bluuebunny/crossref_metadata_2025 huggingface dataset:
Providential Empire? The Established Church of England and the Nineteenth-Century British Empire in India
Authors: Brown Stewart J.
Published: May 2018

In the early nineteenth century, many in Britain believed that their conquests in India had a providential purpose, and that imperial Britain had been called by God to Christianize India through an alliance of Church and empire. In 1813, parliament not only opened India to missionary activity, but also provided India with an established Church, which was largely supported by Indian taxation and formed part of the established Church of England. Many hoped that this union of Church and empire would communicate to India the benefits of England's diocesan and parochial structures, with a settled pastorate, parish churches and schools, and a Christian gentry. As the century progressed, the established Church was steadily enlarged, with a growing number of bishoprics, churches, schools, colleges, missionaries and clergy. But it had only limited success in gaining converts, and many Indians viewed it as a form of colonization. From the 1870s, it was increasingly clear that imperial India would not become Christian. Some began reconceptualizing the providential purpose behind the Indian empire, suggesting that the purpose might be to promote dialogue and understanding between the religions of the East and West, or, through the selfless service of missionaries, to promote moral reform movements in Hinduism and Islam.
Towards a Spiritual Empire: Christian Exegesis of the Universal Census at the Time of Jesus's Birth
Authors: Faitini Tiziana
Published: May 2018

This article focuses on the exegetical interpretation of Luke's narrative of the census (or registration) carried out at the time of Jesus's birth (Luke 2: 1–5). After some brief remarks on the juridical institution of the census (the so-calledprofessio census) in ancient Rome, a selection of the exegetical interpretations of this pericope developed by various ancient and medieval authors is presented. Origen, Ambrose, Orosius, Bede and Bonaventure are discussed, among others. A number of medieval authors, including Dante Alighieri and Bartolus of Saxoferrato, are also considered. The analysis argues, on the one hand, that a spiritualization of the institution of the census occurred and led to the spiritual empire of Christ being seen as replacing the temporal empire of Augustus; on the other, that reference to this institution was used to legitimize political authority in the eyes of believers. This interpretative tradition is thus shown to offer a vivid example of the close intertwining of theological and juridical concepts and practices which has characterized the relationship between the Church and empire from the former's very beginning.
‘Britishersand Protestants’: Protestantism and Imperial British Identities in Britain, Canada and Australia from the 1880s to the 1920s
Authors: Vaughan Géraldine
Published: May 2018

This article explores the links between the assertion of British imperial identities and the anti-Catholic discourse and practices of a network of evangelical societies which existed and flourished in Britain and in the dominions from the halcyon days of the empire to the late 1920s. These bodies shared a broad evangelical definition of Protestantism and defended the notion that religious beliefs and their political implications formed the basis of a common British heritage and identity. Those who identified themselves as Britons in Britain and in the dominions brought forward arguments combining a mixture of pessimistic interpretations of British history since the passing of the Catholic Emancipation Act with anxieties about ongoing Irish Catholic immigration and an alleged global papist plot. They were convinced that Protestantism was key to all civil liberties enjoyed by Britons. Inspired by John Wolffe's pioneering work, the article examines constitutional, theologico-political and socio-national anti-Catholicism across Britain and its dominions.
The ‘Servant of God’: Divine Favour and Instrumentality under Constantine, 318–25
Authors: Pottenger Andrew J.
Published: May 2018

This article focuses on the doctrine of divine favour and instrumentality as viewed from the emperor's own perspective, in relation to the early development of the ‘Arian controversy’ as far as the Council of Nicaea. While modern writers have focused on explicit statements by Constantine to suggest that unity was the emperor's highest priority, this article reveals a pattern by which he sought to manage divine favour and argues that doing so effectively was of primary importance to him. Such a shift in understanding the emperor's priorities adds to the range of explanations for his later apparent inconsistencies as the actual achievement of unity continually eluded him.
Imperiumand the City of God: Augustine on Church and Empire
Authors: Clark Gillian
Published: May 2018

In early fifth-century Roman Africa, Augustine faced pagan opponents who thought that the Roman empire was at risk because Christian emperors banned the worship of its gods, and that Christian ethics were no way to run an empire. He also faced Christian opponents who held that theirs was the true Church, and that the Roman empire was the oppressive power of Babylon. For Augustine, Church and empire consist of people. Everyone belongs either to the heavenly city, the community of all who love God even to disregard of themselves, or to the earthly city, the community of all who love themselves even to disregard of God. The two cities are intermixed until the final judgement shows that some who share Christian sacraments belong to the earthly city, and some officers of empire belong to the heavenly city. Empire manifests the earthly city's desire to dominate, butimperium, the acknowledged right to give orders, is necessary to avoid permanent conflict. Empire, like everything else, is given or permitted by God, for purposes we do not know.
Empire, Ethnic Election and Exegesis in theOpus Caroli (Libri Carolini)
Authors: O'Brien Conor
Published: May 2018

Modern historians have long argued that the early medieval Franks thought themselves to be the chosen people or new Israel, especially as they gained a great empire under the Carolingian dynasty in the late eighth century. TheOpus Caroliof Bishop Theodulf of Orléans has often been cited as one of the clearest expressions of this self-conception as God's elect. A massive work attacking the legitimacy of the Byzantine empire in the context of the iconoclasm dispute during the early 790s, it does indeed contest the Byzantine claim to be the Christian empire. But Theodulf's repeated statement that ‘We are the spiritual Israel’ is best understood not as an assertion of ethnic election, but as a reference to the Christian tradition of Scripture exegesis which should (he argues) underpin both the Frankish and the Byzantine understanding of images. The Carolingian claim to empire rested on the Frankish championing of the universal Church, and its traditions of orthodoxy and correct biblical interpretation.
Super gentes et regna: Papal ‘Empire’ in the Later Eleventh and Twelfth Centuries
Authors: Wiedemann Benedict G. E.
Published: May 2018

