bluuebunny/crossref_metadata_2025 huggingface dataset:
Meningococcal carriage by age in the African meningitis belt: a systematic review and meta-analysis
Authors: Cooper L. V. , Kristiansen P. A. , Christensen H. , Karachaliou A. , Trotter C. L.
Published: June 2019

Meningococcal carriage dynamics drive patterns of invasive disease. The distribution of carriage by age has been well described in Europe, but not in the African meningitis belt, a region characterised by frequent epidemics of meningitis. We aimed to estimate the age-specific prevalence of meningococcal carriage by season in the African meningitis belt. We searched PubMed, Web of Science, the Cochrane Library and grey literature for papers reporting carriage of Neisseria meningitidis in defined age groups in the African meningitis belt. We used a mixed-effects logistic regression to model meningococcal carriage prevalence as a function of age, adjusting for season, location and year. Carriage prevalence increased from low prevalence in infants (0.595% in the rainy season, 95% CI 0.482–0.852%) to a broad peak at age 10 (1.94%, 95% CI 1.87–2.47%), then decreased in adolescence. The odds of carriage were significantly increased during the dry season (OR 1.5 95% CI 1.4–1.7) and during outbreaks (OR 6.7 95% CI 1.6–29). Meningococcal carriage in the African meningitis belt peaks at a younger age compared to Europe. This is consistent with contact studies in Africa, which show that children 10–14 years have the highest frequency of contacts. Targeting older children in Africa for conjugate vaccination may be effective in reducing meningococcal transmission.
A natural barrier in random greedy hypergraph matching
Authors: Bennett Patrick , Bohman Tom
Published: June 2019

Letr⩾ 2 be a fixed constant and let$ {\cal H} $be anr-uniform,D-regular hypergraph onNvertices. Assume further thatD→ ∞ asN→ ∞ and that degrees of pairs of vertices in$ {\cal H} $are at mostLwhereL=D/( logN)ω(1). We consider the random greedy algorithm for forming a matching in$ {\cal H} $. We choose a matching at random by iteratively choosing edges uniformly at random to be in the matching and deleting all edges that share at least one vertex with a chosen edge before moving on to the next choice. This process terminates when there are no edges remaining in the graph. We show that with high probability the proportion of vertices of$ {\cal H} $that are not saturated by the final matching is at most (L/D)(1/(2(r−1)))+o(1). This point is a natural barrier in the analysis of the random greedy hypergraph matching process.
Molding the shape of congenial and structural interventional cardiology: interviews with directors of major congresses
Authors: Goreczny Sebastian , Hijazi Ziyad M. , Qureshi Shakeel A. , Carminati Mario , Kenny Damien , Morgan Gareth J.
Published: June 2019

The range and number of educational and networking events that are available for fellows, trainees, and junior faculty to attend grows every year. Each meeting useful in its own way; each adding value to the development and the growth of an interventionist. Within paediatric, congenital, and structural heart disease, three of the standout meetings are: Pediatric and Interventional Cardiac Symposium (PICS-AICS), Congenital and Structural Interventions (CSI), and International Workshop on Interventional Pediatric and Adult Congenital Cardiology (IPC). All of these were started by leaders in our field; people known to be passionate educators and innovators. International congresses focusing more broadly on congenital cardiac disease in children and adults are rare. These forums allow more interdisciplinary discussions between the interventionist, surgeon, and non-invasive specialists. Purely interventional meetings are essential to allow colleagues to debate and explore the nuances and intricacies of technique and approach, developing concepts to be challenged in wider forums. During the recent 21st PICS-AICS meeting Prof. Ziyad M. Hijazi, Shakeel A. Qureshi, Mario Carminati, and Dr Damien Kenny shared their time to engage in frank, recorded conversations which provide a unique insight in to the process and concepts behind three of our most important educational congresses.
The Carle-Illinois (Urbana, Illinois USA) Treatment Protocol for Law Enforcement K9s: Guidelines for Emergency Medical Services
Authors: Mitek Ashley E. , McMichael Maureen A. , Weir William B. , Smith Michael J. , Schneider Danielle C.
Published: June 2019

This document is a resource for Emergency Medical Services (EMS) treating an injured law enforcement K9 (LEK9) in the field and/or during transport by ambulance to a veterinary hospital. A Joint Task Force on Working Dog Care was created, which included veterinarians, EMS directors, EMS physicians, and canine handlers, who met to develop a treatment protocol for injured LEK9s. The protocol covers many major life-threatening injuries that LEK9s may sustain in the line of duty, and also discusses personnel safety and necessary equipment. This protocol may help train EMS providers to save the life of an injured LEK9.
Institutions, Ideologies, and Comparative Political Theory
Authors: Simon Joshua
Published: June 2019

The growing prominence of comparative political theory has inspired extensive and fruitful methodological reflection, raising important questions about the procedures that political theorists should apply when they select texts for study, interpret their passages, and assess their arguments. But, notably, comparative political theorists have mainly rejected the comparative methods used in the subfield of comparative politics, because they argue that applying the comparative method would compromise both the interpretive and the critical projects that comparative political theory should pursue. In this article, I describe a comparative approach for the study of political ideas that offers unique insight into how the intellectual and institutional contexts that political thinkers occupy influence their ideas. By systematically describing how political thinking varies across time and over space in relation to the contexts within which political thinkers live and work, the comparative method can serve as the foundation for both deconstructive critiques, which reveal the partial interests that political ideas presented as universally advantageous actually serve, and reconstructive critiques, which identify particular thinkers or traditions of political thought that, because of the contexts in which they developed, offer compelling critical perspectives on existing political institutions.
Konstruktvalidität eines universellen Screenings zur unterrichtsnahen und ökonomischen Diagnostik herausfordernden Verhaltens von Schüler_innen – eine Multitrait-Multimethod-Analyse
Authors: Casale Gino , Volpe Robert J. , Hennemann Thomas , Briesch Amy M. , Daniels Brian , Grosche Michael
Published: June 2019

