bluuebunny/crossref_metadata_2025 huggingface dataset:
The combined effect of two westerly jet waveguides on heavy haze in the North China Plain in November and December 2015
Authors: An Xiadong , Sheng Lifang , Liu Qian , Li Chun , Gao Yang , Li Jianping
Published: April 2020

Abstract. Severe haze occurred in the North China Plain (NCP) from November
to December 2015, with a wide spatial range and long duration. In this
paper, the combined effect of the anomalous stationary Rossby waves within
two westerly jet waveguides on this haze event in the NCP is investigated
based on observational visibility data and NCEP/NCAR reanalysis data. The
results show that circulation anomalies in Eurasia caused by the propagation
of anomalous stationary Rossby wave energy along two waveguides within the
westerly jet originating from the Mediterranean were responsible for haze
formation in the NCP. The Rossby waves propagated eastward along the
subtropical westerly jet and the polar front jet, causing an anomalous
anticyclone over the Sea of Japan and anticyclonic wind shear at 850 hPa
over the NCP, which enhanced the anomalous descent in the middle and lower
troposphere and subsequently resulted in a stable lower atmosphere.
Furthermore, the anomalous stationary Rossby waves propagating along the
polar front jet weakened the East Asia trough and Ural ridge and
strengthened the anomalous southerly wind at 850 hPa over the coastal areas
of eastern China, decelerating the East Asia winter monsoon. The above
meteorological conditions modulated haze accumulation in November and
December 2015. Meanwhile, continuous rainfall related to ascending motion
due to Rossby wave propagation along the waveguide provided by the
subtropical westerly jet occurred in a large area of southern China. The
associated latent heat release acted as a heat source, intensifying the
ascending motion over southern China so that the descending motion over the
NCP was strengthened, favoring the maintenance of severe haze. This study
elucidates the formation and maintenance mechanism of large-scale haze in
the NCP in late fall and boreal winter.
Errors in top-down estimates of emissions using a known source
Authors: Angevine Wayne M. , Peischl Jeff , Crawford Alice , Loughner Christopher P. , Pollack Ilana B. , Thompson Chelsea R.
Published: April 2020

Abstract. Air pollutant emissions estimates by top-down methods are subject to a variety of errors and uncertainties. This work uses a known source, a coal-fired power plant, to explore those errors. The known emissions amount and location remove two major types of error, facilitating understanding of other types. Biases and random errors are distinguished. A Lagrangian dispersion model (HYSPLIT) is run forward in time from the known source, and virtual measurements of the resulting tracer plume are compared to actual measurements from research aircraft. Four flights in different years are used to illustrate a variety of conditions. The measurements are analyzed by a mass-balance method, and the assumptions of that method are discussed. Some of those assumptions can be relaxed in analysis of the modeled plume, allowing testing of their validity. Meteorological fields to drive HYSPLIT are provided by the European Center for Medium Range Weather Forecasts Fifth Reanalysis (ERA5). A unique feature of this work is the use of an ensemble of meteorological fields intrinsic to ERA5. This analysis supports reasonably large (30–40 %) uncertainties on top-down analyses.
Heterogeneous nucleation of water vapor on different types of black carbon particles
Authors: Laaksonen Ari , Malila Jussi , Nenes Athanasios
Published: April 2020

Abstract. Heterogeneous nucleation of water vapor on insoluble particles affects cloud formation, precipitation, the hydrological cycle and climate. Despite its importance, heterogeneous nucleation remains a poorly understood phenomenon that relies heavily on empirical information for its quantitative description. Here, we examine heterogeneous nucleation of water vapor on and cloud drop activation of different types of soots, both pure black carbon particles, and black carbon particles mixed with secondary organic matter. We show that the recently developed adsorption nucleation theory quantitatively predicts the nucleation of water and droplet formation upon particles of the various soot types. A surprising consequence of this new understanding is that, with sufficient adsorption site density, soot particles can activate into cloud droplets – even when completely lacking any soluble material.
Can machine learning improve the model representation of TKE dissipation rate in the boundary layer for complex terrain?
Authors: Bodini Nicola , Lundquist Julie K. , Optis Mike
Published: April 2020

Abstract. Current turbulence parameterizations in numerical weather prediction models at the mesoscale assume a local equilibrium between production and dissipation of turbulence. As this assumption does not hold at fine horizontal resolutions, improved ways to represent turbulent kinetic energy (TKE) dissipation rate (ε) are needed. Here, we use a 6-week data set of turbulence measurements from 184 sonic anemometers in complex terrain at the Perdigão field campaign to suggest improved representations of dissipation rate. First, we demonstrate that a widely used Mellor, Yamada, Nakanishi, and Niino (MYNN) parameterization of TKE dissipation rate leads to a large inaccuracy and bias in the representation of ε. Next, we assess the potential of machine-learning techniques to predict TKE dissipation rate from a set of atmospheric and terrain-related features. We train and test several machine-learning algorithms using the data at Perdigão, and we find that multivariate polynomial regressions and random forests can eliminate the bias MYNN currently shows in representing ε, while also reducing the average error by up to 30 %. Of all the variables included in the algorithms, TKE is the variable responsible for most of the variability of ε, and a strong positive correlation exists between the two. These results suggest further consideration of machine-learning techniques to enhance parameterizations of turbulence in numerical weather prediction models.
La máquina de la verdad: paradigma de la telerrealidad de la primera televisión española en competencia (1992-1994)
Authors: Mateos-Pérez Javier
Published: April 2020

