bluuebunny/crossref_metadata_2025 huggingface dataset:
On the violation of the zeroth law of turbulence in space plasmas
Authors: Meyrand R. , Squire J. , Schekochihin A.A. , Dorland W.
Published: May 2021

The zeroth law of turbulence states that, for fixed energy input into large-scale motions, the statistical steady state of a turbulent system is independent of microphysical dissipation properties. This behaviour, which is fundamental to nearly all fluid-like systems from industrial processes to galaxies, occurs because nonlinear processes generate smaller and smaller scales in the flow, until the dissipation – no matter how small – can thermalise the energy input. Using direct numerical simulations and theoretical arguments, we show that in strongly magnetised plasma turbulence such as that recently observed by the Parker Solar Probe spacecraft, the zeroth law is routinely violated. Namely, when such turbulence is ‘imbalanced’ – when the large-scale energy input is dominated by Alfvénic perturbations propagating in one direction (the most common situation in space plasmas) – nonlinear conservation laws imply the existence of a ‘barrier’ at scales near the ion gyroradius. This causes energy to build up over time at large scales. The resulting magnetic-energy spectra bear a strong resemblance to those observedin situ, exhibiting a sharp, steep kinetic transition range above and around the ion-Larmor scale, with flattening at yet smaller scales. The effect thus offers a possible solution to the decade-long puzzle of the position and variability of ion-kinetic spectral breaks in plasma turbulence. The existence of the ‘barrier’ also suggests that, how a plasma is forced at large scales (the imbalance) may have a crucial influence on thermodynamic properties such as the ion-to-electron heating ratio.
British Workers and Ottoman Modernity in Nineteenth-Century Istanbul
Authors: Sefer Akın
Published: May 2021

In the mid-nineteenth century, when the Ottoman state launched an industrialization campaign within the context of increasing contacts between the Ottoman and British governments, hundreds of British industrial workers migrated to Istanbul to work in Ottoman military factories, along with technology transfer from Britain. This article narrates the history of these workers and of the community they established in Istanbul in a period spanning four decades, from the beginning of the mechanization efforts in the 1830s until the economic crisis in the mid-1870s. Drawing on archival evidence from Ottoman and British sources, it analyzes the larger context of British workers’ migration from Britain, their relations with the Ottoman state officials and local workers, and their experiences and struggles in the workplace and the city. Although both British and Ottoman historians have largely ignored their experiences due to their marginal numbers and distinct statuses, these workers actively took part in the Ottoman industrialization process, in the development of capitalist class relations, and in the social, cultural, and spatial transformation of the capital city in the Ottoman age of reforms. By means of this analysis, the article aims to highlight the significance of immigrant workers as actors of the history of large-scale transformations in the late Ottoman Empire as well as underlining the role of trans-imperial labor migration in the history of modernity.
Voicing patterns in stops among heritage speakers of Western Armenian in Lebanon and the US
Authors: Kelly Niamh E. , Keshishian Lara
Published: May 2021

Research on Western Armenian (WA) has described it as having a contrast between voiceless aspirated stops and voiced stops (Fairbanks 1948; Vaux 1998; Baronian 2017). Since there is no monolingual community of WA, all speakers are part of a minority language community, and also speak the majority language. The current study examines speakers from two heritage communities of WA: one in Lebanon, where the majority language is Arabic, and one in the US, where the majority language is English. The speakers in Lebanon were found to have a contrast between voiced and voiceless unaspirated stops, in line with Lebanese Arabic. The speakers in the US were more variable, some having the English pattern of voiceless unaspirated and voiceless aspirated stops, while others had voiceless aspirated stops, but their voiced stops were variable between voiced and voiceless unaspirated. These results indicate L2 transfer in both communities, leading to two different patterns of voicing in WA.
Drilling predation on Antarctic tusk shells: first records on Recent scaphopods from the Southern Hemisphere
Authors: Gordillo Sandra , Malvé Mariano E.
Published: May 2021

Drillholes on shells are one of the few predation marks preserved in fossil molluscs, providing an opportunity to study and quantify predator-prey interactions in the palaeontological record. Among these, reports of drilling predation on scaphopods are rare, and such information from Antarctica is non-existent. We describe the finding of drillholes on scaphopods recovered from Recent mollusc assemblages between depths of 246.5 and 454.0 m in West Antarctica. The predation traces located in the middle sectors of two preyed shells belonging to Siphonodentalium dalli and Dentalium majorinum are identified as Oichnus and are interpreted as produced by naticids, probably Pseudamauropsis aureolutea. These new records constitute the first reports of drilling predation on scaphopods in Antarctica and also for Recent scaphopods of the Southern Hemisphere.
A STORY OF AWE AND CLAY: MOLD-MADE HIEROGLYPHS FROM ALTA VERAPAZ, GUATEMALA
Authors: Sears Erin L. , Grube Nikolai , Garay Alejandro , Woodfill Brent K. S. , Rivas Alexander E.
Published: May 2021

The recent discovery of an ancient Late Classic ceramic production facility in a valley floor, east of the current capital of Cobán in Guatemala, reveals a new ceramic form and provides data concerning regional chronology. Among the remains are thin, mold-made fragments identified as ceramic plaques that have epigraphic information providing a Long Count date for the first time in the Alta Verapaz region. These data correlate with the preliminary ceramic sequences and assist with understanding political-economic interactions that occurred at a time of societal collapse within the southern lowland region.
Prenatal diagnosis of double outlet right ventricle with intact ventricular septum in two foetuses
Authors: Karmegaraj Balaganesh , Srimurugan Balaji , Vaidyanathan Balu
Published: May 2021