Papal relations with monarchs in the later eleventh and twelfth centuries have often been characterized as ‘feudal’, as indicative of some sort of papaldominium mundi, or as an effort to advance papal ‘empire’ over the kingdoms of Christendom. More recent scholarship has drawn a distinction between ‘protection’ and ‘feudal’ relationships with kings. However, the supposed distinction between the papacy's temporal overlordship of rulers and its spiritual protection may have obscured more than it has revealed. It was only after the disputes over lay investiture of bishops in the period 1078–1122 that a distinctive protective relationship began to emerge. Previously, rulers had been willing to ‘accept their kingdom from the pope's hand’ or to participate in ceremonies of investiture. In the twelfth century these relationships became more codified and any suggestion that the papacy actually gave kingdoms to kings faded. Thus, the nature of papal ‘empire’ – or, at least, temporal authority over kings – changed markedly during this period.
Das Gezeiten-Modell
Authors: Bohlscheid Julia , Kirchhof Johannes
Published: May 2018

Zusammenfassung. Die Klinik für Psychiatrie und Psychotherapie am Universitätsklinikum Köln zählte zu den ersten psychiatrischen Einrichtungen in Deutschland, die das Gezeiten-Modell in der Praxis umgesetzt haben. Hierdurch wird Recovery-Orientierung im klinischen Alltag verankert. Julia Bohlscheid und Johannes Kirchhof haben die Erfahrungen mit dem Modell in einem ersten Schritt unsystematisch, in einem zweiten Schritt strukturiert, erfasst.
The Unprecedented 2016–2017 Arctic Sea Ice Growth Season: The Crucial Role of Atmospheric Rivers and Longwave Fluxes
Authors: Hegyi Bradley M. , Taylor Patrick C.
Published: May 2018

The 2016–2017 Arctic sea ice growth season (October–March) exhibited one of the lowest values for end‐of‐season sea ice volume and extent of any year since 1979. An analysis of Modern‐Era Retrospective Analysis for Research and Applications, Version 2 atmospheric reanalysis data and Clouds and the Earth's Radiant Energy System radiative flux data reveals that a record warm and moist Arctic atmosphere supported the reduced sea ice growth. Numerous regional episodes of increased atmospheric temperature and moisture, transported from lower latitudes, increased the cumulative energy input from downwelling longwave surface fluxes. In those same episodes, the efficiency of the atmosphere cooling radiatively to space was reduced, increasing the amount of energy retained in the Arctic atmosphere and reradiated back toward the surface. Overall, the Arctic radiative cooling efficiency shows a decreasing trend since 2000. The results presented highlight the increasing importance of atmospheric forcing on sea ice variability demonstrating that episodic Arctic atmospheric rivers, regions of elevated poleward water vapor transport, and the subsequent surface energy budget response is a critical mechanism actively contributing to the evolution of Arctic sea ice.
Performance Evaluation of an Explicit Lightning Forecasting System
Authors: Dafis S. , Fierro A. , Giannaros T. M. , Kotroni V. , Lagouvardos K. , Mansell E.
Published: May 2018

In this study, an explicit electrification and lightning parameterization scheme implemented within the Weather Research and Forecasting model (E‐WRF, Fierro et al., , https://doi.org/10.1175/MWR‐D‐12‐00278.1) is evaluated against selected lightning diagnostic schemes. Convection‐permitting simulations of 10 high‐impact weather case studies over Greece are compared against lightning observations from the ZEUS ground‐based lightning detection network. The model's ability to accurately simulate these convective events is first evaluated through statistical scores of accumulated rainfall. The simulated flash origin density (FOD) fields are then assessed using statistical neighborhood methods. Overall, the simulated FOD fields have good agreement with the observations. Most of the lightning activity over the sea, however, is generally poorly forecasted. Lightning‐producing events over the sea near Greece mainly occur during the cold season. Thus, lightning forecast with E‐WRF appear to have better skill during the warm season. The simulated areal coverage of FOD using E‐WRF also reduces the false alarms of lightning activity both over land and sea compared to a well‐documented diagnostic lightning prediction scheme. Given its relatively low computational cost, these results support the potential use of E‐WRF for real‐time lightning predictions at convection‐allowing scales.
Stratospheric Injection of Brominated Very Short‐Lived Substances: Aircraft Observations in the Western Pacific and Representation in Global Models
Authors: Wales Pamela A. , Salawitch Ross J. , Nicely Julie M. , Anderson Daniel C. , Canty Timothy P. , Baidar Sunil , Dix Barbara , Koenig Theodore K. , Volkamer Rainer , Chen Dexian , Huey L. Gregory , Tanner David J. , Cuevas Carlos A. , Fernandez Rafael P. , Kinnison Douglas E. , Lamarque Jean‐Francois , Saiz‐Lopez Alfonso , Atlas Elliot L. , Hall Samuel R. , Navarro Maria A. , Pan Laura L. , Schauffler Sue M. , Stell Meghan , Tilmes Simone , Ullmann Kirk , Weinheimer Andrew J. , Akiyoshi Hideharu , Chipperfield Martyn P. , Deushi Makoto , Dhomse Sandip S. , Feng Wuhu , Graf Phoebe , Hossaini Ryan , Jöckel Patrick , Mancini Eva , Michou Martine , Morgenstern Olaf , Oman Luke D. , Pitari Giovanni , Plummer David A. , Revell Laura E. , Rozanov Eugene , Saint‐Martin David , Schofield Robyn , Stenke Andrea , Stone Kane A. , Visioni Daniele , Yamashita Yousuke , Zeng Guang
Published: May 2018

