bluuebunny/crossref_metadata_2025 huggingface dataset:
Justice Speaks: Nemesis, Nature, and Common Law in Aristotle's Rhetoric
Authors: Basil Christine J.
Published: February 2021

This essay explores Aristotle's treatment of the passion of nemesis or “righteous indignation” in his Rhetoric and its relevance to contemporary displays of passion in democratic political orders. It does so by considering Aristotle's perplexing definition of nemesis in relation to two other passions, pity and envy, as well as its significance to his discussion of common law (a transpolitical standard of justice according to nature), which he presents through allusions to Sophocles's Antigone. Aristotle's discussion sheds light on the way in which nemesis, which is aroused in relation to the concern for justice, necessarily takes into consideration questions of moral worth that liberal democratic regimes attempt to relegate to the private sphere.
Counting curves on Hirzebruch surfaces: tropical geometry and the Fock space
Authors: CAVALIERI RENZO , JOHNSON PAUL , MARKWIG HANNAH , RANGANATHAN DHRUV
Published: February 2021

We study the stationary descendant Gromov–Witten theory of toric surfaces by combining and extending a range of techniques – tropical curves, floor diagrams and Fock spaces. A correspondence theorem is established between tropical curves and descendant invariants on toric surfaces using maximal toric degenerations. An intermediate degeneration is then shown to give rise to floor diagrams, giving a geometric interpretation of this well-known bookkeeping tool in tropical geometry. In the process, we extend floor diagram techniques to include descendants in arbitrary genus. These floor diagrams are then used to connect tropical curve counting to the algebra of operators on the bosonic Fock space, and are showno coincide with the Feynman diagrams of appropriate operators. This extends work of a number of researchers, including Block–Göttsche, Cooper–Pandharipande and Block–Gathmann–Markwig.
Homotopic distance between maps
Authors: MACÍAS–VIRGÓS E. , MOSQUERA–LOIS D.
Published: February 2021

We show that well-known invariants like Lusternik–Schnirelmann category and topological complexity are particular cases of a more general notion, that we call homotopic distance between two maps. As a consequence, several properties of those invariants can be proved in a unified way and new results arise.
Integrating region memory management and tag-free generational garbage collection
Authors: ELSMAN MARTIN , HALLENBERG NIELS
Published: February 2021

We present a region-based memory management scheme with support for generational garbage collection. The scheme features a compile-time region inference algorithm, which associates values with logical regions, and builds on a region type system that deploys region types at runtime to avoid the overhead of write barriers and to support partly tag-free garbage collection. The scheme is implemented in the MLKit Standard ML compiler, which generates native x64 machine code. Besides demonstrating a number of important formal properties of the scheme, we measure the scheme’s characteristics, for a number of benchmarks, and compare the performance of the generated executables with the performance of executables generated with the MLton state-of-the-art Standard ML compiler and configurations of the MLKit with and without region inference and generational garbage collection enabled. Although region inference often serves the purpose of generations, combining region inference with generational garbage collection is shown often to be superior to combining region inference with non-generational collection despite the overhead introduced by a larger amount of memory waste, due to region fragmentation.
Assessment of regional and global right ventricular systolic function in children with repaired tetralogy of Fallot
Authors: Caris Elizabeth , Drant Stacey
Published: February 2021

Background:

Echo assessment of right ventricular function is difficult due to its complex geometry and regional differences in wall motion. In patients with repaired tetralogy of Fallot, cardiac MRI is the gold standard for assessment of right ventricular function. There is scant data regarding the correlation of echo measures of right ventricular function with cardiac MRI right ventricular function in the paediatric population.

Methods:

Echocardiographic measures of regional and global right ventricular function were reviewed in 56 patients with repaired tetralogy of Fallot and 27 patients with structurally normal hearts. These measures were compared to global right ventricular ejection fraction by cardiac MRI.

Results:

Despite having the same right ventricular ejection fraction by cardiac MRI as normal controls, patients with repaired tetralogy of Fallot had significantly worse global and regional echocardiographic measures of right ventricular function. Right ventricular fractional area change and fractional shortening of the right ventricular outflow tract correlated best with global right ventricular function by MRI. Incorporation of these measures into a regression model allowed accurate prediction of global right ventricular function by cardiac MRI.

Conclusion:

Children with repaired tetralogy of Fallot have abnormal regional and global right ventricular function compared to patients with normal hearts. Despite the presence of patch material, the right ventricular outflow tract significantly contributes to global right ventricular function by cardiac MRI. When incorporated into a model that includes regional and global echocardiographic measures of right ventricular function, right ventricular outflow tract fractional shortening helps predict global right ventricular function by MRI.
Significance of herbicide order in sequential applications to target weeds in a sunn hemp living mulch
Authors: Bhaskar Vinay , Bellinder Robin R. , Reiners Stephen , Westbrook Anna S. , DiTommaso Antonio
Published: February 2021