We describe two cases of an unusual variant of double outlet right ventricle with intact ventricular septum diagnosed prenatally and confirmed by foetal autopsy in a case. The first case had mitral valve atresia, slit-like left ventricle, and normally related great arteries. The second case had mitral valve atresia, hypoplastic left ventricle, parallel outflows with an interrupted aortic arch.
Effectiveness of the unified protocol for treating co-morbid health anxiety and depression: an empirical case study
Authors: Gaskell Chris , Hague Ben , Kellett Stephen
Published: May 2021

Aims:

The unified protocol (UP) is indicated when patients present with co-morbidity, but no studies have previously investigated the effectiveness of the UP with co-morbid health anxiety and depression.

Method:

An A/B single case design evaluated outcomes for a 27-year-old male presenting with health anxiety and co-morbid depression. Following a 21-day assessment-baseline period containing three sessions, the manualised UP was delivered across a 42-day period containing seven intervention sessions. Four idiographic measures (occurrence and duration of health checking, sleep duration and food intake satisfaction) were collected daily throughout, and two nomothetic measures were collected at four time points.

Results:

All sessions were attended. Number of health checking episodes reduced from four per day to two per day. A 59 minute per day reduction in time spent health checking occurred, and sleep increased by 100 minutes per night. There was little apparent change in terms of food intake satisfaction. There was a reliable and clinically significant reduction in depression.

Discussion:

Further testing of the effectiveness of the UP with co-morbid health anxiety and depression in true single case experimental designs is now indicated.
Swedish Normative Data for Mindmore: A Comprehensive Cognitive Screening Battery, Both Digital and Self-Administrated
Authors: van den Hurk Wobbie , Bergman Ingvar , Machado Alejandra , Bjermo Jonas , Gustavsson Anders
Published: May 2021

Objective:

Cognitive impairment is a key element in most mental disorders. Its objective assessment at initial patient contact in primary care can lead to better adjusted and timely care with personalised treatment and recovery. To enable this, we designed the Mindmore self-administrative cognitive screening battery. What is presented here is normative data for the Mindmore battery for the Swedish population.

Method:

A total of 720 healthy adults (17 to 93 years) completed the Mindmore screening battery, which consists of 14 individual tests across five cognitive domains: attention and processing speed, memory, language, visuospatial functions and executive functions. Regression-based normative data were established for 42 test result measures, investigating linear, non-linear and interaction effects between age, education and sex.

Results:

The test results were most affected by age and to a lesser extent by education and sex. All but one test displayed either linear or accelerated age-related decline, or a U-shaped association with age. All but two tests showed beneficial effects of education, either linear or subsiding after 12 years of educational attainment. Sex affected tests in the memory and executive domains. In three tests, an interaction between age and education revealed an increased benefit of education later in life.

Conclusion:

This study provides normative models for 14 traditional cognitive tests adapted for self-administration through a digital platform. The models will enable more accurate interpretation of test results, hopefully leading to improved clinical decision making and better care for patients with cognitive impairment.
Passionate Speech: On the Uses and Abuses of Anger in Public Debate
Authors: Tanesini Alessandra
Published: May 2021

Anger dominates debates in the public sphere. In this article I argue that there are diverse forms of anger that merit different responses. My focus is especially on two types of anger that I label respectively arrogant and resistant. The first is the characteristic defensive response of those who unwarrantedly arrogate special privileges for themselves. The second is often a source of insight and a form of moral address. I detail some discursive manifestations of these two types of anger. I show that arrogant anger is responsible for attempts to intimidate and humiliate others with whom one disagrees. Whilst resistant anger can be intimidating, it is also essential in communicating moral demands.
The Predicament of Patients
Authors: Kidd Ian James , Carel Havi
Published: May 2021

In this paper we propose that our understanding of pathocentric epistemic injustices can be enriched if they are theorised in terms of predicaments. These are the wider socially scaffolded structures of epistemic challenges, dangers, needs, and threats experienced by ill persons due to their particular emplacement within material, social, and epistemic structures. In previous work we have described certain aspects of these predicaments, such as pathocentric epistemic injustices and pathophobia. A wider systematic perspective is needed to integrate these and other concepts. By thinking predicamentally, we can better understand the interrelated social, epistemic, and practical obstacles experienced by ill persons and connect the many concepts available for theorising them (microaggessions, epistemic injustices, and so on).
How Good Are We At Evaluating Communicated Information?
Authors: Mercier Hugo
Published: May 2021

Are we gullible? Can we be easily influenced by what others tell us, even if they do not deserve our trust? Many strands of research, from social psychology to cultural evolution suggest that humans are by nature conformist and eager to follow prestigious leaders. By contrast, an evolutionary perspective suggests that humans should be vigilant towards communicated information, so as not to be misled too often. Work in experimental psychology shows that humans are equipped with sophisticated mechanisms that allow them to carefully evaluate communicated information. These open vigilance mechanisms lead us to reject messages that clash with our prior beliefs, unless the source of the message has earned our trust, or provides good arguments, in which case we can adaptively change our minds. These mechanisms make us largely immune to mass persuasion, explaining why propaganda, political campaigns, advertising, and other attempts at persuading large groups nearly always fall in deaf ears. However, some false beliefs manage to spread through communication. I argue that most popular false beliefs are held reflectively, which means that they have little effect on our thoughts and behaviors, and that many false beliefs can be socially beneficial. Accepting such beliefs thus reflects a much weaker failure in our evaluation of communicated information than might at first appear.
What is a Question
Authors: Watson Lani
Published: May 2021