Zusammenfassung. Die vorliegende Untersuchung überprüft die Konstruktvalidität einer 16 Items umfassenden Kurzversion der Integrated Teacher Report Form (ITRF), einem universellen und unterrichtsrelevanten Verhaltensscreening zur Diagnostik des externalisierenden Verhaltens von Schüler_innen im Klassenraum. 107 Lehrkräfte bearbeiteten für insgesamt 1048 Schülerinnen und Schüler der ersten bis sechsten Klasse die ITRF sowie zusätzlich jeweils eines von drei im deutschsprachigen Raum etablierten Beurteilungsverfahren. Die Analyse der konvergenten und diskriminanten Validität erfolgt anhand einer Multitrait-Multimethod (MT-MM) Korrelationsmatrix sowie einem strukturprüfenden Correlated Trait-Correlated Method minus 1 [CT-C(M-1)] Modell zur separaten Analyse des Einflusses der Konstrukte (lernbezogene / aufmerksame Verhaltensprobleme, oppositionelle / störende Verhaltensprobleme) und der Methoden (ITRF, zusätzliches Beurteilungsverfahren) auf die erzielten Werte der Beurteilungen. Die Ergebnisse zeigen, dass sich die Stärke der theoretisch postulierten Korrelationen mit den empirischen Daten erwartungskonform abbilden lassen, was auf konvergente und diskriminante Validität hinweist. Die Varianz der ITRF-Werte lässt sich zu einem größeren Anteil durch das zu messende Konstrukt als durch methodenspezifische Einflüsse erklären. Somit liefern unsere Befunde Evidenz für eine angemessene Konstruktvalidität des Verfahrens, weshalb sich die Kurzversion der ITRF für den praktischen Schuleinsatz eignet.
Betriebliche Ausbildungsbedingungen im dualen System – Eine qualitative Meta-Analyse zur Operationalisierung in Auszubildendenbefragungen
Authors: Böhn Svenja , Deutscher Viola
Published: June 2019

Zusammenfassung. Der Frage nach betrieblichen Ausbildungsbedingungen im dualen System kommt nicht zuletzt vor dem Hintergrund steigender unbesetzter Ausbildungsstellen eine hohe Bedeutung zu. Nach wie vor stellt die schriftliche Befragung von Auszubildenden die gängigste Form des Forschungszugangs dar. Bezüglich der Operationalisierung der Charakteristika betrieblicher Ausbildungsbedingungen liegen mittlerweile diverse Testinstrumente vor, deren heterogene Ausgestaltung eine studienübergreifende Betrachtung des Forschungsstandes erschweren. Der Beitrag versucht vor diesem Hintergrund einen Überblick über existierende Testinstrumente zu geben, die auf die Erfassung der Merkmale des Lernens am Arbeitsplatz in der dualen Berufsausbildung abzielen. Diese Zusammenführung und Systematisierung von Items und Skalen erfolgt in Form einer qualitativen Meta-Analyse unter Rückgriff auf 43 standardisierte Befragungsinstrumente mit mehr als 3.300 Items. Angelehnt an das 3-P-Modell von Tynjälä (2013) können die Instrumente zu den betrieblichen Ausbildungsbedingungen im Ergebnis anhand von 30 Kategorien in acht Inhaltsbereiche und fünf Dimensionen inhaltlich ausdifferenziert werden. Dieses Kategoriensystem liefert zunächst einen Überblick über die aktuelle Operationalisierung betrieblicher Ausbildungsbedingungen in Form von zentralen Kategorien. Des Weiteren werden die konkreten Inhaltsbereiche und einzelnen Items transparent, die derzeit in der Forschungspraxis verwendet werden und prinzipiell für Studien zur Verfügung stehen. Damit die Befunde praktischen Nutzen für die Forschungscommunity entfalten können, wird ein Online-Itemkatalog sowie eine Übersicht zu bisher validierten Skalen und Items vorgelegt. Damit sollen künftig zum einen unnötige Neukonstruktionen von Items und Skalen vermieden werden, indem auf bestehende Testinstrumente zurückgegriffen wird. Zum anderen können Reliabilitätsanalysen angeregt werden, die bisher nur für eine Minderheit der Testinstrumente vorliegen. Weiterhin können auf Basis des 3-P-Modells längsschnittlich angelegte Analysen hinsichtlich der Zusammenhänge zwischen Input-, Prozess- und Outputvariablen unterstützt und vergleichende quantitative Meta-Analysen vereinfacht werden, indem Schwierigkeiten hinsichtlich der Einordnung der Ergebnisse über das Kategoriensystem vermieden werden.
Bedingungen und Wirkung des elterlichen Engagements bei Schülerinnen und Schülern mit einer Lese-Rechtschreibstörung
Authors: Fritzler Nicole Jacqueline , Wild Elke
Published: June 2019

