bluuebunny/crossref_metadata_2025 huggingface dataset:
Seeing the value of experiential knowledge through COVID-19
Authors: Atkinson Sarah , Bradby Hannah , Gadebusch Bondio Mariacarla , Hallberg Anna , Macnaugthon Jane , Söderfeldt Ylva
Published: June 2021

Seeing the entwinement of social and epistemic challenges through COVID, we discuss the perils of simplistic appeals to ‘follow the science’. A hardened scientism risks excarbating social conflict and fueling conspiracy beliefs. Instead, we see an opportunity to devise more inclusive medical knowledge practices through endorsing experiential knowledge alongside traditional evidence types.
Detection of Vestibular Schwannoma on Triple-parametric Magnetic Resonance Images Using Convolutional Neural Networks
Authors: Huang Tzu-Hsuan , Lee Wei-Kai , Wu Chih-Chun , Lee Cheng-Chia , Lu Chia-Feng , Yang Huai-Che , Lin Chun-Yi , Chung Wen-Yuh , Wang Po-Shan , Chen Yen-Ling , Wu Hsiu-Mei , Guo Wan-You , Wu Yu-Te
Published: June 2021

Purpose

The first step in typical treatment of vestibular schwannoma (VS) is to localize the tumor region, which is time-consuming and subjective because it relies on repeatedly reviewing different parametric magnetic resonance (MR) images. A reliable, automatic VS detection method can streamline the process.

Methods

A convolutional neural network architecture, namely YOLO-v2 with a residual network as a backbone, was used to detect VS tumors from MR images. To heighten performance, T1-weighted–contrast-enhanced, T2-weighted, and T1-weighted images were combined into triple-channel images for feature learning. The triple-channel images were cropped into three sizes to serve as input images of YOLO-v2. The VS detection effectiveness levels were evaluated for two backbone residual networks that downsampled the inputs by 16 and 32.

Results

The results demonstrated the VS detection capability of YOLO-v2 with a residual network as a backbone model. The average precision was 0.7953 for a model with 416 × 416-pixel input images and 16 instances of downsampling, when both the thresholds of confidence score and intersection-over-union were set to 0.5. In addition, under an appropriate threshold of confidence score, a high average precision, namely 0.8171, was attained by using a model with 448 × 448-pixel input images and 16 instances of downsampling.

Conclusion

We demonstrated successful VS tumor detection by using a YOLO-v2 with a residual network as a backbone model on resized triple-parametric MR images. The results indicated the influence of image size, downsampling strategy, and confidence score threshold on VS tumor detection.
Pediatric drug‐induced sleep endoscopy: An updated review of the literature
Authors: Arganbright Jill M. , Lee Jason C. , Weatherly Robert A.
Published: June 2021

The field of drug‐induced sleep endoscopy (DISE) has grown considerably over the last 10∼15 years, to now include its use in pediatric patients. In this review article, we outline our approach to the use of this technology in Children with Airway Obstruction, most specifically in the management of children with airway obstruction and known or suspected adenotonsillar enlargement.
Reading Wittgenstein's Tractatus
Authors: Engelmann Mauro Luiz
Published: June 2021

This Element presents a concise and accessible view of the central arguments of Wittgenstein's Tractatus Logico-Philosophicus. Starting from the difficulties found in historical and current debates, drawing on the background of Russell's philosophy, and grounded in the ladder structure expressed in the numbering system of the book, this Element presents the central arguments of the Tractatus in three lines of thought. The first concerns the role of the so-called 'ontology' and its relationship to the method of the Tractatus and its logical symbolism, which displays the formal essence of language and world. The second deals with the symbolic unity of language and its role in the 'ladder structure' and explains how and why the book is not self-defeating. The third elucidates Wittgenstein's claim to have solved in essentials all philosophical problems, whose very formulation, he says, rests on misunderstandings.
Extending the theory of planned behaviour to explore the plastic waste minimisation intention of Hong Kong citizens
Authors: So Winnie Wing Mui , Cheng Irene Nga Yee , Cheung Lewis Ting On , Chen Yu , Chow Stephen Cheuk Fai , Fok Lincoln , Lo Sing Kai
Published: June 2021

This study aimed to explore the relationships between situational and psychological factors and Hong Kong citizens’ plastic waste management (PWM) intentions based on an extended theory of planned behaviour model with situational factors. A total of 996 Hong Kong permanent residents were surveyed, and data were analysed using structural equation modelling. The results revealed that situational factors had a direct and positive effect on PWM intention, but also affected PWM intention indirectly through their significant effects on attitude and perceived behavioural control regarding PWM. The implications for environmental education and policy are discussed.
Potential Benefit of Add-on Δ9-Tetrahydrocannabinol in Pediatric Drug-Resistant Epilepsy: A Case Series
Authors: Nowicki Magda , Bourgeois-Tardif Sandrine , Diaz Patrick L. , Hebert Francois Olivier , Sanon Nathalie T. , Champagne Pierre-Olivier , Major Philippe , Sell Erick , Bitton Jonathan , Lewis Evan , Weil Alexander G.
Published: June 2021

