bluuebunny/crossref_metadata_2025 huggingface dataset:
Researchers’ experiences working with community advisory boards: How community member feedback impacted the research
Authors: Brockman Tabetha A. , Balls-Berry Joyce E. , West Ian W. , Valdez-Soto Miguel , Albertie Monica L. , Stephenson Noreen A. , Omar Farhia M. , Moore Mitch , Alemán Marty , Berry Pastor Albert , Karuppana Suganya , Patten Christi A.
Published: March 2021

Introduction:

To assess researchers’ experiences working with community advisory boards (CABs) and perceptions of how community member stakeholder feedback impacted the research.

Methods:

Individual interviews were conducted with researchers (n= 34) who had presented their research to a Mayo Clinic CAB (at MN, AZ, or FL) from 2014 to 2017, with an average interview duration of 10–15 min. Researchers were asked “In what ways did the feedback you received from the CAB influence your research?” A validated, structured, 7-item interview was used to assess domains of the potential influence that CABs had on the research: (1) pre-research (e.g., generated ideas), (2) infrastructure (e.g., budget preparation), (3) research design, (4) implementation (e.g., research recruitment), (5) analysis, (6) dissemination, and (7) post-research. A total mean score was calculated with a possible range of 0–7. In addition, open-ended examples and feedback from researchers in response to each domain were summarized for themes using content analysis.

Results:

Researchers reported that the CAB influenced research in the following domains: pre-research (24%), infrastructure (24%), study design (41%), implementation (41%), analysis (6%), dissemination (24%), and post-research activities (18%). The mean total score was = 1.8 (SD = 1.7, range: 0–6). Open-ended responses revealed major themes of CAB helpfulness in generating/refining ideas, identifying community partners, culturally tailored and targeted recruitment strategies, intervention design and delivery, and dissemination.

Conclusion:

Findings from this preliminary evaluation indicate that despite positive experiences noted in open-ended feedback, the perceived quantitative impact of CAB feedback on the research was moderate. Bidirectional communication between researchers and community member stakeholders has the potential to make clinical and translational research more relevant and appropriate.
FISCAL PESSIMISM IN HISTORICAL PERSPECTIVE: TOCQUEVILLE'S CROSS REVISITED
Authors: Cepeda Isabel , Fraile Balbín Pedro
Published: March 2021

This paper explores Alexis de Tocqueville's thought on fiscal political economy as a forerunner of the modern school of preference falsification and rational irrationality in economic decision making. A good part of the literature has misrepresented Tocqueville as an unconditional optimist regarding the future of fiscal moderation under democracy. Yet, although he initially shared the cautious optimism of most classical economists with respect to taxes under extended suffrage, Tocqueville's view turned more pessimistic in the second volume of his Democracy in America. Universal enfranchisement and democratic governments would lead to higher taxes, more intense income redistribution and government control. Under democracy, the continuous search for unconditional equality would eventually jeopardise liberty and economic growth.
Is There a Cohort Explanation for Declines in Elderly Migration?
Authors: Edmonston Barry , Lee Sharon M. , Wu Zheng
Published: March 2021

Previous research documented a dramatic decline in the residential mobility of elderly Canadians (65 years and older) since 1961. We examine more recent data from the 2011 and 2016 censuses to update findings and extend previous research. We first found that elderly residential mobility has continued to decline. There were substantial declines of 20 per cent and more for all types of residential mobility. Second, descriptive analysis of changes over time in the proportion of the population that lives in a different province than their province of birth for 1871 to the present suggests that the 1906–1925 birth cohorts experienced migration rates that were slightly higher than comparable later cohorts. Third, multivariate analysis of 1971–2016 interprovincial migration data shows that the 1906–1925 birth cohort who entered early adult years during World War II had higher migration rates than earlier or later birth cohorts. The cohort explanation accounted for 10 per cent of the decrease in elderly migration between 1981 and 2016. A cohort explanation can therefore contribute to understanding decreased elderly migration, but many questions remain for future study.
Hierarchical Inclusion: The Untold History of Israel's Affirmative Action for Arab Citizens (1948–68)
Authors: Bloch Ofra
Published: March 2021

The history of Israel's relationship with its Palestinian-Arab minority during the founding decades, from 1948 to 1968, is often portrayed as a story of formal citizenship that concealed large-scale, state-sanctioned oppression under military rule. This article excavates an untold history of employment affirmative action for Palestinian-Arab citizens of Israel during these two decades which does not fit neatly into this story. Drawing on original archival research, it reveals that, during Israel's founding decades, officials adopted hiring quotas for unskilled Arab workers and for educated Arabs; requirements and incentives for hiring Arabs in government offices, Jewish businesses, and organizations; earmarked jobs and established vocational training courses for the Arab population. It demonstrates that interests in safeguarding Jewish control and economic stability aligned with egalitarian aspirations, and motivated state officials to adopt measures that promoted the inclusion of the Arab population in the workforce, albeit on unequal terms. Furthermore, these measures were part of a transformation of the state's attitude towards Arab citizens, from strict military control to a regime of “hierarchical inclusion” entailing gradual integration into the Israeli economy — mostly though its lower tiers and with a second-class status. Tracing the use of these mechanisms, not then called affirmative action but recognizable as such today, to this period of subjected population management, complicates our understanding of both this chapter in Israel's history and of affirmative action more broadly.
Protecting Foreigners: The Refugee Crisis on the Belize–Yucatán Border, 1847–71
Authors: Mongey Vanessa
Published: March 2021

