bluuebunny/crossref_metadata_2025 huggingface dataset:
Ambition, ‘failure’ and the laboratory: Birmingham as a centre of twentieth-century British scientific psychiatry
Authors: Wynter Rebecca
Published: February 2021

This article will reveal how local scientific determination and ambition, in the face of rejection by funders, navigated a path to success and to influence in national policy and international medicine. It will demonstrate that Birmingham, England's ‘second city’, was the key centre for cutting-edge biological psychiatry in Britain in the 1920s and 1930s. The ambitions of Frederick Mott – doyen of biochemistry, neuropathology and neuropsychiatry, until now celebrated as a London figure – to revolutionize psychiatric treatment through science, chimed with those of the City and University of Birmingham's Joint Board of Research for Mental Diseases. Under Mott's direction, shaped by place and inter-professional working, the board's collaborators included psychiatrist Thomas Chivers Graves and world-renowned physiologist J.S. Haldane. However, starved of external money and therefore fresh ideas, as well as oversight, the ‘groupthink’ that emerged created the classic UK focal sepsis theory which, it was widely believed, would yield a cure for mental illness – a cure that never materialized. By tracing the venture's growth, accomplishments and contemporary potential for biochemical, bacterial and therapeutic discoveries – as well as its links with scientist and key government adviser Solly Zuckerman – this article illustrates how ‘failure’ and its ahistorical assessment fundamentally obscure past importance, neglect the early promise offered by later unsuccessful science, and can even hide questionable research.
L'influence du facteur religieux dans le financement des écoles privées au Québec et en Ontario
Authors: Lachance Anne
Published: February 2021

Cet article vise à expliquer les motifs pour lesquels le Québec finance les écoles privées alors que la province voisine, l'Ontario, ne leur apporte aucune aide directe. L'auteure avance que ces politiques sont liées à la configuration religieuse des provinces au moment de l’établissement de leur système d’éducation. Au Québec, où la religion catholique était dominante, l'autorité de l'État sur l'éducation a été contestée jusqu'au milieu du 20esiècle par l’Église catholique. En revanche, en Ontario, les églises protestantes, qui étaient majoritaires, ne sont pas opposées au développement des écoles publiques. L'État s'est alors rapidement imposé comme l'autorité suprême en matière d'éducation. Au 20esiècle, les politiques des gouvernements des deux provinces ont été influencées par l'héritage des décisions prises un siècle plus tôt.
“Do Not Believe Every Spirit”: Discerning the Ethics of Prophetic Agency in Early Christian Culture
Authors: Tibbs Eugene C.
Published: February 2021

In early Christian culture, prophets went into ecstasies while having visions and speaking by means of a spirit (enthusiasm). With the waning of prophetic activity in the second century, enthusiasm was not seen in many communal gatherings. When enthusiasm reemerged in Montanism during the late second century, church leaders claimed that speaking in ecstasy never existed as true prophecy in early Christian culture. They argued that true prophets always prophesied with a sound mind. The ecstasy of Montanism exhibited an unsound mind and looked like demonic possession; thus, Montanist prophecy was rejected as false. This paper theorizes that enthusiasm's absence contributed to the critics of Montanist ecstasy who were not used to enthusiasm and therefore did not recognize it as an early Christian practice.
Influence of nutrient availability on in vitro growth of major bovine mastitis pathogens
Authors: Stürmlin Remo , Gross Josef J. , Wellnitz Olga , Wagner Lea A. , Monney Camille , Oevermann Anna , Bruckmaier Rupert M.
Published: February 2021

The aim of the present study was to investigate the effects of milk composition changes on the in vitro growth of bovine mastitis pathogens. Nutritional requirements of three major bovine mastitis pathogens Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Streptococcus uberis (S. uberis) were investigated in vitro. We used ultra-high temperature (UHT) treated milk with different contents of fat, protein, and carbohydrates to test the influence of the availability of various milk constituents on pathogen growth characteristics. Additionally, the bacterial growth was investigated under experimentally modified nutrient availability by dilution and subsequent supplementation with individual nutrients (carbohydrates, different nitrogen sources, minerals, and different types of B vitamins) either to milk or to a conventional medium (thioglycolate broth, TB). Varying contents of fat, protein or lactose did not affect bacterial growth with the exception of growth of S. uberis being promoted in protein-enriched milk. The addition of nutrients to diluted whole milk and TB partly revealed different effects, indicating that there are media-specific growth limiting factors after dilution. Supplementation of minerals to diluted milk did not affect growth rates of all studied bacteria. Bacterial growth in diluted whole milk was decreased by the addition of high concentrations of amino acids in S. aureus, and by urea and additional B vitamins in E. coli and S. aureus. The growth rate of S. uberis was increased by the addition of B vitamins to diluted whole milk. The present results demonstrate that growth-limiting nutrients differ among pathogen types. Because reduced bacterial growth was only shown in diluted milk or TB, it is unlikely that alterations in nutrient availability occurring as a consequence of physiological changes of milk composition in the cow's udder would directly affect the susceptibility or course of bovine mastitis.
The impact of Horae Subsecivae on the EDD's coverage of western words
Authors: Ruano–García Javier
Published: February 2021