Este artículo propone el análisis exhaustivo del espacio La máquina de la verdad (Tele 5). En su desarrollo se aborda la singularidad del programa, que se convirtió en uno de los paradigmáticos de la telerrealidad en los años noventa, inscribiéndose en el imaginario colectivo y en la historia del medio televisivo español. Muestra de sus señas de identidad fueron los temas y los protagonistas: actuales, polémicos, con implicaciones judiciales; su puesta en escena; y el perfil de su presentador, Julián Lago. El formato se dividía en tres partes: el interrogatorio a una persona pública, que explicaba su versión sobre una polémica; el debate con invitados, que cuestionaban o apoyaban su relato; y el desenlace final, que comprobaba la veracidad de las respuestas del personaje monitorizado por un detector de mentiras. Esta estructura formal y el contenido temático polémico y efectista, consagraron al espacio como una referencia para programas sensacionalistas posteriores.
Desregulación y soberanía del público en la televisión española
Authors: Valhondo Crego José Luis , Gonzalo Salomé Berrocal
Published: April 2020

La desregulación económica de las últimas tres décadas ha afectado globalmente a las prácticas periodísticas de la televisión. La consecuencia más visible de ese cambio tiene que ver con la aparición del género del infoentretenimiento, una hibridación de las funciones temática y pragmática del periodismo en aras de la explotación extensiva e intensiva de las audiencias. A través de un Análisis de Contenido asistido por un software de datos cualitativos, se analizan los posibles efectos del infoentretenimiento a través de una muestra estratégica de El Intermedio; un espacio que representa de modo adecuado las prácticas periodísticas y los contenidos asociados al género. Respecto a lo temático, los resultados señalan que el formato replica la agenda y el framing de la prensa de referencia española. En relación a la función pragmática, el espacio aporta una pléyade de mecanismos retóricos que sugieren un engagement más acusado con los públicos.
Intestinal tuberculosis or Crohn’s disease: a review of the diagnostic models designed to differentiate between these two gastrointestinal diseases
Authors: Limsrivilai Julajak , Pausawasdi Nonthalee
Published: April 2020

Differentiating Crohn’s disease (CD) from intestinal tuberculosis (ITB) is a diagnostic dilemma, particularly in regions where ITB is prevalent and CD incidence is increasing, because both diseases can present quite similarly, and diagnostic tests to identify Mycobacterium tuberculosis in tissue samples have rather poor sensitivity. Studies that were conducted to determine the factors that differentiate CD from ITB identified some significant characteristics, but none of those characteristics are exclusive to either ITB or CD. Many diagnostic models or scoring systems that use one to several diagnostic parameters have been proposed to help distinguish these two intestinal diseases. Early models consisted of parameters common to routine clinical practice, such as clinical features, and endoscopic and pathologic findings. The later models also include more advanced diagnostic parameters like high-resolution imaging and serological testing. However, the number and types of parameters differ among diagnostic models, and the systems used to calculate scoring also vary from model to model. Enhanced awareness and understanding of the currently available diagnostic models will help physicians determine which model(s) is/are most suitable for differentiating CD from ITB in their clinical practice.
Difficult management of chronic cough
Authors: Dąbrowska Marta , Arcimowicz Magdalena
Published: April 2020

Chronic cough affects about 4–10% of adults and has a negative impact on the patients’ quality of life. Chronic cough may be a symptom of many different diseases and its management should be based on treating the underlying cause. The most common cough cause in adults is chronic bronchitis due to smoking. Next, in non-smoking adults upper airway cough syndrome, gastroesophageal reflux and asthma account for the majority of cough reasons. Despite thorough diagnostics and management in 5–10% adults management of chronic cough is unsuccessful. In difficult-to-treat cough neuromodulators and speech therapy may be effective.
OBTAINING DATA LOCATED IN DEVICES OR IT SYSTEMS — SELECTED ISSUES IN LIGHT OF THE PROVISIONS OF CRIMINAL PROCEDURAL LAW
Authors: OLBER PAWEŁ
Published: April 2020

There is a lack of consensus among national law enforcement
and judicial authorities as to which procedural acts are relevant for obtaining
data contained in devices or information systems for evidentiary purposes.
It is easy to fi nd supporters of the search of the information system as well
as those who consider it appropriate to carry out inspections. However, regardless
of many examples and arguments of various persons, it may seem
that the compromise in this respect should be the position of the National
Public Prosecutor’s Offi ce on the procedural practice related to obtaining
data contained in IT equipment or systems for evidentiary purposes. However,
the opinion of the National Prosecutor’s Offi ce does not take into account
legally protected data, and in particular, legal aspects related to obtaining access
to the content of telecommunications, including text messages protected
by telecommunications secrecy. The article is a summary of the previous
considerations regarding the possibility of obtaining data located in IT equipment
or systems. The article also contains the author’s conclusions, based
on, inter alia, methodology for securing digital footprints, intended for all
representatives of national law enforcement and judicial authorities.
SELECTED SOCIAL PATHOLOGIES IN THE PUBLIC SECURITY SPACE
Authors: ZBROSZCZYK DOROTA
Published: April 2020