Zusammenfassung. Basierend auf NEPS-Daten (Startkohorte Klasse 5) werden Bedingungen (ökonomische, kulturelle, zeitliche Ressourcen; Lese- / Rechtschreibkompetenz) des elterlichen schulbezogenen Engagements (Nachhilfenutzung, Kontrolle / Anforderung, Emotionale Unterstützung / Responsivität) von Sekundarstufenschülerinnen und -schülern mit einer Lese-Rechtschreibstörung analysiert ( N = 216). Überdies wird im Längsschnitt die Lese- / Rechtschreibentwicklung (5., 7., 9. Klasse) sowie der Einfluss des elterlichen Engagements auf diese untersucht. Strukturgleichungsmodelle zeigen negative Zusammenhänge der (kulturellen sowie ökonomischen) Ressourcen sowie der Lese- / Rechtschreibkompetenz zur Nachhilfenutzung, wobei hinsichtlich der kulturellen Ressourcen Hinweise auf eine partielle Mediation der Lese- / Rechtschreibkompetenz beobachtet werden. Außerdem sind die kulturellen Ressourcen positiv mit der emotionalen Unterstützung / Responsivität assoziiert. Die Lese- / Rechtschreibkompetenz weist negative Zusammenhänge zu Kontrolle / Anforderung auf. Latente Wachstumskurvenmodelle deuten auf eine Verbesserung der Lesekompetenz sowie einen positiven Einfluss emotionaler Unterstützung / Responsivität auf diese. Praktische Implikationen für die Qualitätssicherung von Bildungsangeboten sowie für die schulische Elternarbeit werden diskutiert.
Satellite Observations of the Diurnal Dynamics of Particulate Organic Carbon in Optically Complex Coastal Oceans: The Continental Shelf Seas of China
Authors: Wei Xiaodao , Shen Fang , Pan Yanqun , Chen Shuguo , Sun Xuerong , Wang Yongchao
Published: June 2019

The continental shelf seas of China (CSSC) broadly encompass the Bohai Sea, the Yellow Sea, and the East China Sea and exhibit highly variable optical properties. Accurate satellite estimates of particulate organic carbon (POC) remain challenging because optimal proxies for remotely sensed POC are largely obscure in these optically complex coastal waters. In this study, optical and biogeochemical data, including the particulate beam attenuation coefficient (cp), particulate backscattering coefficient (bbp), remote sensing reflectance (Rrs), POC, total suspended matter (TSM), and chlorophyll‐a (Chla), were collected over multiple seasons and years in the CSSC. We first classified the study area into three different water types with three different POC retrieval proxies: the TSM for high‐TSM waters, Chla for low‐TSM waters, and Rrs ratio (Rrs(490)/Rrs(555)) for moderate‐TSM waters. A composite POC algorithm using these three optimal proxies was then developed for Geostationary Ocean Color Imager (GOCI) satellite data (hereafter called the POC_CSSC algorithm). The validation results indicated that the accuracy of GOCI‐derived POC was greatly improved with a mean relative error of 32.08%. Application of the POC_CSSC algorithm to GOCI data over a tidally impacted estuary demonstrated the robustness of the algorithm and that tides play different roles in the broad CSSC. More specifically, tides have the strongest influence on nearshore estuarine waters, regulating the progression of high‐POC water masses from estuary to offshore environments, while offshore waters were the least influenced by tides with less variable, low POC concentrations.
Exchange of Water Between the Ross Gyre and ACC Assessed by Lagrangian Particle Tracking
Authors: Roach Christopher J. , Speer Kevin
Published: June 2019

To reach upwelling and downwelling zones deep within the Southern Ocean seasonal sea ice cover, water masses must move across the Antarctic Circumpolar Current and through current systems including the Ross Gyre, Weddell Gyre, and Antarctic Slope Current. In this study we focus our attention on the Lagrangian exchange between the Ross Gyre and surrounding current systems. We conducted numerical experiments using five‐day 3‐D velocity fields from the Southern Ocean State Estimate with a particle tracking package to identify pathways by which waters move from near the Antarctic coastal margins or Antarctic Circumpolar Current into the interior of the Ross Gyre, and to identify the time scales of variability associated with these pathways. Waters from near the Antarctic margins enter the Ross Gyre along the western and northern boundaries of gyre until the gyre separates from the Pacific‐Antarctic Ridge near fracture zones. At this juncture, Antarctic Circumpolar Current‐derived inflow dominates the across‐gyre transport up to the Antarctic margin. Transport and exchange associated with different time‐average components of flow are calculated to determine the relative contributions of high‐ and low‐frequency and time‐mean components.
Can Convolution and Deconvolution Be Used as Tools for Modeling Multicomponent, Mixing‐Limited Reaction Networks?
Authors: Engdahl Nicholas B. , McCallum James L. , Ginn Timothy R.
Published: June 2019

Transfer functions (i.e., convolutions) have been powerful tools for both forward modeling and reconstructing past states of transport systems in a wide range of subsurface flow problems. The advantage of the transfer function is that it is a simple alternative to complicated, distributed parameter models of flow and transport, but the majority of applications of transfer functions in hydrology have been limited to relatively simple cases, like passive tracers or first‐order decay. The central question evaluated in this note is whether or not multicomponent mixing‐limited reactive transport can be represented within a transfer function framework. Our examples consider forward‐in‐time predictions and backward‐in‐time reconstructions of a carbonate system that represents the intrusion of seawater into a freshwater aquifer. The main result is that accurate forward‐in‐time and backward‐in‐time models are developed by posing the problem in terms of conservative components. As with all convolution‐based methods, the results are sensitive to errors and/or noise in the input functions, but we show that smoothed approximations of the requisite functions provide good representations of transport. Given the vast unknowns in any subsurface transport problem, such generalized, reactive transfer function models may have yet unexplored advantages when the trade‐offs between overall computational cost, accuracy, and uncertainty are explored in more detail.
Surveys Say Climate Change Is a Top Election Issue for Democrats
Authors: Showstack Randy
Published: June 2019