This paper examines the contribution of Horae Subsecivae to Joseph Wright's (1855–1930) English Dialect Dictionary (1896–1905) (EDD). Horae Subsecivae (‘spare hours’) is an obscure manuscript glossary that was possibly compiled by Robert Wight of Wotton-under-Edge in c.1777–78, and is now preserved amongst Wright's papers at the Bodleian Library as Bodl. MS Eng. lang. d. 66. Even though it has received little scholarly attention, Horae Subsecivae has a substantial dialect element, with a large number of words cited from Devonshire, Dorset, Cornwall, Gloucestershire, Somerset, Wiltshire and Worcestershire. The manuscript went largely unnoticed by 18th- and 19th-century collections, and remains virtually unknown today perhaps owing to its extensive use of Latin, but it drew the attention of Joseph Wright, who employed it frequently to represent some western dialects. Drawing on the electronic version of the EDD (EDD Online; Markus, 2019a), the paper is situated within forensic dictionary analysis (Coleman & Ogilvie, 2009), which ‘uses evidence-based methodologies to interrogate the dictionaries themselves about decision-making processes involved in their compilation’ (1). In this framework, I combine archival material with quantitative and qualitative approaches to the data retrieved from EDD Online in order to ascertain the proportion of words that are cited from the manuscript, and to assess the treatment they are given. Attention is paid to their function in the context of the dictionary, labels, the western dialects about which the manuscript provides more extensive information, as well as the entries in which it is cited as the only source for words, ascriptions and senses. This paper highlights the outstanding contribution of Horae Subsecivae to the EDD, while stressing that it notably improves our knowledge of lexical variation in the dialects of the South West and the lower West Midlands. They can only benefit from further inspection as they ‘are neither as easily found nor as well researched as those of the north’ (Melchers, 2010: 82).
Interventions to improve vitamin D status in at-risk ethnic groups during pregnancy and early childhood: a systematic review
Authors: Tanna Nuttan K , Alexander Emma C , Lee Charlotte , Lakhanpaul Monica , Popat Rickin M , Almeida-Meza Pamela , Tuck Alice , Manikam Logan , Blair Mitch
Published: February 2021

Objective:

To systematically review the literature with the primary aim of identifying behavioural interventions to improve vitamin D stores in children from at-risk ethnic groups.

Design:

Review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PROSPERO registration number: CRD42017080932. Health Behaviour Model and Behaviour Change Wheel framework constructs used to underpin evaluation of interventions. Methodological quality evaluated using Cochrane Risk of Bias, Cochrane ROBINS-I and NHLBI tools.

Setting:

Databases Cochrane Library, MEDLINE, EMBASE, CINAHL with secondary search of Google Scholar. No country limits set. Papers between January 1990 and February 2018, published in English included. Anticipating study heterogeneity, outcome measures not pre-specified and identified from individual full papers. Updated literature search November 2020.

Participants:

Patient or population including pregnant women, newborns and children aged under 18 years, from Asian or African ethnic groups.

Results:

Of 10 690 articles screened, 298 underwent full-text review, with 24 ultimately included for data extraction. All identified studies conducted a vitamin D pharmacological supplementation intervention, with two also incorporating a behavioural intervention strategy. No study explicitly defined a primary aim of evaluating a behavioural intervention, undertaken to study its effect on vitamin D supplement uptake.

Conclusions:

There is a need to address the paucity of data in ethnic at-risk children on how behavioural interventions ideally developed and co-produced with the community under study, affect and help improve vitamin D uptake, within the antenatal and pregnancy phase as well as during childhood.
Culture, Subjectivity, and Music in Puerto Rico
Authors: Espada-Brignoni Teófilo , Ruiz-Alfaro Frances
Published: February 2021

Abstract. Understanding human phenomena requires an in-depth analysis of the interconnectedness that arises from a particular culture and its history. Subjectivity as well as a collective subjectivity emerges from human productions such as language and art in a specific time and place. In this article, we explore the role of African-based popular music genres such as bomba and plena as ways of negotiating narratives about Puerto Rican society. Popular music encompasses diverse meanings. Puerto Rican folk music’s subjectivity provides narratives that distance Puerto Ricans from an individualistic cosmovision, allowing us to understand the social and political dimensions of this complex Caribbean culture. The events of the summer of 2019, which culminated in the ousting of governor Ricardo Rosselló from his position, illustrate how music can foster social change.
Role of Lithospheric Buoyancy Forces in Driving Deformation in East Africa From 3D Geodynamic Modeling
Authors: Rajaonarison Tahiry A. , Stamps D. Sarah , Naliboff John
Published: February 2021

Despite decades of investigation, the origin of forces driving continental rifting remains highly debated. Deciphering their relative contributions is challenging due to the nonlinear and depth‐dependent nature of lithospheric rheology. Recent geodynamic studies of the East African Rift (EAR) report contradicting results regarding the relative contribution of horizontal mantle tractions and lithospheric buoyancy forces. Here, we use high‐resolution 3D regional numerical modeling of the EAR to isolate the contribution lithospheric buoyancy forces to observed deformation. Modeled surface velocities closely match kinematic models of the Somalian Plate, Victoria Block, and Rovuma Block motions, but provide poor fit to along‐rift surface motions in deforming zones. These results suggest that lithospheric buoyancy forces primarily drive present‐day ∼E‐W extension across the EAR, but intrarift deformation may result from viscous coupling to horizontal asthenospheric flow.
The Footprint of the 11‐Year Solar Cycle in Northeastern Pacific SSTs and Its Influence on the Central Pacific El Niño
Authors: Lin Yong‐Fu , Yu Jin‐Yi , Wu Chau‐Ron , Zheng Fei
Published: February 2021