Pathological behaviour, pathogenic factors (social and cultural
conditions) or other processes affecting the aforementioned situations are
constantly present in human life. It can be said that there is a considerable
diversity and complexity of such phenomena. The issues of social pathologies
discussed in the article concern only selected phenomena, and yet they make
the recipients aware of the scale of the problem.
THE ROLE OF LAW ENFORCEMENT INSTITUTIONS IN PREVENTING AND COMBATING THE CRIME OF HUMAN TRAFFICKING
Authors: ŁYŻWA ANETA
Published: April 2020

The subject of this study is the characteristics of Polish law enforcement
authorities in the fi eld of preventing and combating the crime
of traffi cking in human beings. The author points out that, based on existing
legal regulations in Poland, the foremost burden related to prevention
and prosecution activities of this type of crime lies within the scope of duties
of the prosecutor’s offi ce, the Police, and the Border Guard. Thus, the article
is devoted to a concise description of the indicated entities in terms of their
legal instruments which make it possible to effectively implement the tasks
and duties imposed by law and regulations upon the institutions. In the
author’s assessment, the key role in the system is played by the prosecutor,
who is the only authority sanctioned to make decisions on initiating
the investigation and entrusting its conduct in its entirety or the indicated
scope to other authorities, primarily the Police or the Border Guard. The
prosecutor’s special role also results from the fact of being solely entitled
to draw up and support an indictment in court in cases involving traffi cking
in human beings. Nevertheless, according to the author, in practice, the
main responsibility to carry out procedural and operational activities in this
category of cases lies with the Police and Border Guard. The author points
out that, at present, the Polish law enforcement system has appropriate instruments,
both at the legal and institutional levels, ready for the effective
prevention of and combat against crimes of human traffi cking. However,
bearing in mind that the phenomenon of human traffi cking has, in principle,
a cross-border dimension, the article highlights the aspect of international
cooperation between the relevant institutions established to detect and prosecute
these crimes.
Anthropological Aspects of Security Culture Analyses within the Context of Selected Elements of Threat and Security Typology
Authors: Piwowarski Juliusz , Trzciński Łukasz
Published: April 2020

Both security sciences and security studies have traditionally mainly focused on the state as the most important security subject; however, as anthropology of security and the idea of human security assert, it is the security of a human individual that should be highlighted as well. The authors start from discussing the typologies of threat and security. This leads them to focusing on the idea of human security, a concept first proposed by researchers and then taken up by international organizations. The concept of human security, combined with anthropology of security, constitutes a scientific basis for the shift from the state-centric to the anthropocentric approach to security. The authors corroborate this stance by discussing a range of definitions of the concept of security, which focus on either more general or more specific aspects of security. They favour the more universal understanding of the concept and conclude that security, being the same type of anthropological social construct as other humane values such as beauty, happiness, love, etc., and a phenomenon relating to a great extent to the quality of human existence, should possess its universal essence.
Verpflichtung des Vorstands zur Berücksichtigung betriebswirtschaftlicher Erkenntnisse bei der Entscheidungsfindung
Authors: Riesener Moritz Alexander
Published: April 2020

Sind betriebswirtschaftliche Erkenntnisse von Vorständen im Rahmen unternehmerischer Entscheidungsprozesse verpflichtend zu berücksichtigen? Diese Frage beschäftigt nicht nur die Autoren in der Literatur, sondern auch die Entscheider in der Praxis. Auf Grundlage der aktuellen Sach- und Rechtslage wird diese Frage am Beispiel von M&A-Transaktionen beleuchtet und ein neuer Ansatz zum Verständnis unternehmerischer Entscheidungsprozesse unter verpflichtender Berücksichtigung von Grundsätzen der allgemeinen Entscheidungslehre entwickelt.
Kindeswohl interdisziplinär
Authors: Schmidt Axel , Westhoff Karl
Published: April 2020

Dieser Band schließt die Lücke zwischen Normen, rechtswissenschaftlichen Auslegungen und konsensfähigen humanwissenschaftlichen empirischen Ergebnissen zur Konkretisierung des unbestimmten Rechtsbegriffs Kindeswohl. Die rechtlichen Grundlagen und die zu beachtenden Urteile der höchsten Gerichte zum Kindeswohl stellt der erste Teil des Buches dar; sie sind das Gerüst für den zweiten Teil, der die humanwissenschaftlichen übereinstimmenden empirischen Fakten präsentiert. Die Humanwissenschaften liefern hier ein zu den rechtlichen Entscheidungskriterien korrespondierendes Wertesystem und damit einen Maßstab, das Kindeswohl im Einzelfall zu beurteilen und die Entscheidungsfindung auf eine faktenbasierte Grundlage zu stellen. Dieser interdisziplinäre Ansatz einer humanwissenschaftlichen Kommentierung der rechtlichen Kindeswohlkriterien kann Familienrichtern, Sachverständigen und beruflich involvierten Personen als Arbeitshilfe zur Verfügung gestellt werden.
Die Rozenblum-Doktrin, ihre Fortschreibung bis zur Gegenwart und ihr Vergleich zur Treuepflicht im faktischen GmbH-Konzern
Authors: Krafft Anne Kristin
Published: April 2020