As Democratic candidates debate in Miami, Fla., new surveys indicate that climate change and clean energy are among the top priorities for Democratic voters in 2020.
Coupled External‐Internal Dynamics of Layered Circulation in the South China Sea: A Modeling Study
Authors: Cai Zhongya , Gan Jianping
Published: June 2019

The external inflow/outflow through straits on the periphery of the South China Sea (SCS) and the associated internal response of vertical transport over the broad continental slope form and sustain a cyclonic‐anticyclonic‐cyclonic (CAC) circulation in the upper‐middle‐lower layer in the SCS. We conduct a process‐oriented numerical study to investigate the underlying coupled external‐internal dynamics that remains unknown, despite that the dynamics plays a critical role in forming and sustaining the CAC circulation. External sandwich‐like inflow‐outflow‐inflow in the water column through the Luzon Strait forms a three‐dimensional CAC slope current over the curving slope topography in the SCS basin, in which the downward/upward transport associated with the cross‐slope motion is established. The along‐slope current over the basin provides vorticity through the beta effect and accounts for the most external planetary vorticity input through the strait in the upper layer of the SCS, while the vorticity induced by the vertical transport is the major response to the external vorticity flux in the middle and lower layers. We illustrate the critical role of the vertical transport in linking the vorticity among the different layers for the development and sustenance of the CAC circulation. The vertical transport is associated with the cross‐slope motion due to slope current‐topography interaction, which involves mainly in bottom frictional transport and geostrophic cross‐isobath transport by the pressure gradient force in the along‐slope direction. Pressure gradient force is generated by nonlinear vorticity advection and the beta effect of the background slope current.
Phosphate availability affects fixed nitrogen transfer from diazotrophs to their epibionts
Authors: Schoffelen Niels J , Mohr Wiebke , Ferdelman Timothy G , Duerschlag Julia , Littmann Sten , Ploug Helle , Kuypers Marcel M M
Published: June 2019

Dinitrogen (N2) fixation is a major source of external nitrogen (N) to aquatic ecosystems and therefore exerts control over productivity. Studies have shown that N2 -fixers release freshly fixed N into the environment, but the causes for this N release are largely unclear. Here, we show that the availability of phosphate can directly affect the transfer of freshly fixed N to epibionts in filamentous, diazotrophic cyanobacteria. Stable-isotope incubations coupled to single-cell analyses showed that <1% and ~15% of freshly fixed N was transferred to epibionts of Aphanizomenon and Nodularia, respectively, at phosphate scarcity during a summer bloom in the Baltic Sea. When phosphate was added, the transfer of freshly fixed N to epibionts dropped to about half for Nodularia, whereas the release from Aphanizomenon increased slightly. At the same time, the growth rate of Nodularia roughly doubled, indicating that less freshly fixed N was released and was used for biomass production instead. Phosphate scarcity and the resulting release of freshly fixed N could explain the heavy colonization of Nodularia filaments by microorganisms during summer blooms. As such, the availability of phosphate may directly affect the partitioning of fixed N2 in colonies of diazotrophic cyanobacteria and may impact the interactions with their microbiome.
Bleaching forces coral’s heterotrophy on diazotrophs and Synechococcus
Authors: Meunier Valentine , Bonnet Sophie , Pernice Mathieu , Benavides Mar , Lorrain Anne , Grosso Olivier , Lambert Christophe , Houlbrèque Fanny
Published: June 2019

Coral reefs are threatened by global warming, which disrupts the symbiosis between corals and their photosynthetic symbionts (Symbiodiniaceae), leading to mass coral bleaching. Planktonic diazotrophs or dinitrogen (N2)-fixing prokaryotes are abundant in coral lagoon waters and could be an alternative nutrient source for corals. Here we incubated untreated and bleached coral colonies of Stylophora pistillata with a 15N2-pre-labelled natural plankton assemblage containing diazotrophs. 15N2 assimilation rates in Symbiodiniaceae cells and tissues of bleached corals were 5- and 30-fold higher, respectively, than those measured in untreated corals, demonstrating that corals incorporate more nitrogen derived from planktonic diazotrophs under bleaching conditions. Bleached corals also preferentially fed on Synechococcus, nitrogen-rich picophytoplanktonic cells, instead of Prochlorococcus and picoeukaryotes, which have a lower cellular nitrogen content. By providing an alternative source of bioavailable nitrogen, both the incorporation of nitrogen derived from planktonic diazotrophs and the ingestion of Synechococcus may have profound consequences for coral bleaching recovery, especially for the many coral reef ecosystems characterized by high abundance and activity of planktonic diazotrophs.
Mixed-halide perovskite synthesis by chemical reaction and crystal nucleation under an optical potential
Authors: Islam Md Jahidul , Yuyama Ken-ichi , Takahashi Kiyonori , Nakamura Takayoshi , Konishi Katsuaki , Biju Vasudevanpillai
Published: June 2019

The development of new methods to engineer lead halide perovskite crystals with a controlled band gap and emission properties is an active subject in materials science and chemistry. We present the preparation of mixed-halide lead perovskites by spatially- and temporally- controlled chemical reactions and crystal growth under an optical potential in unsaturated precursor solutions. The crystals are characterized by transmission and photoluminescence spectral measurements and X-ray diffraction analysis. When compared with the spontaneous formation of multiple crystals in saturated precursor solutions, the optical potential creates large single crystals with a high chloride composition, providing distinct blue and green fluorescent crystals of chloride–bromide lead perovskites. We discuss the formation of mixed-halide perovskites from the viewpoints of an increased rate of chemical reaction via the formation and desolvation of precursor complexes and a decreased free energy potential.
Self-assembly of correlated (Ti, V)O2 superlattices with tunable lamella periods by kinetically enhanced spinodal decomposition
Authors: Park Jaeseoung , Kim Gi-Yeop , Song Kyung , Choi Si-Young , Son Junwoo
Published: June 2019