Applying statistical analyses to reanalysis products during the period 1900–2018, this study finds the 11‐year solar cycle to have a significant correlation with sea surface temperature (SST) variations in the Northeastern Pacific. The solar influence is first manifested and amplified in the lower stratosphere, which then alters the strength of Hadley circulation in the troposphere. Lastly, the changes in the sinking branch of the Hadley circulation modulate surface heat fluxes to give rise to the SST footprint. The footprint has a structure similar to that of the Pacific meridional mode (PMM) that is known to be an important trigger of the central Pacific (CP) type of the El Niño‐Southern Oscillation (ENSO). The 11‐year solar cycle is thus shown to contribute to the slow modulation of the CP ENSO and, in particular, to be associated with more CP El Niño (La Niña) events during the active (inactive) phase of the cycle.
Morphological Characteristics of Thousand‐Kilometer‐Scale Es Structures Over China
Authors: Sun Wenjie , Zhao Xiukuan , Hu Lianhuan , Yang Sipeng , Xie Haiyong , Chang Shoumin , Ning Baiqi , Li Jianyong , Liu Libo , Li Guozhu
Published: February 2021

Sporadic E (Es) structures have been observed occasionally covering a large horizontal scale of more than 1,000 km over China. Their onset locations and propagation features, and related generation mechanisms still remain unknown. In this study, a statistical analysis of large‐scale Es structures is performed based on the ionospheric total electron content obtained from ground‐based receiver networks, in combination with data from multiple ionosondes in China. The large‐scale strong Es structures mainly occur during summer months, with dominant horizontal azimuth in the east‐west and northwest‐southeast directions and dimensions of 1,000–3,000 km along the elongation. They predominantly drift southwestward at the speed of 30–210 m/s. The main onset region for the large‐scale Es structures over China is identified for the first time, which is around 20°–45°N and 100°–125°E. Based on the morphological features of large‐scale Es structures, and the observation of concurrent cases of traveling ionospheric disturbances, we surmise that gravity waves could play an important role in the generation of large‐scale Es structures.
Vortex Generation and Auroral Response to a Solar Wind Dynamic Pressure Increase: Event Analyses
Authors: Zhao Jinyan , Shi Quanqi , Tian Anmin , Shen Xiao‐Chen , Weygand James M. , Wang Huizi , Yao Shutao , Ma Xiao , Degeling Alexander William , Rae I. Jonathan , Zhang Hui , Zhang Xiao‐Jia , Bai Shi‐Chen , Shang Wensai , Park Jong‐Sun
Published: February 2021

In this study, we investigate ionospheric responses, including currents and aurorae, to solar wind dynamic pressure (SW Pdyn) sudden increases, which are critical for understanding solar wind‐magnetosphere‐ionosphere coupling. We focus on two similar SW Pdyn pulse events that occurred on January 24, 2012 and November 12, 2010. In both cases, equivalent ionospheric currents (EIC) vortices were generated within about 10 min after the pressure pulse arrival, with a counter‐clockwise rotating vortex (viewed from above) observed on the dusk side in the former case, and a clockwise vortex observed on the dawn side in the latter. Simultaneous ground‐based All‐Sky Imager (ASI) observations in the vicinity of the observed EIC vortex in each case showed that aurorae intensified on the dusk side and diminished on the dawn side. These observations provide direct evidence of the scenario proposed by Shi et al. (2014) that magnetospheric flow vortices generated by a solar wind pressure pulse carry field‐aligned currents into the ionosphere and thereby modulate auroral activity. The dawn/dusk asymmetry in the auroral intensification is a direct result of the opposite sense of vortex rotation on the dawn and dusk sides, which generate oppositely directed field‐aligned currents into/out of the ionosphere.
The 2004–2005 Mt. Etna Compound Lava Flow Field: A Retrospective Analysis by Combining Remote and Field Methods
Authors: Fornaciai Alessandro , Andronico Daniele , Favalli Massimiliano , Spampinato Letizia , Branca Stefano , Lodato Luigi , Bonforte Alessandro , Nannipieri Luca
Published: February 2021

Mapping lava flows frequently during effusive eruptions provides crucial parameters to better understand their dynamics, in turn improving our ability to model lava flow behavior. New photogrammetric methods have recently been developed, shifting the paradigm of photogrammetry from pure method to a multidisciplinary approach able to reduce the cost of volcanic monitoring and widen the potential spectrum of application. In this work, we demonstrate how multi‐view and single‐view photogrammetry methods can be used effectively to extract accurate quantitative information from photographs taken during routine surveys over an active lava flow. One intriguing advantage of these methods is that they can re‐use images acquired previously to extract new data from past eruptions. In particular, we reconstructed quantitatively the evolution of the lava flow field emplaced during 2004–2005 at Mt. Etna, subdivided in five eruptive phases from the earliest simple lava flows to the final compound lava field about 6 months later. Our results show that, in the first week of eruption, lava field formation was characterized by an increasing lava length that followed a power law growth and by a decreasing front velocity that followed a power law as well. Thereafter, the length increasing became almost constant until the developed lava tube system was able to drain the lava for long distances, with the area inundated by lava that grew linearly in the first 20 days. Finally, we demonstrate the crucial role that the syn‐eruptive DEMs acquisition could have to improve our understanding of the emplacement dynamics of complex lava fields.
Reconstructing Ocean Surface Current Combining Altimetry and Future Spaceborne Doppler Data
Authors: Ubelmann Clement , Dibarboure Gérald , Gaultier Lucile , Ponte Aurélien , Ardhuin Fabrice , Ballarotta Maxime , Faugère Yannice
Published: February 2021