Striking a balance between the weed control capacity of living mulches and their competition with the main crop is complex. At rates that avoid severe injury to living mulch, herbicides may reduce their vigor while simultaneously contributing to weed control. In a 2-yr field study carried out in Freeville, NY, we evaluated the effects of various combinations consisting of two herbicides, applied sequentially at reduced rates, on the growth of a sunn hemp living mulch and weeds (including common lambsquarters, common purslane, hairy galinsoga, and Powell amaranth). When a herbicide with primarily POST activity (Type 1; e.g., rimsulfuron, 0.005 to 0.007 kg ai ha−1) was applied first, performance of sunn hemp (1700 to 3900 kg ha−1 dry biomass; 10% to 88% groundcover) was poor and weed growth (25% to 62% groundcover) was high, likely because sunn hemp was severely injured at a young growth stage and was outcompeted by weeds. A follow-up application (approximately 2 wk later) of a herbicide with primarily PRE and residual activities (Type 2; e.g., metribuzin, 0.05 to 0.15 kg ai ha−1), with a surfactant to enhance its POST activity, had little effect on established weeds. However, because sunn hemp was already 20 cm tall at weed emergence, applying a Type 2 herbicide first did not cause severe injury to sunn hemp and reduced weed pressure, thereby also enhancing sunn hemp performance (3,800 to 6,100 kg ha−1 dry biomass; 85% to 94% groundcover). Moreover, the follow-up application of a Type 1 herbicide affected the smaller weeds more (4% to 21% groundcover) than the better-established sunn hemp. Our results demonstrate that an appropriate sequence of herbicides at reduced rates may be important to control weeds while maintaining a healthy living mulch stand.
Reiseimpfungen
Authors: Güdel Daniela S. , Berger Christoph T.
Published: February 2021

Zusammenfassung. Gesundheitsprobleme wie Infektionskrankheiten, Unfälle und kardiovaskuläre Ereignisse sind auf Reisen häufig. Die Prävention von Infektionskrankheiten beruht auf der Risikoreduktion, medikamentöser Prophylaxe und Impfungen. Neben Tipps und Tricks für die allgemeine Reiseberatung in der ambulanten Medizin fokussiert dieser Artikel auf Reiseimpfungen. Systematisch werden die durch Impfung vermeidbaren Krankheiten auf Reisen erläutert inklusive spezifischer Risikobewertung für Kinder, allgemeiner Impfindikation, konkretem Vorgehen und Besonderheiten einzelner Impfungen oder Impfschemata. In regulären hausärztlichen Sprechstundenterminen kommt die Überprüfung des Impfstatus bei Erwachsenen oftmals zu kurz. Die Reiseberatung stellt auch ein ideales und wichtiges Gefäss zur Überprüfung und Vervollständigung der empfohlenen Grundimmunisierungen und Auffrischimpfungen dar. Während bei Reiseimpfungen der Selbstschutz im Vordergrund steht, zählen bei den Basisimpfungen auch altruistische Aspekte wie Herdenimmunität. Impfambivalenz oder Impfskepsis können dabei das Beratungsgespräch erschweren. Eine Reiseimpfberatung kann Anlass geben, allgemeine Ambivalenzen gegenüber Impfungen zu klären. Basierend auf dem Kommunikationskonzept des «Motivational Interviewing» zeigen wir kommunikative Möglichkeiten auf, um in solchen Situationen Ambivalenz und Widerstände zu reduzieren und im Idealfall die Impfbereitschaft durch eine gemeinsame Entscheidungsfindung zu fördern.
Gynäologische Vorsorge
Authors: Ghisu Gian Piero
Published: February 2021

Zusammenfassung. Das Screening zur Zervixkarzinomvorsorge gilt als Erfolgsgeschichte. Seit der Einführung des Pap-Tests in den 1950er-Jahren kam es in der industrialisierten Welt zu einer drastischen Abnahme der Inzidenz und Mortalität der Zervixkarzinome. In Entwicklungsländern und speziell in bestimmten Ländern Afrikas zählt das Zervixkarzinom aufgrund der fehlenden Screening- und Therapiemöglichkeiten nach wie vor zu den häufigsten tödlich verlaufenden Krebserkrankungen. Jahrzehntelang bildeten Pap-Test und Kolposkopie das Fundament der Zervixkarzinomvorsorge. In den frühen 1980er-Jahren wurde bekannt, dass die Zervixkarzinome fast ausnahmslos eine Infektion mit bestimmten humanen Papillomaviren (HPV) voraussetzen. Diese Erkenntnis revolutionierte unter anderem auch das Zervixkarzinomscreening. Die Qualität des Pap-Tests wird durch die Entnahmebedingungen und durch die sog. Interobservervariabilität beeinflusst. Die Zytologie weist insgesamt eine gute Spezifität von 95 % bei einer allerdings schlechteren Sensitivität von 70 % auf. Immunhistochemische Zusatzuntersuchungen mit Bestimmung der Biomarker p16 und Ki-67 können die Sensitivität des Pap-Tests auf 94 % erhöhen (analog HPV-Test), weshalb zytologische Untersuchungen in Ländern mit genügenden Ressourcen und Fachkenntnissen nach wie vor als sehr zuverlässig gelten. Der HPV-Test ist im Gegensatz dazu nicht subjektiv geprägt und weist eine hohe Sensitivität von 94 % auf. Die Spezifität ist allerdings schlechter als beim Pap-Test, weshalb bei einem HPV-basierten Screening ein erhöhtes Risiko unnötiger Abklärungen und Therapien besteht. Die Überlegenheit des HPV- gegenüber dem zytologischen Screening scheint unter definierten Studienbedingungen, allerdings erst nach der zweiten oder dritten Screeningrunde, erwiesen. Erfolgt das Screening wie in der Schweiz opportunistisch, besteht das Risiko des sog. lost follow up. Genau das Nichtwahrnehmen oder unregelmässige Beanspruchen von Screeninguntersuchungen gilt als bedeutendster Risikofaktor für die Entstehung eines Zervixkarzinoms. Auch ist zu bedenken, dass der HPV-Test einzig die aktuelle Viruslast wiedergibt, aber keine Aussage zu Zeitpunkt und Dauer der HPV-Infektion erlaubt. Zur Bestimmung der Langzeitresultate und der Kosteneffektivität sind weitere Studien notwendig.
Sturzprävention bei alten Personen, was hilft?
Authors: Mujanovic Amir , Münzer Thomas
Published: February 2021