Taking mid-nineteenth century Belize as a case study, this article considers the role of migration in forming political, legal, and spatial geographies in a region with weak state institutions and disputed borders. The Caste War—a series of conflicts starting in 1847 in the southeastern Mexican state of Yucatán— resulted in the movement of thousands of people into the neighboring British settlement of Belize. This population movement reshaped the interface between the metropole and the settlement. This was a colony-defining moment in the development of Belize, leading to an extension of imperial control that eventually culminated in the transition to Crown colony in 1871. The refugee crisis was tied to broader Atlantic questions around asylum, law and empire. The benevolent treatment of refugees became the gauge of a “civilized” colony until the refugee crisis turned into a race crisis. This article examines how local administrators used a humanitarian discourse to enshrine white settler colonialism in a territory suddenly inhabited by a foreign-born multi-ethnic majority. The refugee label became a way to secure British sovereignty over the territory and its inhabitants, including non-British subjects, while extracting resources from the newcomers.
PROGRESSIVE TAXATION AND MACROECONOMICS (IN)STABILITY UNDER HOUSEHOLD HETEROGENEITY
Authors: Chen Shu-Hua
Published: March 2021

It has been shown that progressive income taxation may stabilize an otherwise standard representative-agent real business cycle model with an indeterminate steady state against aggregate fluctuations caused by agents’ animal spirits. By contrast, within an identical model that allows for sustained economic growth, progressive taxation could lead to equilibrium indeterminacy and sunspot-driven fluctuations. In the context of household heterogeneity that gives rise to income and asset inequality, the fiscal authority has (at least) two options of setting the baseline level of taxable income: (i) the economy-wide average level of income and (ii) the economy’s steady-state level of per capita income. I show that the adoption of a fiscal rule (i) invalidates the effects that a progressive tax can exert on the model’s local stability properties. Progressive income taxation thus no longer operates as an automatic stabilizer that mitigates belief-driven cyclical fluctuations in a no-growth economy, nor as an automatic destabilizer that leads to local indeterminacy in a sustained-growth economy. If a tax policy rule (ii) is instead adopted, then the existing literature’s findings of the (de)stabilizing roles of progressive taxation are robust to the inclusion of household heterogeneity.
Effects of molecular targeting agents and immune-checkpoint inhibitors in patients with advanced cancer who are near the end of life
Authors: Hiramoto Shuji , Taniyama Tomohiko , Kikuchi Ayako , Hori Tetsuo , Yoshioka Akira , Inoue Akira
Published: March 2021

Background

In recent years, the use of both molecular targeting agents (MTAs) and immune-checkpoint inhibitors (ICIs) tend to occupy important positions in systemic anticancer therapy (SACT). The objective of this study is to describe the predictors of SACT include both MTAs and ICIs near the end of life (EOL) and the effect on EOL care in patients with advanced cancer.

Methods

We analyzed all patients who died of advanced cancer from August 2016 to August 2019, and we analyzed the survival time of patients who underwent anticancer agents excluded due to the loss of information about the last administration of SACT. The primary endpoint of this study was to identify predictors during the last administration of SACT near EOL.

Results

In a multivariate analysis, the Eastern Cooperative Oncology Group performance status (ECOG-PS) (ORs 33.781) was significantly related factors within 14 days of death from the last administration of SACT. Age (ORs 0.412), ECOG-PS (ORs 11.533), primary cancer site of upper GI cancers (ORs 2.205), the number of comorbidities (ORs 0.207), MTAs (ORs 3.139), and ICIs (ORs 3.592) were significantly related factors within 30 days of death. The median survival time (MST) of patients with PS 3–4 was 29 days, while that of patients with both PS 0–2 was 76 days. The prevalence rate of delirium with MTAs was 17.5%, which was significantly lower than that of patients without it (31.8%). The prevalence rate of the mean dose of opioids in patients with ICIs was 97.9 mg/day, which was significantly higher than that of patients without it (44.9 mg/day).

Conclusions

Age, ECOG-PS, primary cancer site, the number of comorbidities, MTAs, and ICIs use were significant associated with SACT near EOL. Information on these factors may aid clinical decision making in referral to palliative care institutes.
Temporal Seismic Velocity Variations: Recovery Following From the 2019 Mw 7.1 Ridgecrest, California Earthquake
Authors: Boschelli Joshua , Moschetti Morgan P. , Sens‐Schönfelder Christoph
Published: March 2021

We investigated seismic velocity changes (dv/v) associated with the 2019 Ridgecrest earthquake sequence with high‐frequency autocorrelations of ambient seismic noise data. Daily autocorrelation functions were computed for the entirety of 2019 and the first quarter of 2020 for broadband stations within the region, including the temporary broadband stations installed during the aftershock deployment. Travel time shifts in the daily autocorrelation functions, relative to the mean autocorrelation waveform, were computed to produce dv/v time series, which are sensitive to the evolving material properties of the shallow crust surrounding the Ridgecrest fault zone (RFZ). A short‐term velocity drop follows the Mw 7.1 earthquake at stations in the vicinity of the rupture surface, while those greater than 50 km away showed no such drop. The maximum, absolute changes in seismic velocity are proportional to the logarithm of distance from the fault rupture and to the peak dynamic strain experienced during the earthquake. Near the areas of the highest coseismic slip within the RFZ, seismic velocities recovered over 3 months. However, in the vicinity of the nearby Garlock fault, where triggered slip manifested, and north of the RFZ, seismic velocities recovered within a month. We interpret the seismic velocity changes and their recovery to be largely due to changes in the physical properties of the shallow crust, such as fault zone damage recovery caused by the earthquake rupture process and in response to the large dynamic stresses of passing seismic waves from the mainshock.
A Volcanic Ash Layer in the Nördlinger Ries Impact Structure (Miocene, Germany): Indication of Crater Fill Geometry and Origins of Long‐Term Crater Floor Sagging
Authors: Arp Gernot , Dunkl István , Jung Dietmar , Karius Volker , Lukács Réka , Zeng Lingqi , Reimer Andreas , Head James W.
Published: March 2021