Two methods for the mapping of ocean surface currents from satellite measurements of sea level and future current vectors are presented and contrasted. Both methods rely on the linear and Gaussian analysis framework with different levels of covariance definitions. The first method separately maps sea level and currents with single‐scale covariance functions and leads to estimates of the geostrophic and ageostrophic circulations. The second maps both measurements simultaneously and projects the circulation onto four contributions: geostrophic, ageostrophic rotary, ageostrophic divergent, and inertial. When compared to the first method, the second mapping moderately improves the resolution of geostrophic currents but significantly improves estimates of the ageostrophic circulation, in particular near‐inertial oscillations. This method offers promising perspectives for reconstructions of the ocean surface circulation. Even the hourly dynamics can be reconstructed from measurements made locally every few days because nearby measurements are coherent enough to help fill the gaps. Based on numerical simulation of ocean surface currents, the proposed SKIM mission that combines a nadir altimeter and a Doppler scatterometer with a 300 km wide swath (with a mean revisit time of 3 days) would allow the reconstruction of 50% of the near‐inertial variance around an 18 h period of oscillation.
Influences of Physical and Biogeochemical Variability of the Central Red Sea During Winter
Authors: Zarokanellos Nikolaos D. , Jones Burton H.
Published: February 2021

The Central Red Sea (CRS) has been characterized by significant eddy activity throughout the year. Weakened wintertime stratification contributes to enhanced vertical exchange. In winter 2014–2015, an extended glider time series in the CRS captured this variability. Surface cooling and stronger winds resulted in deepening of the mixed layer (ML) to nearly 90 m. The vertical distributions of density and oxygen suggest that the ML did not penetrate the nutricline. However, mixing events dispersed phytoplankton from the deep CHL maximum (DCM) throughout the ML, increasing near‐surface chlorophyll. Following the mixing events, a mesoscale cyclonic eddy (CE) grew and intensified, weakening stratification and decreasing the ML depth within the eddy. Where the CE interfaced with an adjacent anticyclonic eddy (AE), the CE DCM subducted beneath the shallower AE DCM leading to a local integrated chlorophyll maximum. Low salinity water containing relatively high chlorophyll and CDOM concentrations, originating from the Gulf of Aden, appeared in late winter. Mesoscale eddy activity resulted in a 160 m upward displacement of the nutricline to ∼60 m, well within the euphotic layer. Remote sensing imagery indicates that these eddies contribute to horizontal dispersion, including exchange between the open sea and coastal coral reefs. When the phytoplankton is distributed through the ML, clear diel variability was evident in the temporal CHL distribution. Because not all of the biogeochemical responses were apparent at the surface, sustained glider observations were essential to understand the temporal and spatial scales and their impact on these processes.
Stronger Variability in the Arctic Ocean Induced by Sea Ice Decline in a Warming Climate: Freshwater Storage, Dynamic Sea Level and Surface Circulation
Authors: Wang Qiang
Published: February 2021

Arctic liquid freshwater content (FWC) influences both regional and large‐scale ocean dynamics and climate. In this study the responses of Arctic FWC, sea surface height (SSH) and surface circulation to different atmospheric circulation modes and the impact of sea ice decline on these responses are investigated by using wind perturbation simulations. The responses are intensified by sea ice decline through its resulting enhancement in ocean surface stress, indicating stronger decadal variability in the Arctic liquid FWC, SSH and ocean circulation in a warming climate. The Arctic Oscillation (AO) and Beaufort High (BH) wind forcing can significantly change Arctic regional and total FWC. Compared to the sea ice condition in the 1980s, the amplitudes of the ocean responses to the same AO forcing are much larger under the sea ice condition in the 2010s for both Arctic total FWC (by up to 50%) and regional SSH and velocity (doubled in some places). Sea ice decline intensifies ocean responses to the BH forcing in the Canada Basin with a similar strength. The Arctic Dipole Anomaly (DA) causes opposite changes in FWC between the Eurasian and Amerasian sectors in the cold decade, with the impact through changing sea ice thermodynamics being nonnegligible compared with that through changing ocean surface stress. Sea ice decline makes the ocean response to DA forcing less regular spatially. This study indicates an increasing vulnerability of the Arctic Ocean to winds in a warming world, which implies that extreme marine events may occur more often in the future.
Dependence of Aerosol‐Droplet Partitioning on Turbulence in a Laboratory Cloud
Authors: Shawon Abu Sayeed Md , Prabhakaran Prasanth , Kinney Greg , Shaw Raymond A. , Cantrell Will
Published: February 2021