Zusammenfassung. Ein erhöhtes Sturzrisiko zu erkennen und entsprechende Massnahmen einzuleiten ist eine wichtige Aufgabe der Grundversorgung. Durch eine gezielte Anamnese und einfache Screening-Untersuchungen lassen sich Personen mit einem erhöhten Risiko rasch identifizieren. Solche Personen profitieren vom systematischen Management reversibler Risikofaktoren von Trainingsprogrammen und nicht zuletzt von der Kombination aus Vitamin D und Kalzium.
Prävention von Fehl- und Überversorgung
Authors: Neuner-Jehle Stefan
Published: February 2021

Zusammenfassung. Fehl- und Überversorgung wird pragmatisch als eine Versorgung definiert, deren potenzieller Schaden den Nutzen überwiegt (Fehlversorgung), oder die über den nötigen Bedarf hinausgeht (Überversorgung). Sie ist eine Herausforderung für Patienten, Betreuer, Politiker und Gesundheitssysteme. Auch in der Schweiz gibt es Fehl- und Überversorgung, wie die nähere Betrachtung von diversen diagnostischen Methoden und therapeutischen Eingriffen zeigt. Die Auslöser von Fehl- und Überversorgung sind vielfältig: Zum Beispiel ermöglicht der technische Fortschritt eine immer frühere Entdeckung von Krankheit, ohne dass dies immer einen Nutzen für den Patienten bedeutet (Überdiagnose). Weitere Gründe sind organisatorische Defizite, angebotsgesteuerte Nachfrage, kommerziell motivierte Erweiterung des Krankheitsbegriffes (disease mongering) und der Einfluss von soziokulturellen Überzeugungen. Entsprechend ist es keine einfache Aufgabe, Fehl- und Überversorgung zu bekämpfen. Als Antwort sind in den letzten Jahren diverse Konzepte und Kampagnen entwickelt worden, wie Quartäre Prävention, Choosing Wisely oder Preventing Overdiagnosis. Deren Ziel ist es, Individuen vor medizinischen Interventionen zu schützen, die mit hoher Wahrscheinlichkeit mehr Schaden als Nutzen anrichten. Was kann die Hausärztin, der Hausarzt zur Prävention von Fehl- und Überversorgung beitragen? Erstens, das Bewusstsein für solche unangemessenen Interventionen zu schärfen und offen dafür zu sein, die eigene professionelle Einstellung kritisch zu hinterfragen. Zweitens hat die Hausärztin, der Hausarzt als Vertrauensperson für den Patienten die einzigartige Gelegenheit, mit ihr / ihm Schaden und Nutzen einer Intervention abzuwägen und in einer partizipativen Art zu diskutieren (Shared Decision Making). Dabei können Techniken wie Team Talk, Option Talk und Decision Talk gewinnbringend zum Einsatz kommen. Zusammenfassend ist der Schutz unserer Patienten vor Fehlversorgung, Überversorgung und Schaden ein wichtiger Teil unserer professionellen Performance.
On the Ion Precipitation due to Field Line Curvature (FLC) and EMIC Wave Scattering and Their Subsequent Impact on Ionospheric Electrodynamics
Authors: Zhu Minghui , Yu Yiqun , Tian Xingbin , Shreedevi P. R. , Jordanova Vania K.
Published: February 2021

Both field line curvature (FLC) and electromagnetic ion cyclotron (EMIC) wave scattering are believed to be associated with energetic ion precipitation, but their relative contributions to ionospheric ion precipitation and subsequent effects are still unclear. In this study, by using a kinetic ring current model, we investigate their impact on the ionosphere from two aspects: the global distribution of ion precipitation and resulting ionospheric conductance. Our results show that the intensity and coverage of ion precipitation due to EMIC waves are larger than that due to FLC scattering, while the latter mostly contributes to ion precipitation in outer regions (L > 4–5). We then estimate the conductance with empirical models using the simulated ion precipitation energy flux. When the EMIC wave associated proton precipitation is included, the conductance is significantly enhanced in the dusk‐to‐midnight sector and has a wide magnetic latitude (MLAT) range from around 52° to 62°, considerably altering the electric potential in the dusk sector, which further influences particle dynamics in the magnetosphere. On the contrary, the proton precipitation caused by FLC scattering only occurs at higher latitudes above MLAT = 60° and the corresponding conductance is slightly enhanced at midnight, with negligible influence on the convective electric potential. Although electron precipitation‐associated conductance is predominant globally, the results show that proton precipitation can also play an important role in ionospheric electrodynamics, especially when EMIC wave‐associated precipitating proton energy flux exceeds that of electrons in the dusk sector, a region where many subauroral coupling processes occur.
Dispersion of Buoyant and Sinking Particles in a Simulated Wind‐ and Wave‐Driven Turbulent Coastal Ocean
Authors: Thoman Todd X. , Kukulka Tobias , Gamble Kathleen
Published: February 2021