Spinodal decomposition, the spontaneous phase separation process of periodic lamellae at the nanometer scale, of correlated oxide ((Ti, V)O2) systems offers a sophisticated route to achieve a new class of mesoscale structures in the form of self-assembled superlattices for possible applications using steep metal–insulator transitions. Here, we achieve the tunable self-assembly of (Ti, V)O2 superlattices with steep transitions (ΔTMI < 5 K) by spinodal decomposition with accurate control of the growth parameters without conventional layer-by-layer growth. Abrupt compositional modulation with alternating Ti-rich and V-rich layers spontaneously occurs along the growth direction because in-plane lattice mismatch is smaller in this direction than in other directions. An increase in the film growth rate thickens periodic alternating lamellae; the phase separation can be kinetically enhanced by adatom impingement during two-dimensional growth, demonstrating that the interplay between mass transport and uphill diffusion yields highly periodic (Ti, V)O2 superlattices with tunable lamellar periods. Our results for creating correlated (Ti, V)O2 oxide superlattices provide a new bottom-up strategy to design rutile oxide tunable nanostructures and present opportunities to design new material platforms for electronic and photonic applications with correlated oxide systems.
Interface-mediated Kirkendall effect and nanoscale void migration in bimetallic nanoparticles during interdiffusion
Authors: Chee See Wee , Wong Zicong Marvin , Baraissov Zhaslan , Tan Shu Fen , Tan Teck Leong , Mirsaidov Utkur
Published: June 2019

At elevated temperatures, bimetallic nanomaterials change their morphologies because of the interdiffusion of atomic species, which also alters their properties. The Kirkendall effect (KE) is a well-known phenomenon associated with such interdiffusion. Here, we show how KE can manifest in bimetallic nanoparticles (NPs) by following core–shell NPs of Au and Pd during heat treatment with in situ transmission electron microscopy. Unlike monometallic NPs, these core–shell NPs did not evolve into hollow core NPs. Instead, nanoscale voids formed at the bimetallic interface and then, migrated to the NP surface. Our results show that: (1) the direction of vacancy flow during interdiffusion reverses due to the higher vacancy formation energy of Pd compared to Au, and (2) nanoscale voids migrate during heating, contrary to conventional assumptions of immobile voids and void shrinkage through vacancy emission. Our results illustrate how void behavior in bimetallic NPs can differ from an idealized picture based on atomic fluxes and have important implications for the design of these materials for high-temperature applications.
Loss of the transcription factor RBPJ induces disease-promoting properties in brain pericytes
Authors: Diéguez-Hurtado Rodrigo , Kato Katsuhiro , Giaimo Benedetto Daniele , Nieminen-Kelhä Melina , Arf Hendrik , Ferrante Francesca , Bartkuhn Marek , Zimmermann Tobias , Bixel M. Gabriele , Eilken Hanna M. , Adams Susanne , Borggrefe Tilman , Vajkoczy Peter , Adams Ralf H.
Published: June 2019

Sufficient vascular supply is indispensable for brain development and function, whereas dysfunctional blood vessels are associated with human diseases such as vascular malformations, stroke or neurodegeneration. Pericytes are capillary-associated mesenchymal cells that limit vascular permeability and protect the brain by preserving blood-brain barrier integrity. Loss of pericytes has been linked to neurodegenerative changes in genetically modified mice. Here, we report that postnatal inactivation of the Rbpj gene, encoding the transcription factor RBPJ, leads to alteration of cell identity markers in brain pericytes, increases local TGFβ signalling, and triggers profound changes in endothelial behaviour. These changes, which are not mimicked by pericyte ablation, imperil vascular stability and induce the acquisition of pathological landmarks associated with cerebral cavernous malformations. In adult mice, loss of Rbpj results in bigger stroke lesions upon ischemic insult. We propose that brain pericytes can acquire deleterious properties that actively enhance vascular lesion formation and promote pathogenic processes.
Isolating hydrogen in hexagonal boron nitride bubbles by a plasma treatment
Authors: He Li , Wang Huishan , Chen Lingxiu , Wang Xiujun , Xie Hong , Jiang Chengxin , Li Chen , Elibol Kenan , Meyer Jannik , Watanabe Kenji , Taniguchi Takashi , Wu Zhangting , Wang Wenhui , Ni Zhenhua , Miao Xiangshui , Zhang Chi , Zhang Daoli , Wang Haomin , Xie Xiaoming
Published: June 2019

Atomically thin hexagonal boron nitride (h-BN) is often regarded as an elastic film that is impermeable to gases. The high stabilities in thermal and chemical properties allow h-BN to serve as a gas barrier under extreme conditions. Here, we demonstrate the isolation of hydrogen in bubbles of h-BN via plasma treatment. Detailed characterizations reveal that the substrates do not show chemical change after treatment. The bubbles are found to withstand thermal treatment in air, even at 800 °C. Scanning transmission electron microscopy investigation shows that the h-BN multilayer has a unique aligned porous stacking nature, which is essential for the character of being transparent to atomic hydrogen but impermeable to hydrogen molecules. In addition, we successfully demonstrated the extraction of hydrogen gases from gaseous compounds or mixtures containing hydrogen element. The successful production of hydrogen bubbles on h-BN flakes has potential for further application in nano/micro-electromechanical systems and hydrogen storage.
Identification of a potent benzoxaborole drug candidate for treating cryptosporidiosis
Authors: Lunde Christopher S. , Stebbins Erin E. , Jumani Rajiv S. , Hasan Md Mahmudul , Miller Peter , Barlow John , Freund Yvonne R. , Berry Pamela , Stefanakis Rianna , Gut Jiri , Rosenthal Philip J. , Love Melissa S. , McNamara Case W. , Easom Eric , Plattner Jacob J. , Jacobs Robert T. , Huston Christopher D.
Published: June 2019