We quantify the stratospheric injection of brominated very short‐lived substances (VSLS) based on aircraft observations acquired in winter 2014 above the Tropical Western Pacific during the CONvective TRansport of Active Species in the Tropics (CONTRAST) and the Airborne Tropical TRopopause EXperiment (ATTREX) campaigns. The overall contribution of VSLS to stratospheric bromine was determined to be 5.0 ± 2.1 ppt, in agreement with the 5 ± 3 ppt estimate provided in the 2014 World Meteorological Organization (WMO) Ozone Assessment report (WMO 2014), but with lower uncertainty. Measurements of organic bromine compounds, including VSLS, were analyzed using CFC‐11 as a reference stratospheric tracer. From this analysis, 2.9 ± 0.6 ppt of bromine enters the stratosphere via organic source gas injection of VSLS. This value is two times the mean bromine content of VSLS measured at the tropical tropopause, for regions outside of the Tropical Western Pacific, summarized in WMO 2014. A photochemical box model, constrained to CONTRAST observations, was used to estimate inorganic bromine from measurements of BrO collected by two instruments. The analysis indicates that 2.1 ± 2.1 ppt of bromine enters the stratosphere via inorganic product gas injection. We also examine the representation of brominated VSLS within 14 global models that participated in the Chemistry‐Climate Model Initiative. The representation of stratospheric bromine in these models generally lies within the range of our empirical estimate. Models that include explicit representations of VSLS compare better with bromine observations in the lower stratosphere than models that utilize longer‐lived chemicals as a surrogate for VSLS.
The Transport of Asian Dust and Combustion Aerosols and Associated Ozone to North America as Observed From a Mountaintop Monitoring Site in the California Coast Range
Authors: Asher Elizabeth C. , Christensen John N. , Post Andrew , Perry Kevin , Cliff Steven S. , Zhao Yongjing , Trousdell Justin , Faloona Ian
Published: May 2018

Aerosol and tropospheric ozone transport to North America has important implications for regional air quality and climate. We present data from Chews Ridge, a remote mountaintop site in California, in February–September 2012, which identifies separate Asian dust and Asian combustion aerosol signals and quantifies exogenous ozone. We use positive matrix factorization of size‐fractionated aerosol X‐ray fluorescence data and 206Pb/207Pb and 208Pb/207Pb isotope measurements to isolate aerosol signals of Asian origins and find good agreement between both types source attribution techniques. Power spectra of Asian dust and Asian combustion signals reveal two distinct peaks, one seasonal (~90 days) and one monthly (~25–30 days). Overall, 89% of the Asian dust signal occurs in March–May, compared with June–September, whereas only 51% of the Asian combustion signal occurs in March–May. Nearly half the Pb observed at Chews Ridge was derived from Asia (46%; 8.3% from Asian dust, 23% from Asian combustion, and 15% of the Asian Pb signal was not explained by the positive matrix factorization). A positive correlation between deseasonalized ozone concentrations and the Asian factors suggests that ozone is elevated by 6.3 ± 0.8 ppb due to transpacific transport. Scanning mobility particle size spectra were also measured from May to September and indicate that new particles are often produced and grow throughout the afternoon during onshore flow. We hypothesize that particle nucleation on the windward edge of the continent is an important source of new particles.
Retrieval of Cloud Condensation Nuclei Number Concentration Profiles From Lidar Extinction and Backscatter Data
Authors: Lv Min , Wang Zhien , Li Zhanqing , Luo Tao , Ferrare Richard , Liu Dong , Wu Decheng , Mao Jietai , Wan Bingcheng , Zhang Fang , Wang Yuying
Published: May 2018

The vertical distribution of aerosols and their capability of serving as cloud condensation nuclei (CCN) are important for improving our understanding of aerosol indirect effects. Although ground‐based and airborne CCN measurements have been made, they are generally scarce, especially at cloud base where it is needed most. We have developed an algorithm for profiling CCN number concentrations using backscatter coefficients at 355, 532, and 1,064 nm and extinction coefficients at 355 and 532 nm from multiwavelength lidar systems. The algorithm considers three distinct types of aerosols (urban industrial, biomass burning, and dust) with bimodal size distributions. The algorithm uses look‐up tables, which were developed based on the ranges of aerosol size distributions obtained from the Aerosol Robotic Network, to efficiently find optimal solutions. CCN number concentrations at five supersaturations (0.07–0.80%) are determined from the retrieved particle size distributions. Retrieval simulations were performed with different combinations of systematic and random errors in lidar‐derived extinction and backscatter coefficients: systematic errors range from −20% to 20% and random errors are up to 15%, which fall within the typical error ranges for most current lidar systems. The potential of this algorithm to retrieve CCN concentrations is further evaluated through comparisons with surface‐based CCN measurements with near‐surface lidar retrievals. This retrieval algorithm would be valuable for aerosol‐cloud interaction studies for which virtually none has employed CCN at cloud base because of the lack of such measurements.
Promoting Competitive Water Resource Use Efficiency at the Water‐Market Scale: An Intercooperative Demand Equilibrium‐Based Approach to Water Trading
Authors: Delorit Justin D. , Block Paul J.
Published: May 2018

