bluuebunny/crossref_metadata_2025 huggingface dataset:
How to Build Your Own ASP-based System?!
Authors: KAMINSKI ROLAND , ROMERO JAVIER , SCHAUB TORSTEN , WANKO PHILIPP
Published: December 2021

Answer Set Programming, or ASP for short, has become a popular and sophisticated approach to declarative problem solving. Its popularity is due to its attractive modeling-grounding-solving workflow that provides an easy approach to problem solving, even for laypersons outside computer science. However, in contrast to ASP’s ease of use, the high degree of sophistication of the underlying technology makes it even hard for ASP experts to put ideas into practice whenever this involves modifying ASP’s machinery. For addressing this issue, this tutorial aims at enabling users to build their own ASP-based systems. More precisely, we show how the ASP system clingo can be used for extending ASP and for implementing customized special-purpose systems. To this end, we propose two alternatives. We begin with a traditional AI technique and show how metaprogramming can be used for extending ASP. This is a rather light approach that relies on clingo’s reification feature to use ASP itself for expressing new functionalities. The second part of this tutorial uses traditional programming (in Python) for manipulating clingo via its application programming interface. This approach allows for changing and controlling the entire model-ground-solve workflow of ASP. Central to this is clingo’s new Application class that allows us to draw on clingo’s infrastructure by customizing processes similar to the one in clingo. For instance, we may apply manipulations to programs’ abstract syntax trees, control various forms of multi-shot solving, and set up theory propagators for foreign inferences. A cross-sectional structure, spanning meta as well as application programming, is clingo’s intermediate format, aspif, that specifies the interface among the underlying grounder and solver. We illustrate the aforementioned concepts and techniques throughout this tutorial by means of examples and several nontrivial case studies. In particular, we show how clingo can be extended by difference constraints and how guess-and-check programming can be implemented with both meta and application programming.
Modalities of Assimilation: Subcultural Currents in Felix Mendelssohn's Lieder Ohne Worte
Authors: Deutsch Dan
Published: December 2021

In this article I examine the impact of Felix Mendelssohn's affiliation with a German-Jewish subculture on his music as reflected in the Lieder ohne Worte (Songs without Words) for piano solo. To better understand the interrelationship between musical formations and sociocultural realities, I associate the real and imaginary tensions between the German, the Jewish, and the German-Jewish with stylistic ambiguities in Mendelssohn's piano songs, which often destabilize the lyrical simplicity projected by the lieder framework through formal complexities that exceed the narrow scope of the piano miniature.

I establish the connections between Mendelssohn's music and sociocultural disposition by identifying a correlation between his so-called stylistic ‘conservatism’ and the anachronistic devotion of German Jewry to the universal ideals of the Enlightenment during the rise of German nationalism. Against this background, I primarily reveal the generic heterogeneity of the Lieder ohne Worte, which feature ‘progressive’ stylistic frameworks associated with the lied traditions yet concurrently point toward the formal ideals of eighteenth-century classicism. And following this, I position the stylistic duality of Mendelssohn's piano songs within a broader context through Heinrich Heine's essay The Romantic School, which sheds crucial light on the negotiation of Jewishness within German culture as it is reflected in aesthetic movements, historical changes, and political climates.
Political Game-Changers: The Importance of Leaders for Newly Emerged Parties in Romania
Authors: Gherghina Sergiu , Grad Marius
Published: December 2021

Party leaders continue to be crucial players in politics. The theories of personalization and presidentialization of party politics reflect the centrality of leaders’ roles. Little attention has been paid to the effects of leaders on the formation and development of newly emerged parties. This article aims to fill that gap by analyzing the effect of leaders on the formation, intra-party cohesion, and membership organization of three newly emerged Romanian parties between 2015 and 2019. The qualitative analysis uses content from primary (party documents and elite discourses) and secondary sources (media reports). The findings indicate that the leaders’ approaches towards party formation and organization differ substantially across the examined parties and explain their cohesion and electoral appeal.
Illuminating a Contorted Slab With a Complex Intraslab Rupture Evolution During the 2021 Mw 7.3 East Cape, New Zealand Earthquake
Authors: Okuwaki Ryo , Hicks Stephen P. , Craig Timothy J. , Fan Wenyuan , Goes Saskia , Wright Tim J. , Yagi Yuji
Published: December 2021

The state‐of‐stress within subducting oceanic plates controls rupture processes of deep intraslab earthquakes. However, little is known about how the large‐scale plate geometry and the stress regime relate to the physical nature of the deep intraslab earthquakes. Here we find, by using globally and locally observed seismic records, that the moment magnitude 7.3 2021 East Cape, New Zealand earthquake was driven by a combination of shallow trench‐normal extension and unexpectedly, deep trench‐parallel compression. We find multiple rupture episodes comprising a mixture of reverse, strike‐slip, and normal faulting. Reverse faulting due to the trench‐parallel compression is unexpected given the apparent subduction direction, so we require a differential buoyancy‐driven stress rotation, which contorts the slab near the edge of the Hikurangi plateau. Our finding highlights that buoyant features in subducting plates may cause diverse rupture behavior of intraslab earthquakes due to the resulting heterogeneous stress state within slabs.
The Eastern Atlantic Basin Pathway for the Export of the North Atlantic Deep Waters
Authors: Zhai Yujia , Yang Jiayan , Wan Xiuquan , Zou Sijia
Published: December 2021

