bluuebunny/crossref_metadata_2025_split huggingface dataset:
Narrative Event Segmentation in the Cortical Reservoir
Authors: Dominey Peter Ford 
Published: April 2021

AbstractDuring continuous perception of movies or stories, awake humans display cortical activity patterns that reveal hierarchical segmentation of event structure. Sensory areas like auditory cortex display high frequency segmentation related to the stimulus, while semantic areas like posterior middle cortex display a lower frequency segmentation related to transitions between events (Baldassano et al. 2017). These hierarchical levels of segmentation are associated with different time constants for processing. Chien and Honey (2020) observed that when two groups of participants heard the same sentence in a narrative, preceded by different contexts, neural responses for the groups were initially different and then gradually aligned. The time constant for alignment followed the segmentation hierarchy: sensory cortices aligned most quickly, followed by mid-level regions, while some higher-order cortical regions took more than 10 seconds to align. These hierarchical segmentation phenomena can be considered in the context of processing related to comprehension. Uchida et al. (2021) recently described a model of discourse comprehension where word meanings are modeled by a language model pre-trained on a billion word corpus (Yamada et al 2020). During discourse comprehension, word meanings are continuously integrated in a recurrent cortical network. The model demonstrates novel discourse and inference processing, in part because of two fundamental characteristics: real-world event semantics are represented in the word embeddings, and these are integrated in a reservoir network which has an inherent gradient of functional time constants due to the recurrent connections. Here we demonstrate how this model displays hierarchical narrative event segmentation properties. The reservoir produces activation patterns that are segmented by the HMM of Baldassano et al (2017) in a manner that is comparable to that of humans. Context construction displays a continuum of time constants across reservoir neuron subset, while context forgetting has a fixed time constant across these subsets. Virtual areas formed by subgroups of reservoir neurons with faster time constants segmented with shorter events, while those with longer time constants preferred longer events. This neurocomputational recurrent neural network simulates narrative event processing as revealed by the fMRI event segmentation algorithm of Baldassano et al (2017), and provides a novel explanation of the asymmetry in narrative forgetting and construction observed by Chien and Honey (2020). The model extends the characterization of online integration processes in discourse to more extended narrative, and demonstrates how reservoir computing provides a useful model of cortical processing of narrative structure.
A gene duplication of a septin provides a developmentally-regulated filament length control mechanism
Authors: Cannon Kevin S. , Vargas-Muniz Jose M. , Billington Neil , Seim Ian , Ekena Joanne , Sellers James , Philippsen Peter , Gladfelter Amy. S. 
Published: April 2021

AbstractSeptins are a family of conserved filament-forming proteins that function in a variety of processes including cell cycle progression, cell morphogenesis and autophagy. Despite their conservation from yeast to humans, the number of septin genes within an organism varies and higher eukaryotes express many septin isoforms due to alternative splicing. It is unclear how variability in septin complex composition influences the biophysical properties of septin polymers. Here we report that a complex duplication event within theCDC11locus in the fungus,Ashbya gossypii, gave rise to two similar, but distinct Cdc11 proteins, Cdc11a and Cdc1b.CDC11btranscription is developmentally regulated producing different ratios of Cdc11a and b complexes duringAshbya’slifecycle. Moreover, deletion of eitherCDC11aorCDC11bresults in distinct cell polarity defects. Remarkably, despite substantial identity in amino acid sequence, Cdc11a and Cdc11b complexes have distinct biophysical properties with clear filament length and membrane-binding ability differences. Thus, septin subunit composition has functional consequences for filament properties and such functional plasticity can be exploited for distinct biophysical properties and cell functions.
CONET: Copy number event tree model of evolutionary tumor history for single-cell data
Authors: Markowska Magda , Cąkała Tomasz , Miasojedow Błażej , Juraeva Dilafruz , Mazur Johanna , Ross Edith , Staub Eike , Szczurek Ewa 
Published: April 2021

AbstractCopy number alterations constitute important phenomena in tumor evolution. Whole genome single cell sequencing gives insight into copy number profiles of individual cells, but is highly noisy. Here, we propose CONET, a probabilistic model for joint inference of the evolutionary tree on copy number events and copy number calling. CONET employs an efficient MCMC procedure to search the space of possible model structures and parameters and utilizes both per-bin and per-breakpoint data. We introduce a range of model priors and penalties for efficient regularization. CONET achieves excellent performance on simulated data and for 260 cells from xenograft breast cancer sample.
The cannabinoid agonist CB-13 produces peripherally mediated analgesia in mice but elicits tolerance and signs of CNS activity with repeated dosing
Authors: Slivicki Richard A. , Yi Jiwon , Brings Victoria E. , Huynh Phuong Nhu , Gereau Robert W. 
Published: April 2021