Activation is the first step in aerosol‐cloud interactions, which have been identified as one of the principal uncertainties in Earth's climate system. Aerosol particles become cloud droplets, or activate, when the ambient saturation ratio exceeds a threshold, which depends on the particle's size and hygroscopicity. In the traditional formulation of the process, only average, uniform saturation ratios are considered. However, turbulent environments like clouds intrinsically have fluctuations around mean values in the scalar fields of temperature and water vapor concentration, which determine the saturation ratio. Through laboratory measurements, we show that these fluctuations are an important parameter that needs to be addressed to fully describe activation. Our results show, even for single‐sized, chemically homogeneous aerosols, that fluctuations blur the correspondence between activation and a particle's size and chemical composition, that turbulence can increase the fraction of aerosol particles which activate, and that the activated fraction decreases monotonically as the concentration of aerosol increases. Taken together, our data demonstrate that fluctuations can have effects equivalent to the aerosol limited and updraft limited regimes, known from adiabatic parcel theory.
Carbon Fluxes and Microbial Activities From Boreal Peatlands Experiencing Permafrost Thaw
Authors: Waldrop M. P. , W. McFarland J. , Manies K. L. , Leewis M. C. , Blazewicz S. J. , Jones M. C. , Neumann R. B. , Keller J. K. , Cohen L. , Euskirchen E. S. , Edgar C. , Turetsky M. R. , Cable W.L.
Published: February 2021

Permafrost thaw in northern ecosystems may cause large quantities of carbon (C) to move from soil to atmospheric pools. Because soil microbial communities play a critical role in regulating C fluxes from soils, we examined microbial activity and greenhouse gas production soon after permafrost thaw and ground collapse (into collapse‐scar bogs), relative to the permafrost plateau or older thaw features. Using multiple field and laboratory‐based assays at a field site in interior Alaska, we show that the youngest collapse‐scar bog had the highest CH4production potential from soil incubations, and, based upon temporal changes in porewater concentrations and13C‐CH4and13C‐CO2, had greater summer in situ rates of respiration, methanogenesis, and surface CH4oxidation. These patterns could be explained by greater C and N availability in the young bog, while alternative terminal electron accepting processes did not play a significant role. Field diffusive CH4fluxes from the young bog were 4.1 times greater in the shoulder season and 1.7–7.2 times greater in winter relative to older bogs, but not during summer. Greater relative CH4flux rates in the shoulder season and winter could be due to reduced CH4oxidation relative to summer, magnifying the importance of differences in production. Both the permafrost plateau and collapse‐scar bogs were sources of C to the atmosphere due in large part to winter C fluxes. In collapse scar bogs, winter is a critical period when differences in thermokarst age translates to differences in surface fluxes.
Multilayered Sporadic‐E Response to the Annular Solar Eclipse on June 21, 2020
Authors: Wang Jin , Zuo Xiaomin , Sun Yang‐Yi , Yu Tao , Wang Yungang , Qiu Lihui , Mao Tian , Yan XiangXiang , Yang Na , qi Yifan , Lei Jiuhou , Sun Lingfeng , Zhao Biqiang
Published: February 2021

A moon shadow of annular solar eclipse passed through East Asia in the afternoon on June 21, 2020, which was a good opportunity to study the rapid ionospheric response to the solar radiation variations. In the study, the high‐frequency echoes recorded by the ionosondes at Wuhan (82.4% obscuration), Xiamen (97.8% obscuration), and Nanning (81.1% obscuration) are analyzed to examine the variations in sporadic‐E (Es) during the obscuration over the East China area. The echoes show not only the variations in the typical signal Es layer below 130 km, but for the first time also the multilayered Es at much higher altitudes (130–190 km) during the eclipse. Specifically, the multilayered Es is only observed over Nanning, while different Es behaviors are observed in the other two stations. The relationship between the formation of the multilayered Es and the uplifted Es near the center path of the moon shadow are examined in the study. The small‐scale atmospheric gravity waves play a key role in modulating the Es behaviors during the eclipse.
An Analytical Model for the Decontamination of Water Distribution Systems Using Slug‐Feed Method of Disinfection
Authors: Qiu Mengning , Salomons Elad , Ostfeld Avi
Published: February 2021

The increasing risk of intentional, negligent, or accidental intrusion of biological, chemical, or radioactive contaminants in water distribution systems is becoming a major concern that has significant and adverse impacts on public health. As such, it is important to have an effective, robust, and flexible plan that can be readily implemented to minimize the impact of these contamination events. However, limited research has been focused on the strategic planning of the decontamination process of the contaminated infrastructure. This paper proposes an analytical method for modeling the slug‐feed method of disinfection given the drainage and disinfectant dosage profiles. The efficacy of the proposed method has been demonstrated by using it as the evaluation function in a genetic algorithm optimization of two case studies. Results show the proposed method exhibits higher robustness compared to the procedures defined in the current standard and literature. The main contributions of this study are to (1) provide a robust and accurate model to describe the slug‐feed method of disinfection, (2) offer additional resource utilization flexibility for water authorities, and (3) providing additional levels of district metered areas prioritization.
Genome-wide analysis suggests the importance of vascular processes and neuroinflammation in late-life antidepressant response
Authors: Marshe Victoria S. , Maciukiewicz Malgorzata , Hauschild Anne-Christin , Islam Farhana , Qin Li , Tiwari Arun K. , Sibille Etienne , Blumberger Daniel M. , Karp Jordan F. , Flint Alastair J. , Turecki Gustavo , Lam Raymond W. , Milev Roumen V. , Frey Benicio N. , Rotzinger Susan , Foster Jane A. , Kennedy Sidney H. , Kennedy James L. , Mulsant Benoit H. , Reynolds Charles F. , Lenze Eric J. , Müller Daniel J.
Published: February 2021

