bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical Study of Heat Transfer from Elliptic Tube in a Fluidized Bed
Authors: Abd-Rabbo M. A. , Sakr R. Y. , Mohammad M. A. , Mandour M. M.
Published: November 2019

In the present work, heat transfer characteristics and flow field from a heated elliptic cylinder immersed in fluidized bed is studied numerically using CFD package. The flow pattern and heat transfer fields around the heated cylinder is predicted using a two fluid Eulerian-Eulerian model coupled with kinetic theory of granular flow (KTGF) with heat transfer. Experiments were carried out under uniform heat flux condition, with air as a fluidizing gas and pulverized coal as a bed material. The Reynolds number based on the equivalent hydraulic diameter, Dh, was ranged from 941to 1263. The simulation results of the present study showed that, for the range of gas velocity considered, at minimum fluidization velocity, Re = 914, the Nuθ is maximum at the sides of the cylinder and minimum at the stagnation, θ=0o, and top, θ=180o, of the cylinder. The average Nusselt number for the elliptic cylinder increases with the increase of the fluidization velocity. The present data is compared with a previous well-known correlation from the literature for a circular cylinder and a reasonable deviation about 11-30% is found.
ABSTINÊNCIA
Authors: Sigal Ana Maria
Published: November 2019

O psicanalista é antes de tudo um cidadão e deve saber-se participante do mundo e da história que lhe concerne. Quando se entende de forma equivocada o princípio da abstinência, ligado ao método analítico, surge uma clínica que não beneficia nem ao analista nem ao analisador. A proposta deste artigo é a de abster-se de desejar pelo outro, ao assumir, com Freud, que a ferramenta principal da análise seja a interpretação, através da qual evitamos satisfazer desejos libidinais e propiciamos que se mantenham necessidades e aspirações do sujeito como forças que impelem para o trabalho analítico. Visitando a história da psicanálise é possível conferir, entretanto, que os conceitos de abstinência e de neutralidade foram mal aproveitados e serviram às instituições psicanalíticas para perseguir membros com participação política na vida pública.
PSICOLOGIA, PSICANÁLISE, ARTE E ENCARCERAMENTO JUVENIL
Authors: D'Icarahy Marlise , Manso de Barros Rita Maria , De Freitas Perez Lucia Maria , Martello Andréa
Published: November 2019

A experiência de encarceramento precoce, frequentemente agravada por violências impetradas, desde o momento da apreensão, tanto por agentes do Estado quanto por anônimos transeuntes e estendida ao interior de instituições públicas, é relatada por inúmeros adolescentes que cumprem medida socioeducativa em meio fechado no Rio de Janeiro. As estatísticas dessa macabra violência permanecem subestimadas. Neste perverso cenário instituído, como a Psicologia, a Psicanálise e a Arte podem contribuir para a elaboração subjetiva dos socioeducandos que vivenciaram tão poderosos traumas, bem como para a transformação de tão cruel status quo?
Cross‐reactive antibody‐dependent cellular cytotoxicity antibodies are increased by recent infection in a household study of influenza transmission
Authors: Valkenburg Sophie A , Fang Vicky J , Leung Nancy HL , Chu Daniel KW , Ip Dennis KM , Perera Ranawaka APM , Wang Yizhuo , Li Athena PY , Peiris JS Malik , Cowling Benjamin J , Poon Leo LM
Published: November 2019

Objectives

Influenza causes a spectrum of disease from asymptomatic infection to fatal outcome, and pre‐existing immunity can alter susceptibility and disease severity. In a household transmission study, we recruited outpatients with confirmed influenza virus infection and prospectively identified secondary infections in their household contacts, therefore identifying infection cases with baseline samples for determining immune‐mediated protection from influenza infection.

Methods

We examined baseline broadly reactive immune correlates of relevance to universal vaccine development, specifically antibody‐dependent cytotoxic (ADCC) antibodies and T‐cell responses in functional assays. Antibodies were assessed in a cell‐based NK cell degranulation assay by flow cytometry, and T‐cell responses were assessed by IFN‐γ intracellular cytokine staining flow cytometry assay.

Results

The magnitude of antibody responses and ADCC function for multiple influenza‐specific proteins was lower in participants who became infected, consolidating the role of pre‐existing antibodies in protection from seasonal influenza virus infection. Among H1N1‐infected contacts, we found that higher levels of pre‐existing H1‐haemagglutinin ADCC responses correlated with reduced symptom severity. Recent infection boosted the titre and magnitude of haemagglutinin‐, neuraminidase‐ and nucleoprotein‐specific ADCC antibodies. Limited T‐cell samples precluded conclusions on the role of pre‐existing T‐cell responses.

Conclusions

Overall, ADCC responses are a protective correlate against influenza virus infection that should be considered in future vaccine development and evaluation.

Influenza‐specific ADCC responses are elevated in uninfected subjects, associated with reduced symptoms and boosted by recent infection, whilst HA stem and NA IgG are also elevated in uninfected participants irrespective of ADCC function.
Institutions for health care price setting and regulation: A comparative review of eight settings
Authors: Barber Sarah L. , Lorenzoni Luca , Ong Paul
Published: November 2019

Background

Price setting and regulation serve as instruments to control volumes of services, while providing incentives for quality, coverage, and efficiency. In recognition of its complexity, many countries have established specific entities to carry out price setting and regulation.