We present five cases of pediatric drug-resistant epilepsy (DRE) that failed management using high cannabidiol (CBD) doses, but had significant reduction in seizure frequency with reintroduction or increasing doses of tetrahydrocannabinol (THC). There is growing evidence supporting the use of whole-plant CBD-rich extracts (containing THC and other cannabinoids) in the treatment of pediatric DRE. Based on our experiences and reports in the literature, we propose that, in patients who fail management with an initial trial of high-dose CBD-focused therapy, there may be a role for add-on THC-focused formulations.
Poisson CNN: Convolutional neural networks for the solution of the Poisson equation on a Cartesian mesh
Authors: Özbay Ali Girayhan , Hamzehloo Arash , Laizet Sylvain , Tzirakis Panagiotis , Rizos Georgios , Schuller Björn
Published: June 2021

The Poisson equation is commonly encountered in engineering, for instance, in computational fluid dynamics (CFD) where it is needed to compute corrections to the pressure field to ensure the incompressibility of the velocity field. In the present work, we propose a novel fully convolutional neural network (CNN) architecture to infer the solution of the Poisson equation on a 2D Cartesian grid with different resolutions given the right-hand side term, arbitrary boundary conditions, and grid parameters. It provides unprecedented versatility for a CNN approach dealing with partial differential equations. The boundary conditions are handled using a novel approach by decomposing the original Poisson problem into a homogeneous Poisson problem plus four inhomogeneous Laplace subproblems. The model is trained using a novel loss function approximating the continuous

$ {L}^p $

norm between the prediction and the target. Even when predicting on grids denser than previously encountered, our model demonstrates encouraging capacity to reproduce the correct solution profile. The proposed model, which outperforms well-known neural network models, can be included in a CFD solver to help with solving the Poisson equation. Analytical test cases indicate that our CNN architecture is capable of predicting the correct solution of a Poisson problem with mean percentage errors below 10%, an improvement by comparison to the first step of conventional iterative methods. Predictions from our model, used as the initial guess to iterative algorithms like Multigrid, can reduce the root mean square error after a single iteration by more than 90% compared to a zero initial guess.
Interpersonal Racism in the Healthcare Workplace: Examining Insidious Collegial Interactions Reinforcing Structural Racism
Authors: Rattani Abbas
Published: June 2021

The traumatic stress experienced by our black healthcare colleagues is often overlooked. This work contextualizes workplace racism, identifies some interpersonal barriers limiting anti-racist growth, and calls for solidarity.
Empire in Fragments: Transatlantic News and Print Media in the Iberian World, ca. 1600–40
Authors: Weststeijn Arthur
Published: June 2021

This article shows how the rise of printed news media during the opening decades of the seventeenth century fomented and fragmented authority in the polycentric Spanish Habsburg empire. Analyzing the making, dissemination, and reception of transatlantic news from Madrid to Mexico and from Lisbon to Lima, the article explores how the influx of fragments of unverifiable information from overseas undermined the possibility of complete knowledge. While the Spanish Crown exploited news media to create a sense of a unified imperial space, the dynamics of distance resulted in uncertainty and the spread of conflicting narratives that fractured central control.
Prosodic prominence in a stressless language: An acoustic investigation of Indonesian
Authors: ATHANASOPOULOU ANGELIKI , VOGEL IRENE , PINCUS NADYA
Published: June 2021

Although it has been proposed that all languages may have some lexical stress property, recent studies of (Standard) Indonesian have concluded, based primarily on perception, that lexical stress is not present in this language. While it is philosophically problematic to prove the non-existence of a phenomenon, we examine data from a large-scale production study for both direct and indirect evidence of stress, contributing to the growing body of literature in this field. In the first case, evidence is sought that indicates that a particular syllable in a word exhibits acoustic properties typically associated with prominence (i.e. fundamental frequency (f0), duration, intensity, vowel quality). In the second case, evidence of enhancement of these properties on a particular syllable under focus is sought, for a more abstract stress property that is not overtly manifested at the word level. Although we find no evidence of lexical prominence, we observe acoustic patterns consistent with a higher level prominence corresponding to focus, manifested by strong (Intonational Phrase) boundary properties. Overall, our findings reveal that there is strong support for a class of languages lacking lexical stress, and in the absence of a stressed syllable to enhance, focus may be manifested prosodically as boundary properties.
Childhood externalizing, internalizing and comorbid problems: distinguishing young adults who think about suicide from those who attempt suicide
Authors: Commisso Melissa , Temcheff Caroline , Orri Massimiliano , Poirier Martine , Lau Marianne , Côté Sylvana , Vitaro Frank , Turecki Gustavo , Tremblay Richard , Geoffroy Marie-Claude
Published: June 2021

Background

While childhood externalizing, internalizing and comorbid problems have been associated with suicidal risk, little is known about their specific associations with suicidal ideation and attempts. We examined associations between childhood externalizing, internalizing and comorbid problems and suicidal ideation (without attempts) and attempts by early adulthood, in males and females.

Method

Participants were from the Quebec Longitudinal Study of Kindergarten Children, a population-based study of kindergarteners in Quebec from 1986 to 1988 and followed-up until 2005. We captured the co-development of teacher-rated externalizing and internalizing problems at age 6–12 using multitrajectories. Using the Diagnostic Interview Schedule administered at age 15 and 22, we identified individuals (1) who never experienced suicidal ideation/attempts, (2) experienced suicidal ideation but never attempted suicide and (3) attempted suicide.