Antidepressant outcomes in older adults with depression is poor, possibly because of comorbidities such as cerebrovascular disease. Therefore, we leveraged multiple genome-wide approaches to understand the genetic architecture of antidepressant response. Our sample included 307 older adults (≥60 years) with current major depression, treated with venlafaxine extended-release for 12 weeks. A standard genome-wide association study (GWAS) was conducted for post-treatment remission status, followed by in silico biological characterization of associated genes, as well as polygenic risk scoring for depression, neurodegenerative and cerebrovascular disease. The top-associated variants for remission status and percentage symptom improvement were PIEZO1 rs12597726 (OR = 0.33 [0.21, 0.51], p = 1.42 × 10−6) and intergenic rs6916777 (Beta = 14.03 [8.47, 19.59], p = 1.25 × 10−6), respectively. Pathway analysis revealed significant contributions from genes involved in the ubiquitin-proteasome system, which regulates intracellular protein degradation with has implications for inflammation, as well as atherosclerotic cardiovascular disease (n = 25 of 190 genes, p = 8.03 × 10−6, FDR-corrected p = 0.01). Given the polygenicity of complex outcomes such as antidepressant response, we also explored 11 polygenic risk scores associated with risk for Alzheimer’s disease and stroke. Of the 11 scores, risk for cardioembolic stroke was the second-best predictor of non-remission, after being male (Accuracy = 0.70 [0.59, 0.79], Sensitivity = 0.72, Specificity = 0.67; p = 2.45 × 10−4). Although our findings did not reach genome-wide significance, they point to previously-implicated mechanisms and provide support for the roles of vascular and inflammatory pathways in LLD. Overall, significant enrichment of genes involved in protein degradation pathways that may be impaired, as well as the predictive capacity of risk for cardioembolic stroke, support a link between late-life depression remission and risk for vascular dysfunction.
Corticostriatal control of defense behavior in mice induced by auditory looming cues
Authors: Li Zhong , Wei Jin-Xing , Zhang Guang-Wei , Huang Junxiang J. , Zingg Brian , Wang Xiyue , Tao Huizhong W. , Zhang Li I.
Published: February 2021

Animals exhibit innate defense behaviors in response to approaching threats cued by the dynamics of sensory inputs of various modalities. The underlying neural circuits have been mostly studied in the visual system, but remain unclear for other modalities. Here, by utilizing sounds with increasing (vs. decreasing) loudness to mimic looming (vs. receding) objects, we find that looming sounds elicit stereotypical sequential defensive reactions: freezing followed by flight. Both behaviors require the activity of auditory cortex, in particular the sustained type of responses, but are differentially mediated by corticostriatal projections primarily innervating D2 neurons in the tail of the striatum and corticocollicular projections to the superior colliculus, respectively. The behavioral transition from freezing to flight can be attributed to the differential temporal dynamics of the striatal and collicular neurons in their responses to looming sound stimuli. Our results reveal an essential role of the striatum in the innate defense control.
Fast and precise single-cell data analysis using a hierarchical autoencoder
Authors: Tran Duc , Nguyen Hung , Tran Bang , La Vecchia Carlo , Luu Hung N. , Nguyen Tin
Published: February 2021

A primary challenge in single-cell RNA sequencing (scRNA-seq) studies comes from the massive amount of data and the excess noise level. To address this challenge, we introduce an analysis framework, named single-cell Decomposition using Hierarchical Autoencoder (scDHA), that reliably extracts representative information of each cell. The scDHA pipeline consists of two core modules. The first module is a non-negative kernel autoencoder able to remove genes or components that have insignificant contributions to the part-based representation of the data. The second module is a stacked Bayesian autoencoder that projects the data onto a low-dimensional space (compressed). To diminish the tendency to overfit of neural networks, we repeatedly perturb the compressed space to learn a more generalized representation of the data. In an extensive analysis, we demonstrate that scDHA outperforms state-of-the-art techniques in many research sub-fields of scRNA-seq analysis, including cell segregation through unsupervised learning, visualization of transcriptome landscape, cell classification, and pseudo-time inference.
Mimicking efferent nerves using a graphdiyne-based artificial synapse with multiple ion diffusion dynamics
Authors: Wei Huanhuan , Shi Rongchao , Sun Lin , Yu Haiyang , Gong Jiangdong , Liu Chao , Xu Zhipeng , Ni Yao , Xu Jialiang , Xu Wentao
Published: February 2021

A graphdiyne-based artificial synapse (GAS), exhibiting intrinsic short-term plasticity, has been proposed to mimic biological signal transmission behavior. The impulse response of the GAS has been reduced to several millivolts with competitive femtowatt-level consumption, exceeding the biological level by orders of magnitude. Most importantly, the GAS is capable of parallelly processing signals transmitted from multiple pre-neurons and therefore realizing dynamic logic and spatiotemporal rules. It is also found that the GAS is thermally stable (at 353 K) and environmentally stable (in a relative humidity up to 35%). Our artificial efferent nerve, connecting the GAS with artificial muscles, has been demonstrated to complete the information integration of pre-neurons and the information output of motor neurons, which is advantageous for coalescing multiple sensory feedbacks and reacting to events. Our synaptic element has potential applications in bioinspired peripheral nervous systems of soft electronics, neurorobotics, and biohybrid systems of brain–computer interfaces.
Janus 3D printed dynamic scaffolds for nanovibration-driven bone regeneration
Authors: Camarero-Espinosa Sandra , Moroni Lorenzo
Published: February 2021