Cryptosporidiosis is a leading cause of life-threatening diarrhea in young children and causes chronic diarrhea in AIDS patients, but the only approved treatment is ineffective in malnourished children and immunocompromised people. We here use a drug repositioning strategy and identify a promising anticryptosporidial drug candidate. Screening a library of benzoxaboroles comprised of analogs to four antiprotozoal chemical scaffolds under pre-clinical development for neglected tropical diseases forCryptosporidiumgrowth inhibitors identifies the 6-carboxamide benzoxaborole AN7973. AN7973 blocks intracellular parasite development, appears to be parasiticidal, and potently inhibits the twoCryptosporidiumspecies most relevant to human health,C. parvumandC. hominis. It is efficacious in murine models of both acute and established infection, and in a neonatal dairy calf model of cryptosporidiosis. AN7973 also possesses favorable safety, stability, and PK parameters, and therefore, is an exciting drug candidate for treating cryptosporidiosis.
Improving risk assessments in conservation ecology
Authors: Ono Kotaro , Langangen Øystein , Stenseth Nils Chr.
Published: June 2019

Conservation efforts and management decisions on the living environment of our planet often rely on the results from statistical models. Yet, these models are imperfect and quantification of risk associated with the estimate of management-relevant quantities becomes crucial in providing robust advice. Here we demonstrate that estimates of risk themselves could be substantially biased but by combining data fitting with an extensive simulation–estimation procedure, one can back-calculate the correct values. We apply the method to 627 time series of population abundance across four taxa using the Gompertz state-space model as an example. We find that the risk of large bias in population status estimate increases with the species’ growth rate, population variability, weaker density dependence, and shorter time series, across taxa. We urge scientists dealing with conservation and management to adopt a similar approach to ensure a more accurate estimate of risk measures and contribute towards a precautionary approach to management.
Publisher Correction: Learning relative values in the striatum induces violations of normative decision making
Authors: Klein Tilmann A. , Ullsperger Markus , Jocham Gerhard
Published: June 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Quantitative single-cell live imaging links HES5 dynamics with cell-state and fate in murine neurogenesis
Authors: Manning Cerys S. , Biga Veronica , Boyd James , Kursawe Jochen , Ymisson Bodvar , Spiller David G. , Sanderson Christopher M. , Galla Tobias , Rattray Magnus , Papalopulu Nancy
Published: June 2019

During embryogenesis cells make fate decisions within complex tissue environments. The levels and dynamics of transcription factor expression regulate these decisions. Here, we use single cell live imaging of an endogenous HES5 reporter and absolute protein quantification to gain a dynamic view of neurogenesis in the embryonic mammalian spinal cord. We report that dividing neural progenitors show both aperiodic and periodic HES5 protein fluctuations. Mathematical modelling suggests that in progenitor cells the HES5 oscillator operates close to its bifurcation boundary where stochastic conversions between dynamics are possible. HES5 expression becomes more frequently periodic as cells transition to differentiation which, coupled with an overall decline in HES5 expression, creates a transient period of oscillations with higher fold expression change. This increases the decoding capacity of HES5 oscillations and correlates with interneuron versus motor neuron cell fate. Thus, HES5 undergoes complex changes in gene expression dynamics as cells differentiate.
Bioinspired extracellular vesicles embedded with black phosphorus for molecular recognition-guided biomineralization
Authors: Wang Yingqian , Hu Xiaoxia , Zhang Lingling , Zhu Chunli , Wang Jie , Li Yingxue , Wang Yulan , Wang Can , Zhang Yufeng , Yuan Quan
Published: June 2019

Extracellular vesicles (EVs) are involved in the regulation of cell physiological activity and the reconstruction of extracellular environment. Matrix vesicles (MVs) are a type of EVs released by bone-related functional cells, and they participate in the regulation of cell mineralization. Here, we report bioinspired MVs embedded with black phosphorus (BP) and functionalized with cell-specific aptamer (denoted as Apt-bioinspired MVs) for stimulating biomineralization. The aptamer can direct bioinspired MVs to targeted cells, and the increasing concentration of inorganic phosphate originating from BP can facilitate cell biomineralization. The photothermal effect of the Apt-bioinspired MVs can also promote the biomineralization process by stimulating the upregulated expression of heat shock proteins and alkaline phosphatase. In addition, the Apt-bioinspired MVs display outstanding bone regeneration performance. Our strategy provides a method for designing bionic tools to study the mechanisms of biological processes and advance the development of medical engineering.
The repressive role of Arabidopsis H2A.Z in transcriptional regulation depends on AtBMI1 activity
Authors: Gómez-Zambrano Ángeles , Merini Wiam , Calonje Myriam
Published: June 2019