The North Atlantic deep water (NADW), according to the classic ocean circulation theory, moves southward as a deep western boundary current (DWBC) even though it may veer into interior and then rejoin DWBC when encountering regional circulation features, such as eddy‐driven recirculation. In potential vorticity dynamics, the eastern side of the Mid‐Atlantic Ridge (MAR) may provide a similar topographic support as the continental slope off the western boundary for a southward transport of NADW. In this article, we quantify the mean meridional NADW transports on both sides of the MAR using a data‐assimilated product and find that the flow in the eastern basin contributes about of the net southward transport of NADW from 50° to 35°N. Our study points to the importance of observing NADW transport variations on the eastern side of the MAR in order to monitor the transport strength of Atlantic Meridional Overturning Circulation.
Blended Dry and Hot Events Index for Monitoring Dry‐Hot Events Over Global Land Areas
Authors: Wu Haijiang , Su Xiaoling , Singh Vijay P.
Published: December 2021

The amplifying effects of disasters caused by compound dry and hot extremes (dry‐hot events) have attracted widespread attention. This study presents a novel Blended Dry and Hot Events Index (BDHI) considering various dry and hot conditions (i.e., dry/hot, dry/cool, wet/hot, and wet/cool conditions). BDHI was applied to monitor dry‐hot events over global land areas during the 1950–2019 period and its performance was compared against that of the Standardized Compound Event Indicator (SCEI), which includes certain unsatisfactory or unclear features. We found that BDHI comprehensively reflected the characteristics of meteorological drought and temperature anomalies in monitoring dry‐hot events. Many regions around the globe have been experiencing more severe dry‐hot events since the 1990s, especially Russia, the USA, China, India, Australia, southern Africa, Europe, and South America. The proposed index is expected to serve as a potential tool for monitoring dry‐hot events and will be useful for managing and mitigating associated risks.
Measurements of Energy Dissipation in the Electron Diffusion Region
Authors: Zhou Meng , Man Hengyan , Yang Yan , Zhong Zhihong , Deng Xiaohua
Published: December 2021

An outstanding question in magnetic reconnection is how the energy being dissipated in the diffusion region. This paper evaluates the quasi‐viscous dissipation in the electron diffusion region (EDR) at Earth's magnetopause by the observations from the Magnetospheric MultiScale mission. We compared two fluid parameters, J·Eˊ and Pi‐D, and found that J·Eˊ and Pi‐D have opposite signs in about half of the examined EDRs. The gyrotropic effect is more important than the nongyrotropic effect for the viscous dissipation in the diffusion region. One intriguing discovery is that electrons are cooled rather than heated in a large portion of the EDRs, with the compressional effect dominates over the viscous effect in electron thermodynamics. Enthalpy flux flowing into or out from the EDR greatly affect the electron entropy variation within the EDR. This study is an important step toward fully resolving the dissipation mystery in reconnection.
Seasonal Seismicity in the Lake Biwa Region of Central Japan Moderately Modulated by Lake Water Storage Changes
Authors: Xue Liang , Fu Yuning , Johnson Christopher W. , Otero Torres Jason J. , Shum C. K. , Bürgmann Roland
Published: December 2021

Seasonal seismicity in Japan has been observed and attributed to variations induced by hydrological loading, as well as atmospheric and pore‐fluid pressure. We examine the seasonal variations of crustal (<15 km depth) and low magnitude (M < 4.5) earthquakes in central Japan near the Biwako‐Seigan Fault Zone (BSFZ), and analyze their correlation with the annual hydrological cycle of nearby Lake Biwa, the largest freshwater lake in Japan. The 2002–2018 lake water storage is estimated using water‐level gauge and satellite altimetry data. Regional surface mass loading from soil moisture and snow predicted by the Global Land Data Assimilation System is used to augment the lake mass variation. We compute the stress and stressing‐rate changes induced by the surface mass loading from lake storage, snow, and soil moisture at seismogenic depth (10 km) along the BSFZ using a finite element model incorporating a 3D Earth structure. The results show that seasonal surface mass loading generates 1–5 kPa peak‐to‐peak Coulomb stress change and 2.5–15 kPa/year stressing‐rate variations on the fault segments along the BSFZ. Two of the four fault segments present significant correlation between local seismicity rate and loading‐derived stress and/or stressing rate changes. Among the hydrological load components, lake water, snow, and soil moisture exhibit different annual phases, and the lake water storage dominates the total annual stress changes. Our analysis indicates that seasonal surface hydrological loads, especially lake water variations, modulate the seismicity rate along the BSFZ in central Japan.
Recoil Leader and Associated Discharge Features Observed During the Progression of a Multi‐Branched Upward Lightning Flash
Authors: Huang Haitao , Wang Daohong , Wu Ting , Takagi Nobuyuki
Published: December 2021