Die Rozenblum-Doktrin – sie stellt nicht etwa ein antiquiertes Rechtsinstitut aus dem letzten Jahrhundert dar, sondern ist auf europäischer und nationaler Ebene als Modell nach wie vor von großer Bedeutung. Dies regte dazu an, sie in ihrer ursprünglichen Form und ihrer Entwicklung einer genauen Untersuchung zu unterziehen. Ziel der Arbeit ist es, die Besonderheiten der Doktrin darzulegen, die insbesondere darin bestehen, Unternehmensgruppen prospektiv zu prägen und so die Außenseiter zu schützen. Vergleichend wird der Blick auf die Treuepflicht im faktischen GmbH-Konzern gelenkt, als alternativen Lösungsansatz des Konzernkonflikts. Hier sind deutliche Unterschiede zu erkennen, vor allem im Hinblick auf die Legitimation des Handelns im Gruppeninteresse und der Anerkennung der wirtschaftlichen Gruppenrealität. Letztlich wird eine prozessual abgesicherte Einfügung der Rozenblum-Doktrin in die Treuepflicht befürwortet, um so auch auf die Kritik an der Treuepflicht einzugehen.
Onlineangebot von Sendeunternehmen
Authors: Schulte zu Sundern Friederike
Published: April 2020

Für Sendeunternehmen war der Rechteerwerb auf Grund der Masse und Vielseitigkeit der von ihnen benötigten Rechte seit jeher mit Schwierigkeiten verbunden. Mit der wachsenden Bedeutung der Vermittlung von audiovisuellen Inhalten über neue Verbreitungswege, insbesondere über „das Internet“ wurden diese Probleme erweitert. Die europäische Kommission versucht diese Probleme teilweise zu adressieren und erließ mit der Portabilitäts-VO und der SatCab-Online-RL entsprechende Reformen. Die vorliegende Arbeit untersucht diese und zeichnet den dem Rechteerwerb der Sendeunternehmen insgesamt zugrunde liegenden urheberrechtlichen Rahmen nach, angefangen von den betroffenen Verwertungsrechten bis zu der Einräumung der Nutzungsrechte.
The Management of Patients with Pneumonia in Family Medicine in Slovenia
Authors: Brlek Aljaž , Bedek Ernestina
Published: April 2020

Background: Pneumonia is among the most common infections treated in family practice. In Slovenia, a comprehensive management of pneumonia at the primary level has not yet been researched, which results in the lack of data regarding guideline adherence. Our aim was to describe the management of patients with pneumonia in family practices and to analyse characteristics of family physicians (FPs) and their practices which influence guideline adherence.Methods: The study was conducted as a cross-sectional research with clinical vignette and questions about characteristics of FPs and their practices, in the form of an online questionnaire; 892 specialists and FPs without specialty, and 320 residents were contacted. Using the guidelines, a proper management protocol for patients with pneumonia was designed and used for the evaluation of respondents’ answers. The collected data were analyzed using logistic regression.Results: The response rate was 475/1212 (39.2 %). When managing patients with pneumonia, 66.7 % of FPs performed a complete blood count with differential, 92.6 % CRP, 54.5 % chest X-ray, 62.6 % prescribed amoxicillin and 29.7 % amoxicillin with clavulanic acid. The correct preliminary diagnosis was provided by 93.7 % of FPs, correct diagnostics by 13.5 %, no referral by 90.3 %, proper treatment by 53.1 % and checkup by 48.8 % of FPs. 3.2 % of FPs exhibited an altogether adequate patient management. Negative association between female FPs and adequate diagnostics, and between FPs older than 45 years and adequate treatment and checkup was noticed.Conclusion: The research indicated many differences in managing pneumonia. Only a small share of FPs completely adhered to the set guidelines.
La expansión del Pensamiento Computacional en Uruguay
Authors: García José Miguel
Published: April 2020

En los últimos años se han desarrollado en Uruguay diversas acciones tendientes a expandir el Pensamiento Computacional en la educación primaria y media. En el presente artículo se relata y reflexiona sobre las actividades desarrolladas en esta línea, así como las acciones para potenciar el Pensamiento Computacional en la educación uruguaya.

In recent years, various actions have been developed in Uruguay to expand Computational Thinking in primary and secondary education. The present article describes and reflects on the activities carried out in this line, as well as the actions to enhance Computational Thinking in Uruguayan education.
Finishing College Classes During COVID-19
Authors: Mullen Michelle , Logan Deirdre
Published: April 2020

This is a tough time for everyone. College students have been asked to leave campus and finish the semester remotely, which may not be something they are used to. While this is a hard adjustment for most college students, this change may be more difficult for young adult college students with mental health conditions. Since trying to finish the semester remotely can be a challenge, we’ve collected some tips that may be helpful. Many of these tips are adapted from our Supporting College Students with Mental Health Conditions in the Wake of COVID-19 here on our website. Michelle Mullen also held a webinar Are You a College Student with a Mental Health Condition? Managing the Wake of COVID: Strategies & Tools to Finish Your Semester that you can find here on our website.
Realism of TRANSAS NTPRO 5000 Radar Simulation in Search and Rescue Training Exercises
Authors: Toman Ivan , Vidan Pero , Barić Mate , Grbić Luka
Published: April 2020