H2A.Z variant has emerged as a critical player in regulating plant responses to environment; however, the mechanism by which H2A.Z mediates this regulation remains unclear. In Arabidopsis, H2A.Z has been proposed to have opposite effects on transcription depending on its localization within the gene. These opposite roles have been assigned by correlating gene expression and H2A.Z enrichment analyses but without considering the impact of possible H2A.Z post-translational modifications. Here, we show that H2A.Z can be monoubiquitinated by the PRC1 components AtBMI1A/B/C. The incorporation of this modification is required for H2A.Z-mediated transcriptional repression through a mechanism that does not require PRC2 activity. Our data suggest that the dual role of H2A.Z in regulating gene expression depends on the modification that it carries, while the levels of H2A.Z within genes depend on the transcriptional activity.
Mesophyll porosity is modulated by the presence of functional stomata
Authors: Lundgren Marjorie R. , Mathers Andrew , Baillie Alice L. , Dunn Jessica , Wilson Matthew J. , Hunt Lee , Pajor Radoslaw , Fradera-Soler Marc , Rolfe Stephen , Osborne Colin P. , Sturrock Craig J. , Gray Julie E. , Mooney Sacha J. , Fleming Andrew J.
Published: June 2019

The formation of stomata and leaf mesophyll airspace must be coordinated to establish an efficient and robust network that facilitates gas exchange for photosynthesis, however the mechanism by which this coordinated development occurs remains unclear. Here, we combine microCT and gas exchange analyses with measures of stomatal size and patterning in a range of wild, domesticated and transgenic lines of wheat and Arabidopsis to show that mesophyll airspace formation is linked to stomatal function in both monocots and eudicots. Our results support the hypothesis that gas flux via stomatal pores influences the degree and spatial patterning of mesophyll airspace formation, and indicate that this relationship has been selected for during the evolution of modern wheat. We propose that the coordination of stomata and mesophyll airspace pattern underpins water use efficiency in crops, providing a target for future improvement.
A split fluorescent reporter with rapid and reversible complementation
Authors: Tebo Alison G. , Gautier Arnaud
Published: June 2019

Interactions between proteins play an essential role in metabolic and signaling pathways, cellular processes and organismal systems. We report the development of splitFAST, a fluorescence complementation system for the visualization of transient protein-protein interactions in living cells. Engineered from the fluorogenic reporter FAST (Fluorescence-Activating and absorption-Shifting Tag), which specifically and reversibly binds fluorogenic hydroxybenzylidene rhodanine (HBR) analogs, splitFAST displays rapid and reversible complementation, allowing the real-time visualization of both the formation and the dissociation of a protein assembly.
A single-nucleus RNA-sequencing pipeline to decipher the molecular anatomy and pathophysiology of human kidneys
Authors: Lake Blue B. , Chen Song , Hoshi Masato , Plongthongkum Nongluk , Salamon Diane , Knoten Amanda , Vijayan Anitha , Venkatesh Ramakrishna , Kim Eric H. , Gao Derek , Gaut Joseph , Zhang Kun , Jain Sanjay
Published: June 2019

Defining cellular and molecular identities within the kidney is necessary to understand its organization and function in health and disease. Here we demonstrate a reproducible method with minimal artifacts for single-nucleus Droplet-based RNA sequencing (snDrop-Seq) that we use to resolve thirty distinct cell populations in human adult kidney. We define molecular transition states along more than ten nephron segments spanning two major kidney regions. We further delineate cell type-specific expression of genes associated with chronic kidney disease, diabetes and hypertension, providing insight into possible targeted therapies. This includes expression of a hypertension-associated mechano-sensory ion channel in mesangial cells, and identification of proximal tubule cell populations defined by pathogenic expression signatures. Our fully optimized, quality-controlled transcriptomic profiling pipeline constitutes a tool for the generation of healthy and diseased molecular atlases applicable to clinical samples.
STING induces early IFN-β in the liver and constrains myeloid cell-mediated dissemination of murine cytomegalovirus
Authors: Tegtmeyer Pia-Katharina , Spanier Julia , Borst Katharina , Becker Jennifer , Riedl André , Hirche Christoph , Ghita Luca , Skerra Jennifer , Baumann Kira , Lienenklaus Stefan , Doering Marius , Ruzsics Zsolt , Kalinke Ulrich
Published: June 2019

Cytomegalovirus is a DNA-encoded β-herpesvirus that induces STING-dependent type 1 interferon responses in macrophages and uses myeloid cells as a vehicle for dissemination. Here we report that STING knockout mice are as resistant to murine cytomegalovirus (MCMV) infection as wild-type controls, whereas mice with a combined Toll-like receptor/RIG-I-like receptor/STING signaling deficiency do not mount type 1 interferon responses and succumb to the infection. Although STING alone is dispensable for survival, early IFN-β induction in Kupffer cells is STING-dependent and controls early hepatic virus propagation. Infection experiments with an inducible reporter MCMV show that STING constrains MCMV replication in myeloid cells and limits viral dissemination via these cells. By contrast, restriction of viral dissemination from hepatocytes to other organs is independent of STING. Thus, during MCMV infection STING is involved in early IFN-β induction in Kupffer cells and the restriction of viral dissemination via myeloid cells, whereas it is dispensable for survival.
Author Correction: Regulation of T cell afferent lymphatic migration by targeting LTβR-mediated non-classical NFκB signaling
Authors: Piao Wenji , Xiong Yanbao , Famulski Konrad , Brinkman C. Colin , Li Lushen , Toney Nicholas , Wagner Chelsea , Saxena Vikas , Simon Thomas , Bromberg Jonathan S.
Published: June 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
LobSig is a multigene predictor of outcome in invasive lobular carcinoma
Authors: McCart Reed Amy E. , Lal Samir , Kutasovic Jamie R. , Wockner Leesa , Robertson Alan , de Luca Xavier M. , Kalita-de Croft Priyakshi , Dalley Andrew J. , Coorey Craig P. , Kuo Luyu , Ferguson Kaltin , Niland Colleen , Miller Gregory , Johnson Julie , Reid Lynne E. , Males Renique , Saunus Jodi M. , Chenevix-Trench Georgia , Coin Lachlan , Lakhani Sunil R. , Simpson Peter T.
Published: June 2019