Since its recognition as an impact structure 60 years ago, no volcanics were anticipated in the circular depression of the 14.8 Ma old Nördlinger Ries. Here, we describe for the first time a volcanic ash‐derived clinoptilolite‐heulandite‐buddingtonite bed within the 330 m thick Miocene lacustrine crater fill. Zircon U‐Pb ages of 14.20 ± 0.08 Ma point to the source of the volcanic ash in the Pannonian Basin, 760 km east of the Ries. The diagenetically derived zeolite‐feldspar bed occurs in laminated claystones of the Ries soda‐lake stage and represents the first unequivocal stratigraphic marker bed in this basin, traceable from marginal surface outcrops to 218 m below surface in the crater center. These relationships demonstrate a deeply bowl‐shaped geometry of crater fill sediments, not explainable by sediment compaction and corresponding stratigraphic backstripping alone. Since most of the claystones formed at shallow water depths, the bowl‐shaped geometry must reflect 134 +23/−49 m of sagging of the crater floor. We attribute the sagging to compaction and closure of the dilatant macro‐porosity of the deeply fractured and brecciated crater floor during basin sedimentation and loading, a process that lasted for more than 0.6 Myr. As a result, the outcrop pattern of the lithostratigraphic crater‐fill units in its present erosional plane forms a concentric pattern. Recognition of this volcanic ash stratigraphic marker in the Ries crater provides insights into the temporal and stratigraphic relationships of crater formation and subsidence that have implications for impact‐hosted lakes on Earth and Mars.
The receptor of the colony-stimulating factor-1 (CSF-1R) is a novel prognostic factor and therapeutic target in follicular lymphoma
Authors: Valero Juan Garcia , Matas-Céspedes Alba , Arenas Fabián , Rodriguez Vanina , Carreras Joaquim , Serrat Neus , Guerrero-Hernández Martina , Yahiaoui Anella , Balagué Olga , Martin Silvia , Capdevila Cristina , Hernández Lluis , Magnano Laura , Rivas-Delgado Alfredo , Tannheimer Stacey , Cid Maria C. , Campo Elías , López-Guillermo Armando , Colomer Dolors , Pérez-Galán Patricia
Published: March 2021

Microenvironment contributes to follicular lymphoma (FL) pathogenesis and impacts survival with macrophages playing a controversial role. In the present study, using FL primary samples and HK follicular dendritic cells (FDC) to mimic the germinal center, together with mouse models, we have analyzed the three-way crosstalk of FL-FDC-macrophages and derived therapeutic opportunities. Ex vivo primary FL-FDC co-cultures (n = 19) and in vivo mouse co-xenografts demonstrated that FL-FDC crosstalk favors tumor growth and, via the secretion of CCL2 and CSF-1, promotes monocyte recruitment, differentiation, and polarization towards an M2-like protumoral phenotype. Moreover, FL-M2 co-cultures displayed enhanced angiogenesis, dissemination, and immunosuppression. Analysis of the CSF-1/CSF-1R pathway uncovered that CSF-1 was significantly higher in serum from grade 3A FL patients, and that high CSF-1R expression in FL biopsies correlated with grade 3A, reduced overall survival and risk of transformation. Furthermore, CSF-1R inhibition with pexidartinib (PLX3397) preferentially affected M2-macrophage viability and polarization program disrupting FL-M2 positive crosstalk. In vivo CSF1-R inhibition caused M2 reduction and repolarization towards M1 macrophages and antitumor effect cooperating with anti-CD20 rituximab. In summary, these results support the role of macrophages in FL pathogenesis and indicate that CSF-1R may be a relevant prognostic factor and a novel therapeutic target cooperating with anti-CD20 immunotherapy.
Plasmonic tweezers: for nanoscale optical trapping and beyond
Authors: Zhang Yuquan , Min Changjun , Dou Xiujie , Wang Xianyou , Urbach Hendrik Paul , Somekh Michael G. , Yuan Xiaocong
Published: March 2021

Optical tweezers and associated manipulation tools in the far field have had a major impact on scientific and engineering research by offering precise manipulation of small objects. More recently, the possibility of performing manipulation with surface plasmons has opened opportunities not feasible with conventional far-field optical methods. The use of surface plasmon techniques enables excitation of hotspots much smaller than the free-space wavelength; with this confinement, the plasmonic field facilitates trapping of various nanostructures and materials with higher precision. The successful manipulation of small particles has fostered numerous and expanding applications. In this paper, we review the principles of and developments in plasmonic tweezers techniques, including both nanostructure-assisted platforms and structureless systems. Construction methods and evaluation criteria of the techniques are presented, aiming to provide a guide for the design and optimization of the systems. The most common novel applications of plasmonic tweezers, namely, sorting and transport, sensing and imaging, and especially those in a biological context, are critically discussed. Finally, we consider the future of the development and new potential applications of this technique and discuss prospects for its impact on science.
Toll-like receptor 4-mediated necroptosis in the development of necrotizing enterocolitis
Authors: Liu Tianjing , Zong Haifeng , Chen Xiaoyu , Li Sihang , Liu Ziyun , Cui Xuewei , Jia Guoqiang , Shi Yongyan
Published: March 2021

Abstract

Background

Dramatic intestinal epithelial cell death leading to barrier dysfunction is one of the mechanism of neonatal necrotizing enterocolitis (NEC), in which Toll-like receptor 4 (TLR4) plays a pivotal role. This study explored the role of necroptosis, a drastic way of cell death in NEC.