AbstractActivation of cannabinoid receptor type 1 (CB1) produces analgesia in a variety of preclinical models of pain; however, engagement of central CB1receptors is accompanied by unwanted side effects, such as tolerance and dependence. Efforts to develop novel analgesics have focused on targeting peripheral CB1receptors to circumvent central CB1-related side effects. In the present study, we evaluated the effects of acute and repeated dosing with the peripherally selective CB1-preferring agonist CB-13 on nociception and central CB1-related phenotypes in an inflammatory model of pain in mice. We also evaluated cellular mechanisms underlying CB-13-induced antinociceptionin vitrousing cultured mouse dorsal root ganglion (DRG) neurons. CB-13 reduced inflammation-induced mechanical allodynia in a peripheral CB1receptor-dependent manner and relieved inflammatory thermal hyperalgesia. In cultured mouse DRG neurons, CB-13 reduced TRPV1 sensitization and neuronal hyperexcitability induced by the inflammatory mediator prostaglandin E2, providing potential mechanistic explanations for the analgesic actions of peripheral CB1receptor activation. With acute dosing, phenotypes associated with central CB1receptor activation occurred only at a dose of CB-13 approximately 10-fold the ED50for reducing allodynia. Strikingly, repeated dosing resulted in both analgesic tolerance and CB1receptor dependence, even at a dose that did not produce central CB1receptor-mediated phenotypes on acute dosing. This suggests repeated CB-13 dosing leads to increased CNS exposure and unwanted engagement of central CB1receptors. Thus, caution is warranted regarding therapeutic use of CB-13 with the goal of avoiding CNS side effects. Nonetheless, the clear analgesic effect of acute peripheral CB1receptor activation suggests that peripherally restricted cannabinoids are a viable target for novel analgesic development.
Spatially coordinated heterochromatinization of distal short tandem repeats in fragile X syndrome
Authors: Zhou Linda , Ge Chunmin , Malachowski Thomas , Kim Ji Hun , Chandradoss Keerthivasan Raanin , Su Chuanbin , Wu Hao , Rojas Alejandro , Wallace Owen , Titus Katelyn R. , Gong Wanfeng , Phillips-Cremins Jennifer E. 
Published: April 2021

AbstractShort tandem repeat (STR) instability is causally linked to pathologic transcriptional silencing in a subset of repeat expansion disorders. In fragile X syndrome (FXS), instability of a single CGG STR tract is thought to repressFMR1via local DNA methylation. Here, we report the acquisition of more than ten Megabase-sized H3K9me3 domains in FXS, including a 5-8 Megabase block aroundFMR1. Distal H3K9me3 domains encompass synaptic genes with STR instability, and spatially co-localize in trans concurrently withFMR1CGG expansion and the dissolution of TADs. CRISPR engineering of mutation-lengthFMR1CGG to normal-length preserves heterochromatin, whereas cut-out to pre-mutation-length attenuates a subset of H3K9me3 domains. Overexpression of a pre-mutation-length CGG de-represses bothFMR1and distal heterochromatinized genes, indicating that long-range H3K9me3-mediated silencing is exquisitely sensitive to STR length. Together, our data uncover a genome-wide surveillance mechanism by which STR tracts spatially communicate over vast distances to heterochromatinize the pathologically unstable genome in FXS.One-Sentence SummaryHeterochromatinization of distal synaptic genes with repeat instability in fragile X is reversible by overexpression of a pre-mutation length CGG tract.
Translation of cellular protein localization by generative adversarial network
Authors: Shigene Kei , Hiasa Yuta , Otake Yoshito , Soufi Mazen , Janewanthanakul Suphamon , Nishimura Tamako , Sato Yoshinobu , Suetsugu Shiro 
Published: April 2021

AbstractThe protein localization in cells had been analyzed by the fluorescent labeling by indirect immunofluorescence and fluorescent protein tagging. However, the relationships between the localizations between different proteins had not been analyzed by artificial intelligence. In this study, we applied the generative adversarial network (GAN) to generate the protein localizations each other, in which the generation was dependent on the types of cells and the relationships between the proteins. Lamellipodia are one of the actin-dependent subcellular structures involved in cell migration and are mainly generated by the Wiskott-Aldrich syndrome protein (WASP)-family verprolin homologous protein 2 (WAVE2) and the membrane remodeling I-BAR domain protein IRSp53. Focal adhesions are another actin-based structure that contains vinculin protein and are essential for cell migration. In contrast, microtubules are not thought to be directly related to actin filaments. The GAN was trained using images of actin filaments paired with WAVE2, vinculin, IRSp53, and microtubules. Then, the generated images of WAVE2, vinculin, and IRSp53 by the GAN showed high similarity to the real images of WAVE2, vinculin, and IRSp53, respectively. However, the microtubule images generated from actin filament images were inferior, corroborating that the microscopic images of actin filaments provide more information about actin-related protein localization. Collectively, this study suggests that the image translation by the GAN can predict the localization of functionally related proteins.
Dermoscopic features of nail psoriasis: Positive correlation with the severity of psoriasis
Authors: Long FangYuan , Zhang ZhiQin , He Fang , Tu Jie , Yin Zhi , Xia JiPing , Lu Yan , Yin ZhiQiang 
Published: April 2021