Water rights law and corresponding markets exist to promote economic water resource use efficiency by permitting water rights holders to trade allocations. In some regions, hydrologic uncertainty drives annual assignment of per‐water right allocation values. Water rights holders, specifically those involved in agricultural production, may use collaborative water resource decision making to mitigate allocation uncertainty and promote economic and social efficiency. Such is the case in semi‐arid North Chile, where interactions between representative farmer groups, treated as resource competitive growers’ cooperatives, and modeled at water market‐scale, can provide both price and water right allocation distribution signals for unregulated, temporary water right markets. For the range of feasible per‐water right allocation values, a coupled agricultural‐economic model is developed to describe the equilibrium distribution of water, the corresponding market price of water rights, and the net surplus generated by collaboration between competing agricultural uses. A static, demand‐based allocation redistribution ruleset is generated by which the cooperatives are constrained to abide. Water right supply and demand inequality impacts at the market‐scale are used to characterize market performance under existing water rights law, and to evaluate the efficacy of intercooperative collaboration over the period 2000–2015. Exclusive intercooperative water trading, following a demand‐based ruleset, produces joint mean annual expected profits 24%–122% larger than a case of no‐interaction, depending on initial rights distribution. The broader insights of this research suggest that water rights holders engaged in agriculture can achieve enhanced benefits by forming crop‐type cooperatives and implementing demand‐based allocation redistribution rulesets.
Variation in the Distribution and Properties of Circumpolar Deep Water in the Eastern Amundsen Sea, on Seasonal Timescales, Using Seal‐Borne Tags
Authors: Mallett Helen K. W. , Boehme Lars , Fedak Mike , Heywood Karen J. , Stevens David P. , Roquet Fabien
Published: May 2018

In the Amundsen Sea, warm saline Circumpolar Deep Water (CDW) crosses the continental shelf toward the vulnerable West Antarctic ice shelves, contributing to their basal melting. Due to lack of observations, little is known about the spatial and temporal variability of CDW, particularly seasonally. A new data set of 6,704 seal tag temperature and salinity profiles in the easternmost trough between February and December 2014 reveals a CDW layer on average 49 dbar thicker in late winter (August to October) than in late summer (February to April), the reverse seasonality of that seen at moorings in the western trough. This layer contains more heat in winter, but on the 27.76 kg/m3 density surface CDW is 0.32°C warmer in summer than in winter, across the northeastern Amundsen Sea, which may indicate that wintertime shoaling offshelf changes CDW properties onshelf. In Pine Island Bay these seasonal changes on density surfaces are reduced, likely by gyre circulation.
Long‐Lasting Response of the Global Thermosphere and Ionosphere to the 21 August 2017 Solar Eclipse
Authors: Lei Jiuhou , Dang Tong , Wang Wenbin , Burns Alan , Zhang Binzheng , Le Huijun
Published: May 2018

Previous studies have been devoted to examining the ionosphere and thermosphere response during the solar eclipse, but the posteclipse response of the global ionosphere and thermosphere has not been well quantified. In this study, for the first time, we quantitatively investigate the posteclipse response of the global ionosphere and thermosphere system to the recent Great American Solar Eclipse using a high‐resolution, global, coupled ionosphere‐thermosphere‐electrodynamics model. It was found that the posteclipse response of the ionosphere and thermosphere is significant and worldwide, which was not expected. Specifically, even 9 hr after the eclipse ended, the globally averaged ionospheric total electron content perturbations were about 0.2 total electron content unit, and the corresponding changes in neutral temperature and winds reached 2 K and 2 m/s. The changes in the global dynamic and energetic processes associated with the solar eclipse contributed to this long‐lasting response of the ionosphere and thermosphere during the posteclipse period.
Generating Coherent Ensemble Forecasts After Hydrological Postprocessing: Adaptations of ECC‐Based Methods
Authors: Bellier Joseph , Zin Isabella , Bontron Guillaume
Published: May 2018

Hydrological ensemble forecasts are frequently miscalibrated, and need to be statistically postprocessed in order to account for the total predictive uncertainty. Very often, this step relies on parametric, univariate techniques that ignore the between‐basins and between‐lead times dependencies. This calls for a procedure referred to as sampling‐reordering, which generates a coherent multivariate ensemble from the marginal postprocessed distributions. The ensemble copula coupling (ECC) approach, which is already popular in the field of meteorological postprocessing, is attractive for hydrological forecasts as it preserves the dependence structure of the raw ensemble assumed as spatially and temporally coherent. However, the existing implementations of ECC have strong limitations when applied to hourly streamflow, due to raw ensembles being frequently nondispersive and to streamflow data being strongly autocorrelated. Based on this diagnosis, this paper investigates several variants of ECC, in particular the addition of a perturbation to the raw ensemble to handle the nondispersive cases, and the smoothing of the temporal trajectories to make them more realistic. The evaluation is conducted on a case study of hydrological forecasting over a set of French basins. The results show that the new variants improve upon the existing ECC implementations, while they remain simple and computationally inexpensive.
The Assessment and Modeling of Perceptual Control: A Transformation in Research Methodology to Address the Replication Crisis
Authors: Mansell Warren , Huddy Vyv
Published: May 2018