Results

The identified profiles were no/low problems (45%), externalizing (29%), internalizing (11%) and comorbid problems (13%). After adjusting for socioeconomic and familial characteristics, children with externalizing (OR 2.00, CI 1.39–2.88), internalizing (OR 2.34, CI 1.51–3.64) and comorbid (OR 3.29, CI 2.05–5.29) problems were at higher risk of attempting suicide (v. non-suicidal) by age 22 than those with low/no problems. Females with comorbid problems were at higher risk of attempting suicide than females with one problem. Childhood problems were not associated with suicidal ideation. Externalizing (OR 2.01, CI 1.29–3.12) and comorbid problems (OR 2.28, CI 1.29–4.03) distinguished individuals who attempted suicide from those who thought about suicide without attempting.

Conclusion

Childhood externalizing problems alone or combined with internalizing problems were associated with suicide attempts, but not ideation (without attempts), suggesting that these problems confer a specific risk for suicide attempts.
From “Leader to Pariah”? On the Dutch Restitutions Committee and the inclusion of the public interest in assessing Nazi-spoliated art claims
Authors: Oost Tabitha I.
Published: June 2021

This article considers the recent and vigorous critique of the Dutch restitution policy on Nazi-looted art in connection with the inclusion of what has been termed the “public interest” in the applicable substantive assessment framework. This assessment framework is entirely based on morally induced policy rules, and it allows the Dutch Restitutions Committee to advise on requests for restitution based on a weighing of interests, including the significance of the work to a museum or public art collection. Although one might question the appropriateness of such interests in a framework designed to remedy historic injustices, it remains to be seen whether this critique is entirely justified. Recent recommendations issued by the Dutch Restitutions Committee indicate that it takes a generous, rather than strict, approach when dealing with requests for restitution. All in all, it seems that both institutional and substantive vulnerability are inevitable if one embarks on a morally induced framework based on mere policy rules rather than legal rules.
Social Identity and Dental Modification at the Postclassic Maya Urban Centre of Mayapan
Authors: Serafin Stanley , Masson Marilyn A. , Peraza Lope Carlos , Kennett Douglas J. , George Richard J.
Published: June 2021

Dental modification represents one interesting aspect of corporeal adornment in human history that directly reflects personal social identity. Tooth filing choices distinguished certain individuals at the urban, Maya political capital of Mayapan from 1150 to 1450ad, along with cranial modification, nose and ear piercings, tattoos and body paint. Here we examine how filing teeth, considered a beautification practice for women at Spanish Contact in the sixteenth century, is distributed across a skeletal sample of males, females, elites and commoners in this city. We evaluate the normative claim of the Colonial period and determine that while predominantly females filed their teeth, most women chose not to. Sculptural art further reveals that male personages associated with the city's feathered serpent priesthood exhibited filed teeth, and we explore the symbolic meaning of filed tooth shape. Assessing the practice in terms of associated archaeological contexts, chronology and bone chemistry reveals that it did not correlate with social class, dietary differences, or birthplace. Residents of Mayapan, a densely inhabited, multi-ethnic city of 20,000, engaged with multiple material expressions of belonging to intersecting imagined communities that crosscut competing influences of polity, city, hometown and family scale identity. Tooth filing reflects identities at the individual or family scale.
Government Targeting of Refugees in the Midst of Epidemics
Authors: Braithwaite Alex , Frith Michael , Savun Burcu , Ghosn Faten
Published: June 2021

We investigate how the outbreak of epidemics can affect host governments’ targeting of refugees and violation of their physical integrity rights. We argue that governments target repression against refugees for two reasons. First, refugees are easily scapegoated for the arrival of epidemics at a time when governments are looking to shift the blame for their own poor performance. Second, crises provide circumstances for governments to engage in opportunistic repression to further their goal of coercing existing refugees to depart and deterring new refugees from arriving. Drawing upon a global dataset of countries for the years 1996 to 2015, we demonstrate that epidemic outbreaks do indeed increase the likelihood and scale of government repression targeting refugee populations. These effects are especially pronounced in countries with higher proportions of refugees hosted and in less democratic countries. Identification of this potential for government repression of refugees during epidemics is important in light of the grave scale of the ongoing COVID-19 pandemic. Our findings suggest the international community should be vigilant for signs of governments’ mistreatment of vulnerable refugee populations to shift focus away from their own poor handling of crises such as the ongoing COVID-19 pandemic and opportunistically advance their goal of reducing the numbers of refugees hosted locally.
Zur Situation von Grundschülerinnen und Grundschülern mit sonderpädagogischem Förderbedarf im Bereich emotionale und soziale Entwicklung im inklusiven Unterricht
Authors: Blumenthal Yvonne , Blumenthal Stefan
Published: June 2021

