest antibiotic consumption. Our findings challenge the conventional wisdom that prescribing practices are the main driver of geographic disparities in antibiotic use.
Development of a Coronavirus Disease 2019 (COVID-19) Application Ontology for the Accrual to Clinical Trials (ACT) network
Authors: Visweswaran Shyam , Samayamuthu Malarkodi J , Morris Michele , Weber Griffin M , MacFadden Douglas , Trevvett Philip , Klann Jeffrey G , Gainer Vivian S , Benoit Barbara , Murphy Shawn N , Patel Lav , Mirkovic Nebojsa , Borovskiy Yuliya , Johnson Robert D , Wyatt Matthew C , Wang Amy Y , Follett Robert W , Chau Ngan , Zhu Wenhong , Abajian Mark , Chuang Amy , Bahroos Neil , Reeder Phillip , Xie Donglu , Cai Jennifer , Sendro Elaina R , Toto Robert D , Firestein Gary S , Nadler Lee M , Reis Steven E
Published: April 2021

Clinical data networks that leverage large volumes of data in electronic health records (EHRs) are significant resources for research on coronavirus disease 2019 (COVID-19). Data harmonization is a key challenge in seamless use of multisite EHRs for COVID-19 research. We developed a COVID-19 application ontology in the national Accrual to Clinical Trials (ACT) network that enables harmonization of data elements that are critical to COVID-19 research. The ontology contains over 50 000 concepts in the domains of diagnosis, procedures, medications, and laboratory tests. In particular, it has computational phenotypes to characterize the course of illness and outcomes, derived terms, and harmonized value sets for severe acute respiratory syndrome coronavirus 2 laboratory tests. The ontology was deployed and validated on the ACT COVID-19 network that consists of 9 academic health centers with data on 14.5M patients. This ontology, which is freely available to the entire research community on GitHub at https://github.com/shyamvis/ACT-COVID-Ontology, will be useful for harmonizing EHRs for COVID-19 research beyond the ACT network.
Development and Validation of a Stability-Indicating Reversed-Phase High-Performance Liquid Chromatography Method for Assay of Doramectin and Estimation of its Related Substances in Commercial Batches of Doramectin Drug Substance
Authors: Wang Lin , Wimalasinghe Rasangi , Padivitage Nilusha , Rustum Abu M
Published: April 2021

Background

Doramectin is a broad-spectrum antiparasitic drug used in veterinary medicine. It belongs to the family of avermectins, which possess a macrocyclic lactone structure, and is widely used for the treatment of parasites.

Objective

This study aimed to develop a stability-indicating reversed-phase (RP) HPLC method for the assay and identification of doramectin including identification and estimation of its related substances in commercial batches of doramectin drug substance.

Method

Methanol was used to dissolve and prepare doramectin samples. Doramectin and its related substances were separated on a HALO C8 (100 mm × 4.6 mm i.d., 2.7 µm particle size) column maintained at 40 °C using an isocratic HPLC method with a mobile phase composed of acetonitrile–water (70 + 30, v/v). Analytes were detected with UV detection at 245 nm and quantitated against a single point external reference standard of doramectin. The LOQ of the method is 0.1% of the target concentration as described in the method.

Results

The HPLC method can separate all analytes of interest by an isocratic elution within 10 min. The method was validated according to the guidelines described in the International Conference on Harmonization Q2(R1).

Conclusions

The HPLC method for assay of doramectin and estimation of its related substances was successfully developed, validated, and demonstrated to be accurate, robust, specific, and stability-indicating.

Highlights

This is the first known paper to report an HPLC method for assay of doramectin and estimation of its related substances in commercial batches of doramectin drug substance.
Stories Collectively Engage Listeners’ Brains: Enhanced Intersubject Correlations during Reception of Personal Narratives
Authors: Grall Clare , Tamborini Ron , Weber René , Schmälzle Ralf
Published: April 2021

Audiences’ engagement with mediated messages lies at the center of media effects research. However, the neurocognitive components underlying audience engagement remain unclear. A neuroimaging study was conducted to determine whether personal narratives engage the brains of audience members more than non-narrative messages and to investigate the brain regions that facilitate this effect. Intersubject correlations of brain activity during message exposure showed that listening to personal narratives elicited strong audience engagement as evidenced by robust correlations across participants’ frontal and parietal lobes compared to a nonpersonal control text and a reversed language control stimulus. Thus, personal narratives were received and processed more consistently and reliably within specific brain regions. The findings contribute toward a biologically informed explanation for how personal narratives engage audiences to convey information.
Chronotopic Cartography: Mapping Literary Time-Space
Authors: Bushell Sally , Butler James , Hay Duncan , Hutcheon Rebecca , Butterworth Alex
Published: April 2021

This short methods paper emerges out of the AHRC-funded ‘Chronotopic Cartographies’ project for the digital mapping of place and space as represented in works of literature. The primary aim of that project was to find a way of mapping and visualizing represented literary worlds for which there is no corresponding real ‘ground’. A solution was found in the form of topological graphs which allow for relative rather than absolute mapping (but also permit a relative imaginary map to be lain on top of a pre-existing cartesian form). Using a spatial schema to chunk out the text in terms of chronotopic (time-space) zones enables the generation of a series of visualizations that show different kinds of spatio-temporal constructions in texts. The visualizations are centred upon nodes that consist of chronotopes (e.g. ‘the road’) as well as locations (e.g. ‘road to Geneva’); connections between them of different kinds and toporefs within them (references to other places from this one). The paper will articulate core methods from the project, outlining the stages involved in the process, from marking up the text, using a custom-made schema, through graph generation and into the implications for analysis. This will be illustrated in relation to two Victorian texts: the realist space of Dickens’s Oliver Twist; and the abstract poetic space of Browning’s ‘Childe Roland to the Dark Tower Came’.
Semantic tagging and the Nordic tradition of everyman’s rights
Authors: Kettunen Kimmo , La Mela Matti
Published: April 2021

This article uses semantic tagging to analyse the Nordic concept of everyman’s rights (a right of public access to nature) in protocols of the Finnish parliament. In the analysis, we use a novel tool, a lexical semantic tagger for Finnish (Finnish-language Semantic Tagger), which is used to tag key discussions about everyman’s rights in the Finnish parliament. The article has two contributions as follows: first, it presents a method that combines semantic tagging and similarity analysis of corpora (keyness) for studying the formation of political concepts in large textual data. Secondly, it sheds light on the Nordic access rights and the underlying customary everyman’s rights. Despite its central role in public debate, the history of the concept has not been well researched. Our analysis shows that the legislative context could be clearly detected with our approach, and that the method allowed us to describe shifts in the meaning of everyman’s rights in the legislative discussion.