Replication in the behavioral sciences is a matter of considerable debate. We describe a series of fundamental interrelated conceptual and methodological issues with current research that undermine replication and we explain how they could be addressed. Conceptually, we need a shift (a) from verbally described theories to mathematically specified theories, (b) from lineal stimulus-cognition-response theories to closed-loop theories that model behavior as feeding back to sensory input via the environment, and (c) from theories that “chunk” responses to theories that acknowledge the continuous, dynamic nature of behavior. A closely related shift in methodology would involve studies that attempt to model each individual's performance as a continuous and dynamic activity within a closed-loop process. We explain how this shift can be made within a single framework—perceptual control theory (PCT)—that regards behavior as the control of perceptual input. We report evidence of multiple replication using this approach within visual tracking, and go on to demonstrate in practical research terms how the same overarching principle can guide research across diverse domains of psychology and the behavioral sciences, promoting their coherent integration. We describe ways to address current challenges to this approach and provide recommendations for how researchers can manage the transition.
Functional interplay between E2F7 and ribosomal rRNA gene transcription regulates protein synthesis
Authors: Coutts Amanda S , Munro Shonagh , La Thangue Nicholas B
Published: May 2018

A prerequisite for protein synthesis is the transcription of ribosomal rRNA genes by RNA polymerase I (Pol I), which controls ribosome biogenesis. UBF (upstream binding factor) is one of the main Pol I transcription factors located in the nucleolus that activates rRNA gene transcription. E2F7 is an atypical E2F family member that acts as a transcriptional repressor of E2F target genes, and thereby contributes to cell cycle arrest. Here, we describe an unexpected role for E2F7 in regulating rRNA gene transcription. We have found that E2F7 localises to the perinucleolar region, and further that E2F7 is able to exert repressive effects on Pol I transcription. At the mechanistic level, this is achieved in part by E2F7 hindering UBF recruitment to the rRNA gene promoter region, and thereby reducing rRNA gene transcription, which in turn compromises global protein synthesis. Our results expand the target gene repertoire influenced by E2F7 to include Pol I-regulated genes, and more generally suggest a mechanism mediated by effects on Pol I transcription where E2F7 links cell cycle arrest with protein synthesis.
The ginsenoside PPD exerts anti-endometriosis effects by suppressing estrogen receptor-mediated inhibition of endometrial stromal cell autophagy and NK cell cytotoxicity
Authors: Zhang Bing , Zhou Wen-Jie , Gu Chun-Jie , Wu Ke , Yang Hui-Li , Mei Jie , Yu Jia-Jun , Hou Xiao-Fan , Sun Jian-Song , Xu Feng-Yuan , Li Da-Jin , Jin Li-Ping , Li Ming-Qing
Published: May 2018

Endometriosis (EMS) is an estrogen-dependent gynecological disease with a low autophagy level of ectopic endometrial stromal cells (eESCs). Impaired NK cell cytotoxic activity is involved in the clearance obstruction of the ectopic endometrial tissue in the abdominopelvic cavity. Protopanaxadiol (PPD) and protopanaxatriol (PPT) are two metabolites of ginsenosides, which have profound biological functions, such as anti-cancer activities. However, the role and mechanism of ginsenosides and metabolites in endometriosis are completely unknown. Here, we found that the compounds PPD, PPT, ginsenoside-Rg3 (G-Rg3), ginsenoside-Rh2 (G-Rh2), and esculentoside A (EsA) led to significant decreases in the viability of eESCs, particularly PPD (IC50 = 30.64 µM). In vitro and in vivo experiments showed that PPD promoted the expression of progesterone receptor (PR) and downregulated the expression of estrogen receptor α (ERα) in eESCs. Treatment with PPD obviously induced the autophagy of eESCs and reversed the inhibitory effect of estrogen on eESC autophagy. In addition, eESCs pretreated with PPD enhanced the cytotoxic activity of NK cells in response to eESCs. PPD decreased the numbers and suppressed the growth of ectopic lesions in a mouse EMS model. These results suggest that PPD plays a role in anti-EMS activation, possibly by restricting estrogen-mediated autophagy regulation and enhancing the cytotoxicity of NK cells. This result provides a scientific basis for potential therapeutic strategies to treat EMS by PPD or further structural modification.
The novel 19q13 KRAB zinc-finger tumour suppressor ZNF382 is frequently methylated in oesophageal squamous cell carcinoma and antagonises Wnt/β-catenin signalling
Authors: Zhang Chong , Xiang Tingxiu , Li Shuman , Ye Lin , Feng Yixiao , Pei Lijiao , Li Lili , Wang Xiangyu , Sun Ran , Ren Guosheng , Tao Qian
Published: May 2018