In this study, the results of an evaluation of current navigational simulator Transas NTPRO 5000 ability of realistic training in search operations by radar has been presented. By testing the performance of detecting different targets at various distances from the vessel model and comparing the results to the theoretical models of radar limitations from the literature, we found that the equipment can be used in search and rescue training, but with several important limitations. Some aspects of radar simulation in the current simulator version is considered as acceptably realistic, but we identified several points where the results showed significant deviations from the theoretical models. Those points limit the equipment's ability to perform some aspects of search-by-radar training, and the instructors are advised to carefully set up exercises in a way that those shortcomings are avoided during student training.
Using the capacity of preferential tax regimes of the regional investment projects and special investment contracts for the development of cluster approach in the Russian Federation
Authors: Bakhshian Emma
Published: April 2020

The subject of this research is the theoretical and practical aspects of implementation of the regional investment projects (RIP) and special investment contracts (SIC), and prospects of their use as the instruments for incentivizing the development of innovation and industrial clusters in Russia. The article reveals the essence of cluster approach and its evolution in the Russian practice. The author meticulously examines the peculiarities of preferential tax regimes within the framework of RIP and SIC. Special attention is given to the conceptual changes of the legislation on SIC, and analysis of their impact upon the efficiency of the mechanism of SIC. The following conclusions were made: 1) preferential tax regime of RIP, being convenient, transparent and highly demanded by representatives of business sector, is presented as promising for supporting cluster participants; 2) novelties of the legislation on SIC contribute to the increase of its attractiveness for investors, including cluster participants; 3) tax regime of SIC may serve as the instrument for incentivizing such vectors of development of the cluster approach in Russia, as realization of joint projects of cluster participants, development of interregional clusters and intercluster cooperation.
Phenotypic plasticity as a mechanism of cave colonization and adaptation
Authors: Bilandžija Helena , Hollifield Breanna , Steck Mireille , Meng Guanliang , Ng Mandy , Koch Andrew D , Gračan Romana , Ćetković Helena , Porter Megan L , Renner Kenneth J , Jeffery William
Published: April 2020

A widely accepted model for the evolution of cave animals posits colonization by surface ancestors followed by the acquisition of adaptations over many generations. However, the speed of cave adaptation in some species suggests mechanisms operating over shorter timescales. To address these mechanisms, we used Astyanax mexicanus, a teleost with ancestral surface morphs (surface fish, SF) and derived cave morphs (cavefish, CF). We exposed SF to completely dark conditions and identified numerous altered traits at both the gene expression and phenotypic levels. Remarkably, most of these alterations mimicked CF phenotypes. Our results indicate that many cave-related traits can appear within a single generation by phenotypic plasticity. In the next generation, plasticity can be further refined. The initial plastic responses are random in adaptive outcome but may determine the subsequent course of evolution. Our study suggests that phenotypic plasticity contributes to the rapid evolution of cave-related traits in A. mexicanus.
Reconfiguration of functional brain networks and metabolic cost converge during task performance
Authors: Hahn Andreas , Breakspear Michael , Rischka Lucas , Wadsak Wolfgang , Godbersen Godber M , Pichler Verena , Michenthaler Paul , Vanicek Thomas , Hacker Marcus , Kasper Siegfried , Lanzenberger Rupert , Cocchi Luca
Published: April 2020

The ability to solve cognitive tasks depends upon adaptive changes in the organization of whole-brain functional networks. However, the link between task-induced network reconfigurations and their underlying energy demands is poorly understood. We address this by multimodal network analyses integrating functional and molecular neuroimaging acquired concurrently during a complex cognitive task. Task engagement elicited a marked increase in the association between glucose consumption and functional brain network reorganization. This convergence between metabolic and neural processes was specific to feedforward connections linking the visual and dorsal attention networks, in accordance with task requirements of visuo-spatial reasoning. Further increases in cognitive load above initial task engagement did not affect the relationship between metabolism and network reorganization but only modulated existing interactions. Our findings show how the upregulation of key computational mechanisms to support cognitive performance unveils the complex, interdependent changes in neural metabolism and neuro-vascular responses.
Shape selection and mis-assembly in viral capsid formation by elastic frustration
Authors: Mendoza Carlos I , Reguera David
Published: April 2020

The successful assembly of a closed protein shell (or capsid) is a key step in the replication of viruses and in the production of artificial viral cages for bio/nanotechnological applications. During self-assembly, the favorable binding energy competes with the energetic cost of the growing edge and the elastic stresses generated due to the curvature of the capsid. As a result, incomplete structures such as open caps, cylindrical or ribbon-shaped shells may emerge, preventing the successful replication of viruses. Using elasticity theory and coarse-grained simulations, we analyze the conditions required for these processes to occur and their significance for empty virus self-assembly. We find that the outcome of the assembly can be recast into a universal phase diagram showing that viruses with high mechanical resistance cannot be self-assembled directly as spherical structures. The results of our study justify the need of a maturation step and suggest promising routes to hinder viral infections by inducing mis-assembly.
Sex-determining genes distinctly regulate courtship capability and target preference via sexually dimorphic neurons
Authors: Ishii Kenichi , Wohl Margot , DeSouza Andre , Asahina Kenta
Published: April 2020