Zusammenfassung. Die vorliegende Studie untersucht im Längsschnitt über zwei Testzeitpunkte, inwiefern sich inklusiv beschulte Grundschülerinnen und -schüler mit einem Förderbedarf emotionale und soziale Entwicklung (SPF esE) in Hinblick auf die Einschätzung des Klassenklimas, des Gefühl des Angenommenseins durch die Lehrkraft (aus Selbstsicht) und die soziale Partizipation (aus Selbst- und Peersicht) von den Peers ihrer Klasse ohne SPF esE unterscheiden. Die Erhebung fand an insgesamt 999 Kindern, darunter N = 66 mit SPF esE, zum Ende der dritten und vierten Klassenstufe mit ausgewählten Skalen des Fragebogens zur Erfassung der emotionalen und sozialen Schulerfahrungen (FEESS 3–4, Rauer & Schuck, 2003 ) sowie einer soziometrischen Nominierung statt. Neben den Analysen des Effekts des SPF esE wurden die Einflüsse der Ausprägungen einzelner internalisierender sowie externalisierender Problemskalen des Strengths and Difficulties Questionnaire (SDQ; Goodman, 2001 ) differenziert betrachtet. Zusammenfassend zeigt sich, dass der SPF esE einen signifikanten, negativen Einfluss auf alle untersuchten abhängigen Variablen, bei durchgängig hohen Effektstärken, hatte. Zwar konnten positive Entwicklungen für diese Kinder in Hinblick auf die selbst wahrgenommene soziale Integration und des Gefühls des Angenommenseins durch die Lehrkraft über die Zeit abgebildet werden, die Effektstärken fallen jedoch klein aus. Differenzierte Analysen verdeutlichen, dass sich bei höheren Ausprägungen externalisierender Verhaltensprobleme sowie höheren Ausprägungen von Peerproblemen (internalisierende Skala) die Einschätzung des Klassenklimas, der Akzeptanz durch die Peers und die Lehrkraft reduzierte sowie eine höhere Ablehnung durch die Peers bestand. Internalisierende Verhaltensprobleme im Sinne emotionaler Probleme hatten keinen bedeutsamen Einfluss auf die Ausprägung der hier untersuchten abhängigen Variablen. Vereinzelt waren signifikante Interaktionen der Problemskalen mit der Zeit festzuhalten (positiver Effekt von emotionalen Problemen auf den Ablehnungsstatus, positive Effekte von externalisierenden Verhaltensproblemen auf das Gefühl des Angenommenseins und auf den Wahlstatus), die Effektstärken waren jedoch gering.
The Roles of the Magnetopause and Plasmapause in Storm‐Time ULF Wave Power Enhancements
Authors: Sandhu J. K. , Rae I. J. , Staples F. A. , Hartley D. P. , Walach M.‐T. , Elsden T. , Murphy K. R.
Published: June 2021

Ultra low frequency (ULF) waves play a crucial role in transporting and coupling energy within the magnetosphere. During geomagnetic storms, dayside magnetospheric ULF wave power is highly variable with strong enhancements that are dominated by elevated solar wind driving. However, the radial distribution of ULF wave power is complex ‐ controlled interdependently by external solar wind driving and the internal magnetospheric structuring. We conducted a statistical analysis of observed storm‐time ULF wave power from the Van Allen Probes spacecraft within 2012–2016. Focusing on the dayside (06 < magnetic local time ≤ 15), we observe large enhancements across 3 < L < 6 and a steep L dependence during the main phase. We consider how accounting for concurrent magnetopause and plasmapause locations may reduce statistical variability and improve parameterization of spatial trends over and above using the L value. Ordering storm time ULF wave power by L provides the weakest dependences from those considered, whereas ordering by distance from the magnetopause is more effective. We also explore dependences on local plasma density and find that spatially localized ULF wave power enhancements are confined within high density patches in the afternoon sector (likely plasmaspheric plumes). The results have critical implications for empirical models of ULF wave power and radial diffusion coefficients. We highlight the necessity of improved characterization of the highly distorted storm‐time cold plasma density distribution, in order to more accurately predict ULF wave power.
Disruption of nucleocytoplasmic trafficking as a cellular senescence driver
Authors: Park Ji-Hwan , Ryu Sung Jin , Kim Byung Ju , Cho Hyun-Ji , Park Chi Hyun , Choi Hyo Jei Claudia , Jang Eun-Jin , Yang Eun Jae , Hwang Jeong-A , Woo Seung-Hwa , Lee Jun Hyung , Park Ji Hwan , Choi Kyung-Mi , Kwon Young-Yon , Lee Cheol-Koo , Park Joon Tae , Cho Sung Chun , Lee Yun-Il , Lee Sung Bae , Han Jeong A. , Cho Kyung A , Kim Min-Sik , Hwang Daehee , Lee Young-Sam , Park Sang Chul
Published: June 2021

Senescent cells exhibit a reduced response to intrinsic and extrinsic stimuli. This diminished reaction may be explained by the disrupted transmission of nuclear signals. However, this hypothesis requires more evidence before it can be accepted as a mechanism of cellular senescence. A proteomic analysis of the cytoplasmic and nuclear fractions obtained from young and senescent cells revealed disruption of nucleocytoplasmic trafficking (NCT) as an essential feature of replicative senescence (RS) at the global level. Blocking NCT either chemically or genetically induced the acquisition of an RS-like senescence phenotype, named nuclear barrier-induced senescence (NBIS). A transcriptome analysis revealed that, among various types of cellular senescence, NBIS exhibited a gene expression pattern most similar to that of RS. Core proteomic and transcriptomic patterns common to both RS and NBIS included upregulation of the endocytosis-lysosome network and downregulation of NCT in senescent cells, patterns also observed in an aging yeast model. These results imply coordinated aging-dependent reduction in the transmission of extrinsic signals to the nucleus and in the nucleus-to-cytoplasm supply of proteins/RNAs. We further showed that the aging-associated decrease in Sp1 transcription factor expression was critical for the downregulation of NCT. Our results suggest that NBIS is a modality of cellular senescence that may represent the nature of physiological aging in eukaryotes.
Effect of the traditional Chinese medicine Pinggan-Qianyang decoction on SIRT1–PTEN signaling in vascular aging in spontaneously hypertensive rats
Authors: Cui Zhang , Jiamei Yao , Yushu Yang , Xia Fang , Haiyan Yang , Zhang Dan , Qiong Chen , Guangwei Zhong
Published: June 2021