Methods

The expression of necroptotic proteins was tested in NEC intestinal tissue and compared with controls. NEC was induced in neonatal wild-type mice and a necroptosis inhibitor was given to investigate whether NEC could be relieved. The general condition, macroscopic scoring, and histological evaluations were performed. The expression of tight junction proteins, inflammatory cytokines, and necroptosis-related proteins was measured, and barrier function was examined. Then, NEC was induced in TLR4-knockout pups to confirm the role of TLR4 in necroptosis.

Results

Necroptotic proteins were significantly upregulated in both NEC patient and animal models, together with the expression of TLR4. NEC could be relieved and inflammatory infiltration was decreased by necrostatin-1s. TLR4-knockout mice showed milder tissue degradation and less necroptosis after NEC induction.

Conclusions

Necroptosis is an essential pathological process of NEC. TLR4 may be one stimulator of necroptosis in NEC. Inhibiting the intestinal cell necroptosis might be a useful strategy in the treatment of NEC.

Impact

Necroptosis is a key pathological process in NEC, which appears to involve TLR4.

Anti-necroptosis treatment is a promising strategy that could significantly relieve the symptoms of NEC.
Immune complex-induced apoptosis and concurrent immune complex clearance are anti-inflammatory neutrophil functions
Authors: Karmakar Utsa , Chu Julia Y. , Sundaram Kruthika , Astier Anne L. , Garside Hannah , Hansen Carsten G. , Dransfield Ian , Vermeren Sonja
Published: March 2021

Persistent neutrophilic inflammation drives host damage in autoimmune diseases that are characterized by abundant immune complexes. Insoluble immune complexes (iICs) potently activate pro-inflammatory neutrophil effector functions. We and others have shown that iICs also promote resolution of inflammation via stimulation of neutrophil apoptosis. We demonstrate here that iICs trigger FcγRIIa-dependent neutrophil macropinocytosis, leading to the rapid uptake, and subsequent degradation of iICs. We provide evidence that concurrent iIC-induced neutrophil apoptosis is distinct from phagocytosis-induced cell death. First, uptake of iICs occurs by FcγRII-stimulated macropinocytosis, rather than phagocytosis. Second, production of reactive oxygen species, but not iIC-internalization is a pre-requisite for iIC-induced neutrophil apoptosis. Our findings identify a previously unknown mechanism by which neutrophils can remove pro-inflammatory iICs from the circulation. Together iIC clearance and iIC-induced neutrophil apoptosis may act to prevent the potential escalation of neutrophilic inflammation in response to iICs.
The role of PKM2 nuclear translocation in the constant activation of the NF-κB signaling pathway in cancer-associated fibroblasts
Authors: Gu Junjie , Li Xuechun , Zhao Lin , Yang Ying , Xue Chunling , Gao Yang , Li Jing , Han Qin , Sun Zhao , Bai Chunmei , Zhao Robert Chunhua
Published: March 2021

Cancer-associated fibroblasts (CAFs) play critical roles in cancer progression by regulating tumor cell proliferation, angiogenesis, and metastasis. Recent studies demonstrated that CAFs induce inhibitory immune cell infiltration and chemotherapy resistance in gastric cancer by activating the NF-κB signaling pathway to secrete IL6, IL8, and other inflammatory factors. Inhibition of the NF-κB signaling pathway in CAFs might be a potential therapeutic strategy in gastric cancer. However, how the NF-κB pathway is activated in CAFs remains unclear. We showed that mesenchymal stem cells (MSCs) differentiated into CAFs, induced by the exosomes derived from gastric cancer cells. During the process of differentiation from MSCs into CAFs, we showed that nuclear PKM2 expression was continuously upregulated and associated with NF-κB P65 acetylation, contributing to P65 nuclear retention in CAFs and constant transcription of IL-6, IL-8, and other inflammatory factors, thus promoting gastric cancer cell proliferation. We showed that NF-κB P65 acetylation was induced by P300. We showed that nuclear PKM2 was derived from exosomes of gastric cancer cell lines and the positive feedback loop induced by PKM2-P65 combination. It is also proved that P300 inhibitors can inhibit tumor proliferation in an AGS subcutaneous xenograft tumor model. Our study showed that gastric cancer cells influence the continuous activation of the NF-κB signaling pathway in CAFs by secreting gastric cancer exosomes containing PKM2, thus inducing abnormal metabolism and inflammation activation. This study provides a new therapeutic target for CAF normalization or deactivation strategies.
Imagining and constraining ferrovolcanic eruptions and landscapes through large-scale experiments
Authors: Soldati A. , Farrell J. A. , Wysocki R. , Karson J. A.
Published: March 2021

Ferrovolcanism, yet to be directly observed, is the most exotic and poorly understood predicted manifestation of planetary volcanism. Large-scale experiments carried out at the Syracuse Lava Project offer insight into the emplacement dynamics of metallic flows as well as coeval metallic and silicate flows. Here, we find that, under the same environmental conditions, higher-density/lower-viscosity metallic lava moves ten times faster than lower-density/higher-viscosity silicate lava. The overall morphology of the silicate flow is not significantly affected by the co-emplacement of a metallic flow. Rather, the metallic flow is largely decoupled from the silicate flow, occurring mainly in braided channels underneath the silicate flow and as low-relief breakouts from the silicate flow front. Turbulent interactions at the metallic-silicate flow interface result in mingling of the two liquids, preserved as erosional surfaces and sharp contacts. The results have important implications for the interpretation of possible ferrovolcanic landscapes across our solar system.
Markerless tracking of an entire honey bee colony
Authors: Bozek Katarzyna , Hebert Laetitia , Portugal Yoann , Mikheyev Alexander S. , Stephens Greg J.
Published: March 2021