Using a high‐speed video camera and a high‐speed optical imaging system, we observed a multi‐branched upward lightning flash that exhibited several special discharge features. One special feature is that a series of recoil leaders and the subsequent discharges caused by the connection of some recoil leaders to a conducting channel could extend a discharge channel like a leader. Another special feature is that the subsequent discharge could be similar to either a return stroke (RS) or an M‐component or something between. It seems that when a recoil leader initiated in a more conductive channel with a closer distance to a conducting channel, its subsequent discharge is similar to an M‐component. In cases with opposite conditions, the subsequent discharge will become similar to a RS. In conditions between the above two cases, a discharge that is intermediate between the RS and M‐component will occur.
T cell receptor (TCR) signaling in health and disease
Authors: Shah Kinjal , Al-Haidari Amr , Sun Jianmin , Kazi Julhash U.
Published: December 2021

Interaction of the T cell receptor (TCR) with an MHC-antigenic peptide complex results in changes at the molecular and cellular levels in T cells. The outside environmental cues are translated into various signal transduction pathways within the cell, which mediate the activation of various genes with the help of specific transcription factors. These signaling networks propagate with the help of various effector enzymes, such as kinases, phosphatases, and phospholipases. Integration of these disparate signal transduction pathways is done with the help of adaptor proteins that are non-enzymatic in function and that serve as a scaffold for various protein–protein interactions. This process aids in connecting the proximal to distal signaling pathways, thereby contributing to the full activation of T cells. This review provides a comprehensive snapshot of the various molecules involved in regulating T cell receptor signaling, covering both enzymes and adaptors, and will discuss their role in human disease.
Natural Language Processing markers in first episode psychosis and people at clinical high-risk
Authors: Morgan Sarah E. , Diederen Kelly , Vértes Petra E. , Ip Samantha H. Y. , Wang Bo , Thompson Bethany , Demjaha Arsime , De Micheli Andrea , Oliver Dominic , Liakata Maria , Fusar-Poli Paolo , Spencer Tom J. , McGuire Philip
Published: December 2021

Recent work has suggested that disorganised speech might be a powerful predictor of later psychotic illness in clinical high risk subjects. To that end, several automated measures to quantify disorganisation of transcribed speech have been proposed. However, it remains unclear which measures are most strongly associated with psychosis, how different measures are related to each other and what the best strategies are to collect speech data from participants. Here, we assessed whether twelve automated Natural Language Processing markers could differentiate transcribed speech excerpts from subjects at clinical high risk for psychosis, first episode psychosis patients and healthy control subjects (total N = 54). In-line with previous work, several measures showed significant differences between groups, including semantic coherence, speech graph connectivity and a measure of whether speech was on-topic, the latter of which outperformed the related measure of tangentiality. Most NLP measures examined were only weakly related to each other, suggesting they provide complementary information. Finally, we compared the ability of transcribed speech generated using different tasks to differentiate the groups. Speech generated from picture descriptions of the Thematic Apperception Test and a story re-telling task outperformed free speech, suggesting that choice of speech generation method may be an important consideration. Overall, quantitative speech markers represent a promising direction for future clinical applications.
Vesicle shape transformations driven by confined active filaments
Authors: Peterson Matthew S. E. , Baskaran Aparna , Hagan Michael F.
Published: December 2021

In active matter systems, deformable boundaries provide a mechanism to organize internal active stresses. To study a minimal model of such a system, we perform particle-based simulations of an elastic vesicle containing a collection of polar active filaments. The interplay between the active stress organization due to interparticle interactions and that due to the deformability of the confinement leads to a variety of filament spatiotemporal organizations that have not been observed in bulk systems or under rigid confinement, including highly-aligned rings and caps. In turn, these filament assemblies drive dramatic and tunable transformations of the vesicle shape and its dynamics. We present simple scaling models that reveal the mechanisms underlying these emergent behaviors and yield design principles for engineering active materials with targeted shape dynamics.
Hyperbolic optics and superlensing in room-temperature KTN from self-induced k-space topological transitions
Authors: Gelkop Yehonatan , Di Mei Fabrizio , Frishman Sagi , Garcia Yehudit , Falsi Ludovica , Perepelitsa Galina , Conti Claudio , DelRe Eugenio , Agranat Aharon J.
Published: December 2021

A hyperbolic medium will transfer super-resolved optical waveforms with no distortion, support negative refraction, superlensing, and harbor nontrivial topological photonic phases. Evidence of hyperbolic effects is found in periodic and resonant systems for weakly diffracting beams, in metasurfaces, and even naturally in layered systems. At present, an actual hyperbolic propagation requires the use of metamaterials, a solution that is accompanied by constraints on wavelength, geometry, and considerable losses. We show how nonlinearity can transform a bulk KTN perovskite into a broadband 3D hyperbolic substance for visible light, manifesting negative refraction and superlensing at room-temperature. The phenomenon is a consequence of giant electro-optic response to the electric field generated by the thermal diffusion of photogenerated charges. Results open new scenarios in the exploration of enhanced light-matter interaction and in the design of broadband photonic devices.
Cell-specific alterations in Pitx1 regulatory landscape activation caused by the loss of a single enhancer
Authors: Rouco Raquel , Bompadre Olimpia , Rauseo Antonella , Fazio Olivier , Peraldi Rodrigue , Thorel Fabrizio , Andrey Guillaume
Published: December 2021