Methods

The aim of the study is to investigate institutions established for health care price setting and regulation and determine how countries have implemented pricing strategies. Eight settings were selected for case studies: Australia, England, France, Germany, Japan, Republic of Korea, Thailand, and Maryland in the United States. Each identified the agency responsible, their role and function, and resources for implementation.

Results

In England, Japan, Korea, and Thailand, government entities conduct price setting and regulation. In Australia, France, Germany, and Maryland, independent entities were established. Their responsibilities include costing health services, establishing prices, negotiating with stakeholders, and publishing price and quality data for consumers.

Conclusions

Dedicated institutions have been established to carry out costing, price setting, and negotiation, and providing consumer information. Characteristics of successful systems include formal systems of communication with stakeholders, freedom from conflicts of interest, and the mandate to provide public information. Substantial investments in price regulatory systems have been made to attain coverage, quality, and efficiency.
Health Risk Assessment and Source Apportionment for Heavy Metals in a Southern Chinese Reservoir Impacted by Stone Mining Activities
Authors: Zeng Yue , Yang Yue , Li Yunqin , Zou Jie , Wang Qianfeng , Jin Zhifan , Zeng Jingyu , Hou Song
Published: November 2019

Metal contaminants in drinking water pose a potential threat to human health. Metal elements (Fe, Mn, Cu, Cr, Cd, As, and Pb) in Shanzi Reservoir, China, a drinking water source for nearby cities, were measured in 2013 and 2014. The distribution characteristics of metal elements in water were identified and a health risk assessment model was used to evaluate potential harm. Principal component analysis and cluster analysis were used to determine the main sources of metal pollutants. The results showed that Pb and As exceeded the standard at some sampling sites, whereas other metal elements met the drinking water standards. The spatial distribution of metal elements was extremely uneven and might be affected by either the geochemical environment or human activities in the study region. The total risk value of metals (5 × 10–5 a–1) was below the recommended value of the United States Environmental Protection Agency (USEPA), the total cancer risk was higher than the total noncancer risk, and both risks were higher for children than for adults. Arsenic was the priority control pollutant, and the priority control site was located upstream of the reservoir. Source analysis showed that Fe, Mn, and Cu were mainly from soil formation and stone mining and processing industries; Pb and As were mainly from agricultural activities, free dumping and burning of domestic garbage, and atmospheric deposition from transportation emissions; Cd was mainly from agricultural application of fertilizers and pesticides; and Cr was from the stone mining and processing industry and from the electroplating and metal manufacturing industries. Integr Environ Assess Manag 2020;16:342–352. © 2019 SETAC

KEY POINTS

Spatial distribution of metals was extremely variable, most likely due to variations in human activities. Total risk value of metals was below the recommended value of the USEPA, total cancer risk was higher than the total noncancer risk, and both risks were higher for children than for adults. Arsenic was the priority control pollutant. Source analysis showed that metals were affected by the parent material and human activities, especially stone plate mining and processing upstream.
Effects of Liraglutide and Behavioral Weight Loss on Food Cravings, Eating Behaviors, and Eating Disorder Psychopathology
Authors: Chao Ariana M. , Wadden Thomas A. , Walsh Olivia A. , Gruber Kathryn A. , Alamuddin Naji , Berkowitz Robert I. , Tronieri Jena S.
Published: November 2019

Objective

This exploratory analysis examined the effects of intensive behavioral therapy (IBT) for obesity (“IBT‐alone”), IBT plus liraglutide 3.0 mg/d (“IBT‐liraglutide”), and IBT plus liraglutide 3.0 mg/d plus 12 weeks of a portion‐controlled diet that provided 1,000 to 1,200 kcal/d (“Multicomponent”) on changes in food cravings, eating behaviors, and eating disorder psychopathology at 24 and 52 weeks post randomization.

Methods

Adults with obesity (mean age = 47.6 ± 11.8 years and BMI = 38.4 ± 4.9 kg/m2; 79.3% female; 54.0% non‐Hispanic white; 44.7% black) were randomized to IBT‐alone (n = 50), IBT‐liraglutide (n = 50), or Multicomponent (n = 50).

Results

At weeks 24 and 52, liraglutide‐treated groups reported significantly larger declines in weight concern relative to the IBT‐alone group. At week 24, compared with IBT‐alone, liraglutide‐treated groups reported significantly greater reductions in dietary disinhibition, global eating disorder psychopathology, and shape concern. The Multicomponent group had significantly greater reductions in binge eating at week 24 relative to the IBT‐alone group. However, differences among groups were no longer significant at week 52. Groups did not differ in total food cravings at week 24 or 52.

Conclusions

The combination of liraglutide and IBT was associated with greater short‐term improvements in dietary disinhibition, global eating disorder psychopathology, and shape concern than IBT alone.
Long‐term role of cooling the underlying permafrost of the crushed rock structure embankment along the Qinghai–Xizang railway
Authors: Wu Qingbai , Zhao Hongting , Zhang Zhongqiong , Chen Ji , Liu Yongzhi
Published: November 2019