In shallow coastal oceans, turbulent flows driven by surface winds and waves and constrained by a solid bottom disperse particles. This work examines the mechanisms driving horizontal and vertical dispersion of buoyant and sinking particles for times much greater than turbulent integral time scales. Turbulent fields are modeled using a wind‐stress driven large eddy simulation (LES), incorporating wave‐driven Langmuir turbulence, surface breaking wave turbulent kinetic energy inputs, and a solid bottom boundary. A Lagrangian stochastic model is paired to the LES to incorporate Lagrangian particle tracking. Within a subset of intermediate buoyant rise velocities, particles experience synergistic vertical mixing in which breaking waves (BW) inject particles into Langmuir downwelling velocities sufficient to drive deep mixing. Along‐wind dispersion is controlled by vertical shear in mean along‐wind velocities. Wind and bottom friction‐driven vertical shear enhances dispersion of buoyant and sinking particles, while energetic turbulent mixing, such as from BW, dampens shear dispersion. Strongly rising and sinking particles trapped at the ocean surface and bottom, respectively, experience no vertical shear, resulting in low rates of along‐wind dispersion. Crosswind dispersion is shaped by particle advection in wind‐aligned fields of counter‐rotating Langmuir and Couette roll cells. Langmuir cells enhance crosswind dispersion in neutrally to intermediately buoyant particles through enhanced cell hopping. Surface trapping restricts particles to Langmuir convergence regions, strongly inhibiting crosswind dispersion. In shallow coastal systems, particle dispersion depends heavily on particle buoyancy and wave‐dependent turbulent effects.
Observations of the Impacts of Millimeter‐ to Centimeter‐Scale Heterogeneities on Relative Permeability and Trapping in Carbonate Rocks
Authors: Manoorkar Sojwal , Jackson Samuel J. , Krevor Samuel
Published: February 2021

Carbonate rock reservoirs are dominated by heterogeneity across a large and continuous range of spatial scales. We study the impact of heterogeneities on relative permeability and residual trapping for three carbonate rocks selected for their distinct spatial scales of rock texture. The Indiana limestone comprises millimeter‐scale heterogeneities, the Estaillades limestone consists of half‐centimeter‐scale heterogeneities, and the Edwards dolomite includes decimeter‐scale heterogeneity. Along with routine characterization of rock samples, steady‐state N2–deionized water drainage relative permeability measurements are made for each rock at two distinct total flow rates, at least 1 order of magnitude apart. The variation in flow potential across the core results in observations of fluid distribution, core‐average relative permeability, and residual trapping obtained for a range of continuum‐scale capillary number . The relative permeability curves for all rocks shift to the right of the water saturation axis with increasing flow potential; the nitrogen relative permeability increases while the water relative permeability decreases. However, the magnitude of the shift depends on the spatial scale of heterogeneity. An inspection of 3D saturation distributions in the cores and estimation of the capillary numbers of flow shows that the rock with the largest heterogeneity is capillary flow dominated throughout the range of injection rates tested; observations in the Indiana and Estaillades carbonates traverse capillary to viscous dominated flow regimes, with commensurate flow rate dependence in the relative permeability. In all cases, residual trapping is poorly described by the Land model.
Exciton diffusion exceeding 1 µm: run, exciton, run!
Authors: Dursun Ibrahim , Guzelturk Burak
Published: February 2021

Exciton diffusion lengths reaching the micrometer length scale have long been desired in solution-processed semiconductors but have remained unattainable using conventional materials to date. Now halide perovskite nanocrystal films show unprecedented exciton migration with diffusion lengths approaching 1 µm owing to the efficient combination of radiative and nonradiative energy transfer.
Addiction as a brain disease revised: why it still matters, and the need for consilience
Authors: Heilig Markus , MacKillop James , Martinez Diana , Rehm Jürgen , Leggio Lorenzo , Vanderschuren Louk J. M. J.
Published: February 2021

The view that substance addiction is a brain disease, although widely accepted in the neuroscience community, has become subject to acerbic criticism in recent years. These criticisms state that the brain disease view is deterministic, fails to account for heterogeneity in remission and recovery, places too much emphasis on a compulsive dimension of addiction, and that a specific neural signature of addiction has not been identified. We acknowledge that some of these criticisms have merit, but assert that the foundational premise that addiction has a neurobiological basis is fundamentally sound. We also emphasize that denying that addiction is a brain disease is a harmful standpoint since it contributes to reducing access to healthcare and treatment, the consequences of which are catastrophic. Here, we therefore address these criticisms, and in doing so provide a contemporary update of the brain disease view of addiction. We provide arguments to support this view, discuss why apparently spontaneous remission does not negate it, and how seemingly compulsive behaviors can co-exist with the sensitivity to alternative reinforcement in addiction. Most importantly, we argue that the brain is the biological substrate from which both addiction and the capacity for behavior change arise, arguing for an intensified neuroscientific study of recovery. More broadly, we propose that these disagreements reveal the need for multidisciplinary research that integrates neuroscientific, behavioral, clinical, and sociocultural perspectives.
Reconfigurable all-dielectric metalens with diffraction-limited performance
Authors: Shalaginov Mikhail Y. , An Sensong , Zhang Yifei , Yang Fan , Su Peter , Liberman Vladimir , Chou Jeffrey B. , Roberts Christopher M. , Kang Myungkoo , Rios Carlos , Du Qingyang , Fowler Clayton , Agarwal Anuradha , Richardson Kathleen A. , Rivero-Baleine Clara , Zhang Hualiang , Hu Juejun , Gu Tian
Published: February 2021

Active metasurfaces, whose optical properties can be modulated post-fabrication, have emerged as an intensively explored field in recent years. The efforts to date, however, still face major performance limitations in tuning range, optical quality, and efficiency, especially for non-mechanical actuation mechanisms. In this paper, we introduce an active metasurface platform combining phase tuning in the full 2π range and diffraction-limited performance using an all-dielectric, low-loss architecture based on optical phase change materials (O-PCMs). We present a generic design principle enabling binary switching of metasurfaces between arbitrary phase profiles and propose a new figure-of-merit (FOM) tailored for reconfigurable meta-optics. We implement the approach to realize a high-performance varifocal metalens operating at 5.2 μm wavelength. The reconfigurable metalens features a record large switching contrast ratio of 29.5 dB. We further validate aberration-free and multi-depth imaging using the metalens, which represents a key experimental demonstration of a non-mechanical tunable metalens with diffraction-limited performance.
Network models of primary melanoma microenvironments identify key melanoma regulators underlying prognosis
Authors: Song Won-Min , Agrawal Praveen , Von Itter Richard , Fontanals-Cirera Barbara , Wang Minghui , Zhou Xianxiao , Mahal Lara K. , Hernando Eva , Zhang Bin
Published: February 2021