For successful mating, a male animal must execute effective courtship behaviors toward a receptive target sex, which is female. Whether the courtship execution capability and upregulation of courtship toward females are specified through separable sex-determining genetic pathways remains uncharacterized. Here, we found that one of the two Drosophila sex-determining genes, doublesex (dsx), specifies a male-specific neuronal component that serves as an execution mechanism for courtship behavior, whereas fruitless (fru) is required for enhancement of courtship behavior toward females. The dsx-dependent courtship execution mechanism includes a specific subclass within a neuronal cluster that co-express dsx and fru. This cluster contains at least another subclass that is specified cooperatively by both dsx and fru. Although these neuronal populations can also promote aggressive behavior toward male flies, this capacity requires fru-dependent mechanisms. Our results uncover how sex-determining genes specify execution capability and female-specific enhancement of courtship behavior through separable yet cooperative neurogenetic mechanisms.
Layered roles of fruitless isoforms in specification and function of male aggression-promoting neurons in Drosophila
Authors: Wohl Margot , Ishii Kenichi , Asahina Kenta
Published: April 2020

Inter-male aggressive behavior is a prominent sexually dimorphic behavior. Neural circuits that underlie aggressive behavior are therefore likely under the control of sex-determining genes. However, the neurogenetic mechanism that generates sex-specific aggressive behavior remains largely unknown. Here, we found that a neuronal class specified by one of the Drosophila sex determining genes, fruitless (fru), belongs to the neural circuit that generates male-type aggressive behavior. This neuronal class can promote aggressive behavior independent of another sex determining gene, doublesex (dsx), although dsx is involved in ensuring that aggressive behavior is performed only toward males. We also found that three fru isoforms with different DNA binding domains show a division of labor on male aggressive behaviors. A dominant role of fru in specifying sex-specific aggressive behavior may underscore a genetic mechanism that allows male-type aggressive behavior to evolve at least partially independently from courtship behavior, which is under different selective pressures.
Multimeric single-domain antibody complexes protect against bunyavirus infections
Authors: Wichgers Schreur Paul J , van de Water Sandra , Harmsen Michiel , Bermúdez-Méndez Erick , Drabek Dubravka , Grosveld Frank , Wernike Kerstin , Beer Martin , Aebischer Andrea , Daramola Olalekan , Rodriguez Conde Sara , Brennan Karen , Kozub Dorota , Søndergaard Kristiansen Maiken , Mistry Kieran K , Deng Ziyan , Hellert Jan , Guardado-Calvo Pablo , Rey Félix A , van Keulen Lucien , Kortekaas Jeroen
Published: April 2020

The World Health Organization has included three bunyaviruses posing an increasing threat to human health on the Blueprint list of viruses likely to cause major epidemics and for which no, or insufficient countermeasures exist. Here, we describe a broadly applicable strategy, based on llama-derived single-domain antibodies (VHHs), for the development of bunyavirus biotherapeutics. The method was validated using the zoonotic Rift Valley fever virus (RVFV) and Schmallenberg virus (SBV), an emerging pathogen of ruminants, as model pathogens. VHH building blocks were assembled into highly potent neutralizing complexes using bacterial superglue technology. The multimeric complexes were shown to reduce and prevent virus-induced morbidity and mortality in mice upon prophylactic administration. Bispecific molecules engineered to present two different VHHs fused to an Fc domain were further shown to be effective upon therapeutic administration. The presented VHH-based technology holds great promise for the development of bunyavirus antiviral therapies.
Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma
Authors: Murata Kenji , Nakatsugawa Munehide , Rahman Muhammed A , Nguyen Linh T , Millar Douglas G , Mulder David T , Sugata Kenji , Saijo Hiroshi , Matsunaga Yukiko , Kagoya Yuki , Guo Tingxi , Anczurowski Mark , Wang Chung-Hsi , Burt Brian D , Ly Dalam , Saso Kayoko , Easson Alexandra , Goldstein David P , Reedijk Michael , Ghazarian Danny , Pugh Trevor J , Butler Marcus O , Mak Tak W , Ohashi Pamela S , Hirano Naoto
Published: April 2020

HLA-restricted T cell responses can induce antitumor effects in cancer patients. Previous human T cell research has largely focused on the few HLA alleles prevalent in a subset of ethnic groups. Here, using a panel of newly developed peptide-exchangeable peptide/HLA multimers and artificial antigen-presenting cells for 25 different class I alleles and greater than 800 peptides, we systematically and comprehensively mapped shared antigenic epitopes recognized by tumor-infiltrating T lymphocytes (TILs) from eight melanoma patients for all their class I alleles. We were able to determine the specificity, on average, of 12.2% of the TILs recognizing a mean of 3.1 shared antigen-derived epitopes across HLA-A, B, and C. Furthermore, we isolated a number of cognate T cell receptor genes with tumor reactivity. Our novel strategy allows for a more complete examination of the immune response and development of novel cancer immunotherapy not limited by HLA allele prevalence or tumor mutation burden.
Activated αIIbβ3 on platelets mediates flow-dependent NETosis via SLC44A2
Authors: Constantinescu-Bercu Adela , Grassi Luigi , Frontini Mattia , Salles-Crawley Isabelle I , Woollard Kevin , Crawley James TB
Published: April 2020