Understanding the long‐term role of cooling the underlying permafrost of the crushed rock structure embankment (CRSE) along the Qinghai–Xizang Railway (QXR) is crucial for the railway's safe operation. The thermal regime of the permafrost under the CRSE is analyzed here using monitoring data of soil temperature from 2005 to 2015. The results show that the CRSE plays an important long‐term role in cooling the underlying permafrost under the present climate change conditions; however, different types of CRSEs have different cooling effects. A U‐shaped crushed rock embankment and a crushed rock berm embankment with debris rock revetment can maintain the cooling of the permafrost underlying the embankment under a future climate warming of 1.0°C. Moreover, under an increase in air temperature of 0.5°C, a crushed‐based rock embankment and a crushed rock revetment embankment can maintain the cooling of the underlying permafrost when its mean annual ground temperature is below −1.0°C. The long‐term role of cooling the underlying permafrost of CRSEs indicates that the QXR must use reinforcing engineering techniques to ensure its safe operation and adaptation to a temperature increase of 1.5°C.
Distributionally robust optimization with multiple time scales: valuation of a thermal power plant
Authors: van Ackooij Wim , Escobar Debora Daniela , Glanzer Martin , Pflug Georg Ch.
Published: November 2019

The valuation of a real option is preferably done with the inclusion of uncertainties in the model, since the value depends on future costs and revenues, which are not perfectly known today. The usual value of the option is defined as the maximal expected (discounted) profit one may achieve under optimal management of the operation. However, also this approach has its limitations, since quite often the models for costs and revenues are subject to model error. Under a prudent valuation, the possible model error should be incorporated into the calculation. In this paper, we consider the valuation of a power plant under ambiguity of probability models for costs and revenues. The valuation is done by stochastic dynamic programming and on top of it, we use a dynamic ambiguity model for obtaining the prudent minimax valuation. For the valuation of the power plant under model ambiguity we introduce a distance based on the Wasserstein distance. Another highlight of this paper is the multiscale approach, since decision stages are defined on a weekly basis, while the random costs and revenues appear on a much finer scale. The idea of bridging stochastic processes is used to link the weekly decision scale with the finer simulation scale. The applicability of the introduced concepts is broad and not limited to the motivating valuation problem.
Sequential Monte Carlo with transformations
Authors: Everitt Richard G. , Culliford Richard , Medina-Aguayo Felipe , Wilson Daniel J.
Published: November 2019

This paper examines methodology for performing Bayesian inference sequentially on a sequence of posteriors on spaces of different dimensions. For this, we use sequential Monte Carlo samplers, introducing the innovation of using deterministic transformations to move particles effectively between target distributions with different dimensions. This approach, combined with adaptive methods, yields an extremely flexible and general algorithm for Bayesian model comparison that is suitable for use in applications where the acceptance rate in reversible jump Markov chain Monte Carlo is low. We use this approach on model comparison for mixture models, and for inferring coalescent trees sequentially, as data arrives.
Improving the consistency of usage labelling in dictionaries with TEI Lex?0
Authors: Salgado Ana , Costa Rute , Tasovac Toma
Published: November 2019

This paper analyzes the application of usage labels in three representative lexicographic works, namely the Portuguese, Spanish, and French Academy Dictionaries as a starting point for creating a consistent classifcation of usage labels and their encoding in accordance with TEI Lex-0. The use of labels is not always entirely consistent within individual dictionaries and even less so across diferent lexicographic projects. This makes the tasks of accurately classifying and encoding them quite diffcult. This difculty is compounded by the diferences and partial incompatibilities found in the lexicographic literature on the treatment of diasystemic information. We address the existing literature and the initial classifcation of TEI Lex-0, and argue for the need to introduce some changes to TEI Lex-0, most notably in terms of diatextual labels. Finally, we argue that the existing classifcations based on examples rather than on clear and explicit defnitions of classifcation categories will always lack in precision and lead to mutually incompatible encodings of diferent dictionaries. We propose a set of defnitions for usage label categories that can be adopted by TEI Lex-0 and used in other similar attempts to create interoperable lexical resources. An agreement on usage label categories is a frst and necessary step before proceeding in the direction of harmonizing and standardizing the actual values of usage labels across various dictionaries and across diferent languages.
The affective origins of the Industrial Revolution
Authors: Huntsinger Jeffrey R. , Raoul Akila
Published: November 2019

We suggest in this commentary an emotional origin of the Industrial Revolution. Specifically, increased living standards directly preceding the Industrial Revolution produced increased happiness and subjective well-being that, in turn, fueled the explosion of innovation and economic growth experienced in industrial England.
Hungry for inclusion: Exposure to peer victimization and heightened social monitoring in adolescent girls
Authors: Telzer Eva H. , Fowler Carina H. , Davis Megan M. , Rudolph Karen D.
Published: November 2019

Belonging to a social group is one of the most important factors contributing to well-being. The Belonging Regulation model proposes that humans possess a social monitoring system (SMS) that evaluates social inclusion and monitors belonging needs. Here, we used a prospective longitudinal design to examine links between peer victimization experienced across 7 years and social monitoring at the behavioral and neural level in adolescent girls (n= 38,Mage= 15.43 years,SD= .33). Participants completed a social evaluation task during a functional magnetic resonance imaging (fMRI) scan. More severe peer victimization was associated with increased activation to in-group versus out-group peers in the amygdala, ventral striatum, fusiform gyrus, and temporoparietal junction. Moreover, participants who displayed increased activation in these regions reported lower social self esteem and higher levels of internalizing and externalizing symptoms. These results suggest that exposure to peer victimization across the school years is associated with heightened social monitoring at the neural level during adolescence, which has potential adverse implications for girls’ adjustment and well-being.
Zwischen Stuhl und Bank
Authors: Bregenzer Ursula , Kupferschmid Stephan , Müller Reto
Published: November 2019