AbstractDermoscopy is an efficient and non‐invasive technique which has been widely used in the diagnosis of nail disorders including nail psoriasis (NP). Many nail dermoscopic features are considered as clues to NP. The aim of this study was to investigate specific dermoscopic features of fingernail psoriasis and the correlation between the severity of nail lesions or systemic inflammation, and psoriasis severity of skin and nail. This observational study recruited 135 patients with fingernail psoriasis (1186 fingernails) and 30 patients with onychomycosis (80 fingernails). All of the involved fingernails were examined with a handheld dermatoscope. The Nail Psoriasis Severity Index score (NAPSI) score, Psoriasis Area and Severity Index (PASI) score, body surface area (BSA), and detailed history of patients with psoriasis were recorded. Mann–WhitneyU‐test, χ2‐test, Spearman’s correlation, and Kruskal–Wallis H‐test were used for statistical analysis, and the significance threshold wasp < 0.05. The trial registration number was 2020‐SR‐045. We identified onycholysis as the most common feature (93.3%) of fingernail psoriasis. Red lunula, longitudinal fissures, transverse grooves, nail plate crumbling, trachyonychia, oil‐dropping sign, erythematous border of an onycholytic area, subungual hyperkeratosis, and dilated streaky capillaries were relevant to NP severity (p < 0.05). Red lunula, transverse grooves, nail plate crumbling, trachyonychia, oil‐dropping sign, erythematous border of an onycholytic area, splinter hemorrhages, and dilated streaky capillaries were relevant to systemic inflammation severity (p < 0.05). The total NAPSI score was positively associated with the PASI score and BSA (p < 0.0001). The thumb had a higher NAPSI score than the other fingers (p < 0.05). In conclusion, dermoscopic features can improve the accuracy of diagnosis of nail psoriasis, and have correlations with psoriasis severity.
Unpacking the politics of legislative debates
Authors: FERNANDES JORGE M. , DEBUS MARC , BÄCK HANNA 
Published: April 2021

AbstractLegislative debates are a thriving field in comparative politics. They make representation work by offering legislators the opportunity to take the floor and represent their constituents. In this paper, we review the key theoretical concepts and empirical findings in a maturing field. We begin by addressing what legislative debates are and why we should study them to learn about inter‐ and intra‐party politics. Next, we look at the contributions springing from Proksch and Slapin's ground‐breaking model. In so doing, our review suggests that recent work extends the original model to include further dimensions of legislative debates. Third, we examine the role of legislative debates as mechanisms of representation, focusing on gender. Four, we examine the challenges of the comparative analysis of legislative debates. Finally, we map the road ahead by discussing four avenues of future research and some key questions that remain unanswered.
Palatability and profitability of co‐occurring seeds alter indirect interactions among rodent‐dispersed trees
Authors: XIAO Zhishu , HOLYOAK Marcel , KREBS Charles J. , HUANG Xiaoqun 
Published: April 2021

AbstractBeyond direct species interactions, seed dispersal is potentially affected by indirect seed–seed interactions among co‐occurring nut‐bearing trees which are mediated by scatter‐hoarding animals as shared seed dispersers. A relevant question in such systems is to what extent different functional traits related to food palatability and profitability affect the kinds of indirect interactions that occur among co‐occurring seeds, and the consequences for seed dispersal. We used field experiments to track seed dispersal with individually tagged seeds in both monospecific and mixed seed communities. We measured indirect effects based on 3 seed–seed species pairs from the family Fagaceae with contrasting seed size, tannin level, and dormancy in a subtropical forest in Southwest China. When all else was equal, the presence of adjacently placed seeds with contrasting seed traits created different indirect effects measured through a variety of dispersal‐related indicators. Apparent mutualism was reciprocal due to increasing seed dispersal in mixed seed patches with mixed differences in seed tannins and dormancy. However, differences in either seed size or dormancy in co‐occurring adjacently placed seeds caused apparent competition with reduced seed removal or seed dispersal (distance) in at least one species. Our study supports the hypothesis that different functional traits related to food palatability and profitability in co‐occurring seeds modify foraging decisions of scatter‐hoarding animals, and subsequently cause indirect effects on seed dispersal among rodent‐dispersed trees. We conclude that such indirect effects mediated by shared seed dispersers may act as an important determinant of seed dispersal for co‐fruiting animal‐dispersed trees in many natural forests.
Commentary: ‘Profitability’, Curated Narratives and Spatial Governance and their Impacts on Urban Migration and the Lives of Migrants
Authors: Aubrey Dyfed 
Published: April 2021