From cells in tissue, to bird flocks, to human crowds, living systems display a stunning variety of collective behaviors. Yet quantifying such phenomena first requires tracking a significant fraction of the group members in natural conditions, a substantial and ongoing challenge. We present a comprehensive, computational method for tracking an entire colony of the honey bee Apis mellifera using high-resolution video on a natural honeycomb background. We adapt a convolutional neural network (CNN) segmentation architecture to automatically identify bee and brood cell positions, body orientations and within-cell states. We achieve high accuracy (~10% body width error in position, ~10° error in orientation, and true positive rate > 90%) and demonstrate months-long monitoring of sociometric colony fluctuations. These fluctuations include ~24 h cycles in the counted detections, negative correlation between bee and brood, and nightly enhancement of bees inside comb cells. We combine detected positions with visual features of organism-centered images to track individuals over time and through challenging occluding events, recovering ~79% of bee trajectories from five observation hives over 5 min timespans. The trajectories reveal important individual behaviors, including waggle dances and crawling inside comb cells. Our results provide opportunities for the quantitative study of collective bee behavior and for advancing tracking techniques of crowded systems.
Proximity control of interlayer exciton-phonon hybridization in van der Waals heterostructures
Authors: Merkl Philipp , Yong Chaw-Keong , Liebich Marlene , Hofmeister Isabella , Berghäuser Gunnar , Malic Ermin , Huber Rupert
Published: March 2021

Van der Waals stacking has provided unprecedented flexibility in shaping many-body interactions by controlling electronic quantum confinement and orbital overlap. Theory has predicted that also electron-phonon coupling critically influences the quantum ground state of low-dimensional systems. Here we introduce proximity-controlled strong-coupling between Coulomb correlations and lattice dynamics in neighbouring van der Waals materials, creating new electrically neutral hybrid eigenmodes. Specifically, we explore how the internal orbital 1s-2p transition of Coulomb-bound electron-hole pairs in monolayer tungsten diselenide resonantly hybridizes with lattice vibrations of a polar capping layer of gypsum, giving rise to exciton-phonon mixed eigenmodes, called excitonic Lyman polarons. Tuning orbital exciton resonances across the vibrational resonances, we observe distinct anticrossing and polarons with adjustable exciton and phonon compositions. Such proximity-induced hybridization can be further controlled by quantum designing the spatial wavefunction overlap of excitons and phonons, providing a promising new strategy to engineer novel ground states of two-dimensional systems.
Quasi-continuous melting of model polymer monolayers prompts reinterpretation of polymer melting
Authors: Zhang Ruibin , Fall William S. , Hall Kyle Wm. , Gehring Gillian A. , Zeng Xiangbing , Ungar Goran
Published: March 2021

Condensed matter textbooks teach us that melting cannot be continuous and indeed experience, including with polymers and other long-chain compounds, tells us that it is a strongly first-order transition. However, here we report nearly continuous melting of monolayers of ultralong n-alkane C390H782on graphite, observed by AFM and reproduced by mean-field theory and MD simulation. On heating, the crystal-melt interface moves steadily and reversibly from chain ends inward. Remarkably, the final melting point is 80 K above that of the bulk, and equilibrium crystallinity decreases continuously from ~100% to <50% prior to final melting. We show that the similarity in melting behavior of polymers and non-polymers is coincidental. In the bulk, the intermediate melting stages of long-chain crystals are forbidden by steric overcrowding at the crystal-liquid interface. However, there is no crowding in a monolayer as chain segments can escape to the third dimension.
Red blood cell mannoses as phagocytic ligands mediating both sickle cell anaemia and malaria resistance
Authors: Cao Huan , Antonopoulos Aristotelis , Henderson Sadie , Wassall Heather , Brewin John , Masson Alanna , Shepherd Jenna , Konieczny Gabriela , Patel Bhinal , Williams Maria-Louise , Davie Adam , Forrester Megan A. , Hall Lindsay , Minter Beverley , Tampakis Dimitris , Moss Michael , Lennon Charlotte , Pickford Wendy , Erwig Lars , Robertson Beverley , Dell Anne , Brown Gordon D. , Wilson Heather M. , Rees David C. , Haslam Stuart M. , Alexandra Rowe J. , Barker Robert N. , Vickers Mark A.
Published: March 2021

In both sickle cell disease and malaria, red blood cells (RBCs) are phagocytosed in the spleen, but receptor-ligand pairs mediating uptake have not been identified. Here, we report that patches of high mannose N-glycans (Man5-9GlcNAc2), expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. We find that extravascular hemolysis in sickle cell disease correlates with high mannose glycan levels on RBCs. Furthermore, Plasmodium falciparum-infected RBCs expose surface mannose N-glycans, which occur at significantly higher levels on infected RBCs from sickle cell trait subjects compared to those lacking hemoglobin S. The glycans are associated with high molecular weight complexes and protease-resistant, lower molecular weight fragments containing spectrin. Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait.
Controlling pairing of π-conjugated electrons in 2D covalent organic radical frameworks via in-plane strain
Authors: Alcón Isaac , Santiago Raúl , Ribas-Arino Jordi , Deumal Mercè , Moreira Ibério de P. R. , Bromley Stefan T.
Published: March 2021