Developmental genes are frequently controlled by multiple enhancers sharing similar specificities. As a result, deletions of such regulatory elements have often failed to reveal their full function. Here, we use thePitx1testbed locus to characterize in detail the regulatory and cellular identity alterations following the deletion of one of its enhancers (Pen). By combining single cell transcriptomics and an in-embryo cell tracing approach, we observe an increased fraction ofPitx1non/low-expressing cells and a decreased fraction ofPitx1high-expressing cells. We find that the over-representation ofPitx1non/low-expressing cells originates from a failure of thePitx1locus to coordinate enhancer activities and 3D chromatin changes. This locusmis-activation induces a localized heterochrony and a concurrent loss of irregular connective tissue, eventually leading to a clubfoot phenotype. This data suggests that, in some cases, redundant enhancers may be used to locally enforce a robust activation of their host regulatory landscapes.
Comparison of potential drinking water source contamination across one hundred U.S. cities
Authors: Turner Sean W. D. , Rice Jennie S. , Nelson Kristian D. , Vernon Chris R. , McManamay Ryan , Dickson Kerim , Marston Landon
Published: December 2021

Drinking water supplies of cities are exposed to potential contamination arising from land use and other anthropogenic activities in local and distal source watersheds. Because water quality sampling surveys are often piecemeal, regionally inconsistent, and incomplete with respect to unregulated contaminants, the United States lacks a detailed comparison of potential source water contamination across all of its large cities. Here we combine national-scale geospatial datasets with hydrologic simulations to compute two metrics representing potential contamination of water supplies from point and nonpoint sources for over a hundred U.S. cities. We reveal enormous diversity in anthropogenic activities across watersheds with corresponding disparities in the potential contamination of drinking water supplies to cities. Approximately 5% of large cities rely on water that is composed primarily of runoff from non-pristine lands (e.g., agriculture, residential, industrial), while four-fifths of all large cities that withdraw surface water are exposed to treated wastewater in their supplies.
Existence of a continental-scale river system in eastern Tibet during the late Cretaceous–early Palaeogene
Authors: Zhao Xudong , Zhang Huiping , Hetzel Ralf , Kirby Eric , Duvall Alison R. , Whipple Kelin X. , Xiong Jianguo , Li Yifei , Pang Jianzhang , Wang Ying , Wang Ping , Liu Kang , Ma Pengfei , Zhang Bo , Li Xuemei , Zhang Jiawei , Zhang Peizhen
Published: December 2021

The establishment of continental-scale drainage systems on Earth is largely controlled by topography related to plate boundary deformation and buoyant mantle. Drainage patterns of the great rivers in Asia are thought to be highly dynamic during the Cenozoic collision of India and Eurasia, but the drainage pattern and landscape evolution prior to the development of high topography in eastern Tibet remain largely unknown. Here we report the results of petro-stratigraphy, heavy-mineral analysis, and detrital zircon U-Pb dating from late Cretaceous–early Palaeogene sedimentary basin strata along the present-day eastern margin of the Tibetan Plateau. Similarities in the provenance signatures among basins indicate that a continental-scale fluvial system once drained southward into the Neo-Tethyan Ocean. These results challenge existing models of drainage networks that flowed toward the East Asian marginal seas and require revisions to inference of palaeo-topography during the Late Cretaceous. The presence of a continent-scale river may have provided a stable long-term base level which, in turn, facilitated the development of an extensive low-relief landscape that is preserved atop interfluves above the deeply incised canyons of eastern Tibet.
Cyclin/Forkhead-mediated coordination of cyclin waves: an autonomous oscillator rationalizing the quantitative model of Cdk control for budding yeast
Authors: Barberis Matteo
Published: December 2021