Questions are, in many respects, the hallmarks of the philosopher's trade. They are passed down from one generation to the next and yet, throughout history, philosophers have had relatively little to say about questions. In particular, few have asked or tried to answer the question ‘what is a question'. I call this the ‘Question Question’ and I offer an answer to it in this paper, furnishing philosophical analysis with the results of a large online survey, which has been running for more than a decade.
Rape Myths: What are They and What can We do About Them?
Authors: Jenkins Katharine
Published: May 2021

In this paper, I aim to shed some light on what rape myths are and what we can do about them. I start by giving a brief overview of some common rape myths. I then use two philosophical tools to offer a perspective on rape myths. First, I show that we can usefully see rape myths as an example of what Miranda Fricker has termed ‘epistemic injustice’, which is a type of wrong that concerns our role as knowers. Then, I show that it is important to recognise that rape myths are instances of misogyny. This word is of course a more familiar one, but I'll be drawing on a specific philosophical account of what misogyny is, developed by Kate Manne, that I think is useful here. Finally, I briefly consider some upshots of these claims.
Multi-band planar diplexers with sub-sets of frequency-contiguous transmission bands
Authors: Gómez-García Roberto , Yang Li , Muñoz-Ferreras José-María , Psychogiou Dimitra
Published: May 2021

A class of multi-band planar diplexer with sub-sets of frequency-contiguous transmission bands is reported. Such a radio frequency (RF) device is suitable for lightweight high-frequency receivers aimed at multi-band/multi-purpose mobile satellite communications systems. It consists of two channelizing filters, each of them being made up of the in-series cascade connection of replicas of a constituent multi-passband/multi-embedded-stopband filtering stage. This building filtering stage defines a multi-passband transfer function for each channel, in which each main transmission band is split into various sub-passbands by the multi-stopband part. In this manner, each split passband gives rise to several sub-passbands that are imbricated with their counterpart ones of the other channel. The theoretical RF operational principles of the proposed multi-band diplexer approach with sub-sets of imbricated passbands are detailed by means of a coupling–routing–diagram formalism. Besides, the generation of additional transmission zeros in each channelizing filter for higher-selectivity realizations by exploiting cross-coupling techniques into it is also detailed. Furthermore, for experimental demonstration purposes, a microstrip proof-of-concept prototype of second-order octo-band diplexer in the frequency range of 1.5–2.5 GHz that consists of two quad-band channelizing filters with pairs of imbricated passbands is developed and characterized.
Changes in the Semantic Construction of Compassion after the Cognitively-Based Compassion Training (CBCT®) in Women Breast Cancer Survivors
Authors: González-Hernández Edgar , Campos Daniel , Diego-Pedro Rebeca , Romero Rocío , Baños Rosa , Negi Lobsang Tenzin , Cebolla Ausias J.
Published: May 2021

The growing body of research on compassion has demonstrated its benefits for healthcare and wellbeing. However, there is no clear agreement about a definition for compassion, given the novelty of the research on this construct and its religious roots. The aim of this study is to analyze the mental semantic construction of compassion in Spanish-speaking women breast cancer survivors, and the effects of the Cognitively-Based Compassion Training (CBCT®) on the modification of this definition, compared to treatment-as-usual (TAU), at baseline, post-intervention, and six-month follow-up. Participants were 56 women breast cancer survivors from a randomized clinical trial. The Osgood’s Semantic Differential categories (evaluative, potency, and activity scales) were adapted to assess the semantic construction of compassion. At baseline, participants had an undefined idea about compassion. The CBCT influenced subjects’ semantic construction of what it means to be compassionate. Findings could lead to future investigations and compassion programs that adapt to a specific culture or population.
Young Women on the MoveBritain circa 1880–1950
Authors: Pooley Colin G. , Pooley Marilyn E.
Published: May 2021

Travel is an essential part of everyday life for most people, and it inevitably brings inconvenience at times, but women have often experienced particular and distinctive constraints and harassments while traveling that may inhibit or reduce their mobility. However, we know relatively little in detail about how, why, and how much women traveled in the past. This article provides new evidence about female mobility in nineteenth- and twentieth-century Britain by analyzing the daily movements that were recorded in the personal diaries of nine young women. The diary entries show that all the women traveled frequently both alone and with others, used a variety of transport technologies that were available at the time, and rarely recorded incidents that caused them concern or alarm. Mobility was not only essential for carrying out everyday activities but it was also central to the development of friendships and, especially, courting. Both social class and location did have some influence on the ways in which the young women traveled, on their freedom to travel alone, and on the inconveniences they faced. However, overall, the similarities between the experiences of the nine diarists were much greater than the differences. Although it is not possible to generalize widely from just nine accounts, these diaries do provide new insights into female mobility in the past.
Omega Band Magnetospheric Source Location: A Statistical Model‐Based Study
Authors: Andreeva V. A. , Apatenkov S. V. , Gordeev E. I. , Partamies N. , Kauristie K.
Published: May 2021