Controlling the electronic states of molecules is a fundamental challenge for future sub-nanoscale device technologies. π-conjugated bi-radicals are very attractive systems in this respect as they possess two energetically close, but optically and magnetically distinct, electronic states: the open-shell antiferromagnetic/paramagnetic and the closed-shell quinoidal diamagnetic states. While it has been shown that it is possible to statically induce one electronic ground state or the other by chemical design, the external dynamical control of these states in a rapid and reproducible manner still awaits experimental realization. Here, via quantum chemical calculations, we demonstrate that in-plane uniaxial strain of 2D covalently linked arrays of radical units leads to smooth and reversible conformational changes at the molecular scale that, in turn, induce robust transitions between the two kinds of electronic distributions. Our results pave a general route towards the external control, and thus technological exploitation, of molecular-scale electronic states in organic 2D materials.
Control of a programmed cell death pathway in Pseudomonas aeruginosa by an antiterminator
Authors: Peña Jennifer M. , Prezioso Samantha M. , McFarland Kirsty A. , Kambara Tracy K. , Ramsey Kathryn M. , Deighan Padraig , Dove Simon L.
Published: March 2021

In Pseudomonas aeruginosa the alp system encodes a programmed cell death pathway that is switched on in a subset of cells in response to DNA damage and is linked to the virulence of the organism. Here we show that the central regulator of this pathway, AlpA, exerts its effects by acting as an antiterminator rather than a transcription activator. In particular, we present evidence that AlpA positively regulates the alpBCDE cell lysis genes, as well as genes in a second newly identified target locus, by recognizing specific DNA sites within the promoter, then binding RNA polymerase directly and allowing it to bypass intrinsic terminators positioned downstream. AlpA thus functions in a mechanistically unusual manner to control the expression of virulence genes in this opportunistic pathogen.
Sea urchin-like microstructure pressure sensors with an ultra-broad range and high sensitivity
Authors: Wang Xiu-man , Tao Lu-qi , Yuan Min , Wang Ze-ping , Yu Jiabing , Xie Dingli , Luo Feng , Chen Xianping , Wong ChingPing
Published: March 2021

Sensitivity and pressure range are two significant parameters of pressure sensors. Existing pressure sensors have difficulty achieving both high sensitivity and a wide pressure range. Therefore, we propose a new pressure sensor with a ternary nanocomposite Fe2O3/C@SnO2. The sea urchin-like Fe2O3 structure promotes signal transduction and protects Fe2O3 needles from mechanical breaking, while the acetylene carbon black improves the conductivity of Fe2O3. Moreover, one part of the SnO2 nanoparticles adheres to the surfaces of Fe2O3 needles and forms Fe2O3/SnO2 heterostructures, while its other part disperses into the carbon layer to form SnO2@C structure. Collectively, the synergistic effects of the three structures (Fe2O3/C, Fe2O3/SnO2 and SnO2@C) improves on the limited pressure response range of a single structure. The experimental results demonstrate that the Fe2O3/C@SnO2 pressure sensor exhibits high sensitivity (680 kPa−1), fast response (10 ms), broad range (up to 150 kPa), and good reproducibility (over 3500 cycles under a pressure of 110 kPa), implying that the new pressure sensor has wide application prospects especially in wearable electronic devices and health monitoring.
Basalt derived from highly refractory mantle sources during early Izu-Bonin-Mariana arc development
Authors: Li He , Arculus Richard J. , Ishizuka Osamu , Hickey-Vargas Rosemary , Yogodzinski Gene M. , McCarthy Anders , Kusano Yuki , Brandl Philipp A. , Savov Ivan P. , Tepley Frank J. , Sun Weidong
Published: March 2021

The magmatic character of early subduction zone and arc development is unlike mature systems. Low-Ti-K tholeiitic basalts and boninites dominate the early Izu-Bonin-Mariana (IBM) system. Basalts recovered from the Amami Sankaku Basin (ASB), underlying and located west of the IBM’s oldest remnant arc, erupted at ~49 Ma. This was 3 million years after subduction inception (51-52 Ma) represented by forearc basalt (FAB), at the tipping point between FAB-boninite and typical arc magmatism. We show ASB basalts are low-Ti-K, aluminous spinel-bearing tholeiites, distinct compared to mid-ocean ridge (MOR), backarc basin, island arc or ocean island basalts. Their upper mantle source was hot, reduced, refractory peridotite, indicating prior melt extraction. ASB basalts transferred rapidly from pressures (~0.7-2 GPa) at the plagioclase-spinel peridotite facies boundary to the surface. Vestiges of a polybaric-polythermal mineralogy are preserved in this basalt, and were not obliterated during persistent recharge-mix-tap-fractionate regimes typical of MOR or mature arcs.
Leidenfrost droplet trampolining
Authors: Graeber Gustav , Regulagadda Kartik , Hodel Pascal , Küttel Christian , Landolf Dominic , Schutzius Thomas M. , Poulikakos Dimos
Published: March 2021