Age-related functional decline is a physiological phenomenon that occurs in all organ systems. However, the acceleration and early occurrence of this process are observed in cardiovascular pathologies, including hypertension. This study aimed to investigate SIRT1–PTEN signaling in aortic tissue from spontaneously hypertensive rats (SHRs) and changes in SIRT1 and PTEN expression following treatment with Pinggan-Qianyang decoction (PGQYD) and explore the mechanism involved in the treatment of hypertensive vascular aging with traditional Chinese medicine. In this study, we used two rat models: spontaneously hypertensive rats (SHRs) at 14 and 64 weeks of age and WKY rats at 64 weeks of age. The degree of irritability and rotation tolerance time were evaluated to determine the effects of PGQYD on animal behavior. The morphology of the thoracic aorta was examined by hematoxylin-eosin (HE) and Masson staining and electron microscopy. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and superoxide dismutase (SOD) and anti-superoxide anion content were detected. Senescence-associated β-galactosidase (SA-β-Gal) staining was used to observe the thoracic aorta during vascular aging. RT-qPCR, immunofluorescence, and Western blot analysis were performed to detect changes in the mRNA and protein expression of p53, p21, SIRT1, and PTEN in rat aortic tissues. Behavioral tests and histological and morphological analyses showed the remarkable amelioration of vascular aging after PGQYD treatment compared with that in the older SHRs. Moreover, PGQYD significantly decreased vascular aging in SHRs, as indicated by reduced SA-β-Gal staining, NADPH oxidase activity, and p53 and p21 expression, and increased anti-superoxide anion and SOD content. Furthermore, PGQYD increased SIRT1 and PTEN expression, but the downregulated expression of SIRT1 induced by a SIRT1 inhibitor abolished the PGQYD-induced antiaging effects on gene expression and antioxidant activity and enhanced PTEN expression. PGQYD could ameliorate vascular aging effects in SHRs, which may have been mediated via the regulation of SIRT1–PTEN signaling in aortic tissue.
Dinosaur biodiversity declined well before the asteroid impact, influenced by ecological and environmental pressures
Authors: Condamine Fabien L. , Guinot Guillaume , Benton Michael J. , Currie Philip J.
Published: June 2021

The question why non-avian dinosaurs went extinct 66 million years ago (Ma) remains unresolved because of the coarseness of the fossil record. A sudden extinction caused by an asteroid is the most accepted hypothesis but it is debated whether dinosaurs were in decline or not before the impact. We analyse the speciation-extinction dynamics for six key dinosaur families, and find a decline across dinosaurs, where diversification shifted to a declining-diversity pattern ~76 Ma. We investigate the influence of ecological and physical factors, and find that the decline of dinosaurs was likely driven by global climate cooling and herbivorous diversity drop. The latter is likely due to hadrosaurs outcompeting other herbivores. We also estimate that extinction risk is related to species age during the decline, suggesting a lack of evolutionary novelty or adaptation to changing environments. These results support an environmentally driven decline of non-avian dinosaurs well before the asteroid impact.
Predicting lapses of attention with sleep-like slow waves
Authors: Andrillon Thomas , Burns Angus , Mackay Teigane , Windt Jennifer , Tsuchiya Naotsugu
Published: June 2021

Attentional lapses occur commonly and are associated with mind wandering, where focus is turned to thoughts unrelated to ongoing tasks and environmental demands, or mind blanking, where the stream of consciousness itself comes to a halt. To understand the neural mechanisms underlying attentional lapses, we studied the behaviour, subjective experience and neural activity of healthy participants performing a task. Random interruptions prompted participants to indicate their mental states as task-focused, mind-wandering or mind-blanking. Using high-density electroencephalography, we report here that spatially and temporally localized slow waves, a pattern of neural activity characteristic of the transition toward sleep, accompany behavioural markers of lapses and preceded reports of mind wandering and mind blanking. The location of slow waves could distinguish between sluggish and impulsive behaviours, and between mind wandering and mind blanking. Our results suggest attentional lapses share a common physiological origin: the emergence of local sleep-like activity within the awake brain.
Self-assembly of N-heterocyclic carbenes on Au(111)
Authors: Inayeh Alex , Groome Ryan R. K. , Singh Ishwar , Veinot Alex J. , de Lima Felipe Crasto , Miwa Roberto H. , Crudden Cathleen M. , McLean Alastair B.
Published: June 2021

Although the self-assembly of organic ligands on gold has been dominated by sulfur-based ligands for decades, a new ligand class, N-heterocyclic carbenes (NHCs), has appeared as an interesting alternative. However, fundamental questions surrounding self-assembly of this new ligand remain unanswered. Herein, we describe the effect of NHC structure, surface coverage, and substrate temperature on mobility, thermal stability, NHC surface geometry, and self-assembly. Analysis of NHC adsorption and self-assembly by scanning tunneling microscopy and density functional theory have revealed the importance of NHC-surface interactions and attractive NHC-NHC interactions on NHC monolayer structures. A remarkable way these interactions manifest is the need for a threshold NHC surface coverage to produce upright, adatom-mediated adsorption motifs with low surface diffusion. NHC wingtip structure is also critical, with primary substituents leading to the formation of flat-lying NHC2Au complexes, which have high mobility when isolated, but self-assemble into stable ordered lattices at higher surface concentrations. These and other studies of NHC surface chemistry will be crucial for the success of these next-generation monolayers.
Allosteric drug transport mechanism of multidrug transporter AcrB
Authors: Tam Heng-Keat , Foong Wuen Ee , Oswald Christine , Herrmann Andrea , Zeng Hui , Pos Klaas M.
Published: June 2021