Melanoma is the most lethal skin malignancy, driven by genetic and epigenetic alterations in the complex tumour microenvironment. While large-scale molecular profiling of melanoma has identified molecular signatures associated with melanoma progression, comprehensive systems-level modeling remains elusive. This study builds up predictive gene network models of molecular alterations in primary melanoma by integrating large-scale bulk-based multi-omic and single-cell transcriptomic data. Incorporating clinical, epigenetic, and proteomic data into these networks reveals key subnetworks, cell types, and regulators underlying melanoma progression. Tumors with high immune infiltrates are found to be associated with good prognosis, presumably due to induced CD8+ T-cell cytotoxicity, via MYO1F-mediated M1-polarization of macrophages. Seventeen key drivers of the gene subnetworks associated with poor prognosis, including the transcription factor ZNF180, are tested for their pro-tumorigenic effects in vitro. The anti-tumor effect of silencing ZNF180 is further validated using in vivo xenografts. Experimentally validated targets of ZNF180 are enriched in the ZNF180 centered network and the known pathways such as melanoma cell maintenance and immune cell infiltration. The transcriptional networks and their critical regulators provide insights into the molecular mechanisms of melanomagenesis and pave the way for developing therapeutic strategies for melanoma.
Author Correction: Simulating the ghost: quantum dynamics of the solvated electron
Authors: Lan Jinggang , Kapil Venkat , Gasparotto Piero , Ceriotti Michele , Iannuzzi Marcella , Rybkin Vladimir V.
Published: February 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21706-2
Genome sequences of Tropheus moorii and Petrochromis trewavasae, two eco-morphologically divergent cichlid fishes endemic to Lake Tanganyika
Authors: Fischer C. , Koblmüller S. , Börger C. , Michelitsch G. , Trajanoski S. , Schlötterer C. , Guelly C. , Thallinger G. G. , Sturmbauer C.
Published: February 2021

With more than 1000 species, East African cichlid fishes represent the fastest and most species-rich vertebrate radiation known, providing an ideal model to tackle molecular mechanisms underlying recurrent adaptive diversification. We add high-quality genome reconstructions for two phylogenetic key species of a lineage that diverged about ~ 3–9 million years ago (mya), representing the earliest split of the so-called modern haplochromines that seeded additional radiations such as those in Lake Malawi and Victoria. Along with the annotated genomes we analysed discriminating genomic features of the study species, each representing an extreme trophic morphology, one being an algae browser and the other an algae grazer. The genomes ofTropheus moorii(TM) andPetrochromis trewavasae(PT) comprise 911 and 918 Mbp with 40,300 and 39,600 predicted genes, respectively. Our DNA sequence data are based on 5 and 6 individuals of TM and PT, and the transcriptomic sequences of one individual per species and sex, respectively. Concerning variation, on average we observed 1 variant per 220 bp (interspecific), and 1 variant per 2540 bp (PT vs PT)/1561 bp (TM vs TM) (intraspecific). GO enrichment analysis of gene regions affected by variants revealed several candidates which may influence phenotype modifications related to facial and jaw morphology, such as genes belonging to the Hedgehog pathway (SHH,SMO,WNT9A) and the BMP and GLI families.
Single-cell RNA sequencing reveals developmental heterogeneity among Plasmodium berghei sporozoites
Authors: Ruberto Anthony A. , Bourke Caitlin , Merienne Nicolas , Obadia Thomas , Amino Rogerio , Mueller Ivo
Published: February 2021

In the malaria-causing parasite’s life cycle, Plasmodium sporozoites must travel from the midgut of a mosquito to the salivary glands before they can infect a mammalian host. However, only a fraction of sporozoites complete the journey. Since salivary gland invasion is required for transmission of sporozoites, insights at the molecular level can contribute to strategies for malaria prevention. Recent advances in single-cell RNA sequencing provide an opportunity to assess sporozoite heterogeneity at a resolution unattainable by bulk RNA sequencing methods. In this study, we use a droplet-based single-cell RNA sequencing workflow to analyze the transcriptomes of over 8000 Plasmodium berghei sporozoites derived from the midguts and salivary glands of Anopheles stephensi mosquitoes. The detection of known marker genes confirms the successful capture and sequencing of samples composed of a mixed population of sporozoites. Using data integration, clustering, and trajectory analyses, we reveal differences in gene expression profiles of individual sporozoites, and identify both annotated and unannotated markers associated with sporozoite development. Our work highlights the utility of a high-throughput workflow for the transcriptomic profiling of Plasmodium sporozoites, and provides new insights into gene usage during the parasite’s development in the mosquito.
Spatial distribution of physiologic 12-lead QRS complex
Authors: Hnatkova Katerina , Andršová Irena , Toman Ondřej , Smetana Peter , Huster Katharina M. , Šišáková Martina , Barthel Petra , Novotný Tomáš , Schmidt Georg , Malik Marek
Published: February 2021