Zusammenfassung. Die große Herausforderung der Adoleszentenpsychiatrie liegt darin, dass neben der Persönlichkeitsentwicklung, den körperlichen und hormonellen Veränderungen, dem Entwicklungsprozess diverser Hirnregionen und der Anpassung der psychosozialen Rolle zusätzlich psychische Störungen hinzukommen. Veränderte Verhaltensweisen sind somit nicht immer eindeutig dem einen oder anderen Prozess zuzuordnen. Dies führt dazu, dass die Frage nach dem ‚Huhn oder Ei‘ sehr relevant ist. Was ist ursächlich? Was ist Folge welchen Phänomens? Weiter beeinflussen sich diese Prozesse gegenseitig. Das interprofessionelle psychiatrische Team ist daher um zusätzliche Akteure aus der Pädagogik erweitert, was eine komplexere Behandlungsorganisation bedeutet. Eine Unterbrechung in der Finanzierung und der Wechsel der Zuständigkeiten mit der Vollendung des 18. Lebensjahres sind weitere Hürden in der psychiatrischen Versorgung junger Menschen.
Wie kann „gute Zusammen-Arbeit“ gelingen?
Authors: Jähnke Anke , Andersson Sven , Rühle Andersson Sabine , Hegedüs Anna
Published: November 2019

Zusammenfassung. Der vorliegende Artikel entstand ausgehend von einem Workshop, der von den Autor_innen gemeinsam am Dreiländerkongress Pflege in der Psychiatrie 2018 zum Thema „Gute Arbeit“ gestaltet wurde. Bei diesem Workshop stand der Trialog, d. h. die gleichberechtigte Zusammenarbeit von Psychiatrie- Erfahrenen, fachkundigen Angehörigen und Fachpersonen, im Mittelpunkt. Diese verschiedenen Perspektiven spiegelten sich auch in der Zusammensetzung des Workshop-Teams wider. Wir wollten nicht nur forschungsgestützt über Trialog reden, sondern die Diskussion gestützt auf eigene Erfahrungen aus dem Leben bereichern. Ziel war, die Teilnehmenden anzuregen, sich über den möglichen Beitrag von Angehörigen auszutauschen, was denn konkret eine „gute Zusammen-Arbeit“ zwischen Psychiatrie-Erfahrenen, Angehörigen und Fachpersonen ausmacht und wie sie erreicht werden kann.
Impact of Flow Bursts in the Auroral Zone on the Ionosphere and Thermosphere
Authors: Deng Yue , Heelis Roderick , Lyons Larry R. , Nishimura Yukitoshi , Gabrielse Christine
Published: November 2019

High‐latitude ionospheric plasma flows often contain embedded localized velocity enhancements with associated plasma density structures. Localized strong flows are significant energy sources to the thermosphere that are not contained in present empirical models of plasma convection. In this study, Global Ionosphere‐Thermosphere model, a nonhydrostatic model with flexible resolution, has been utilized to evaluate the influence of such localized strong enhancements of forcing on the global dynamics of the upper atmosphere. Specifically, three idealized configurations of flow burst have been examined, one flow burst with the typical spatial scale seen in the auroral zone, two neighboring flow bursts with the same spatial scale, and one flow burst with doubled spatial scale. The comparison between the cases with and without the flow burst illustrates that one regular‐sized flow burst at midnight can cause the neutral density to increase by 5% and the horizontal wind to increase by ∼30 m/s at 300 km altitude. The associated enhancement in the electron precipitation can increase total electron content by 15%( 1 TECU) during the first 15 min. Two simultaneous flow bursts can cause a rich wave structure with multiple wavelengths in traveling atmospheric disturbances due to wave‐wave interactions. A flow burst with doubled spatial size can increase the impact on the ionosphere/thermosphere by 2 times or even more. The outcome of this study illustrates substantial local and nonlocal responses of the ionosphere‐thermosphere system to the mesoscale energy and momentum inputs from the magnetosphere.
The First Terrestrial Electron Beam Observed by the Atmosphere‐Space Interactions Monitor
Authors: Sarria D. , Kochkin P. , Østgaard N. , Lehtinen N. , Mezentsev A. , Marisaldi M. , Carlson B. E. , Maiorana C. , Albrechtsen K. , Neubert T. , Reglero V. , Ullaland K. , Yang S. , Genov G. , Qureshi B. H. , Budtz‐Jørgensen C. , Kuvvetli I. , Christiansen F. , Chanrion O. , Heumesser M. , Dimitriadou K. , Navarro‐González J. , Connell P. , Eyles C.
Published: November 2019

We report the first Terrestrial Electron Beam detected by the Atmosphere‐Space Interactions Monitor. It happened on 16 September 2018. The Atmosphere‐Space Interactions Monitor Modular X and Gamma ray Sensor recorded a 2 ms long event, with a softer spectrum than typically recorded for Terrestrial Gamma ray Flashes (TGFs). The lightning discharge associated to this event was found in the World Wide Lightning Location Network data, close to the northern footpoint of the magnetic field line that intercepts the International Space Station location. Imaging from a GOES‐R geostationary satellite shows that the source TGF was produced close to an overshooting top of a thunderstorm. Monte‐Carlo simulations were performed to reproduce the observed light curve and energy spectrum. The event can be explained by the secondary electrons and positrons produced by the TGF (i.e., the Terrestrial Electron Beam), even if about 3.5% to 10% of the detected counts may be due to direct TGF photons. A source TGF with a Gaussian angular distribution with standard deviation between 20.6° and 29.8° was found to reproduce the measurement. Assuming an isotropic angular distribution within a cone, compatible half angles are between 30.6° and 41.9°, in agreement with previous studies. The number of required photons for the source TGF could be estimated for various assumption of the source (altitude of production and angular distribution) and is estimated between 1017.2 and 1018.9 photons, that is, compatible with the current consensus.
Anisotropy and Inhomogeneity in Drifter Dispersion
Authors: Huntley Helga S. , Lipphardt B. L. , Kirwan A. D.
Published: November 2019