Auroral omega bands have been observed since the 1960s and their ionospheric electrodynamic properties are well established. At the same time magnetospheric source is poorly investigated leaving a room for few competing hypotheses on how the omega band forms. Here we present the statistical study of the projections of about 400 omega bands from the ionosphere to magnetosphere to investigate the location and properties of a possible omega source region in the magnetosphere. We used the Magnetometers—Ionospheric Radars—All‐sky Cameras Large Experiment all‐sky images on the list of individual omega structures (Partamies et al., 2017, http://doi.org/10.5194/angeo-35-1069-2017) which were observed in the Fennoscandian Lapland in the period of 1997–2007, and a new empirical magnetic field model (Tsyganenko & Andreeva, 2016, https://doi.org/10.1002/2016ja023217) to identify the magnetospheric equatorial projection of the observed omegas. We found that 90% of the auroral omega structures map to the radial distances of 6–14 RE from the Earth, coinciding with the bursty bulk flow braking region. An average magnetic field configuration in the vicinity of magnetospheric omega projections corresponds approximately to the transition region between tail‐ and dipole‐like magnetic configuration. Velocity estimates for omega projections reveal the dawnward as well as the radial propagation in the magnetosphere with a typical speed of up to few tens of km/s. It is shown that the source of omega structures propagates earthward in most of the events.
Climate‐Change Controls on River Delta Avulsion Location and Frequency
Authors: Chadwick A. J. , Lamb M. P.
Published: May 2021

Coastal rivers that build deltas undergo repeated avulsion events—that is, abrupt changes in river course—which we need to understand to predict land building and flood hazards in coastal landscapes. Climate change can impact water discharge, flood frequency, sediment supply, and sea level, all of which could impact avulsion location and frequency. Here we present results from quasi‐2D morphodynamic simulations of repeated delta‐lobe construction and avulsion to explore how avulsion location and frequency are affected by changes in relative sea level, sediment supply, and flood regime. Model results indicate that relative sea‐level rise drives more frequent avulsions that occur at a distance from the shoreline set by backwater hydrodynamics. Reducing the sediment supply relative to transport capacity has little impact on deltaic avulsions, because, despite incision in the upstream trunk channel, deltas can still aggrade as a result of progradation. However, increasing the sediment supply relative to transport capacity can shift avulsions upstream of the backwater zone because aggradation in the trunk channel outpaces progradation‐induced delta aggradation. Increasing frequency of overbank floods causes less frequent avulsions because floods scour the riverbed within the backwater zone, slowing net aggradation rates. Results provide a framework to assess upstream and downstream controls on avulsion patterns over glacial‐interglacial cycles, and the impact of land use and anthropogenic climate change on deltas.
Geometry and Kinematics of Bivergent Extension in the Southern Cycladic Archipelago: Constraining an Extensional Hinge Zone on Sikinos Island, Aegean Sea, Greece
Authors: Ring Uwe , Glodny Johannes
Published: May 2021

We report the results of a field study on Sikinos Island in the Aegean extensional province of Greece and propose a hinge zone controlling incipient bivergent extension in the southern Cyclades. A first deformation event led to top‐S thrusting of the Cycladic Blueschist Unit (CBU) onto the Cycladic basement in the Oligocene. The mean kinematic vorticity number (Wm) during this event is between 0.56 and 0.63 in the CBU, and 0.72 to 0.84 in the basement, indicating general‐shear deformation with about equal components of pure and simple shear. The strain geometry was close to plane strain. Subsequent lower‐greenschist‐facies extensional shearing was also by general‐shear deformation; however, the pure‐shear component was distinctly greater (Wm = 0.3–0.41). The degree of subvertical pure‐shear flattening increases structurally upward and explains alternating top‐N and top‐S shear senses over large parts of the island. Along with an increased coaxial deformation component, the strain geometry became oblate. Published quantitative data from nearby Ios Island are similar and both data sets define an extensional hinge zone between top‐N extensional deformation across large parts of the central and northern Cyclades and top‐S extensional deformation at the southern and western fringe of the archipelago. This extensional hinge zone is an important large‐scale structure forming early in the history of lithospheric extension due to southward retreat of the Hellenic slab.
Optimizing Spatial Allocation of COVID‐19 Vaccine by Agent‐Based Spatiotemporal Simulations
Authors: Zhou Shuli , Zhou Suhong , Zheng Zhong , Lu Junwen
Published: May 2021