The normal physiologic range of QRS complex duration spans between 80 and 125 ms with known differences between females and males which cannot be explained by the anatomical variations of heart sizes. To investigate the reasons for the sex differences as well as for the wide range of normal values, a technology is proposed based on the singular value decomposition and on the separation of different orthogonal components of the QRS complex. This allows classification of the proportions of different components representing the 3-dimensional representation of the electrocardiographic signal as well as classification of components that go beyond the 3-dimensional representation and that correspond to the degree of intricate convolutions of the depolarisation sequence. The technology was applied to 382,019 individual 10-s ECG samples recorded in 639 healthy subjects (311 females and 328 males) aged 33.8 ± 9.4 years. The analyses showed that QRS duration was mainly influenced by the proportions of the first two orthogonal components of the QRS complex. The first component demonstrated statistically significantly larger proportion of the total QRS power (expressed by the absolute area of the complex in all independent ECG leads) in females than in males (64.2 ± 11.6% vs 59.7 ± 11.9%, p < 0.00001—measured at resting heart rate of 60 beats per minute) while the second component demonstrated larger proportion of the QRS power in males compared to females (33.1 ± 11.9% vs 29.6 ± 11.4%, p < 0.001). The analysis also showed that the components attributable to localised depolarisation sequence abnormalities were significantly larger in males compared to females (2.85 ± 1.08% vs 2.42 ± 0.87%, p < 0.00001). In addition to the demonstration of the technology, the study concludes that the detailed convolution of the depolarisation waveform is individual, and that smoother and less intricate depolarisation propagation is the mechanism likely responsible for shorter QRS duration in females.
Complex biology of constitutional ring chromosomes structure and (in)stability revealed by somatic cell reprogramming
Authors: Nikitina T. V. , Kashevarova A. A. , Gridina M. M. , Lopatkina M. E. , Khabarova A. A. , Yakovleva Yu. S. , Menzorov A. G. , Minina Yu. A. , Pristyazhnyuk I. E. , Vasilyev S. A. , Fedotov D. A. , Serov O. L. , Lebedev I. N.
Published: February 2021

Human ring chromosomes are often unstable during mitosis, and daughter cells can be partially or completely aneuploid. We studied the mitotic stability of four ring chromosomes, 8, 13, 18, and 22, in long-term cultures of skin fibroblasts and induced pluripotent stem cells (iPSCs) by GTG karyotyping and aCGH. Ring chromosome loss and secondary aberrations were observed in all fibroblast cultures except for r(18). We found monosomy, fragmentation, and translocation of indexed chromosomes. In iPSCs, aCGH revealed striking differences in mitotic stability both between iPSC lines with different rings and, in some cases, between cell lines with the same ring chromosome. We registered the spontaneous rescue of karyotype 46,XY,r(8) to 46,XY in all six iPSC lines through ring chromosome loss and intact homologue duplication with isoUPD(8)pat occurrence, as proven by SNP genotype distribution analysis. In iPSCs with other ring chromosomes, karyotype correction was not observed. Our results suggest that spontaneous correction of the karyotype with ring chromosomes in iPSCs is not universal and that pluripotency is compatible with a wide range of derivative karyotypes. We conclude that marked variability in the frequency of secondary rearrangements exists in both fibroblast and iPSC cultures, expanding the clinical significance of the constitutional ring chromosome.
A comparative analysis of SLA-DRB1 genetic diversity in Colombian (creoles and commercial line) and worldwide swine populations
Authors: Celis-Giraldo Carmen Teresa , Bohórquez Michel David , Camargo Milena , Suárez Carlos Fernando , Camargo Anny , Rodríguez-Obediente Kewin , Martínez Alejandra , Lucero Carlos Edmundo , Hernández Byron , Manzano-Román Raúl , Patarroyo Manuel Alfonso
Published: February 2021

Analysing pig class II mayor histocompatibility complex (MHC) molecules is mainly related to antigen presentation. Identifying frequently-occurring alleles in pig populations is an important aspect to be considered when developing peptide-based vaccines. Colombian creole pig populations have had to adapt to local conditions since entering Colombia; a recent census has shown low amounts of pigs which is why they are considered protected by the Colombian government. Commercial hybrids are more attractive regarding production. This research has been aimed at describing the allele distribution of Colombian pigs from diverse genetic backgrounds and comparing ColombianSLA-DRB1locus diversity to that of internationally reported populations. TwentySLA-DRB1alleles were identified in the six populations analysed here using sequence-based typing. The amount of alleles ranged from six (Manta and Casco Mula) to nine (San Pedreño). Only one allele (01:02) having > 5% frequency was shared by all three commercial line populations. Allele 02:01:01 was shared by five populations (around > 5% frequency). Global FSTindicated that pig populations were clearly structured, as 20.6% of total allele frequency variation was explained by differences between populations (FST = 0.206). This study’s results confirmed that the greatest diversity occurred in wild boars, thereby contrasting with low diversity in domestic pig populations.
Mild catalytic defects of tert rs61748181 polymorphism affect the clinical presentation of chronic obstructive pulmonary disease
Authors: Xu Jialin , de Oliveira Diego Madureira , Trudeau Matthew A. , Yang Yang , Chin Jessica J. Y. , Sin Don D. , Sandford Andrew J. , Wong Judy M. Y.
Published: February 2021