Ocean flows are known to be locally anisotropic and inhomogeneous. Nonetheless, the ocean's statistical dispersion properties are traditionally assumed to be isotropic and homogeneous. Here, we investigate the effect of local anisotropy and inhomogeneity on dispersion statistics, using a unique data set of roughly 300 near‐surface drifters that were launched within 10 days in the summer of 2012. The unique launch strategy based on nested triplets resulted in an unusually large number of nearly colocated drifter pairs. Thus, this data set is ideally suited for an estimate of the directional bias and inhomogeneity effects inherent in drifter pair statistics.

Several metrics are proposed to assess the time evolution of anisotropy and inhomogeneity effects at multiple initial separation scales (100 m, 200 m, 500 m, 1 km, and 10 km). Locally, statistically significant anisotropy and inhomogeneity are observed at all scales, although anisotropy is noticeably less at 10 km, suggesting that the energetic processes driving anisotropic dispersion operate primarily at smaller scales. Moreover, averaged over a sufficient variety of different flow regimes, the signature of both anisotropy and inhomogeneity in dispersion metrics lessens. These trends hold generally across all scales, with longer time scales associated with larger spatial scales. The results indicate that oceanic dispersion is statistically isotropic and homogeneous over large swaths, but for an application in a specific location, local anisotropy and inhomogeneity matter. What size swath is large enough is situation dependent: For this specific data set, statistics had to be evaluated over multiple deployments, giving a required area greater than 150 km2.
Unraveling the Mechanisms That Cause Cyclic Channel‐Shoal Dynamics of Ebb‐Tidal Deltas: A Numerical Modeling Study
Authors: Lenstra Klaas J. H. , Ridderinkhof Wim , van der Vegt Maarten
Published: November 2019

The morphodynamics of many ebb‐tidal deltas include cyclic patterns of channel deflection and breaching associated with sandy shoals migrating and attaching to the downdrift coast. These channel‐shoal dynamics result from the complex combination of tides and waves; however, their precise role and the physical mechanisms forcing the cyclic patterns are unknown. Here, we use Delft3D/SWAN to simulate their periodic behavior and to study the underlying mechanisms during different phases of the cyclic behavior. The model forcing was such that different ratios between tidal prism and littoral drift were obtained. Two different types of cyclic behavior were modeled, namely, ebb tidal delta breaching and outer delta breaching. The typical time scale of modeled cyclic behavior generally increases with increasing tidal prism and decreasing littoral drift. No cyclic channel‐shoal dynamics were found for high‐ratio tidal prims/littoral drift. Classically, channel deflection and shoal growth have been attributed to waves and the breaching solely to tidal currents. We confirm that shoal formation and channel deflection are forced by wave‐induced currents and sediment concentrations. However, the subsequent shoal growth can only be explained by tides and waves operating simultaneously. Moreover, the breaching of ebb tidal deltas is not a tide‐only effect because waves entrain the sediment that is transported by the ebb flow. In fact, there exists an optimum wave height; that is, larger waves cause further channel rotation rather than channel breaching. Furthermore, temporal variations in the sediment exchange between the back‐barrier basin and the sea are found to be an inherent feature of the modeled ebb tidal delta breaching.
Evaluation of Implicit‐Explicit Additive Runge‐Kutta Integrators for the HOMME‐NH Dynamical Core
Authors: Vogl Christopher J. , Steyer Andrew , Reynolds Daniel R. , Ullrich Paul A. , Woodward Carol S.
Published: November 2019

The nonhydrostatic High‐Order Method Modeling Environment (HOMME‐NH) atmospheric dynamical core supports acoustic waves that propagate significantly faster than the advective wind speed, thus greatly limiting the time step size that can be used with standard explicit time integration methods. Resolving acoustic waves is unnecessary for accurate climate and weather prediction. This numerical stiffness is addressed herein by considering implicit‐explicit additive Runge‐Kutta (ARK IMEX) methods that can treat the acoustic waves in a stable manner without requiring implicit treatment of nonstiff modes. Various ARK IMEX methods are evaluated for their efficiency in producing accurate solutions, ability to take large time step sizes, and sensitivity to grid cell length ratio. Both the gravity wave test and baroclinic instability test from the 2012 Dynamical Core Model Intercomparison Project are used to recommend 5 of the 27 ARK IMEX methods tested for use in HOMME‐NH.
Super-resolution localization photoacoustic microscopy using intrinsic red blood cells as contrast absorbers
Authors: Kim Jongbeom , Kim Jin Young , Jeon Seungwan , BAIK Jin Woo , Cho Seong Hee , Kim Chulhong
Published: November 2019