A liquid droplet dispensed over a sufficiently hot surface does not make contact but instead hovers on a cushion of its own self-generated vapor. Since its discovery in 1756, this so-called Leidenfrost effect has been intensively studied. Here we report a remarkable self-propulsion mechanism of Leidenfrost droplets against gravity, that we term Leidenfrost droplet trampolining. Leidenfrost droplets gently deposited on fully rigid surfaces experience self-induced spontaneous oscillations and start to gradually bounce from an initial resting altitude to increasing heights, thereby violating the traditionally accepted Leidenfrost equilibrium. We found that the continuously draining vapor cushion initiates and fuels Leidenfrost trampolining by inducing ripples on the droplet bottom surface, which translate into pressure oscillations and induce self-sustained periodic vertical droplet bouncing over a broad range of experimental conditions.
An engineered CRISPR-Cas12a variant and DNA-RNA hybrid guides enable robust and rapid COVID-19 testing
Authors: Ooi Kean Hean , Liu Mengying Mandy , Tay Jie Wen Douglas , Teo Seok Yee , Kaewsapsak Pornchai , Jin Shengyang , Lee Chun Kiat , Hou Jingwen , Maurer-Stroh Sebastian , Lin Weisi , Yan Benedict , Yan Gabriel , Gao Yong-Gui , Tan Meng How
Published: March 2021

Extensive testing is essential to break the transmission of SARS-CoV-2, which causes the ongoing COVID-19 pandemic. Here, we present a CRISPR-based diagnostic assay that is robust to viral genome mutations and temperature, produces results fast, can be applied directly on nasopharyngeal (NP) specimens without RNA purification, and incorporates a human internal control within the same reaction. Specifically, we show that the use of an engineered AsCas12a enzyme enables detection of wildtype and mutated SARS-CoV-2 and allows us to perform the detection step with loop-mediated isothermal amplification (LAMP) at 60-65 °C. We also find that the use of hybrid DNA-RNA guides increases the rate of reaction, enabling our test to be completed within 30 minutes. Utilizing clinical samples from 72 patients with COVID-19 infection and 57 healthy individuals, we demonstrate that our test exhibits a specificity and positive predictive value of 100% with a sensitivity of 50 and 1000 copies per reaction (or 2 and 40 copies per microliter) for purified RNA samples and unpurified NP specimens respectively.
Diel niche variation in mammals associated with expanded trait space
Authors: Cox D. T. C. , Gardner A. S. , Gaston K. J.
Published: March 2021

Mammalian life shows huge diversity, but most groups remain nocturnal in their activity pattern. A key unresolved question is whether mammal species that have diversified into different diel niches occupy unique regions of functional trait space. For 5,104 extant mammals we show here that daytime-active species (cathemeral or diurnal) evolved trait combinations along different gradients from those of nocturnal and crepuscular species. Hypervolumes of five major functional traits (body mass, litter size, diet, foraging strata, habitat breadth) reveal that 30% of diurnal trait space is unique, compared to 55% of nocturnal trait space. Almost half of trait space (44%) of species with apparently obligate diel niches is shared with those that can switch, suggesting that more species than currently realised may be somewhat flexible in their activity patterns. Increasingly, conservation measures have focused on protecting functionally unique species; for mammals, protecting functional distinctiveness requires a focus across diel niches.
Measurement of the neutron charge radius and the role of its constituents
Authors: Atac H. , Constantinou M. , Meziani Z.-E. , Paolone M. , Sparveris N.
Published: March 2021

The neutron is a cornerstone in our depiction of the visible universe. Despite the neutron zero-net electric charge, the asymmetric distribution of the positively- (up) and negatively-charged (down) quarks, a result of the complex quark-gluon dynamics, lead to a negative value for its squared charge radius, $$\langle {r}_{{\rm{n}}}^{2}\rangle$$
⟨

r

n

2

⟩
. The precise measurement of the neutron’s charge radius thus emerges as an essential part of unraveling its structure. Here we report on a $$\langle {r}_{{\rm{n}}}^{2}\rangle$$
⟨

r

n

2

⟩
measurement, based on the extraction of the neutron electric form factor, $${G}_{{\rm{E}}}^{{\rm{n}}}$$

G

E

n

, at low four-momentum transfer squared (Q2) by exploiting the long known connection between the N → Δ quadrupole transitions and the neutron electric form factor. Our result, $$\langle {r}_{{\rm{n}}}^{2}\rangle =-0.110\pm 0.008\,({{\rm{fm}}}^{2})$$
⟨

r

n

2

⟩
=
−
0.110
±
0.008

(

fm

2

)

, addresses long standing unresolved discrepancies in the $$\langle {r}_{{\rm{n}}}^{2}\rangle$$
⟨

r

n

2

⟩
determination. The dynamics of the strong nuclear force can be viewed through the precise picture of the neutron’s constituent distributions that result into the non-zero $$\langle {r}_{{\rm{n}}}^{2}\rangle$$
⟨

r

n

2

⟩
value.
Adjusting the energy of interfacial states in organic photovoltaics for maximum efficiency
Authors: Gasparini Nicola , Camargo Franco V. A. , Frühwald Stefan , Nagahara Tetsuhiko , Classen Andrej , Roland Steffen , Wadsworth Andrew , Gregoriou Vasilis G. , Chochos Christos L. , Neher Dieter , Salvador Michael , Baran Derya , McCulloch Iain , Görling Andreas , Lüer Larry , Cerullo Giulio , Brabec Christoph J.
Published: March 2021

A critical bottleneck for improving the performance of organic solar cells (OSC) is minimising non-radiative losses in the interfacial charge-transfer (CT) state via the formation of hybrid energetic states. This requires small energetic offsets often detrimental for high external quantum efficiency (EQE). Here, we obtain OSC with both non-radiative voltage losses (0.24 V) and photocurrent losses (EQE > 80%) simultaneously minimised. The interfacial CT states separate into free carriers with ≈40-ps time constant. We combine device and spectroscopic data to model the thermodynamics of charge separation and extraction, revealing that the relatively high performance of the devices arises from an optimal adjustment of the CT state energy, which determines how the available overall driving force is efficiently used to maximize both exciton splitting and charge separation. The model proposed is universal for donor:acceptor (D:A) with low driving forces and predicts which D:A will benefit from a morphology optimization for highly efficient OSC.
BioAIEgens derived from rosin: how does molecular motion affect their photophysical processes in solid state?
Authors: Cai Xu-Min , Lin Yuting , Li Ying , Chen Xinfei , Wang Zaiyu , Zhao Xueqian , Huang Shenlin , Zhao Zheng , Tang Ben Zhong
Published: March 2021