Chronic obstructive pulmonary disease (COPD) is a disorder of accelerated lung aging. Multiple pieces of evidence support that the aging biomarker short telomeres, which can be caused by mutations in telomerase reverse transcriptase (TERT), contribute to COPD pathogenesis. We hypothesized that short telomere risk-associated single nucleotide polymorphisms (SNPs) in TERT, while not able to drive COPD development, nonetheless modify the disease presentation. We set out to test the SNP carrying status in a longitudinal study of smokers with COPD and found that rapid decline of FEV1 in lung function was associated with the minor allele of rs61748181 (adjusted odds ratio 2.49, p = 0.038). Biochemical evaluation of ex vivo engineered human cell models revealed that primary cells expressing the minor allele of rs61748181 had suboptimal telomere length maintenance due to reduced telomerase catalytic activity, despite having comparable cell growth kinetics as WT-TERT expressing cells. This ex vivo observation translated clinically in that shorter telomeres were found in minor allele carriers in a sub-population of COPD patients with non-declining lung function, over the 5-year period of the longitudinal study. Collectively, our data suggest that functional TERT SNPs with mild catalytic defects are nonetheless implicated in the clinical presentation of COPD.
Skewness of X-chromosome inactivation increases with age and varies across birth cohorts in elderly Danish women
Authors: Mengel-From Jonas , Lindahl-Jacobsen Rune , Nygaard Marianne , Soerensen Mette , Ørstavik Karen Helene , Hertz Jens Michael , Andersen-Ranberg Karen , Tan Qihua , Christensen Kaare
Published: February 2021

Mosaicism in blood varies with age, and cross-sectional studies indicate that for women, skewness of X-chromosomal mosaicism increases with age. This pattern could, however, also be due to less X-inactivation in more recent birth cohorts. Skewed X-chromosome inactivation was here measured longitudinally by the HUMARA assay in 67 septuagenarian and octogenarian women assessed at 2 time points, 10 years apart, and in 10 centenarian women assessed at 2 time points, 2–7 years apart. Skewed X-chromosome inactivation was also compared in 293 age-matched septuagenarian twins born in 1917–1923 and 1931–1937, and 212 centenarians born in 1895, 1905 and 1915. The longitudinal study of septuagenarians and octogenarians revealed that 16% (95% CI 7–29%) of the women developed skewed X-inactivation over a 10-year period. In the cross-sectional across-birth cohort study, the earlier-born septuagenarian (1917–1923) and centenarian women (1895) had a higher degree of skewness than the respective recent age-matched birth cohorts, which indicates that the women in the more recent cohorts, after the age of 70, had not only changed degree of skewness with age, they had also undergone less age-related hematopoietic sub-clone expansion. This may be a result of improved living conditions and better medical treatment in the more recent birth cohorts.
In silico detection of SARS-CoV-2 specific B-cell epitopes and validation in ELISA for serological diagnosis of COVID-19
Authors: Phan Isabelle Q. , Subramanian Sandhya , Kim David , Murphy Michael , Pettie Deleah , Carter Lauren , Anishchenko Ivan , Barrett Lynn K. , Craig Justin , Tillery Logan , Shek Roger , Harrington Whitney E. , Koelle David M. , Wald Anna , Veesler David , King Neil , Boonyaratanakornkit Jim , Isoherranen Nina , Greninger Alexander L. , Jerome Keith R. , Chu Helen , Staker Bart , Stewart Lance , Myler Peter J. , Van Voorhis Wesley C.
Published: February 2021

Rapid generation of diagnostics is paramount to understand epidemiology and to control the spread of emerging infectious diseases such as COVID-19. Computational methods to predict serodiagnostic epitopes that are specific for the pathogen could help accelerate the development of new diagnostics. A systematic survey of 27 SARS-CoV-2 proteins was conducted to assess whether existing B-cell epitope prediction methods, combined with comprehensive mining of sequence databases and structural data, could predict whether a particular protein would be suitable for serodiagnosis. Nine of the predictions were validated with recombinant SARS-CoV-2 proteins in the ELISA format using plasma and sera from patients with SARS-CoV-2 infection, and a further 11 predictions were compared to the recent literature. Results appeared to be in agreement with 12 of the predictions, in disagreement with 3, while a further 5 were deemed inconclusive. We showed that two of our top five candidates, the N-terminal fragment of the nucleoprotein and the receptor-binding domain of the spike protein, have the highest sensitivity and specificity and signal-to-noise ratio for detecting COVID-19 sera/plasma by ELISA. Mixing the two antigens together for coating ELISA plates led to a sensitivity of 94% (N = 80 samples from persons with RT-PCR confirmed SARS-CoV-2 infection), and a specificity of 97.2% (N = 106 control samples).
Allelopathic effect of Artemisia argyi on the germination and growth of various weeds
Authors: Li Jinxin , Chen Le , Chen Qiaohuan , Miao Yuhuan , Peng Zheng , Huang Bisheng , Guo Lanping , Liu Dahui , Du Hongzhi
Published: February 2021

Allelopathy means that one plant produces chemical substances to affect the growth and development of other plants. Usually, allelochemicals can stimulate or inhibit the germination and growth of plants, which have been considered as potential strategy for drug development of environmentally friendly biological herbicides. Obviously, the discovery of plant materials with extensive sources, low cost and markedly allelopathic effect will have far-reaching ecological impacts as the biological herbicide. At present, a large number of researches have already reported that certain plant-derived allelochemicals can inhibit weed growth. In this study, the allelopathic effect of Artemisia argyi was investigated via a series of laboratory experiments and field trial. Firstly, water-soluble extracts exhibited the strongest allelopathic inhibitory effects on various plants under incubator conditions, after the different extracts authenticated by UPLC-Q-TOF-MS. Then, the allelopathic effect of the A. argyi was systematacially evaluated on the seed germination and growth of Brassica pekinensis, Lactuca sativa, Oryza sativa, Portulaca oleracea, Oxalis corniculata and Setaria viridis in pot experiments, it suggested that the A. argyi could inhibit both dicotyledons and monocotyledons not only by seed germination but also by seedling growth. Furthermore, field trial showed that the A. argyi significantly inhibited the growth of weeds in Chrysanthemum morifolium field with no adverse effect on the growth of C. morifolium. At last, RNA-Seq analysis and key gene detection analysis indicated that A.argyi inhibited the germination and growth of weed via multi-targets and multi-paths while the inhibiting of chlorophyll synthesis of target plants was one of the key mechanisms. In summary, the A. argyi was confirmed as a potential raw material for the development of preventive herbicides against various weeds in this research. Importantly, this discovery maybe provide scientific evidence for the research and development of environmentally friendly herbicides in the future.
The pelvic flexure separates distinct microbial communities in the equine hindgut
Authors: Reed Kailee J. , Kunz Isabelle G. Z. , Scare Jessica A. , Nielsen Martin K. , Turk Philip J. , Coleman Robert J. , Coleman Stephen J.
Published: February 2021