Photoacoustic microscopy (PAM) has become a premier microscopy tool that can provide the anatomical, functional, and molecular information of animals and humans in vivo. However, conventional PAM systems suffer from limited temporal and/or spatial resolution. Here, we present a fast PAM system and an agent-free localization method based on a stable and commercial galvanometer scanner with a custom-made scanning mirror (L-PAM-GS). This novel hardware implementation enhances the temporal resolution significantly while maintaining a high signal-to-noise ratio (SNR). These improvements allow us to photoacoustically and noninvasively observe the microvasculatures of small animals and humans in vivo. Furthermore, the functional hemodynamics, namely, the blood flow rate in the microvasculature, is successfully monitored and quantified in vivo. More importantly, thanks to the high SNR and fast B-mode rate (500 Hz), by localizing photoacoustic signals from captured red blood cells without any contrast agent, unresolved microvessels are clearly distinguished, and the spatial resolution is improved by a factor of 2.5 in vivo. L-PAM-GS has great potential in various fields, such as neurology, oncology, and pathology.
Identification of novel common variants associated with chronic pain using conditional false discovery rate analysis with major depressive disorder and assessment of pleiotropic effects of LRFN5
Authors: Johnston Keira J. A. , Adams Mark J. , Nicholl Barbara I. , Ward Joey , Strawbridge Rona J. , McIntosh Andrew M. , Smith Daniel J. , Bailey Mark E. S.
Published: November 2019

Chronic pain is a complex trait that is moderately heritable and genetically, as well as phenotypically, correlated with major depressive disorder (MDD). Use of the conditional false discovery rate (cFDR) approach, which leverages pleiotropy identified from existing GWAS outputs, has been successful in discovering novel associated variants in related phenotypes. Here, genome-wide association study outputs for both von Korff chronic pain grade and for MDD were used to identify variants meeting a cFDR threshold for each outcome phenotype separately, as well as a conjunctional cFDR (ccFDR) threshold for both phenotypes together. Using a moderately conservative threshold, we identified a total of 11 novel single nucleotide polymorphisms (SNPs), six of which were associated with chronic pain grade and nine of which were associated with MDD. Four SNPs on chromosome 14 were associated with both chronic pain grade and MDD. SNPs associated only with chronic pain grade were located withinSLC16A7on chromosome 12. SNPs associated only with MDD were located either in a gene-dense region on chromosome 1 harbouringLINC01360,LRRIQ3, FPGTandFPGT-TNNI3K, or within/close toLRFN5on chromosome 14. The SNPs associated with both outcomes were also located withinLRFN5. Several of the SNPs on chromosomes 1 and 14 were identified as being associated with expression levels of nearby genes in the brain and central nervous system. Overall, using the cFDR approach, we identified several novel genetic loci associated with chronic pain and we describe likely pleiotropic effects of a recently identified MDD locus on chronic pain.
The association between antibodies to neurotropic pathogens and bipolar disorder
Authors: Snijders Gijsje J. L. J. , van Mierlo Hans C. , Boks Marco P. , Begemann Marieke J. H. , Sutterland Arjen L. , Litjens Manja , Ophoff Roel A. , Kahn René S. , de Witte Lot D.
Published: November 2019

Exposure to neurotropic pathogens has been hypothesized to be a risk factor for the development of bipolar disorder (BD). However, evidence so far is inconsistent. We, therefore, analyzed the seroprevalence and titer levels of IgG antibodies against several herpesviruses and Toxoplasma gondii (T. gondii) in plasma of 760 patients with a bipolar disorder, 144 first-degree matched relatives and 132 controls of the Dutch Bipolar (DB) Cohort using ELISA. In addition, we performed a literature-based meta-analysis on the seroprevalence of IgG antibodies against these pathogens (n = 14). Our results in the DB Cohort and subsequent meta-analysis (n = 2364 BD patients, n = 5101 controls) show no association between exposure to herpesviruses and bipolar disorder (HSV-1 [adjusted OR 0.842, 95% CI 0.567–1.230], HSV-2 [adjusted OR 0.877, 95% CI 0.437–1.761], CMV [adjusted OR 0.884 95% CI 0.603–1.295], EBV [adjusted OR 0.968 95% CI 0.658–1.423]). In the DB Cohort, we did not find an association between bipolar disorder and T. gondii titer or seroprevalence either [adjusted OR 1.018, 95% CI 0.672–1.542]. The overall OR was not significant for T. gondii [OR: 1.4, 95% CI 0.95–1.90, p = 0.09), but subgroup analyses in age groups below 40 years showed a significantly increased seroprevalence of T. gondii IgGs in BD [OR: 1.8 (95% CI 1.10–2.89, p = 0.021]. Our meta-analysis indicates that T. gondii exposure may be a risk factor for BD in certain subpopulations.
Down-regulation of TUFM impairs host cell interaction and virulence by Paracoccidioides brasiliensis
Authors: Marcos Caroline Maria , Tamer Gabrielle , de Oliveira Haroldo Cesar , Assato Patricia Akemi , Scorzoni Liliana , Santos Claudia Tavares , de Lacorte Singulani Junya , de Fátima da Silva Julhiany , de Almeida Rodrigo , de Paula e Silva Ana Carolina Alves , da Silva Rosangela Aparecida Moraes , de Andrade Cleverton Roberto , Tamayo Diana Patricia , Lopez Angela Maria , Barbosa Natália Moreira , Zanelli Cleslei Fernando , Hernandez- Ruiz Orville , McEwen Juan G. , Mendes-Giannini Maria José Soares , Fusco-Almeida Ana Marisa
Published: November 2019