The application of physical stimuli to cell cultures has shown potential to modulate multiple cellular functions including migration, differentiation and survival. However, the relevance of these in vitro models to future potential extrapolation in vivo depends on whether stimuli can be applied “externally”, without invasive procedures. Here, we report on the fabrication and exploitation of dynamic additive-manufactured Janus scaffolds that are activated on-command via external application of ultrasounds, resulting in a mechanical nanovibration that is transmitted to the surrounding cells. Janus scaffolds were spontaneously formed via phase-segregation of biodegradable polycaprolactone (PCL) and polylactide (PLA) blends during the manufacturing process and behave as ultrasound transducers (acoustic to mechanical) where the PLA and PCL phases represent the active and backing materials, respectively. Remote stimulation of Janus scaffolds led to enhanced cell proliferation, matrix deposition and osteogenic differentiation of seeded human bone marrow derived stromal cells (hBMSCs) via formation and activation of voltage-gated calcium ion channels.
Machine learning identifies candidates for drug repurposing in Alzheimer’s disease
Authors: Rodriguez Steve , Hug Clemens , Todorov Petar , Moret Nienke , Boswell Sarah A. , Evans Kyle , Zhou George , Johnson Nathan T. , Hyman Bradley T. , Sorger Peter K. , Albers Mark W. , Sokolov Artem
Published: February 2021

Clinical trials of novel therapeutics for Alzheimer’s Disease (AD) have consumed a large amount of time and resources with largely negative results. Repurposing drugs already approved by the Food and Drug Administration (FDA) for another indication is a more rapid and less expensive option. We present DRIAD (Drug Repurposing In AD), a machine learning framework that quantifies potential associations between the pathology of AD severity (the Braak stage) and molecular mechanisms as encoded in lists of gene names. DRIAD is applied to lists of genes arising from perturbations in differentiated human neural cell cultures by 80 FDA-approved and clinically tested drugs, producing a ranked list of possible repurposing candidates. Top-scoring drugs are inspected for common trends among their targets. We propose that the DRIAD method can be used to nominate drugs that, after additional validation and identification of relevant pharmacodynamic biomarker(s), could be readily evaluated in a clinical trial.
Targeting NSD2-mediated SRC-3 liquid–liquid phase separation sensitizes bortezomib treatment in multiple myeloma
Authors: Liu Jing , Xie Ying , Guo Jing , Li Xin , Wang Jingjing , Jiang Hongmei , Peng Ziyi , Wang Jingya , Wang Sheng , Li Qian , Ye Linquan , Zhong Yuping , Zhang Qiguo , Liu Xiaozhi , Lonard David M. , Wang Jin , O’Malley Bert W. , Liu Zhiqiang
Published: February 2021

Development of chemoresistance is the main reason for failure of clinical management of multiple myeloma (MM), but the genetic and epigenetic aberrations that interact to confer such chemoresistance remains unknown. In the present study, we find that high steroid receptor coactivator-3 (SRC-3) expression is correlated with relapse/refractory and poor outcomes in MM patients treated with bortezomib (BTZ)-based regimens. Furthermore, in immortalized cell lines, high SRC-3 enhances resistance to proteasome inhibitor (PI)-induced apoptosis. Overexpressed histone methyltransferase NSD2 in patients bearing a t(4;14) translocation or in BTZ-resistant MM cells coordinates elevated SRC-3 by enhancing its liquid–liquid phase separation to supranormally modify histone H3 lysine 36 dimethylation (H3K36me2) modifications on promoters of anti-apoptotic genes. Targeting SRC-3 or interference of its interactions with NSD2 using a newly developed inhibitor, SI-2, sensitizes BTZ treatment and overcomes drug resistance both in vitro and in vivo. Taken together, our findings elucidate a previously unrecognized orchestration of SRC-3 and NSD2 in acquired drug resistance of MM and suggest that SI-2 may be efficacious for overcoming drug resistance in MM patients.
No mafic layer in 80 km thick Tibetan crust
Authors: Wang Gaochun , Thybo Hans , Artemieva Irina M.
Published: February 2021

All models of the magmatic and plate tectonic processes that create continental crust predict the presence of a mafic lower crust. Earlier proposed crustal doubling in Tibet and the Himalayas by underthrusting of the Indian plate requires the presence of a mafic layer with high seismic P-wave velocity (Vp > 7.0 km/s) above the Moho. Our new seismic data demonstrates that some of the thickest crust on Earth in the middle Lhasa Terrane has exceptionally low velocity (Vp < 6.7 km/s) throughout the whole 80 km thick crust. Observed deep crustal earthquakes throughout the crustal column and thick lithosphere from seismic tomography imply low temperature crust. Therefore, the whole crust must consist of felsic rocks as any mafic layer would have high velocity unless the temperature of the crust were high. Our results form basis for alternative models for the formation of extremely thick juvenile crust with predominantly felsic composition in continental collision zones.
The combined effects of simulated microgravity and X-ray radiation on MC3T3-E1 cells and rat femurs
Authors: Dong Jingjing , Wang Honghui , Li Gaozhi , Wang Ke , Tan Yingjun , Zhang Lijun , Wang Yixuan , Hu Zebing , Cao Xinsheng , Shi Fei , Zhang Shu
Published: February 2021