Zinc finger proteins (ZFPs) are the largest transcription factor family in mammals. About one-third of ZFPs are Krüppel-associated box domain (KRAB)-ZFPs and involved in the regulation of cell differentiation/proliferation/apoptosis and neoplastic transformation. We recently identified ZNF382 as a novel KRAB-ZFP epigenetically inactivated in multiple cancers due to frequent promoter CpG methylation. However, its epigenetic alterations, biological functions/mechanism and clinical significance in oesophageal squamous cell carcinoma (ESCC) are still unknown. Here, we demonstrate that ZNF382 expression was suppressed in ESCC due to aberrant promoter methylation, but highly expressed in normal oesophagus tissues. ZNF382 promoter methylation is correlated with ESCC differentiation levels. Restoration of ZNF382 expression in silenced ESCC cells suppressed tumour cell proliferation and metastasis through inducing cell apoptosis. Importantly, ZNF382 suppressed Wnt/β-catenin signalling and downstream target gene expression, likely through binding directly to FZD1 and DVL2 promoters. In summary, our findings demonstrate that ZNF382 functions as a bona fide tumour suppressor inhibiting ESCC pathogenesis through inhibiting the Wnt/β-catenin signalling pathway.
Bacterial encapsulins as orthogonal compartments for mammalian cell engineering
Authors: Sigmund Felix , Massner Christoph , Erdmann Philipp , Stelzl Anja , Rolbieski Hannes , Desai Mitul , Bricault Sarah , Wörner Tobias P. , Snijder Joost , Geerlof Arie , Fuchs Helmut , Hrabĕ de Angelis Martin , Heck Albert J. R. , Jasanoff Alan , Ntziachristos Vasilis , Plitzko Jürgen , Westmeyer Gil G.
Published: May 2018

We genetically controlled compartmentalization in eukaryotic cells by heterologous expression of bacterial encapsulin shell and cargo proteins to engineer enclosed enzymatic reactions and size-constrained metal biomineralization. The shell protein (EncA) from Myxococcus xanthus auto-assembles into nanocompartments inside mammalian cells to which sets of native (EncB,C,D) and engineered cargo proteins self-target enabling localized bimolecular fluorescence and enzyme complementation. Encapsulation of the enzyme tyrosinase leads to the confinement of toxic melanin production for robust detection via multispectral optoacoustic tomography (MSOT). Co-expression of ferritin-like native cargo (EncB,C) results in efficient iron sequestration producing substantial contrast by magnetic resonance imaging (MRI) and allowing for magnetic cell sorting. The monodisperse, spherical, and iron-loading nanoshells are also excellent genetically encoded reporters for electron microscopy (EM). In general, eukaryotically expressed encapsulins enable cellular engineering of spatially confined multicomponent processes with versatile applications in multiscale molecular imaging, as well as intriguing implications for metabolic engineering and cellular therapy.
Phenotypic diversification by enhanced genome restructuring after induction of multiple DNA double-strand breaks
Authors: Muramoto Nobuhiko , Oda Arisa , Tanaka Hidenori , Nakamura Takahiro , Kugou Kazuto , Suda Kazuki , Kobayashi Aki , Yoneda Shiori , Ikeuchi Akinori , Sugimoto Hiroki , Kondo Satoshi , Ohto Chikara , Shibata Takehiko , Mitsukawa Norihiro , Ohta Kunihiro
Published: May 2018

DNA double-strand break (DSB)-mediated genome rearrangements are assumed to provide diverse raw genetic materials enabling accelerated adaptive evolution; however, it remains unclear about the consequences of massive simultaneous DSB formation in cells and their resulting phenotypic impact. Here, we establish an artificial genome-restructuring technology by conditionally introducing multiple genomic DSBs in vivo using a temperature-dependent endonuclease TaqI. Application in yeast and Arabidopsis thaliana generates strains with phenotypes, including improved ethanol production from xylose at higher temperature and increased plant biomass, that are stably inherited to offspring after multiple passages. High-throughput genome resequencing revealed that these strains harbor diverse rearrangements, including copy number variations, translocations in retrotransposons, and direct end-joinings at TaqI-cleavage sites. Furthermore, large-scale rearrangements occur frequently in diploid yeasts (28.1%) and tetraploid plants (46.3%), whereas haploid yeasts and diploid plants undergo minimal rearrangement. This genome-restructuring system (TAQing system) will enable rapid genome breeding and aid genome-evolution studies.
Stepwise control of host–guest interaction using a coordination polymer gel
Authors: Mukhopadhyay Rahul Dev , Das Gourab , Ajayaghosh Ayyappanpillai
Published: May 2018

Precise control of host–guest interaction as seen in biological processes is difficult to achieve with artificial systems. Herein we have exploited the thermodynamic benefits of a system in equilibrium to achieve controlled stepwise release and capture of cyclodextrin (guest) using a coordination polymer (Mg-CP) as the host and temperature as the stimulus. Since temperature is not a precision stimulus for artificial host–guest interaction, the present system is a distinct prototype that manifests temperature-controlled natural host–guest interaction. The described coordination polymeric host system, when incorporated into a hydrogel matrix, provides a microenvironment that facilitates the stepwise release of α-CD in response to temperature variation within a quasi-solid state. The work demonstrated here may pave the way towards thermally controlled delivery and monitoring of otherwise spectroscopically silent molecules such as cyclodextrins.
MLL-fusion-driven leukemia requires SETD2 to safeguard genomic integrity
Authors: Skucha Anna , Ebner Jessica , Schmöllerl Johannes , Roth Mareike , Eder Thomas , César-Razquin Adrián , Stukalov Alexey , Vittori Sarah , Muhar Matthias , Lu Bin , Aichinger Martin , Jude Julian , Müller André C. , Győrffy Balázs , Vakoc Christopher R. , Valent Peter , Bennett Keiryn L. , Zuber Johannes , Superti-Furga Giulio , Grebien Florian
Published: May 2018