The genus Paracoccidioides consist of dimorphic fungi geographically limited to the subtropical regions of Latin America, which are responsible for causing deep systemic mycosis in humans. However, the molecular mechanisms by which Paracoccidioides spp. causes the disease remain poorly understood. Paracoccidioides spp. harbor genes that encode proteins involved in host cell interaction and mitochondrial function, which together are required for pathogenicity and mediate virulence. Previously, we identified TufM (previously known as EF-Tu) in Paracoccidioides brasiliensis (PbTufM) and suggested that it may be involved in the pathogenicity of this fungus. In this study, we examined the effects of downregulating PbTUFM using a silenced strain with a 55% reduction in PbTUFM expression obtained by antisense-RNA (aRNA) technology. Silencing PbTUFM yielded phenotypic differences, such as altered translation elongation, respiratory defects, increased sensitivity of yeast cells to reactive oxygen stress, survival after macrophage phagocytosis, and reduced interaction with pneumocytes. These results were associated with reduced virulence in Galleria mellonella and murine infection models, emphasizing the importance of PbTufM in the full virulence of P. brasiliensis and its potential as a target for antifungal agents against paracoccidioidomycosis.
Non-genomic effects of the Pregnane X Receptor negatively regulate platelet functions, thrombosis and haemostasis
Authors: Flora Gagan D. , Sahli Khaled A. , Sasikumar Parvathy , Holbrook Lisa-Marie , Stainer Alexander R. , AlOuda Sarah K. , Crescente Marilena , Sage Tanya , Unsworth Amanda J. , Gibbins Jonathan M.
Published: November 2019

The pregnane X receptor (PXR) is a nuclear receptor (NR), involved in the detoxification of xenobiotic compounds. Recently, its presence was reported in the human vasculature and its ligands were proposed to exhibit anti-atherosclerotic effects. Since platelets contribute towards the development of atherosclerosis and possess numerous NRs, we investigated the expression of PXR in platelets along with the ability of its ligands to modulate platelet activation. The expression of PXR in human platelets was confirmed using immunoprecipitation analysis. Treatment with PXR ligands was found to inhibit platelet functions stimulated by a range of agonists, with platelet aggregation, granule secretion, adhesion and spreading on fibrinogen all attenuated along with a reduction in thrombus formation (bothin vitroandin vivo). The effects of PXR ligands were observed in a species-specific manner, and the human-specific ligand, SR12813, was observed to attenuate thrombus formationin vivoin humanised PXR transgenic mice. PXR ligand-mediated inhibition of platelet function was found to be associated with the inhibition of Src-family kinases (SFKs). This study identifies acute, non-genomic regulatory effects of PXR ligands on platelet function and thrombus formation. In combination with the emerging anti-atherosclerotic properties of PXR ligands, these anti-thrombotic effects may provide additional cardio-protective benefits.
FlySilico: Flux balance modeling of Drosophila larval growth and resource allocation
Authors: Schönborn Jürgen Wilhelm , Jehrke Lisa , Mettler-Altmann Tabea , Beller Mathias
Published: November 2019

Organisms depend on a highly connected and regulated network of biochemical reactions fueling life sustaining and growth promoting functions. While details of this metabolic network are well established, knowledge of the superordinate regulatory design principles is limited. Here, we investigated by iterative wet lab and modeling experiments the resource allocation process during the larval development of Drosophila melanogaster. We chose this system, as survival of the animals depends on the successful allocation of their available resources to the conflicting processes of growth and storage metabolite deposition. First, we generated “FlySilico”, a curated metabolic network of Drosophila, and performed time-resolved growth and metabolite measurements with larvae raised on a holidic diet. Subsequently, we performed flux balance analysis simulations and tested the predictive power of our model by simulating the impact of diet alterations on growth and metabolism. Our predictions correctly identified the essential amino acids as growth limiting factor, and metabolic flux differences in agreement with our experimental data. Thus, we present a framework to study important questions of resource allocation in a multicellular organism including process priorization and optimality principles.
Identification of cell context-dependent YAP-associated proteins reveals β1 and β4 integrin mediate YAP translocation independently of cell spreading
Authors: Lee Joanna Y. , Dominguez Antonia A. , Nam Sungmin , Stowers Ryan S. , Qi Lei. S , Chaudhuri Ovijit
Published: November 2019

Yes-associated protein (YAP) is a transcriptional regulator and mechanotransducer, relaying extracellular matrix (ECM) stiffness into proliferative gene expression in 2D culture. Previous studies show that YAP activation is dependent on F-actin stress fiber mediated nuclear pore opening, however the protein mediators of YAP translocation remain unclear. Here, we show that YAP co-localizes with F-actin during activating conditions, such as sparse plating and culturing on stiff 2D substrates. To identify proteins mediating YAP translocation, we performed co-immunoprecipitation followed by mass spectrometry (co-IP/MS) for proteins that differentially associated with YAP under activating conditions. Interestingly, YAP preferentially associates with β1 integrin under activating conditions, and β4 integrin under inactivating conditions. In activating conditions, CRISPR/Cas9 knockout (KO) of β1 integrin (ΔITGB1) resulted in decreased cell area, which correlated with decreased YAP nuclear localization. ΔITGB1 did not significantly affect the slope of the correlation between YAP nuclear localization with area, but did decrease overall nuclear YAP independently of cell spreading. In contrast, β4 integrin KO (ΔITGB4) cells showed no change in cell area and similarly decreased nuclear YAP. These results reveal proteins that differentially associate with YAP during activation, which may aid in regulating YAP nuclear translocation.
Freezing of gaze during action preparation under threat imminence
Authors: Rösler Lara , Gamer Matthias
Published: November 2019