Optimizing allocation of vaccine, a highly scarce resource, is an urgent and critical issue during fighting against on‐going COVID‐19 epidemic. Prior studies suggested that vaccine should be prioritized by age and risk groups, but few of them have considered the spatial prioritization strategy. This study aims to examine the spatial heterogeneity of COVID‐19 transmission in the city naturally, and optimize vaccine distribution strategies considering spatial prioritization. We proposed an integrated spatial model of agent‐based model and SEIR (susceptible‐exposed‐infected‐recovered). It simulated spatiotemporal process of COVID‐19 transmission in a realistic urban context. Individual movements were represented by trajectories of 8,146 randomly sampled mobile phone users on December 28, 2016 in Guangzhou, China, 90% of whom aged 18–60. Simulations were conducted under seven scenarios. Scenarios 1 and 2 examined natural spreading process of COVID‐19 and its final state of herd immunity. Scenarios 3–6 applied four vaccination strategies (random strategy, age strategy, space strategy, and space & age strategy), and identified the optimal vaccine strategy. Scenario 7 assessed the most appropriate vaccine coverage. The results demonstrates herd immunity is heterogeneously distributed in space, thus, vaccine intervention strategies should be spatialized. Among four strategies, space & age strategy is substantially most efficient, with 7.7% fewer in attack rate and 44 days longer than random strategy under 20% vaccine uptake. Space & age strategy requires 30%–40% vaccine coverage to control the epidemic, while the coverage for a random strategy is 60%–70% as a comparison. The application of our research would greatly improves the effectiveness of the vaccine usability.
Corals Reveal an Unprecedented Decrease of Arabian Sea Upwelling During the Current Warming Era
Authors: Watanabe Takaaki K. , Watanabe Tsuyoshi , Pfeiffer Miriam , Hu Hsun‐Ming , Shen Chuan‐Chou , Yamazaki Atsuko
Published: May 2021

Upwelling in the Arabian Sea driven by the Indian summer monsoon pumps deep, cold, and eutrophic seawater to the sea surface every summer. The Indian summer monsoon and the Arabian Sea upwelling were expected to intensify with global warming, following the hypothesis that the Eurasian landmass would warm faster than the Indian Ocean. Contrary to expectations, the northern Indian Ocean currently warms faster than the Indian subcontinent. A weakening of the Indian summer monsoon circulation is reported, which possibly weakens the Arabian Sea upwelling. However, a lack of observations limits understanding of current and historical changes of the Arabian Sea upwelling. Here, we reconstruct the Arabian Sea upwelling over the past millennium using modern and fossil corals. Our coral records show that the Arabian Sea upwelling intensity was very stable over the last millennium and unprecedentedly declines at present. Our finding implies anthropogenic forcing likely weakens the Arabian Sea upwelling.
Localized Anisotropy in the Mantle Transition Zone Due to Flow Through Slab Gaps
Authors: Zhang Han , Schmandt Brandon , Zhang Jin S.
Published: May 2021

Measurement of anisotropy advances our understanding of mantle dynamics by linking remote seismic observations to local deformation state through constraints from mineral physics. The Pacific Northwest records the largest depth‐integrated anisotropic signals across the western United States but the depths contributing to the total signal are unclear. We used the amplitudes of orthogonally polarized P‐to‐S converted phases from the mantle transition zone boundaries to identify anisotropy within the ∼400–700 km deep layer. Significant anisotropy is found near slab gaps imaged by prior tomography. Focusing of mantle flow through slab gaps may lead to locally elevated stress that enhances lattice preferred orientation of anisotropic minerals within the transition zone, such as wadsleyite.
Heterogeneous Reaction of CaCO3 With NO2 at Different Relative Humidities: Kinetics, Mechanisms, and Impacts on Aerosol Hygroscopicity
Authors: Jia Xiaohong , Gu Wenjun , Peng Chao , Li Rui , Chen Lanxiadi , Wang Hongli , Wang Haichao , Wang Xinming , Tang Mingjin
Published: May 2021

Heterogeneous reaction of NO2 with CaCO3, an abundant and reactive component in mineral dust aerosol, was investigated in this work at different relative humidifies (RH, up to 80%), using a fixed‐bed reactor. Ion chromatograph and a vapor sorption analyzer were employed to measure changes in particulate nitrate and water with reaction time (up to 24 h). When NO2 concentration was ∼10 ppmv (∼2.5 × 1014 molecule cm−3), CaCO3 showed very low reactivity toward NO2 at <1% RH, and γ(NO2) was estimated to be <2 × 10−8; consequently, no significant change in hygroscopicity of CaCO3 particles was observed after reaction with NO2 for 24 h at <1% RH, as the amount of nitrate formed was very limited. Heterogeneous reactivity was significantly enhanced at elevated RH (20%–80%), and during the reaction CaCO3 was covered with a deliquesced layer resulting from water uptake by formed nitrate; in addition, the average γ(NO2) was determined to be (1.21 ± 0.45) × 10−7, independent of RH (20%–80%) and reaction time (3–24 h). After reaction with 10 ppmv NO2 for 24 h at elevated RH (20%–80%), the mass of particulate water associated with reacted CaCO3 at 90% RH was equal to ∼45% of the mass of unreacted CaCO3, suggesting that heterogeneous reaction of CaCO3 with NO2 at 20%–80% RH could substantially increase its hygroscopicity. Overall, our laboratory study suggested that heterogeneous reaction with NO2 may significantly impact composition and hygroscopicity of CaCO3 particles.
FLT3 tyrosine kinase inhibitors synergize with BCL-2 inhibition to eliminate FLT3/ITD acute leukemia cells through BIM activation
Authors: Zhu Ruiqi , Li Li , Nguyen Bao , Seo Jaesung , Wu Min , Seale Tessa , Levis Mark , Duffield Amy , Hu Yu , Small Donald
Published: May 2021