MLL-fusions represent a large group of leukemia drivers, whose diversity originates from the vast molecular heterogeneity of C-terminal fusion partners of MLL. While studies of selected MLL-fusions have revealed critical molecular pathways, unifying mechanisms across all MLL-fusions remain poorly understood. We present the first comprehensive survey of protein–protein interactions of seven distantly related MLL-fusion proteins. Functional investigation of 128 conserved MLL-fusion-interactors identifies a specific role for the lysine methyltransferase SETD2 in MLL-leukemia. SETD2 loss causes growth arrest and differentiation of AML cells, and leads to increased DNA damage. In addition to its role in H3K36 tri-methylation, SETD2 is required to maintain high H3K79 di-methylation and MLL-AF9-binding to critical target genes, such as Hoxa9. SETD2 loss synergizes with pharmacologic inhibition of the H3K79 methyltransferase DOT1L to induce DNA damage, growth arrest, differentiation, and apoptosis. These results uncover a dependency for SETD2 during MLL-leukemogenesis, revealing a novel actionable vulnerability in this disease.
Optical wireless link between a nanoscale antenna and a transducing rectenna
Authors: Dasgupta Arindam , Mennemanteuil Marie-Maxime , Buret Mickaël , Cazier Nicolas , Colas-des-Francs Gérard , Bouhelier Alexandre
Published: May 2018

Initiated as a cable-replacement solution, short-range wireless power transfer has rapidly become ubiquitous in the development of modern high-data throughput networking in centimeter to meter accessibility range. Wireless technology is now penetrating a higher level of system integration for chip-to-chip and on-chip radiofrequency interconnects. However, standard CMOS integrated millimeter-wave antennas have typical size commensurable with the operating wavelength, and are thus an unrealistic solution for downsizing transmitters and receivers to the micrometer and nanometer scale. Herein, we demonstrate a light-in and electrical signal-out, on-chip wireless near-infrared link between a 220 nm optical antenna and a sub-nanometer rectifying antenna converting the transmitted optical energy into direct electrical current. The co-integration of subwavelength optical functional devices with electronic transduction offers a disruptive solution to interface photons and electrons at the nanoscale for on-chip wireless optical interconnects.
TAK1 mediates microenvironment-triggered autocrine signals and promotes triple-negative breast cancer lung metastasis
Authors: Iriondo Oihana , Liu Yarong , Lee Grace , Elhodaky Mostafa , Jimenez Christian , Li Lin , Lang Julie , Wang Pin , Yu Min
Published: May 2018

Triple-negative breast cancer (TNBC) is a highly metastatic subtype of breast cancer that has limited therapeutic options. Thus, developing novel treatments for metastatic TNBC is an urgent need. Here, we show that nanoparticle-mediated delivery of transforming growth factor-β1-activated kinase-1 (TAK1) inhibitor 5Z-7-Oxozeaenol can inhibit TNBC lung metastasis in most animals tested. P38 is a central signal downstream of TAK1 in TNBC cells in TAK1-mediated response to multiple cytokines. Following co-culturing with macrophages or fibroblasts, TNBC cells express interleukin-1 (IL1) or tumor necrosis factor-α (TNFα), respectively. Compared to TAK1 inhibition, suppressing IL1 signaling with recombinant IL1 receptor antagonist (IL1RA) is less efficient in reducing lung metastasis, possibly due to the additional TAK1 signals coming from distinct stromal cells. Together, these observations suggest that TAK1 may play a central role in promoting TNBC cell adaptation to the lung microenvironment by facilitating positive feedback signaling mediated by P38. Approaches targeting the key TAK1-P38 signal could offer a novel means for suppressing TNBC lung metastasis.
Activity of acetyltransferase toxins involved in Salmonella persister formation during macrophage infection
Authors: Rycroft Julian A. , Gollan Bridget , Grabe Grzegorz J. , Hall Alexander , Cheverton Angela M. , Larrouy-Maumus Gerald , Hare Stephen A. , Helaine Sophie
Published: May 2018

Non-typhoidal Salmonella strains are responsible for invasive infections associated with high mortality and recurrence in sub-Saharan Africa, and there is strong evidence for clonal relapse following antibiotic treatment. Persisters are non-growing bacteria that are thought to be responsible for the recalcitrance of many infections to antibiotics. Toxin–antitoxin systems are stress-responsive elements that are important for Salmonella persister formation, specifically during infection. Here, we report the analysis of persister formation of clinical invasive strains of Salmonella Typhimurium and Enteritidis in human primary macrophages. We show that all the invasive clinical isolates of both serovars that we tested produce high levels of persisters following internalization by human macrophages. Our genome comparison reveals that S. Enteritidis and S. Typhimurium strains contain three acetyltransferase toxins that we characterize structurally and functionally. We show that all induce the persister state by inhibiting translation through acetylation of aminoacyl-tRNAs. However, they differ in their potency and target partially different subsets of aminoacyl-tRNAs, potentially accounting for their non-redundant effect.
Immune system correlates of extensive limb swelling in response to conjugated pneumococcal vaccination
Authors: Recher Mike , Hirsiger Julia R. , Bigler Marc B. , Iff Martin , Lemaître Barbara , Scherer Kathrin , Häusermann Peter , Siegrist Claire-Anne , Berger Christoph T.
Published: May 2018