Networks of interacting molecules organize topology, amount, and timing of biological functions. Systems biology concepts required to pin down ‘network motifs’ or ‘design principles’ for time-dependent processes have been developed for the cell division cycle, through integration of predictive computer modeling with quantitative experimentation. A dynamic coordination of sequential waves of cyclin-dependent kinases (cyclin/Cdk) with the transcription factors network offers insights to investigate how incompatible processes are kept separate in time during the eukaryotic cell cycle. Here this coordination is discussed for the Forkhead transcription factors in light of missing gaps in the current knowledge of cell cycle control in budding yeast. An emergent design principle is proposed where cyclin waves are synchronized by a cyclin/Cdk-mediated feed-forward regulation through the Forkhead as a transcriptional timer. This design is rationalized by the bidirectional interaction between mitotic cyclins and the Forkhead transcriptional timer, resulting in an autonomous oscillator that may be instrumental for a well-timed progression throughout the cell cycle. The regulation centered around the cyclin/Cdk–Forkhead axis can be pivotal to timely coordinate cell cycle dynamics, thereby to actuate the quantitative model of Cdk control.
An open-access database and analysis tool for perovskite solar cells based on the FAIR data principles
Authors: Jacobsson T. Jesper , Hultqvist Adam , García-Fernández Alberto , Anand Aman , Al-Ashouri Amran , Hagfeldt Anders , Crovetto Andrea , Abate Antonio , Ricciardulli Antonio Gaetano , Vijayan Anuja , Kulkarni Ashish , Anderson Assaf Y. , Darwich Barbara Primera , Yang Bowen , Coles Brendan L. , Perini Carlo A. R. , Rehermann Carolin , Ramirez Daniel , Fairen-Jimenez David , Di Girolamo Diego , Jia Donglin , Avila Elena , Juarez-Perez Emilio J. , Baumann Fanny , Mathies Florian , González G. S. Anaya , Boschloo Gerrit , Nasti Giuseppe , Paramasivam Gopinath , Martínez-Denegri Guillermo , Näsström Hampus , Michaels Hannes , Köbler Hans , Wu Hua , Benesperi Iacopo , Dar M. Ibrahim , Bayrak Pehlivan Ilknur , Gould Isaac E. , Vagott Jacob N. , Dagar Janardan , Kettle Jeff , Yang Jie , Li Jinzhao , Smith Joel A. , Pascual Jorge , Jerónimo-Rendón Jose J. , Montoya Juan Felipe , Correa-Baena Juan-Pablo , Qiu Junming , Wang Junxin , Sveinbjörnsson Kári , Hirselandt Katrin , Dey Krishanu , Frohna Kyle , Mathies Lena , Castriotta Luigi A. , Aldamasy Mahmoud. H. , Vasquez-Montoya Manuel , Ruiz-Preciado Marco A. , Flatken Marion A. , Khenkin Mark V. , Grischek Max , Kedia Mayank , Saliba Michael , Anaya Miguel , Veldhoen Misha , Arora Neha , Shargaieva Oleksandra , Maus Oliver , Game Onkar S. , Yudilevich Ori , Fassl Paul , Zhou Qisen , Betancur Rafael , Munir Rahim , Patidar Rahul , Stranks Samuel D. , Alam Shahidul , Kar Shaoni , Unold Thomas , Abzieher Tobias , Edvinsson Tomas , David Tudur Wyn , Paetzold Ulrich W. , Zia Waqas , Fu Weifei , Zuo Weiwei , Schröder Vincent R. F. , Tress Wolfgang , Zhang Xiaoliang , Chiang Yu-Hsien , Iqbal Zafar , Xie Zhiqiang , Unger Eva
Published: December 2021

Large datasets are now ubiquitous as technology enables higher-throughput experiments, but rarely can a research field truly benefit from the research data generated due to inconsistent formatting, undocumented storage or improper dissemination. Here we extract all the meaningful device data from peer-reviewed papers on metal-halide perovskite solar cells published so far and make them available in a database. We collect data from over 42,400 photovoltaic devices with up to 100 parameters per device. We then develop open-source and accessible procedures to analyse the data, providing examples of insights that can be gleaned from the analysis of a large dataset. The database, graphics and analysis tools are made available to the community and will continue to evolve as an open-source initiative. This approach of extensively capturing the progress of an entire field, including sorting, interactive exploration and graphical representation of the data, will be applicable to many fields in materials science, engineering and biosciences.
CRISPR/Cas9-mediated base-editing enables a chain reaction through sequential repair of sgRNA scaffold mutations
Authors: Fukushima Tsuyoshi , Tanaka Yosuke , Adachi Keito , Masuyama Nanami , Tsuchiya Akiho , Asada Shuhei , Ishiguro Soh , Mori Hideto , Seki Motoaki , Yachie Nozomu , Goyama Susumu , Kitamura Toshio
Published: December 2021

Cell behavior is controlled by complex gene regulatory networks. Although studies have uncovered diverse roles of individual genes, it has been challenging to record or control sequential genetic events in living cells. In this study, we designed two cellular chain reaction systems that enable sequential sgRNA activation in mammalian cells using a nickase Cas9 tethering of a cytosine nucleotide deaminase (nCas9-CDA). In these systems, thymidine (T)-to-cytosine (C) substitutions in the scaffold region of the sgRNA or the TATA box-containing loxP sequence (TATAloxP) are corrected by the nCas9-CDA, leading to activation of the next sgRNA. These reactions can occur multiple times, resulting in cellular chain reactions. As a proof of concept, we established a chain reaction by repairing sgRNA scaffold mutations in 293 T cells. Importantly, the results obtained in yeast or in vitro did not match those obtained in mammalian cells, suggesting that in vivo chain reactions need to be optimized in appropriate cellular contexts. Our system may lay the foundation for building cellular chain reaction systems that have a broad utility in the future biomedical research.
Nutrient metabolism in the liver and muscle of juvenile blunt snout bream (Megalobrama amblycephala) in response to dietary methionine levels
Authors: Ji Ke , Liang Hualiang , Ren Mingchun , Ge Xianping , Pan Liangkun , Yu Heng
Published: December 2021