Gram-negative bacteria maintain an intrinsic resistance mechanism against entry of noxious compounds by utilizing highly efficient efflux pumps. The E. coli AcrAB-TolC drug efflux pump contains the inner membrane H+/drug antiporter AcrB comprising three functionally interdependent protomers, cycling consecutively through the loose (L), tight (T) and open (O) state during cooperative catalysis. Here, we present 13 X-ray structures of AcrB in intermediate states of the transport cycle. Structure-based mutational analysis combined with drug susceptibility assays indicate that drugs are guided through dedicated transport channels toward the drug binding pockets. A co-structure obtained in the combined presence of erythromycin, linezolid, oxacillin and fusidic acid shows binding of fusidic acid deeply inside the T protomer transmembrane domain. Thiol cross-link substrate protection assays indicate that this transmembrane domain-binding site can also accommodate oxacillin or novobiocin but not erythromycin or linezolid. AcrB-mediated drug transport is suggested to be allosterically modulated in presence of multiple drugs.
Fast and strong amplifiers of natural selection
Authors: Tkadlec Josef , Pavlogiannis Andreas , Chatterjee Krishnendu , Nowak Martin A.
Published: June 2021

Selection and random drift determine the probability that novel mutations fixate in a population. Population structure is known to affect the dynamics of the evolutionary process. Amplifiers of selection are population structures that increase the fixation probability of beneficial mutants compared to well-mixed populations. Over the past 15 years, extensive research has produced remarkable structures called strong amplifiers which guarantee that every beneficial mutation fixates with high probability. But strong amplification has come at the cost of considerably delaying the fixation event, which can slow down the overall rate of evolution. However, the precise relationship between fixation probability and time has remained elusive. Here we characterize the slowdown effect of strong amplification. First, we prove that all strong amplifiers must delay the fixation event at least to some extent. Second, we construct strong amplifiers that delay the fixation event only marginally as compared to the well-mixed populations. Our results thus establish a tight relationship between fixation probability and time: Strong amplification always comes at a cost of a slowdown, but more than a marginal slowdown is not needed.
Resolution of tissue signatures of therapy response in patients with recurrent GBM treated with neoadjuvant anti-PD1
Authors: Lu Yue , Ng Alphonsus H. C. , Chow Frances E. , Everson Richard G. , Helmink Beth A. , Tetzlaff Michael T. , Thakur Rohit , Wargo Jennifer A. , Cloughesy Timothy F. , Prins Robert M. , Heath James R.
Published: June 2021

The response of patients with recurrent glioblastoma multiforme to neoadjuvant immune checkpoint blockade has been challenging to interpret due to the inter-patient and intra-tumor heterogeneity. We report on a comparative analysis of tumor tissues collected from patients with recurrent glioblastoma and high-risk melanoma, both treated with neoadjuvant checkpoint blockade. We develop a framework that uses multiplex spatial protein profiling, machine learning-based image analysis, and data-driven computational models to investigate the pathophysiological and molecular factors within the tumor microenvironment that influence treatment response. Using melanoma to guide the interpretation of glioblastoma analyses, we interrogate the protein expression in microscopic compartments of tumors, and determine the correlates of cytotoxic CD8+ T cells, tumor growth, treatment response, and immune cell-cell interaction. This work reveals similarities shared between glioblastoma and melanoma, immunosuppressive factors that are unique to the glioblastoma microenvironment, and potential co-targets for enhancing the efficacy of neoadjuvant immune checkpoint blockade.
Ferroelectric-tuned van der Waals heterojunction with band alignment evolution
Authors: Chen Yan , Wang Xudong , Huang Le , Wang Xiaoting , Jiang Wei , Wang Zhen , Wang Peng , Wu Binmin , Lin Tie , Shen Hong , Wei Zhongming , Hu Weida , Meng Xiangjian , Chu Junhao , Wang Jianlu
Published: June 2021

Van der Waals integration with abundant two-dimensional materials provides a broad basis for assembling functional devices. In a specific van der Waals heterojunction, the band alignment engineering is crucial and feasible to realize high performance and multifunctionality. Here, we design a ferroelectric-tuned van der Waals heterojunction device structure by integrating a GeSe/MoS2 VHJ and poly (vinylidene fluoride-trifluoroethylene)-based ferroelectric polymer. An ultrahigh electric field derived from the ferroelectric polarization can effectively modulate the band alignment of the GeSe/MoS2 heterojunction. Band alignment transition of the heterojunction from type II to type I is demonstrated. The combination of anisotropic GeSe with MoS2 realizes a high-performance polarization-sensitive photodetector exhibiting low dark current of approximately 1.5 pA, quick response of 14 μs, and high detectivity of 4.7 × 1012 Jones. Dichroism ratios are also enhanced by ferroelectric polarization in a broad spectrum from visible to near-infrared. The ferroelectric-tuned GeSe/MoS2 van der Waals heterojunction has great potential for multifunctional detection applications in sophisticated light information sensing. More profoundly, the ferroelectric-tuned van der Waals heterojunction structure provides a valid band-engineering approach to creating versatile devices.
Structural basis of DNA synthesis opposite 8-oxoguanine by human PrimPol primase-polymerase
Authors: Rechkoblit Olga , Johnson Robert E. , Gupta Yogesh K. , Prakash Louise , Prakash Satya , Aggarwal Aneel K.
Published: June 2021