Tyrosine kinase inhibitors (TKIs) targeting FLT3 have shown activity but when used alone have achieved limited success in clinical trials, suggesting the need for combination with other drugs. We investigated the combination of FLT3 TKIs (Gilteritinib or Sorafenib), with Venetoclax, a BCL-2 selective inhibitor (BCL-2i), on FLT3/ITD leukemia cells. The combination of a FLT3 TKI and a BCL-2i synergistically reduced cell proliferation and enhanced apoptosis/cell death in FLT3/ITD cell lines and primary AML samples. Venetoclax also re-sensitized FLT3 TKI-resistant cells to Gilteritinib or Sorafenib treatment, mediated through MAPK pathway inhibition. Gilteritinib treatment alone dissociated BIM from MCL-1 but increased the binding of BIM to BCL-2. Venetoclax treatment enhanced the binding of BIM to MCL-1 but dissociated BIM from BCL-2. Treatment with the drugs together resulted in dissociation of BIM from both BCL-2 and MCL-1, with an increased binding of BIM to the cell death mediator BAX, leading to increased apoptosis. These findings suggest that Venetoclax mitigates the unintended pro-survival effects of FLT3 TKI mainly through the dissociation of BIM and BCL-2 and also decreased BIM expression. This study provides evidence that the addition of BCL-2i enhances the effect of FLT3 TKI therapy in FLT3/ITD AML treatment.
Multimodal prognosis of negative symptom severity in individuals at increased risk of developing psychosis
Authors: Hauke Daniel J. , Schmidt André , Studerus Erich , Andreou Christina , Riecher-Rössler Anita , Radua Joaquim , Kambeitz Joseph , Ruef Anne , Dwyer Dominic B. , Kambeitz-Ilankovic Lana , Lichtenstein Theresa , Sanfelici Rachele , Penzel Nora , Haas Shalaila S. , Antonucci Linda A. , Lalousis Paris Alexandros , Chisholm Katharine , Schultze-Lutter Frauke , Ruhrmann Stephan , Hietala Jarmo , Brambilla Paolo , Koutsouleris Nikolaos , Meisenzahl Eva , Pantelis Christos , Rosen Marlene , Salokangas Raimo K. R. , Upthegrove Rachel , Wood Stephen J. , Borgwardt Stefan ,   and the PRONIA Group
Published: May 2021

Negative symptoms occur frequently in individuals at clinical high risk (CHR) for psychosis and contribute to functional impairments. The aim of this study was to predict negative symptom severity in CHR after 9 months. Predictive models either included baseline negative symptoms measured with the Structured Interview for Psychosis-Risk Syndromes (SIPS-N), whole-brain gyrification, or both to forecast negative symptoms of at least moderate severity in 94 CHR. We also conducted sequential risk stratification to stratify CHR into different risk groups based on the SIPS-N and gyrification model. Additionally, we assessed the models’ ability to predict functional outcomes in CHR and their transdiagnostic generalizability to predict negative symptoms in 96 patients with recent-onset psychosis (ROP) and 97 patients with recent-onset depression (ROD). Baseline SIPS-N and gyrification predicted moderate/severe negative symptoms with significant balanced accuracies of 68 and 62%, while the combined model achieved 73% accuracy. Sequential risk stratification stratified CHR into a high (83%), medium (40–64%), and low (19%) risk group regarding their risk of having moderate/severe negative symptoms at 9 months follow-up. The baseline SIPS-N model was also able to predict social (61%), but not role functioning (59%) at above-chance accuracies, whereas the gyrification model achieved significant accuracies in predicting both social (76%) and role (74%) functioning in CHR. Finally, only the baseline SIPS-N model showed transdiagnostic generalization to ROP (63%). This study delivers a multimodal prognostic model to identify those CHR with a clinically relevant negative symptom severity and functional impairments, potentially requiring further therapeutic consideration.
Parsing variability in borderline personality disorder: a meta-analysis of neuroimaging studies
Authors: Degasperi Giorgia , Cristea Ioana Alina , Di Rosa Elisa , Costa Cristiano , Gentili Claudio
Published: May 2021

Though a plethora of functional magnetic resonance imaging (fMRI) studies explored the neurobiological underpinnings of borderline personality disorder (BPD), findings across different tasks were divergent. We conducted a systematic review and activation likelihood estimation (ALE) meta-analysis on the fMRI studies conducted in BPD patients compared to healthy controls (HC). We systematically searched PubMed and PsychINFO from inception until July 9th 2020 using combinations of database-specific terms like ‘fMRI’, ‘Neuroimaging’, ‘borderline’. Eligible studies employed task-based fMRI of the brain in participants of any age diagnosed with BPD compared to HC, during any behavioral task and providing a direct contrast between the groups. From 762 entries, we inspected 92 reports full-texts and included 52 studies (describing 54 experiments). Across all experiments, the HC > BPD and BPD > HC meta-analyses did not yield any cluster of significant convergence of differences. Analyses restricted to studies of emotion processing revealed two significant clusters of activation in the bilateral hippocampal/amygdala complex and anterior cingulate for the BPD > HC meta-analysis. Fail-safe N and single study sensitivity analysis suggested significant findings were not robust. For the subgroup of emotional processing experiments, on a restricted number of experiments providing results for each group separately, another meta-analysis method (difference of convergence) showed a significant cluster in the insula/inferior frontal gyrus for the HC > BPD contrast. No consistent pattern of alteration in brain activity for BPD was evidenced suggesting substantial heterogeneity of processes and populations studied. A pattern of amygdala dysfunction emerged across emotion processing tasks, indicating a potential pathophysiological mechanism that could be transdiagnostic.
Epigenetic regulation of intestinal peptide transporter PEPT1 as a potential strategy for colorectal cancer sensitization
Authors: Wang Yanhong , Wang Jiaqi , Yang Lingrong , Qiu Liqing , Hua Yuhui , Wu Shixiu , Zeng Su , Yu Lushan , Zheng Xiaoli
Published: May 2021