Platelet-neutrophil interactions are important for innate immunity, but also contribute to the pathogenesis of deep vein thrombosis, myocardial infarction and stroke. Here we report that, under flow, von Willebrand factor/glycoprotein Ibα-dependent platelet ‘priming’ induces integrin αIIbβ3activation that, in turn, mediates neutrophil and T-cell binding. Binding of platelet αIIbβ3to SLC44A2 on neutrophils leads to mechanosensitive-dependent production of highly prothrombotic neutrophil extracellular traps. A polymorphism inSLC44A2(rs2288904-A) present in 22% of the population causes an R154Q substitution in an extracellular loop of SLC44A2 that is protective against venous thrombosis results in severely impaired binding to both activated αIIbβ3and VWF-primed platelets. This was confirmed using neutrophils homozygous for theSLC44A2R154Q polymorphism. Taken together, these data reveal a previously unreported mode of platelet-neutrophil crosstalk, mechanosensitive NET production, and provide mechanistic insight into the protective effect of theSLC44A2rs2288904-A polymorphism in venous thrombosis.
EphA7 promotes myogenic differentiation via cell-cell contact
Authors: Arnold Laura L , Cecchini Alessandra , Stark Danny A , Ihnat Jacqueline , Craigg Rebecca N , Carter Amory , Zino Sammy , Cornelison DDW
Published: April 2020

The conversion of proliferating skeletal muscle precursors (myoblasts) to terminally-differentiated myocytes is a critical step in skeletal muscle development and repair. We show that EphA7, a juxtacrine signaling receptor, is expressed on myocytes during embryonic and fetal myogenesis and on nascent myofibers during muscle regeneration in vivo. In EphA7-/- mice, hindlimb muscles possess fewer myofibers at birth, and those myofibers are reduced in size and have fewer myonuclei and reduced overall numbers of precursor cells throughout postnatal life. Adult EphA7-/- mice have reduced numbers of satellite cells and exhibit delayed and protracted muscle regeneration, and satellite cell-derived myogenic cells from EphA7-/- mice are delayed in their expression of differentiation markers in vitro. Exogenous EphA7 extracellular domain will rescue the null phenotype in vitro, and will also enhance commitment to differentiation in WT cells. We propose a model in which EphA7 expression on differentiated myocytes promotes commitment of adjacent myoblasts to terminal differentiation.
Slo2 potassium channel function depends on RNA editing-regulated expression of a SCYL1 protein
Authors: Niu Long-Gang , Liu Ping , Wang Zhao-Wen , Chen Bojun
Published: April 2020

Slo2 potassium channels play important roles in neuronal function, and their mutations in humans may cause epilepsies and cognitive defects. However, it is largely unknown how Slo2 is regulated by other proteins. Here we show that the function of C. elegans Slo2 (SLO-2) depends on adr-1, a gene important to RNA editing. ADR-1 promotes SLO-2 function not by editing the transcripts of slo-2 but those of scyl-1, which encodes an orthologue of mammalian SCYL1. Transcripts of scyl-1 are greatly decreased in adr-1 mutants due to deficient RNA editing at a single adenosine in their 3’-UTR. SCYL-1 physically interacts with SLO-2 in neurons. Single-channel open probability (Po) of neuronal SLO-2 is ~50% lower in scyl-1 knockout mutant than wild type. Moreover, human Slo2.2/Slack Po is doubled by SCYL1 in a heterologous expression system. These results suggest that SCYL-1/SCYL1 is an evolutionarily conserved regulator of Slo2 channels.
Vascular permeability in retinopathy is regulated by VEGFR2 Y949 signaling to VE-cadherin
Authors: Smith Ross O , Ninchoji Takeshi , Gordon Emma , André Helder , Dejana Elisabetta , Vestweber Dietmar , Kvanta Anders , Claesson-Welsh Lena
Published: April 2020

Edema stemming from leaky blood vessels is common in eye diseases such as age-related macular degeneration and diabetic retinopathy. Whereas therapies targeting vascular endothelial growth factor A (VEGFA) can suppress leakage, side-effects include vascular rarefaction and geographic atrophy. By challenging mouse models representing different steps in VEGFA/VEGF receptor 2 (VEGFR2)-induced vascular permeability, we show that targeting signaling downstream of VEGFR2 pY949 limits vascular permeability in retinopathy induced by high oxygen or by laser-wounding. Although suppressed permeability is accompanied by reduced pathological neoangiogenesis in oxygen-induced retinopathy, similarly sized lesions leak less in mutant mice, separating regulation of permeability from angiogenesis. Strikingly, vascular endothelial (VE)-cadherin phosphorylation at the Y685, but not Y658, residue is reduced when VEGFR2 pY949 signaling is impaired. These findings support a mechanism whereby VE-cadherin Y685 phosphorylation is selectively associated with excessive vascular leakage. Therapeutically, targeting VEGFR2-regulated VE-cadherin phosphorylation could suppress edema while leaving other VEGFR2-dependent functions intact.
A neuropeptide regulates fighting behavior in Drosophila melanogaster
Authors: Wu Fengming , Deng Bowen , Xiao Na , Wang Tao , Li Yining , Wang Rencong , Shi Kai , Luo Dong-Gen , Rao Yi , Zhou Chuan
Published: April 2020