PrimPol is a human DNA polymerase-primase that localizes to mitochondria and nucleus and bypasses the major oxidative lesion 7,8-dihydro-8-oxoguanine (oxoG) via translesion synthesis, in mostly error-free manner. We present structures of PrimPol insertion complexes with a DNA template-primer and correct dCTP or erroneous dATP opposite the lesion, as well as extension complexes with C or A as a 3′−terminal primer base. We show that during the insertion of C and extension from it, the active site is unperturbed, reflecting the readiness of PrimPol to accommodate oxoG(anti). The misinsertion of A opposite oxoG(syn) also does not alter the active site, and is likely less favorable due to lower thermodynamic stability of the oxoG(syn)•A base-pair. During the extension step, oxoG(syn) induces an opening of its base-pair with A or misalignment of the 3′-A primer terminus. Together, the structures show how PrimPol accurately synthesizes DNA opposite oxidatively damaged DNA in human cells.
Design of carbon supports for metal-catalyzed acetylene hydrochlorination
Authors: Kaiser Selina K. , Surin Ivan , Amorós-Pérez Ana , Büchele Simon , Krumeich Frank , Clark Adam H. , Román-Martínez Maria C. , Lillo-Ródenas Maria A. , Pérez-Ramírez Javier
Published: June 2021

For decades, carbons have been the support of choice in acetylene hydrochlorination, a key industrial process for polyvinyl chloride manufacture. However, no unequivocal design criteria could be established to date, due to the complex interplay between the carbon host and the metal nanostructure. Herein, we disentangle the roles of carbon in determining activity and stability of platinum-, ruthenium-, and gold-based hydrochlorination catalysts and derive descriptors for optimal host design, by systematically varying the porous properties and surface functionalization of carbon, while preserving the active metal sites. The acetylene adsorption capacity is identified as central activity descriptor, while the density of acidic oxygen sites determines the coking tendency and thus catalyst stability. With this understanding, a platinum single-atom catalyst is developed with stable catalytic performance under two-fold accelerated deactivation conditions compared to the state-of-the-art system, marking a step ahead towards sustainable PVC production.
Iron-dependent apoptosis causes embryotoxicity in inflamed and obese pregnancy
Authors: Fisher Allison L. , Sangkhae Veena , Balušíková Kamila , Palaskas Nicolaos J. , Ganz Tomas , Nemeth Elizabeta
Published: June 2021

Iron is essential for a healthy pregnancy, and iron supplementation is nearly universally recommended, regardless of maternal iron status. A signal of potential harm is the U-shaped association between maternal ferritin, a marker of iron stores, and risk of adverse pregnancy outcomes. However, ferritin is also induced by inflammation and may overestimate iron stores during inflammation or infection. In this study, we use mouse models to determine whether maternal iron loading, inflammation, or their interaction cause poor pregnancy outcomes. Only maternal exposure to both iron excess and inflammation, but not either condition alone, causes embryo malformations and demise. Maternal iron excess potentiates embryo injury during both LPS-induced acute inflammation and obesity-induced chronic mild inflammation. The adverse interaction depends on TNFα signaling, causes apoptosis of placental and embryo endothelium, and is prevented by anti-TNFα or antioxidant treatment. Our findings raise important questions about the safety of indiscriminate iron supplementation during pregnancy.
Ubiquitous organic molecule-based free-standing nanowires with ultra-high aspect ratios
Authors: Kamiya Koshi , Kayama Kazuto , Nobuoka Masaki , Sakaguchi Shugo , Sakurai Tsuneaki , Kawata Minori , Tsutsui Yusuke , Suda Masayuki , Idesaki Akira , Koshikawa Hiroshi , Sugimoto Masaki , Lakshmi G. B. V. S. , Avasthi D. K. , Seki Shu
Published: June 2021

The critical dimension of semiconductor devices is approaching the single-nm regime, and a variety of practical devices of this scale are targeted for production. Planar structures of nano-devices are still the center of fabrication techniques, which limit further integration of devices into a chip. Extension into 3D space is a promising strategy for future; however, the surface interaction in 3D nanospace make it hard to integrate nanostructures with ultrahigh aspect ratios. Here we report a unique technique using high-energy charged particles to produce free-standing 1D organic nanostructures with high aspect ratios over 100 and controlled number density. Along the straight trajectory of particles penetrating the films of various sublimable organic molecules, 1D nanowires were formed with approximately 10~15 nm thickness and controlled length. An all-dry process was developed to isolate the nanowires, and planar or coaxial heterojunction structures were built into the nanowires. Electrical and structural functions of the developed standing nanowire arrays were investigated, demonstrating the potential of the present ultrathin organic nanowire systems.
The bacterial toxin ExoU requires a host trafficking chaperone for transportation and to induce necrosis
Authors: Deruelle Vincent , Bouillot Stéphanie , Job Viviana , Taillebourg Emmanuel , Fauvarque Marie-Odile , Attrée Ina , Huber Philippe
Published: June 2021