Human intestinal peptide transporter PEPT1 is commonly repressed in human colorectal cancer (CRC), yet its relationship with sensitivity to the common CRC treatment ubenimex has not previously been elucidated. In this study, we confirmed PEPT1 suppression in CRC using real-time quantitative polymerase chain reaction and western blotting and then investigated the underlying epigenetic pathways involved using bisulfite sequencing, chromatin immunoprecipitation, siRNA knockdown, and reporter gene assays. We found that PEPT1 transcriptional repression was due to both DNMT1-mediated DNA methylation of the proximal promoter region and HDAC1-mediated histone deacetylation, which blocked P300-mediated H3K18/27Ac at the PEPT1 distal promoter. Finally, the effects of the epigenetic activation of PEPT1 on the CRC response to ubenimex were evaluated using sequential combination therapy of decitabine and ubenimex both in vitro and in xenografts. In conclusion, epigenetic silencing of PEPT1 due to increased DNMT1 and HDAC1 expression plays a vital role in the poor response of CRC to ubenimex.
Cerebrovascular diseases in two patients with entire NSD1 deletion
Authors: Itai Toshiyuki , Miyatake Satoko , Hatano Taku , Hattori Nobutaka , Ohno Atsuko , Aoki Yusuke , Itomi Kazuya , Mori Harushi , Saitsu Hirotomo , Matsumoto Naomichi
Published: May 2021

We describe two patients with NSD1 deletion, who presented with early-onset, or recurrent cerebrovascular diseases (CVDs). A 39-year-old female showed developmental delay and abnormal gait in infancy, and developed slowly-progressive intellectual disability and movement disorders. Brain imaging suggested recurrent parenchymal hemorrhages. A 6-year-old male had tremor as a neonate and brain imaging revealed subdural hematoma and brain contusion. This report suggests possible involvement of CVDs associated with NSD1 deletion.
Mining mutation contexts across the cancer genome to map tumor site of origin
Authors: Chakraborty Saptarshi , Martin Axel , Guan Zoe , Begg Colin B. , Shen Ronglai
Published: May 2021

The vast preponderance of somatic mutations in a typical cancer are either extremely rare or have never been previously recorded in available databases that track somatic mutations. These constitute a hidden genome that contrasts the relatively small number of mutations that occur frequently, the properties of which have been studied in depth. Here we demonstrate that this hidden genome contains much more accurate information than common mutations for the purpose of identifying the site of origin of primary cancers in settings where this is unknown. We accomplish this using a projection-based statistical method that achieves a highly effective signal condensation, by leveraging DNA sequence and epigenetic contexts using a set of meta-features that embody the mutation contexts of rare variants throughout the genome.
Versatile non-luminescent color palette based on guest exchange dynamics in paramagnetic cavitands
Authors: Goren Elad , Avram Liat , Bar-Shir Amnon
Published: May 2021

Multicolor luminescent portrayal of complexed arrays is indispensable for many aspects of science and technology. Nevertheless, challenges such as inaccessible readouts from opaque objects, a limited visible-light spectrum and restricted spectral resolution call for alternative approaches for multicolor representation. Here, we present a strategy for spatial COlor Display by Exploiting Host-guest Dynamics (CODE-HD), comprising a paramagnetic cavitand library and various guests. First, a set of lanthanide-cradled α-cyclodextrins (Ln-CDs) is designed to induce pseudo-contact shifts in the19F-NMR spectrum ofLn-CD-bound guest. Then, capitalizing on reversible host-guest binding dynamics and using magnetization-transfer19F-MRI, pseudo-colored maps of complexed arrays are acquired and applied in molecular-steganography scenarios, showing CODE-HD’s ability to generate versatile outputs for information encoding. By exploiting the widely shifted resonances induced byLn-CDs, the guest versatility and supramolecular systems' reversibility, CODE-HD provides a switchable, polychromatic palette, as an advanced strategy for light-free, multicolor-mapping.
Identifying molecules as biosignatures with assembly theory and mass spectrometry
Authors: Marshall Stuart M. , Mathis Cole , Carrick Emma , Keenan Graham , Cooper Geoffrey J. T. , Graham Heather , Craven Matthew , Gromski Piotr S. , Moore Douglas G. , Walker Sara. I. , Cronin Leroy
Published: May 2021

The search for alien life is hard because we do not know what signatures are unique to life. We show why complex molecules found in high abundance are universal biosignatures and demonstrate the first intrinsic experimentally tractable measure of molecular complexity, called the molecular assembly index (MA). To do this we calculate the complexity of several million molecules and validate that their complexity can be experimentally determined by mass spectrometry. This approach allows us to identify molecular biosignatures from a set of diverse samples from around the world, outer space, and the laboratory, demonstrating it is possible to build a life detection experiment based on MA that could be deployed to extraterrestrial locations, and used as a complexity scale to quantify constraints needed to direct prebiotically plausible processes in the laboratory. Such an approach is vital for finding life elsewhere in the universe or creating de-novo life in the lab.
MPP8 is essential for sustaining self-renewal of ground-state pluripotent stem cells
Authors: Müller Iris , Moroni Ann Sophie , Shlyueva Daria , Sahadevan Sudeep , Schoof Erwin M. , Radzisheuskaya Aliaksandra , Højfeldt Jonas W. , Tatar Tülin , Koche Richard P. , Huang Chang , Helin Kristian
Published: May 2021