Invasive lobular carcinoma (ILC) is the most common special type of breast cancer, and is characterized by functional loss of E-cadherin, resulting in cellular adhesion defects. ILC typically present as estrogen receptor positive, grade 2 breast cancers, with a good short-term prognosis. Several large-scale molecular profiling studies have now dissected the unique genomics of ILC. We have undertaken an integrative analysis of gene expression and DNA copy number to identify novel drivers and prognostic biomarkers, using in-house (n = 25), METABRIC (n = 125) and TCGA (n = 146) samples. Using in silico integrative analyses, a 194-gene set was derived that is highly prognostic in ILC (P = 1.20 × 10−5)—we named this metagene ‘LobSig’. Assessing a 10-year follow-up period, LobSig outperformed the Nottingham Prognostic Index, PAM50 risk-of-recurrence (Prosigna), OncotypeDx, and Genomic Grade Index (MapQuantDx) in a stepwise, multivariate Cox proportional hazards model, particularly in grade 2 ILC cases (χ2, P = 9.0 × 10−6), which are difficult to prognosticate clinically. Importantly, LobSig status predicted outcome with 94.6% accuracy amongst cases classified as ‘moderate-risk’ according to Nottingham Prognostic Index in the METABRIC cohort. Network analysis identified few candidate pathways, though genesets related to proliferation were identified, and a LobSig-high phenotype was associated with the TCGA proliferative subtype (χ2, P < 8.86 × 10−4). ILC with a poor outcome as predicted by LobSig were enriched with mutations in ERBB2, ERBB3, TP53, AKT1 and ROS1. LobSig has the potential to be a clinically relevant prognostic signature and warrants further development.
Primary care implications of the British Thoracic Society Guidelines for bronchiectasis in adults 2019
Authors: Gruffydd-Jones Kevin , Keeley Duncan , Knowles Vikki , Recabarren Ximena , Woodward Alex , Sullivan Anita L. , Loebinger Michael R. , Payne Karen , Harvey Alex , Grillo Lizzie , Welham Sally A. , Hill Adam T.
Published: June 2019

The British Thoracic Society (BTS) Guidelines for Bronchiectasis in adults were published in January 2019, and comprise recommendations for treatment from primary to tertiary care. Here, we outline the practical implications of these guidelines for primary care practitioners. A diagnosis of bronchiectasis should be considered when a patient presents with a recurrent or persistent (>8 weeks) productive cough. A definitive diagnosis is made by using thin-section chest computed tomography (CT). Once diagnosed, patients should be initially assessed by a specialist respiratory team and a shared management plan formulated with the patient, the specialist and primary care teams. The cornerstone of primary care management is physiotherapy to improve airway sputum clearance and maximise exercise capacity, with prompt treatment of acute exacerbations with antibiotics.
Mapping global development potential for renewable energy, fossil fuels, mining and agriculture sectors
Authors: Oakleaf James R. , Kennedy Christina M. , Baruch-Mordo Sharon , Gerber James S. , West Paul C. , Johnson Justin A. , Kiesecker Joseph
Published: June 2019

Mapping suitable land for development is essential to land use planning efforts that aim to model, anticipate, and manage trade-offs between economic development and the environment. Previous land suitability assessments have generally focused on a few development sectors or lack consistent methodologies, thereby limiting our ability to plan for cumulative development pressures across geographic regions. Here, we generated 1-km spatially-explicit global land suitability maps, referred to as “development potential indices” (DPIs), for 13 sectors related to renewable energy (concentrated solar power, photovoltaic solar, wind, hydropower), fossil fuels (coal, conventional and unconventional oil and gas), mining (metallic, non-metallic), and agriculture (crop, biofuels expansion). To do so, we applied spatial multi-criteria decision analysis techniques that accounted for both resource potential and development feasibility. For each DPI, we examined both uncertainty and sensitivity, and spatially validated the map using locations of planned development. We illustrate how these DPIs can be used to elucidate potential individual sector expansion and cumulative development patterns.
ZNF518B gene up-regulation promotes dissemination of tumour cells and is governed by epigenetic mechanisms in colorectal cancer
Authors: Gimeno-Valiente Francisco , Riffo-Campos Ángela L. , Vallet-Sánchez Azahara , Siscar-Lewin Sofía , Gambardella Valentina , Tarazona Noelia , Cervantes Andrés , Franco Luis , Castillo Josefa , López-Rodas Gerardo
Published: June 2019

Most of colorectal cancer CRC-related death is due to metastasis and the finding of markers for prognosis of invasiveness, constitutes an appealing challenge. Here, after analysing cDNA array containing 43 tumour and 5 normal mucosa samples, we report that the expression of the ZNF518B gene as a whole and that of its two major splicing isoforms are significantly increased in tumours. The canonical isoform was also up-regulated in a patients’ cohort containing 70 tumour and 69 adjacent tissue samples. The effects of silencing ZNF518B on the phenotype of CRC cell lines were then studied. The gene does not affect cell proliferation, but plays a significant role in cell migration and invasiveness and induces changes in the epithelial-to-mesenchymal transition markers, suggesting that ZNF518B favours tumour cell dissemination. To study the regulation of the gene, transcription-related changes in nucleosomal organisation and epigenetic marks around the transcriptional start site were analysed. The positioning of a nucleosome over the transcription start site and the differential presence of the epigenetic marks H3K9ac, H3K27ac, H3K4me3 and H3K9me3 correlate with gene expression. Inhibition of histone deacetylases increases the transcription of ZNF518B, which may be a candidate for invasiveness prognosis in CRC and a target for epigenetic drugs.