Pseudomonas aeruginosa can cause nosocomial infections, especially in ventilated or cystic fibrosis patients. Highly pathogenic isolates express the phospholipase ExoU, an effector of the type III secretion system that acts on plasma membrane lipids, causing membrane rupture and host cell necrosis. Here, we use a genome-wide screen to discover that ExoU requires DNAJC5, a host chaperone, for its necrotic activity. DNAJC5 is known to participate in an unconventional secretory pathway for misfolded proteins involving anterograde vesicular trafficking. We show that DNAJC5-deficient human cells, or Drosophila flies knocked-down for the DNAJC5 orthologue, are largely resistant to ExoU-dependent virulence. ExoU colocalizes with DNAJC5-positive vesicles in the host cytoplasm. DNAJC5 mutations preventing vesicle trafficking (previously identified in adult neuronal ceroid lipofuscinosis, a human congenital disease) inhibit ExoU-dependent cell lysis. Our results suggest that, once injected into the host cytoplasm, ExoU docks to DNAJC5-positive secretory vesicles to reach the plasma membrane, where it can exert its phospholipase activity
Cnidarian-bilaterian comparison reveals the ancestral regulatory logic of the β-catenin dependent axial patterning
Authors: Lebedeva Tatiana , Aman Andrew J. , Graf Thomas , Niedermoser Isabell , Zimmermann Bob , Kraus Yulia , Schatka Magdalena , Demilly Adrien , Technau Ulrich , Genikhovich Grigory
Published: June 2021

In animals, body axis patterning is based on the concentration-dependent interpretation of graded morphogen signals, which enables correct positioning of the anatomical structures. The most ancient axis patterning system acting across animal phyla relies on β-catenin signaling, which directs gastrulation, and patterns the main body axis. However, within Bilateria, the patterning logic varies significantly between protostomes and deuterostomes. To deduce the ancestral principles of β-catenin-dependent axial patterning, we investigate the oral–aboral axis patterning in the sea anemone Nematostella—a member of the bilaterian sister group Cnidaria. Here we elucidate the regulatory logic by which more orally expressed β-catenin targets repress more aborally expressed β-catenin targets, and progressively restrict the initially global, maternally provided aboral identity. Similar regulatory logic of β-catenin-dependent patterning in Nematostella and deuterostomes suggests a common evolutionary origin of these processes and the equivalence of the cnidarian oral–aboral and the bilaterian posterior–anterior body axes.
Broadening INPP5E phenotypic spectrum: detection of rare variants in syndromic and non-syndromic IRD
Authors: Sangermano Riccardo , Deitch Iris , Peter Virginie G. , Ba-Abbad Rola , Place Emily M. , Zampaglione Erin , Wagner Naomi E. , Fulton Anne B. , Coutinho-Santos Luisa , Rosin Boris , Dunet Vincent , AlTalbishi Ala’a , Banin Eyal , Sousa Ana Berta , Neves Mariana , Larson Anna , Quinodoz Mathieu , Michaelides Michel , Ben-Yosef Tamar , Pierce Eric A. , Rivolta Carlo , Webster Andrew R. , Arno Gavin , Sharon Dror , Huckfeldt Rachel M. , Bujakowska Kinga M.
Published: June 2021

Pathogenic variants in INPP5E cause Joubert syndrome (JBTS), a ciliopathy with retinal involvement. However, despite sporadic cases in large cohort sequencing studies, a clear association with non-syndromic inherited retinal degenerations (IRDs) has not been made. We validate this association by reporting 16 non-syndromic IRD patients from ten families with bi-allelic mutations in INPP5E. Additional two patients showed early onset IRD with limited JBTS features. Detailed phenotypic description for all probands is presented. We report 14 rare INPP5E variants, 12 of which have not been reported in previous studies. We present tertiary protein modeling and analyze all INPP5E variants for deleteriousness and phenotypic correlation. We observe that the combined impact of INPP5E variants in JBTS and non-syndromic IRD patients does not reveal a clear genotype–phenotype correlation, suggesting the involvement of genetic modifiers. Our study cements the wide phenotypic spectrum of INPP5E disease, adding proof that sequence defects in this gene can lead to early-onset non-syndromic IRD.
Biomedical potential of Anabaena variabilis NCCU-441 based Selenium nanoparticles and their comparison with commercial nanoparticles
Authors: Afzal Bushra , Yasin Durdana , Naaz Haleema , Sami Neha , Zaki Almaz , Rizvi Moshahid Alam , Kumar Raj , Srivastava Pooja , Fatma Tasneem
Published: June 2021

Selenium nanoparticles (SeNPs) are gaining importance in the field of medicines due to their high surface area and unique properties than their other forms of selenium. In this study, biogenic selenium nanoparticles (B-SeNPs) were synthesized using cyanobacteria and their bioactivities (antioxidant, antimicrobial, anticancer and biocompatibility) were determined for comparison with commercially available chemically synthesized selenium nanoparticles (C-SeNPs). Color change of reaction mixture from sky blue to orange-red indicated the synthesis of biogenic SeNPs (B-SeNPs). UV–Vis spectra of the reaction mixture exhibited peak at 266 nm. During optimization, 30 °C of temperature, 24 h of time and 1:2 concentration ratio of sodium selenite and cell extract represented the best condition for SeNPs synthesis. Various functional groups and biochemical compounds present in the aqueous extract of Anabaena variabilis NCCU-441, which may have possibly influenced the reduction process of SeNPs were identified by FT-IR spectrum and GC–MS. The synthesized cyanobacterial SeNPs were orange red in color, spherical in shape, 10.8 nm in size and amorphous in nature. The B-SeNPs showed better anti-oxidant (DPPH, FRAP, SOR and ABTS assays), anti-microbial (antibacterial and antifungal) and anti-cancer activitities along with its biocompatibility in comparison to C-SeNPs suggesting higher probability of their biomedical application.