Deciphering the mechanisms that control the pluripotent ground state is key for understanding embryonic development. Nonetheless, the epigenetic regulation of ground-state mouse embryonic stem cells (mESCs) is not fully understood. Here, we identify the epigenetic protein MPP8 as being essential for ground-state pluripotency. Its depletion leads to cell cycle arrest and spontaneous differentiation. MPP8 has been suggested to repress LINE1 elements by recruiting the human silencing hub (HUSH) complex to H3K9me3-rich regions. Unexpectedly, we find that LINE1 elements are efficiently repressed by MPP8 lacking the chromodomain, while the unannotated C-terminus is essential for its function. Moreover, we show that SETDB1 recruits MPP8 to its genomic target loci, whereas transcriptional repression of LINE1 elements is maintained without retaining H3K9me3 levels. Taken together, our findings demonstrate that MPP8 protects the DNA-hypomethylated pluripotent ground state through its association with the HUSH core complex, however, independently of detectable chromatin binding and maintenance of H3K9me3.
Dynamic fingerprint of fractionalized excitations in single-crystalline Cu3Zn(OH)6FBr
Authors: Fu Ying , Lin Miao-Ling , Wang Le , Liu Qiye , Huang Lianglong , Jiang Wenrui , Hao Zhanyang , Liu Cai , Zhang Hu , Shi Xingqiang , Zhang Jun , Dai Junfeng , Yu Dapeng , Ye Fei , Lee Patrick A. , Tan Ping-Heng , Mei Jia-Wei
Published: May 2021

Beyond the absence of long-range magnetic orders, the most prominent feature of the elusive quantum spin liquid (QSL) state is the existence of fractionalized spin excitations, i.e., spinons. When the system orders, the spin-wave excitation appears as the bound state of the spinon-antispinon pair. Although scarcely reported, a direct comparison between similar compounds illustrates the evolution from spinon to magnon. Here, we perform the Raman scattering on single crystals of two quantum kagome antiferromagnets, of which one is the kagome QSL candidate Cu3Zn(OH)6FBr, and another is an antiferromagnetically ordered compound EuCu3(OH)6Cl3. In Cu3Zn(OH)6FBr, we identify a unique one spinon-antispinon pair component in the E2g magnetic Raman continuum, providing strong evidence for deconfined spinon excitations. In contrast, a sharp magnon peak emerges from the one-pair spinon continuum in the Eg magnetic Raman response once EuCu3(OH)6Cl3 undergoes the antiferromagnetic order transition. From the comparative Raman studies, we can regard the magnon mode as the spinon-antispinon bound state, and the spinon confinement drives the magnetic ordering.
Global health effects of future atmospheric mercury emissions
Authors: Zhang Yanxu , Song Zhengcheng , Huang Shaojian , Zhang Peng , Peng Yiming , Wu Peipei , Gu Jing , Dutkiewicz Stephanie , Zhang Huanxin , Wu Shiliang , Wang Feiyue , Chen Long , Wang Shuxiao , Li Ping
Published: May 2021

Mercury is a potent neurotoxin that poses health risks to the global population. Anthropogenic mercury emissions to the atmosphere are projected to decrease in the future due to enhanced policy efforts such as the Minamata Convention, a legally-binding international treaty entered into force in 2017. Here, we report the development of a comprehensive climate-atmosphere-land-ocean-ecosystem and exposure-risk model framework for mercury and its application to project the health effects of future atmospheric emissions. Our results show that the accumulated health effects associated with mercury exposure during 2010–2050 are $19 (95% confidence interval: 4.7–54) trillion (2020 USD) realized to 2050 (3% discount rate) for the current policy scenario. Our results suggest a substantial increase in global human health cost if emission reduction actions are delayed. This comprehensive modeling approach provides a much-needed tool to help parties to evaluate the effectiveness of Hg emission controls as required by the Minamata Convention.
Electrochemical C−C bond cleavage of cyclopropanes towards the synthesis of 1,3-difunctionalized molecules
Authors: Peng Pan , Yan Xingxiu , Zhang Ke , Liu Zhao , Zeng Li , Chen Yixuan , Zhang Heng , Lei Aiwen
Published: May 2021

Electrochemistry has a lot of inherent advantages in organic synthesis and many redox reactions have been achieved under electrochemical condition. However, the electrochemical C−C bond cleavage and functionalization reactions are less studied. Here we develop electrochemical C−C bond cleavage and 1,3-difuntionalization of arylcyclopropanes under catalyst-free and external-oxidant-free conditions. 1,3-difluorination, 1,3-oxyfluorination and 1,3-dioxygenation of arylcyclopropanes are achieved with a high chemo- and regioselectivity by the strategic choice of nucleophiles. This protocol has good functional groups tolerance and can be scaled up. Mechanistic studies demonstrate that arylcyclopropane radical cation obtained from the anode oxidation and the subsequently generated benzyl carbonium are the key intermediates in this transformation. This development provides a scenario for constructing 1,3-difunctionalized molecules.