When confronted with threatening stimuli, animals typically respond with freezing behavior characterized by reduced movement and heart rate deceleration. Freezing-like responses during threat anticipation have also been observed in humans and are associated with anxiety. Recent evidence yet suggests that freezing does not necessarily reflect helpless immobility but can also aid the preparation of a threat escape. To investigate which further behavioral responses human freezing encompasses, we presented 50 young adults (10 male) with aversive stimuli that could sometimes be avoided while measuring gaze, cardiovascular and electrodermal activity. In trials in which the threat could be escaped, participants displayed reduced heart rate, increased electrodermal activity and reduced visual exploration. Furthermore, heart rate deceleration and restricted visual exploration predicted the speed of flight responses. These results provide evidence for freezing behavior in measures of visual exploration and suggest that such responding is adaptive in preparing the subsequent escape of approaching threats.
Analysis of free chlorine in aqueous solution at very low concentration with lateral flow tests
Authors: Schwenke K. Uta , Spiehl Dieter , Krauße Marcel , Riedler Laura , Ruppenthal Anna , Villforth Klaus , Meckel Tobias , Biesalski Markus , Rupprecht Daniel , Schwall Gerhard
Published: November 2019

Test strips are convenient tools for rapid, semi-quantitative analysis of a variety of parameters by dipping them for a few seconds in a sample solution followed by a simple colorimetric read-out. Their sensitivity is mainly determined by the reactivity of the test dyes on the reaction zone and is not sufficient for some applications. The detection limit of commercially available free chlorine test strips, for example, is at present not low enough to confirm the absence of this analyte as disinfectant in rinsing solutions after disinfection or to control required residual amounts of chlorine in drinking water. Therefore, we developed a user-friendly lateral flow test which is capable to detect very low amounts of free chlorine. The latter relies on a larger sample volume passing the reaction zone as compared to simple dip test strips. An amount of as low as 0.05 ppm chlorine can, however, only be detected if oxidation stable flow test substrates are used. The eventually developed flow test reaches a 10x higher sensitivity than a commercial dip test. The result is obtained within 4–5 min flow time, whereby no action is required by the user during this analysis time.
Publisher Correction: Real-Time Selective Sequencing with RUBRIC: Read Until with Basecall and Reference-Informed Criteria
Authors: Edwards Harrison S. , Krishnakumar Raga , Sinha Anupama , Bird Sara W. , Patel Kamlesh D. , Bartsch Michael S.
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Structural basis for phospholipase A2-like toxin inhibition by the synthetic compound Varespladib (LY315920)
Authors: Salvador Guilherme H. M. , Gomes Antoniel A. S. , Bryan-Quirós Wendy , Fernández Julián , Lewin Matthew R. , Gutiérrez José María , Lomonte Bruno , Fontes Marcos R. M.
Published: November 2019

The World Health Organization recently listed snakebite envenoming as a Neglected Tropical Disease, proposing strategies to significantly reduce the global burden of this complex pathology by 2030. In this context, effective adjuvant treatments to complement conventional antivenom therapy based on inhibitory molecules for specific venom toxins have gained renewed interest. Varespladib (LY315920) is a synthetic molecule clinically tested to block inflammatory cascades of several diseases associated with elevated levels of secreted phospholipase A2 (sPLA2). Most recently, Varespladib was tested against several whole snake venoms and isolated PLA2 toxins, demonstrating potent inhibitory activity. Herein, we describe the first structural and functional study of the complex between Varespladib and a PLA2-like snake venom toxin (MjTX-II). In vitro and in vivo experiments showed this compound’s capacity to inhibit the cytotoxic and myotoxic effects of MjTX-II from the medically important South American snake, Bothrops moojeni. Crystallographic and bioinformatics analyses revealed interactions of Varespladib with two specific regions of the toxin, suggesting inhibition occurs by physical blockage of its allosteric activation, preventing the alignment of its functional sites and, consequently, impairing its ability to disrupt membranes. Furthermore, based on the analysis of several crystallographic structures, a distinction between toxin activators and inhibitors is proposed.
Abnormal Osteoblastic Response to Leptin in Patients with Adolescent Idiopathic Scoliosis
Authors: Man Gene Chi-Wai , Tam Elisa Man-Shan , Wong Yi Shun , Hung Vivian Wing-Ying , Hu Zongshan , Lam Tsz Ping , Liu Zhen , Cheung Wing Hoi , Ng Tzi Bun , Zhu Zezhang , Qiu Yong , Cheng Jack Chun-Yiu
Published: November 2019

Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional structural deformity of the spine with unknown etiology. Although leptin has been postulated as one of the etiologic factors in AIS, its effects on osteoblastic activity remain unknown. Herein, we conducted this study to investigate whether there are abnormal functional responses to leptin and abnormal expression of leptin receptor in AIS osteoblasts. In vitro assays were performed with osteoblasts isolated from 12 severe AIS girls and 6 non-AIS controls. The osteoblasts were exposed to different concentrations of leptin (0, 10, 100, 1000 ng/mL). The effects of leptin on cell proliferation, differentiation and mineralization were determined. Protein expressions of leptin receptor (LEP-R) under basal and osteogenic conditions were also evaluated by Western blot. Our results showed that leptin significantly stimulated osteoblasts from non-AIS subjects to proliferate, differentiate and mineralized. However, in the AIS group, the stimulatory effects of leptin on cell proliferation, differentiation, and mineralization were not observed. In addition, no statistically significant difference in the expression of leptin receptor under both basal and osteogenic conditions was found between AIS and control group. In conclusion, these findings might help to explain the low bone mass and deranged bone quality that is clinically associated with AIS girls.