Microgravity is well-known to induce Osteopenia. However, the combined effects of microgravity and radiation that commonly exist in space have not been broadly elucidated. This research investigates the combined effects on MC3T3-E1 cells and rat femurs. In MC3T3-E1 cells, simulated microgravity and X-ray radiation, alone or combination, show decreased cell activity, increased apoptosis rates by flow cytometric analysis, and decreased Runx2 and increased Caspase-3 mRNA and protein expressions. In rat femurs, simulated microgravity and X-ray radiation, alone or combination, show increased bone loss by micro-CT test and Masson staining, decreased serum BALP levels and Runx2 mRNA expressions, and increased serum CTX-1 levels and Caspase-3 mRNA expressions. The strongest effect is observed in the combined group in MC3T3-E1 cells and rat femurs. These findings suggest that the combination of microgravity and radiation exacerbates the effects of either treatment alone on MC3T3-E1 cells and rat femurs.
Fundamental insights into the stabilisation and chemical degradation of the corrosion product scales
Authors: Yue Xiaoqi , Zhang Lei , Hua Yong
Published: February 2021

Carbonate stability plays a crucial role in clarifying the evolution and protection of the naturally formed corrosion scales on the steel surface in the application of geothermal production. In this paper, the stability of the corrosion scales from both micro and atomic level are studied via a combination of electrochemistry, surface analysis and first-principle calculation. The chemical and physical characterisation of various iron–calcium mixed carbonates are experimentally analysed and results are compared with the first-principle calculation. In the presence of Ca2+, the preferential loss of Ca during the dissolution experiments was observed, the interactions within the crystal weaken where Ca2+ co-precipitation, confirmed by a faster degradation rate for Ca0.51Fe0.49CO3 than FeCO3. This work reveals the degradation and protection performance of the naturally formed carbonate layers and provides insights into understanding the corrosion product stability and chemical breakdown of the corrosion scales.
Quantum Hall phases emerging from atom–photon interactions
Authors: Poshakinskiy Alexander V. , Zhong Janet , Ke Yongguan , Olekhno Nikita A. , Lee Chaohong , Kivshar Yuri S. , Poddubny Alexander N.
Published: February 2021

We reveal the emergence of quantum Hall phases, topological edge states, spectral Landau levels, and Hofstadter butterfly spectra in the two-particle Hilbert space of an array of periodically spaced two-level atoms coupled to a waveguide (waveguide quantum electrodynamics). While the topological edge states of photons require fine-tuned spatial or temporal modulations of the parameters to generate synthetic magnetic fields and the quantum Hall effect, here we demonstrate that a synthetic magnetic field can be self-induced solely by atom–photon interactions. The fact that topological order can be self-induced in what is arguably the simplest possible quantum structure shows the richness of these waveguide quantum electrodynamics systems. We believe that our findings will advance several research disciplines including quantum optics, many-body physics, and nonlinear topological photonics, and that it will set an important reference point for the future experiments on qubit arrays and quantum simulators.
Microbiome-based environmental monitoring of a dairy processing facility highlights the challenges associated with low microbial-load samples
Authors: McHugh Aoife J. , Yap Min , Crispie Fiona , Feehily Conor , Hill Colin , Cotter Paul D.
Published: February 2021

Efficient and accurate identification of microorganisms throughout the food chain can potentially allow the identification of sources of contamination and the timely implementation of control measures. High throughput DNA sequencing represents a potential means through which microbial monitoring can be enhanced. While Illumina sequencing platforms are most typically used, newer portable platforms, such as the Oxford Nanopore Technologies (ONT) MinION, offer the potential for rapid analysis of food chain microbiomes. Initial assessment of the ability of rapid MinION-based sequencing to identify microbes within a simple mock metagenomic mixture is performed. Subsequently, we compare the performance of both ONT and Illumina sequencing for environmental monitoring of an active food processing facility. Overall, ONT MinION sequencing provides accurate classification to species level, comparable to Illumina-derived outputs. However, while the MinION-based approach provides a means of easy library preparations and portability, the high concentrations of DNA needed is a limiting factor.
Immunogenicity of standard, high-dose, MF59-adjuvanted, and recombinant-HA seasonal influenza vaccination in older adults
Authors: Li Athena P. Y. , Cohen Carolyn A. , Leung Nancy H. L. , Fang Vicky J. , Gangappa Shivaprakash , Sambhara Suryaprakash , Levine Min Z. , Iuliano A. Danielle , Perera Ranawaka A. P. M. , Ip Dennis K. M. , Peiris J. S. Malik , Thompson Mark G. , Cowling Benjamin J. , Valkenburg Sophie A.
Published: February 2021

The vaccine efficacy of standard-dose seasonal inactivated influenza vaccines (S-IIV) can be improved by the use of vaccines with higher antigen content or adjuvants. We conducted a randomized controlled trial in older adults to compare cellular and antibody responses of S-IIV versus enhanced vaccines (eIIV): MF59-adjuvanted (A-eIIV), high-dose (H-eIIV), and recombinant-hemagglutinin (HA) (R-eIIV). All vaccines induced comparable H3-HA-specific IgG and elevated antibody-dependent cellular cytotoxicity (ADCC) activity at day 30 post vaccination. H3-HA-specific ADCC responses were greatest following H-eIIV. Only A-eIIV increased H3-HA-IgG avidity, HA-stalk IgG and ADCC activity. eIIVs also increased polyfunctional CD4+ and CD8+ T cell responses, while cellular immune responses were skewed toward single-cytokine-producing T cells among S-IIV subjects. Our study provides further immunological evidence for the preferential use of eIIVs in older adults as each vaccine platform had an advantage over the standard-dose vaccine in terms of NK cell activation, HA-stalk antibodies, and T cell responses.