Pneumococcal conjugate vaccine (PCV) is recommended for adults with chronic disease. Extensive limb swelling (ELS) is an acute vigorous local inflammatory reaction following vaccination. Predisposing immune system correlates and the influence of ELS on vaccine responses are not known. Here, we report a case of a 67-year-old woman with a history of multiple pneumonias who had a detailed immunological work-up pre-vaccination because of suspected immunodeficiency. Four days following a first vaccination with PCV13 she developed ELS—mimicking erysipelas. Treatment with 20 mg cortisone completely alleviated symptoms within 2 days. Skin biopsy showed a dense dermal and subdermal infiltration dominated by CD4+ T cells and macrophages. In a multiplexed serotype-specific measurement of the anti-pneumococcal IgG response, the patient showed very broad and strong vaccine responses. Pre-vaccination titers were low for the vaccine serotypes. We did not find in vivo nor in vitro evidence of an excessive T cell response to the diphtheria-derived PCV carrier protein. However, we could demonstrate a high antibody titer to a non-vaccine serotype, indicating in vivo pre-exposure to pneumococcus bacteria. Thus, traces of pneumococcal proteins included in PCV13 may have boosted pre-existing pneumococcus-specific T helper cells, which subsequently orchestrated ELS. Our case raises awareness for the risk of vaccine-induced ELS, especially in patients with a history of recurrent pneumococcal disease and thus partial immunity.
Development of an Algorithm to Identify Patients with Physician-Documented Insomnia
Authors: Kartoun Uri , Aggarwal Rahul , Beam Andrew L. , Pai Jennifer K. , Chatterjee Arnaub K. , Fitzgerald Timothy P. , Kohane Isaac S. , Shaw Stanley Y.
Published: May 2018

We developed an insomnia classification algorithm by interrogating an electronic medical records (EMR) database of 314,292 patients. The patients received care at Massachusetts General Hospital (MGH), Brigham and Women’s Hospital (BWH), or both, between 1992 and 2010. Our algorithm combined structured variables (such as International Classification of Diseases 9th Revision [ICD-9] codes, prescriptions, laboratory observations) and unstructured variables (such as text mentions of sleep and psychiatric disorders in clinical narrative notes). The highest classification performance of our algorithm was achieved when it included a combination of structured variables (billing codes for insomnia, common psychiatric conditions, and joint disorders) and unstructured variables (sleep disorders and psychiatric disorders). Our algorithm had superior performance in identifying insomnia patients compared to billing codes alone (area under the receiver operating characteristic curve [AUROC] = 0.83 vs. 0.55 with 95% confidence intervals [CI] of 0.76–0.90 and 0.51–0.58, respectively). When applied to the 314,292-patient population, our algorithm classified 36,810 of the patients with insomnia, of which less than 17% had a billing code for insomnia. In conclusion, an insomnia classification algorithm that incorporates clinical notes is superior to one based solely on billing codes. Compared to traditional methods, our study demonstrates that a classification algorithm that incorporates physician notes can more accurately, comprehensively, and quickly identify large cohorts of insomnia patients.
Magneto-absorption spectra of hydrogen-like yellow exciton series in cuprous oxide: excitons in strong magnetic fields
Authors: Artyukhin Sergey , Fishman Dmitry , Faugeras Clément , Potemski Marek , Revcolevschi Alexandre , Mostovoy Maxim , Loosdrecht Paul H. M. van
Published: May 2018

We study the absorption spectra of the yellow excitons in Cu2O in high magnetic fields using polarization-resolved optical absorption measurements with a high frequency resolution. We show that the symmetry of the yellow exciton results in unusual selection rules for the optical absorption of polarized light and that the mixing of ortho- and para- excitons in magnetic field is important. The calculation of the energies of the yellow exciton series in strong and weak magnetic field limits suggests that a broad n = 2 line is comprized by two closely overlapping lines, gives a good fit to experimental data and allows to interpret the complex structure of excitonic levels.
Author Correction: White Matter and Gray Matter Segmentation in 4D Computed Tomography
Authors: Manniesing Rashindra , Oei Marcel T. H. , Oostveen Luuk J. , Melendez Jaime , Smit Ewoud J. , Platel Bram , Sánchez Clara I. , Meijer Frederick J. A. , Prokop Mathias , van Ginneken Bram
Published: May 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Author Correction: Zika Virus in Salivary Glands of Five Different Species of Wild-Caught Mosquitoes from Mexico
Authors: Elizondo-Quiroga Darwin , Medina-Sánchez Aarón , Sánchez-González Jorge M. , Eckert Kristen Allison , Villalobos-Sánchez Erendira , Navarro-Zúñiga Antonio Rigoberto , Sánchez-Tejeda Gustavo , Correa-Morales Fabián , González-Acosta Cassandra , Arias Carlos F. , López Susana , del Ángel Rosa María , Pando-Robles Victoria , Elizondo-Quiroga Armando E.
Published: May 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Author Correction: High-temperature operation of electrical injection type-II (GaIn)As/Ga(AsSb)/(GaIn)As “W”-quantum well lasers emitting at 1.3 µm
Authors: Fuchs C. , Brüggemann A. , Weseloh M. J. , Berger C. , Möller C. , Reinhard S. , Hader J. , Moloney J. V. , Bäumner A. , Koch S. W. , Stolz W.
Published: May 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Author Correction: Analysis of mutations in pncA reveals non-overlapping patterns among various lineages of Mycobacterium tuberculosis
Authors: Baddam Ramani , Kumar Narender , Wieler Lothar H. , Lankapalli Aditya Kumar , Ahmed Niyaz , Peacock Sharon J. , Semmler Torsten
Published: May 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.