A 75-day rearing trial was designed to study the response of juvenile Megalobrama amblycephala to dietary methionine (Met) levels. Three practical diets with graded Met levels (0.40%, 0.84% and 1.28% dry matter) were prepared to feed the juvenile fish. The results showed that the 0.84% Met diet significantly improved the growth compared with 0.40% diets. Compared with 0.84% and 1.28% Met, 0.40% Met significantly increased the hepatic lipid content, while decreasing the muscular lipid and glycogen contents. 0.40% Met decreased the protein levels of phospho-Eukaryotic initiation factor 4E binding protein-1 (p-4e-bp1), 4e-bp1 and Ribosomal protein S6 kinase 1 in the liver, compared with 0.84% diet, while an increasing trend was observed in the muscle. Met supplementation tended to decrease and increase lipid synthesis in the liver and muscle, respectively, via changing mRNA levels of sterol regulatory element-binding protein 1, fatty acid synthetase and acetyl-CoA carboxylase. 1.28% dietary Met promoted fatty acid β-oxidation and lipolysis in both the liver and muscle by increasing carnitine palmitoyl transferase 1, peroxisome proliferator activated receptor alpha, lipoprotein lipase and lipase mRNA levels. Compared with 0.40% and 0.84% dietary Met, 1.28% Met enhanced the mRNA levels of hepatic gluconeogenesis related genes phosphoenolpyruvate carboxykinase (pepck), and glucose-6-phosphatase, and muscular glycolysis related genes phosphofructokinase (pfk), and pyruvate kinase (pk). The mRNA levels of hepatic pfk, pk and glucokinase were markedly downregulated by 1.28% Met compared with 0.84% level. Muscular pepck, glycogen synthase, and hepatic glucose transporters 2 mRNA levels were induced by 1.28% Met. Generally, deficient Met level decreased the growth of juvenile Megalobrama amblycephala, and the different nutrient metabolism responses to dietary Met were revealed in the liver and muscle.
Mixoplankton interferences in dilution grazing experiments
Authors: Duarte Ferreira Guilherme , Romano Filomena , Medić Nikola , Pitta Paraskevi , Hansen Per Juel , Flynn Kevin J. , Mitra Aditee , Calbet Albert
Published: December 2021

It remains unclear as to how mixoplankton (coupled phototrophy and phagotrophy in one cell) affects the estimation of grazing rates obtained from the widely used dilution grazing technique. To address this issue, we prepared laboratory-controlled dilution experiments with known mixtures of phyto-, protozoo-, and mixoplankton, operated under different light regimes and species combinations. Our results evidenced that chlorophyll is an inadequate proxy for phytoplankton when mixoplankton are present. Conversely, species-specific cellular counts could assist (although not fully solve) in the integration of mixoplanktonic activity in a dilution experiment. Moreover, cell counts can expose prey selectivity patterns and intraguild interactions among grazers. Our results also demonstrated that whole community approaches mimic reality better than single-species laboratory experiments. We also confirmed that light is required for protozoo- and mixoplankton to correctly express their feeding activity, and that overall diurnal grazing is higher than nocturnal. Thus, we recommend that a detailed examination of initial and final plankton communities should become routine in dilution experiments, and that incubations should preferably be started at the beginning of both day and night periods. Finally, we hypothesize that in silico approaches may help disentangle the contribution of mixoplankton to the community grazing of a given system.
Transgenic refractory Aedes aegypti lines are resistant to multiple serotypes of dengue virus
Authors: Liu Wei-Liang , Hsu Chia-Wei , Chan Shih-Peng , Yen Pei-Shi , Su Matthew P. , Li Jian-Chiuan , Li Hsing-Han , Cheng Lie , Tang Cheng-Kang , Ko Shih-Hsun , Tsai Huai-Kuang , Tsai Zing Tsung-Yeh , Akbari Omar S. , Failloux Anna-Bella , Chen Chun-Hong
Published: December 2021

The areas where dengue virus (DENV) is endemic have expanded rapidly, driven in part by the global spread ofAedesspecies, which act as disease vectors. DENV replicates in the mosquito midgut and is disseminated to the mosquito’s salivary glands for amplification. Thus, blocking virus infection or replication in the tissues of the mosquito may be a viable strategy for reducing the incidence of DENV transmission to humans. Here we used the marinerMos1 transposase to create anAedes aegyptiline that expresses virus-specific miRNA hairpins capable of blocking DENV replication. These microRNA are driven by the blood-meal-inducible carboxypeptidase A promoter or by the polyubiquitin promoter. The transgenic mosquitoes exhibited significantly lower infection rates and viral titers for most DENV serotypes 7 days after receiving an infectious blood meal. The treatment was also effective at day 14 post infection after a second blood meal had been administered. In viral transmission assay, we found there was significantly reduced transmission in these lines. These transgenic mosquitoes were effective in silencing most of the DENV genome; such an approach may be employed to control a dengue fever epidemic.
Artefactual depiction of predator–prey trophic linkages in global soils
Authors: Wyckhuys Kris A. G. , Nguyen Ha , Fonte Steven J.
Published: December 2021

Soil invertebrates contribute to multiple ecosystem services, including pest control, nutrient cycling, and soil structural regulation, yet trophic interactions that determine their diversity and activity in soils remain critically understudied. Here, we systematically review literature (1966–2020) on feeding habits of soil arthropods and macrofauna and summarize empirically studied predator–prey linkages across ecosystem types, geographies and taxa. Out of 522 unique predators and 372 prey organisms (constituting 1947 predator–prey linkages), the vast majority (> 75%) are only covered in a single study. We report a mean of just 3.0 ± 4.7 documented linkages per organism, with pronounced taxonomic biases. In general, model organisms and crop pests (generally Insecta) are well-studied, while important soil-dwelling predators, fungivores and detritivores (e.g., Collembola, Chilopoda and Malacostraca) remain largely ignored. We argue that broader food-web based research approaches, considering multiple linkages per organism and targeting neglected taxa, are needed to inform science-driven management of soil communities and associated ecosystem services.
A prospective study of the relationships between movement and glycemic control during day and night in pregnancy
Authors: Behravesh Masoud , Fernandez-Tajes Juan , Estampador Angela C. , Varga Tibor V. , Gunnarsson Ómar S. , Strevens Helena , Timpka Simon , Franks Paul W.
Published: December 2021