Aggressive behavior is regulated by various neuromodulators such as neuropeptides and biogenic amines. Here we found that the neuropeptide Drosulfakinin (Dsk) modulates aggression in Drosophila melanogaster. Knock-out of Dsk or Dsk receptor CCKLR-17D1 reduced aggression. Activation and inactivation of Dsk-expressing neurons increased and decreased male aggressive behavior, respectively. Moreover, data from transsynaptic tracing, electrophysiology and behavioral epistasis reveal that Dsk-expressing neurons function downstream of a subset of P1 neurons (P1a-splitGAL4) to control fighting behavior. In addition, winners show increased calcium activity in Dsk-expressing neurons. Conditional overexpression of Dsk promotes social dominance, suggesting a positive correlation between Dsk signaling and winning effects. The mammalian ortholog CCK has been implicated in mammal aggression, thus our work suggests a conserved neuromodulatory system for the modulation of aggressive behavior.
The evolutionary history and genomics of European blackcap migration
Authors: Delmore Kira , Illera Juan Carlos , Pérez-Tris Javier , Segelbacher Gernot , Lugo Ramos Juan S , Durieux Gillian , Ishigohoka Jun , Liedvogel Miriam
Published: April 2020

Seasonal migration is a taxonomically widespread behaviour that integrates across many traits. The European blackcap exhibits enormous variation in migration and is renowned for research on its evolution and genetic basis. We assembled a reference genome for blackcaps and obtained whole genome resequencing data from individuals across its breeding range. Analyses of population structure and demography suggested divergence began ~30,000 ya, with evidence for one admixture event between migrant and resident continent birds ~5000 ya. The propensity to migrate, orientation and distance of migration all map to a small number of genomic regions that do not overlap with results from other species, suggesting that there are multiple ways to generate variation in migration. Strongly associated single nucleotide polymorphisms (SNPs) were located in regulatory regions of candidate genes that may serve as major regulators of the migratory syndrome. Evidence for selection on shared variation was documented, providing a mechanism by which rapid changes may evolve.
A discrete subtype of neural progenitor crucial for cortical folding in the gyrencephalic mammalian brain
Authors: Matsumoto Naoyuki , Tanaka Satoshi , Horiike Toshihide , Shinmyo Yohei , Kawasaki Hiroshi
Published: April 2020

An increase in the diversity of neural progenitor subtypes and folding of the cerebral cortex are characteristic features which appeared during the evolution of the mammalian brain. Here, we show that the expansion of a specific subtype of neural progenitor is crucial for cortical folding. We found that outer radial glial (oRG) cells can be subdivided by HOPX expression in the gyrencephalic cerebral cortex of ferrets. Compared with HOPX-negative oRG cells, HOPX-positive oRG cells had high self-renewal activity and were accumulated in prospective gyral regions. Using our in vivo genetic manipulation technique for ferrets, we found that the number of HOPX-positive oRG cells and their self-renewal activity were regulated by sonic hedgehog (Shh) signaling. Importantly, suppressing Shh signaling reduced HOPX-positive oRG cells and cortical folding, while enhancing it had opposing effects. Our results reveal a novel subtype of neural progenitor important for cortical folding in gyrencephalic mammalian cerebral cortex.
Population coupling predicts the plasticity of stimulus responses in cortical circuits
Authors: Sweeney Yann , Clopath Claudia
Published: April 2020

Some neurons have stimulus responses that are stable over days, whereas other neurons have highly plastic stimulus responses. Using a recurrent network model, we explore whether this could be due to an underlying diversity in their synaptic plasticity. We find that, in a network with diverse learning rates, neurons with fast rates are more coupled to population activity than neurons with slow rates. This plasticity-coupling link predicts that neurons with high population coupling exhibit more long-term stimulus response variability than neurons with low population coupling. We substantiate this prediction using recordings from the Allen Brain Observatory, finding that a neuron’s population coupling is correlated with the plasticity of its orientation preference. Simulations of a simple perceptual learning task suggest a particular functional architecture: a stable ‘backbone’ of stimulus representation formed by neurons with low population coupling, on top of which lies a flexible substrate of neurons with high population coupling.
Pseudogenes, RNAs and new reproducibility norms
Authors: Calin George A
Published: April 2020

The partial success of a study to reproduce experiments that linked pseudogenes and cancer proves that understanding RNA networks is more complicated than expected.
Data-driven classification of the certainty of scholarly assertions
Authors: Prieto Mario , Deus Helena , de Waard Anita , Schultes Erik , García-Jiménez Beatriz , Wilkinson Mark D.
Published: April 2020

The grammatical structures scholars use to express their assertions are intended to convey various degrees of certainty or speculation. Prior studies have suggested a variety of categorization systems for scholarly certainty; however, these have not been objectively tested for their validity, particularly with respect to representing the interpretation by the reader, rather than the intention of the author. In this study, we use a series of questionnaires to determine how researchers classify various scholarly assertions, using three distinct certainty classification systems. We find that there are three distinct categories of certainty along a spectrum from high to low. We show that these categories can be detected in an automated manner, using a machine learning model, with a cross-validation accuracy of 89.2% relative to an author-annotated corpus, and 82.2% accuracy against a publicly-annotated corpus. This finding provides an opportunity for contextual metadata related to certainty to be captured as a part of text-mining pipelines, which currently miss these subtle linguistic cues. We provide an exemplar machine-accessible representation—a Nanopublication—where certainty category is embedded as metadata in a formal, ontology-based manner within text-mined scholarly assertions.