The exploration of artificial luminogens with bright emission has been fully developed with the advancement of synthetic chemistry. However, many of them face problems like weakened emission in the aggregated state as well as poor renewability and sustainability. Therefore, the development of renewable and sustainable luminogens with anti-quenching function in the solid state, as well as to unveil the key factors that influence their luminescence behavior become highly significant. Herein, a new class of natural rosin-derived luminogens with aggregation-induced emission property (AIEgens) have been facilely obtained with good biocompatibility and targeted organelle imaging capability as well as photochromic behavior in the solid state. Mechanistic study indicates that the introduction of the alicyclic moiety helps suppress the excited-state molecular motion to enhance the solid-state emission. The current work fundamentally elucidates the role of alicyclic moiety in luminogen design and practically demonstrates a new source to large-scalely obtain biocompatible AIEgens.
Molecular basis of V-ATPase inhibition by bafilomycin A1
Authors: Wang Rong , Wang Jin , Hassan Abdirahman , Lee Chia-Hsueh , Xie Xiao-Song , Li Xiaochun
Published: March 2021

Pharmacological inhibition of vacuolar-type H+-ATPase (V-ATPase) by its specific inhibitor can abrogate tumor metastasis, prevent autophagy, and reduce cellular signaling responses. Bafilomycin A1, a member of macrolide antibiotics and an autophagy inhibitor, serves as a specific and potent V-ATPases inhibitor. Although there are many V-ATPase structures reported, the molecular basis of specific inhibitors on V-ATPase remains unknown. Here, we report the cryo-EM structure of bafilomycin A1 bound intact bovine V-ATPase at an overall resolution of 3.6-Å. The structure reveals six bafilomycin A1 molecules bound to the c-ring. One bafilomycin A1 molecule engages with two c subunits and disrupts the interactions between the c-ring and subunit a, thereby preventing proton translocation. Structural and sequence analyses demonstrate that the bafilomycin A1-binding residues are conserved in yeast and mammalian species and the 7’-hydroxyl group of bafilomycin A1 acts as a unique feature recognized by subunit c.
Author Correction: SciBet as a portable and fast single cell type identifier
Authors: Li Chenwei , Liu Baolin , Kang Boxi , Liu Zedao , Liu Yedan , Chen Changya , Ren Xianwen , Zhang Zemin
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22248-3
Publisher Correction: Southern Ocean in-situ temperature trends over 25 years emerge from interannual variability
Authors: Auger Matthis , Morrow Rosemary , Kestenare Elodie , Sallée Jean-Baptiste , Cowley Rebecca
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22318-6
The biofilm matrix scaffold of Pseudomonas aeruginosa contains G-quadruplex extracellular DNA structures
Authors: Seviour Thomas , Winnerdy Fernaldo Richtia , Wong Lan Li , Shi Xiangyan , Mugunthan Sudarsan , Foo Yong Hwee , Castaing Remi , Adav Sunil S. , Subramoni Sujatha , Kohli Gurjeet Singh , Shewan Heather M. , Stokes Jason R. , Rice Scott A. , Phan Anh Tuân , Kjelleberg Staffan
Published: March 2021

Extracellular DNA, or eDNA, is recognised as a critical biofilm component; however, it is not understood how it forms networked matrix structures. Here, we isolate eDNA from static-culture Pseudomonas aeruginosa biofilms using ionic liquids to preserve its biophysical signatures of fluid viscoelasticity and the temperature dependency of DNA transitions. We describe a loss of eDNA network structure as resulting from a change in nucleic acid conformation, and propose that its ability to form viscoelastic structures is key to its role in building biofilm matrices. Solid-state analysis of isolated eDNA, as a proxy for eDNA structure in biofilms, reveals non-canonical Hoogsteen base pairs, triads or tetrads involving thymine or uracil, and guanine, suggesting that the eDNA forms G-quadruplex structures. These are less abundant in chromosomal DNA and disappear when eDNA undergoes conformation transition. We verify the occurrence of G-quadruplex structures in the extracellular matrix of intact static and flow-cell biofilms of P. aeruginosa, as displayed by the matrix to G-quadruplex-specific antibody binding, and validate the loss of G-quadruplex structures in vivo to occur coincident with the disappearance of eDNA fibres. Given their stability, understanding how extracellular G-quadruplex structures form will elucidate how P. aeruginosa eDNA builds viscoelastic networks, which are a foundational biofilm property.
Extracellular amoebal-vesicles: potential transmission vehicles for respiratory viruses
Authors: Dey Rafik , Folkins Melanie A. , Ashbolt Nicholas J.
Published: March 2021

Human respiratory syncytial virus (RSV) is a major cause of acute respiratory tract infections in children and immunocompromised adults worldwide. Here we report that amoebae-release respirable-sized vesicles containing high concentrations of infectious RSV that persisted for the duration of the experiment. Given the ubiquity of amoebae in moist environments, our results suggest that extracellular amoebal-vesicles could contribute to the environmental persistence of respiratory viruses, including potential resistance to disinfection processes and thereby offering novel pathways for viral dissemination and transmission.