Both disturbed sleep and lack of exercise can disrupt metabolism in pregnancy. Accelerometery was used to objectively assess movement during waking (physical activity) and movement during sleeping (sleep disturbance) periods and evaluated relationships with continuous blood glucose variation during pregnancy. Data was analysed prospectively. 15-women without pre-existing diabetes mellitus wore continuous glucose monitors and triaxial accelerometers from February through June 2018 in Sweden. The relationships between physical activity and sleep disturbance with blood glucose rate of change were assessed. An interaction term was fitted to determine difference in the relationship between movement and glucose variation, conditional on waking/sleeping. Total movement was inversely related to glucose rate of change (p < 0.001, 95% CI (− 0.037, − 0.026)). Stratified analyses showed total physical activity was inversely related to glucose rate of change (p < 0.001, 95% CI (− 0.040, − 0.028)), whereas sleep disturbance was not related to glucose rate of change (p = 0.07, 95% CI (< − 0.001, 0.013)). The interaction term was positively related to glucose rate of change (p < 0.001, 95% CI (0.029, 0.047)). This study provides temporal evidence of a relationship between total movement and glycemic control in pregnancy, which is conditional on time of day. Movement is beneficially related with glycemic control while awake, but not during sleep.
Fusion of multi-scale bag of deep visual words features of chest X-ray images to detect COVID-19 infection
Authors: Sitaula Chiranjibi , Shahi Tej Bahadur , Aryal Sunil , Marzbanrad Faezeh
Published: December 2021

Chest X-ray (CXR) images have been one of the important diagnosis tools used in the COVID-19 disease diagnosis. Deep learning (DL)-based methods have been used heavily to analyze these images. Compared to other DL-based methods, the bag of deep visual words-based method (BoDVW) proposed recently is shown to be a prominent representation of CXR images for their better discriminability. However, single-scale BoDVW features are insufficient to capture the detailed semantic information of the infected regions in the lungs as the resolution of such images varies in real application. In this paper, we propose a new multi-scale bag of deep visual words (MBoDVW) features, which exploits three different scales of the 4thpooling layer’s output feature map achieved from VGG-16 model. For MBoDVW-based features, we perform the Convolution with Max pooling operation over the 4thpooling layer using three different kernels:$$1 \times 1$$1×1,$$2 \times 2$$2×2, and$$3 \times 3$$3×3. We evaluate our proposed features with the Support Vector Machine (SVM) classification algorithm on four CXR public datasets (CD1, CD2, CD3, and CD4) with over 5000 CXR images. Experimental results show that our method produces stable and prominent classification accuracy (84.37%, 88.88%, 90.29%, and 83.65% on CD1, CD2, CD3, and CD4, respectively).
Impact of different renal function equations on direct oral anticoagulant concentrations
Authors: Lin Shin-Yi , Kuo Ching-Hua , Huang Tao-Min , Peng Yu-Fong , Huang Chih-Fen , Tang Sung-Chun , Jeng Jiann-Shing
Published: December 2021

The purpose of this study is to investigate the correlation between glomerular filtration rate (GFR) estimated by different renal function equations and non-vitamin K antagonist oral anticoagulant concentration. Atrial fibrillation patients who aged ≥ 20 years and used dabigatran, rivaroxaban, or apixaban for thromboembolism prevention were enrolled to collect blood samples and measure drug concentrations using ultra-high-performance liquid chromatography with tandem mass spectrometry. The GFR was estimated using the Cockroft–Gault formula (abbreviated as creatinine clearance, CrCL), Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI) featuring both creatinine and cystatin C, and the Modification of Diet in Renal Disease Study equation (MDRD). Multivariate regression was used to investigate the associations of different renal function estimates with drug concentrations. A total of 511 participants were enrolled, including 146 dabigatran users, 164 rivaroxaban users and 201 apixaban users. Compared to clinical trials, 35.4% of dabigatran, 4.9% of rivaroxaban, and 5.5% of apixaban concentrations were higher than the expected range (p < 0.001). CKD-EPI and MDRD estimates classified fewer patients as having GFR < 50 mL/min than CrCL in all 3 groups. Both CrCL and CKD-EPI were associated with higher-than-expected ranges of dabigatran or rivaroxaban concentrations. Nevertheless, none of the renal function equations was associated with higher-than-expected apixaban concentrations. For participants aged ≥ 75 years, CKD-EPI may be associated with higher-than-expected trough concentration of dabigatran. In conclusion, CrCL and CKD-EPI both can be used to identify patients with high trough concentrations of dabigatran or rivaroxaban. Among elderly patients who used dabigatran, CKD-EPI may be associated with increased drug concentration.
Changes of plasma nitric oxide, endothelin-1, and blood coagulation following intravitreal conbercept
Authors: Yi Quan-Yong , Chen Li-Shuang , Shen Yu , Liao Yan-Hong , Wang Yan-Yan , Yang Jie , Jin Yuanhui , Cheng Lingyun
Published: December 2021