As hindgut fermenters, horses are especially dependent on the microbiota residing in their cecum and large intestines. Interactions between these microbial populations and the horse are critical for maintaining gut homeostasis, which supports proper digestion. The current project was motivated to determine if any features of the fecal microbiota are informative of the microbial communities from the cecum, ventral colon, or dorsal colon. Digesta from the cecum, ventral colon, dorsal colon and feces were collected from 6 yearling miniature horses. Microbial DNA was isolated and the microbiota from each sample was characterized by profiling the V4 region of the 16S rRNA. Principal coordinate analysis of the beta diversity results revealed significant (p = 0.0001; F = 5.2393) similarities between the microbial populations from cecal and ventral colon and the dorsal colon and fecal samples, however, there was little overlap between the proximal and distal ends of the hindgut. These distinct population structures observed in our results coincide with the pelvic flexure, which itself separates intestinal compartments with distinct roles in digestive physiology. An indicator species analysis confirmed the population differences, supported by the identification of several microbial families characteristic of the compartments upstream of the pelvic flexure that were not represented following it. Our data suggest that the fecal microbiota is not informative of the proximal hindgut but can provide insight into communities of the distal compartments. Further, our results suggest that the pelvic flexure might be an important anatomical landmark relative to the microbial communities in the equine large intestine.
Lysosome repositioning as an autophagy escape mechanism by Mycobacterium tuberculosis Beijing strain
Authors: Laopanupong Thanida , Prombutara Pinidphon , Kanjanasirirat Phongthon , Benjaskulluecha Salisa , Boonmee Atsadang , Palaga Tanapat , Méresse Stephane , Paha Jiraporn , Siregar Tegar Adriansyah Putra , Khumpanied Tanawadee , Borwornpinyo Suparerk , Chaiprasert Angkana , Utaisincharoen Pongsak , Ponpuak Marisa
Published: February 2021

Induction of host cell autophagy by starvation was shown to enhance lysosomal delivery to mycobacterial phagosomes, resulting in the restriction of Mycobacterium tuberculosis reference strain H37Rv. Our previous study showed that strains belonging to M. tuberculosis Beijing genotype resisted starvation-induced autophagic elimination but the factors involved remained unclear. Here, we conducted RNA-Seq of macrophages infected with the autophagy-resistant Beijing strain (BJN) compared to macrophages infected with H37Rv upon autophagy induction by starvation. Results identified several genes uniquely upregulated in BJN-infected macrophages but not in H37Rv-infected cells, including those encoding Kxd1 and Plekhm2, which function in lysosome positioning towards the cell periphery. Unlike H37Rv, BJN suppressed enhanced lysosome positioning towards the perinuclear region and lysosomal delivery to its phagosome upon autophagy induction by starvation, while depletion of Kxd1 and Plekhm2 reverted such effects, resulting in restriction of BJN intracellular survival upon autophagy induction by starvation. Taken together, these data indicated that Kxd1 and Plekhm2 are important for the BJN strain to suppress lysosome positioning towards the perinuclear region and lysosomal delivery into its phagosome during autophagy induction by starvation to evade starvation-induced autophagic restriction.
Increasing ENSO–rainfall variability due to changes in future tropical temperature–rainfall relationship
Authors: Yun Kyung-Sook , Lee June-Yi , Timmermann Axel , Stein Karl , Stuecker Malte F. , Fyfe John C. , Chung Eui-Seok
Published: February 2021

Intensification of El Niño-Southern Oscillation (ENSO)-rainfall variability in response to global warming is a robust feature across Coupled Model Intercomparison Project (CMIP) iterations, regardless of a lack of robust projected changes in ENSO-sea-surface temperature (SST) variability. Previous studies attributed this intensification to an increase in mean SST and moisture convergence over the central-to-eastern Pacific, without explicitly considering underlying nonlinear SST–rainfall relationship changes. Here, by analyzing changes of the tropical SST–rainfall relationship of CMIP6 models, we present a mechanism linking the mean SST rise to amplifying ENSO–rainfall variability. We show that the slope of the SST–rainfall function over Niño3 region becomes steeper in a warmer climate, ~42.1% increase in 2050–2099 relative to 1950–1999, due to the increase in Clausius–Clapeyron-driven moisture sensitivity, ~16.2%, and dynamic contributions, ~25.9%. A theoretical reconstruction of ENSO–rainfall variability further supports this mechanism. Our results imply ENSO’s hydrological impacts increase nonlinearly in response to global warming.
Multicolor-Raman analysis of Korean paintworks: emission-like Raman collection efficiency
Authors: Bae Chang Hyun , Song Si Won , Lim Soo Yeong , Yoo Seonyoung , Lee Chang Sug , Park Chan Ryang , Kim Gyuho , Kim Hyung Min
Published: February 2021

It has been reported that the scattering cross-sections of resonance Raman spectra strongly depend on the resonance between the laser's excitation energy and the electronic absorption band of pigments in solution.