Intravitreal anti-VEGF (anti-vascular endothelial growth factor) biologics have revolutionized the pharmacological management of chorioretinal diseases. However, the systemic adverse events such as stroke or bleeding are the concerns for many patients and physicians. The mechanism to develop these side effects are poorly understood. Consecutive 95 patients with retinal diseases were studied for their blood activated partial thromboplastin time (APTT), prothrombin time (PT), international normalized ratio (INR), and concentration of fibrinogen before and after intravitreal conbercept. Additionally, plasma nitric oxide (NO) and endothelin-1 (ET-1) were investigated on 38 of the 95 patients. Compared with the pre-injection, 4-week post-injection values of APTT and PT were increased by 0.582 s (p = 0.038, paired t test) and by 0.086 s (p = 0.080, paired t test; p = 0.0475, Sign test), respectively. At the same time, fibrinogen decreased by 0.048 g/L. Plasma levels of NO or ET-1 or VEGF did not significantly change from pre-injection levels. Our findings advanced the understanding of mechanism for systemic side effects associated with intravitreal anti-VEGF and emphasized paying more attention to higher risk of possible bleedings for patients following intravitreal conbercept.
Increased resting state connectivity in the anterior default mode network of idiopathic epileptic dogs
Authors: Beckmann Katrin M. , Wang-Leandro Adriano , Richter Henning , Bektas Rima N. , Steffen Frank , Dennler Matthias , Carrera Ines , Haller Sven
Published: December 2021

Epilepsy is one of the most common chronic, neurological diseases in humans and dogs and considered to be a network disease. In human epilepsy altered functional connectivity in different large-scale networks have been identified with functional resting state magnetic resonance imaging. Since large-scale resting state networks have been consistently identified in anesthetised dogs’ application of this technique became promising in canine epilepsy research. The aim of the present study was to investigate differences in large-scale resting state networks in epileptic dogs compared to healthy controls. Our hypothesis was, that large-scale networks differ between epileptic dogs and healthy control dogs. A group of 17 dogs (Border Collies and Greater Swiss Mountain Dogs) with idiopathic epilepsy was compared to 20 healthy control dogs under a standardized sevoflurane anaesthesia protocol. Group level independent component analysis with dimensionality of 20 components, dual regression and two-sample t test were performed and revealed significantly increased functional connectivity in the anterior default mode network of idiopathic epileptic dogs compared to healthy control dogs (p = 0.00060). This group level differences between epileptic dogs and healthy control dogs identified using a rather simple data driven approach could serve as a starting point for more advanced resting state network analysis in epileptic dogs.
Recent trends in global insecticide use for disease vector control and potential implications for resistance management
Authors: van den Berg Henk , da Silva Bezerra Haroldo Sergio , Al-Eryani Samira , Chanda Emmanuel , Nagpal Bhupender N. , Knox Tessa B. , Velayudhan Raman , Yadav Rajpal S.
Published: December 2021

Insecticides have played a major role in the prevention, control, and elimination of vector-borne diseases, but insecticide resistance threatens the efficacy of available vector control tools. A global survey was conducted to investigate vector control insecticide use from 2010 to 2019. Out of 140 countries selected as sample for the study, 87 countries responded. Also, data on ex-factory deliveries of insecticide-treated nets (ITNs) were analyzed. Insecticide operational use was highest for control of malaria, followed by dengue, leishmaniasis and Chagas disease. Vector control relied on few insecticide classes with pyrethroids the most used overall. Results indicated that IRS programs have been slow to react to detection of pyrethroid resistance, while proactive resistance management using insecticides with unrelated modes of action was generally weak. The intensive use of recently introduced insecticide products raised concern about product stewardship regarding the preservation of insecticide susceptibility in vector populations. Resistance management was weakest for control of dengue, leishmaniasis or Chagas disease. Therefore, it will be vital that vector control programs coordinate on insecticide procurement, planning, implementation, resistance monitoring, and capacity building. Moreover, increased consideration should be given to alternative vector control tools that prevent the development of insecticide resistance.
Protein embeddings and deep learning predict binding residues for various ligand classes
Authors: Littmann Maria , Heinzinger Michael , Dallago Christian , Weissenow Konstantin , Rost Burkhard
Published: December 2021

One important aspect of protein function is the binding of proteins to ligands, including small molecules, metal ions, and macromolecules such as DNA or RNA. Despite decades of experimental progress many binding sites remain obscure. Here, we proposed bindEmbed21, a method predicting whether a protein residue binds to metal ions, nucleic acids, or small molecules. The Artificial Intelligence (AI)-based method exclusively uses embeddings from the Transformer-based protein Language Model (pLM) ProtT5 as input. Using only single sequences without creating multiple sequence alignments (MSAs), bindEmbed21DL outperformed MSA-based predictions. Combination with homology-based inference increased performance to F1 = 48 ± 3% (95% CI) and MCC = 0.46 ± 0.04 when merging all three ligand classes into one. All results were confirmed by three independent data sets. Focusing on very reliably predicted residues could complement experimental evidence: For the 25% most strongly predicted binding residues, at least 73% were correctly predicted even when ignoring the problem of missing experimental annotations. The new method bindEmbed21 is fast, simple, and broadly applicable—neither using structure nor MSAs. Thereby, it found binding residues in over 42% of all human proteins not otherwise implied in binding and predicted about 6% of all residues as binding to metal ions, nucleic acids, or small molecules.