AbstractThis commentary reviews ‘The ‘Badlands’ of the ‘Balkan Route’: policy and spatial effects on urban refugee housing’, by Gemma Bird, Jelena Obradovic‐Wochnik, Amanda Beattie and Patrycja Rozbicka; ‘Walking in Jozi: Guided Tours, Insecurity and Urban Regeneration in Inner City Johannesburg’ by Lena Opfermann, and ‘Curating (im)mobility: Peri‐urban agency in the Lwandle Migrant Labour Museum’ by Stefanie Kappler, and explores common threads running through the three articles, namely ‘profitability’, curated narratives and spatial governance, and their impact on ‘othering’ migrants and entrenching inequality.
Inequality and the Socioeconomic Dimensions of Mobility in Protests: The Cases of Quito and Santiago
Authors: Díaz Pabón Fabio Andrés , Palacio Ludeña María Gabriela 
Published: April 2021

AbstractMobility is a multifaceted concept with social, economic and political implications. This article reflects on the role of mobility and its relation to precarity in the emergence of protests in both Quito (Ecuador) and Santiago (Chile) in 2019 by examining the interplay between mobility and inequality. It argues that the announced increases in transport and fuel costs in Chile and Ecuador exposed obstacles to spatial and social mobility and existing inequalities. Although the protests arose in response to the announced reduction in fuel subsidies and possible increases in transport costs, we propose that they reflect a deeper issue, relating to the vulnerability of the livelihoods of significant segments of the population, despite the fact that both Quito and Santiago have seen improvements in several poverty and inequality indicators in recent years. We discuss how mobility and geography relate to patterns of structural marginalisation that are not necessarily evident from aggregate economic indicators, and how understanding inequality in terms of the ‘right to the city’ and access to public services explain the protests in both countries as a response to existing segregation and deep‐seated inequalities.
The Impact of Risk and the Potential for Loss on Managers' Demand for Audit Quality*
Authors: Hurley Patrick J. , Mayhew Brian W. , Obermire Kara M. , Tegeler Amy C. 
Published: April 2021

ABSTRACTThis study uses experimental economic markets to investigate the impact of risk and the potential for loss on managers' demand for audit quality. We posit that these two important contextual factors influence managers' audit quality preferences. We study these factors because they are ubiquitous to companies, and we focus on their influence on managers because managers continue to play a significant role in the auditor hiring process and we know relatively little about their auditor preferences. We predict that risk, the potential for loss, and their interaction will each decrease manager demand for high audit quality due to a desire to achieve greater reporting flexibility. Experimental results are consistent with our predictions; specifically, increased risk, the potential for loss, and to a lesser extent their interaction, significantly reduce managers' likelihood of hiring the best available auditor in the market. Path analysis indicates that this reduction in audit quality demand leads to increases in misreporting. Finally, we observe investors overpaying for assets to a greater extent when managers hire lower‐quality auditors. Our results show that the contextual factors of risk and the potential for loss, which are ubiquitous to companies, can reduce demand for audit quality, which can increase misreporting behavior and ultimately harm investors.
Positive Spillovers from Negative Campaigning
Authors: Galasso Vincenzo , Nannicini Tommaso , Nunnari Salvatore 
Published: April 2021

AbstractNegative advertising is frequent in electoral campaigns, despite its ambiguous effectiveness: Negativity may reduce voters' evaluation of the targeted politician but may have a backlash effect for the attacker. We study the effect of negative advertising in electoral races with more than two candidates with a large‐scale field experiment during an electoral campaign for mayor in Italy and a survey experiment in a fictitious mayoral campaign. In our field experiment, we find a strong, positive spillover effect on the third main candidate (neither the target nor the attacker). This effect is confirmed in our survey experiment, which creates a controlled environment with no ideological components or strategic voting. The negative ad has no impact on the targeted incumbent, has a sizable backlash effect on the attacker, and largely benefits the idle candidate. The attacker is perceived as less cooperative, less likely to lead a successful government, and more ideologically extreme.
A mathematical model to identify optimal combinations of drug targets for dupilumab poor responders in atopic dermatitis
Authors: Miyano Takuya , Irvine Alan D. , Tanaka Reiko J. 
Published: April 2021

AbstractBackgroundSeveral biologics for atopic dermatitis (AD) have demonstrated good efficacy in clinical trials, but with a substantial proportion of patients being identified as poor responders. This study aims to understand the pathophysiological backgrounds of patient variability in drug response, especially for dupilumab, and to identify promising drug targets in dupilumab poor responders.MethodsWe conducted model‐based meta‐analysis of recent clinical trials of AD biologics and developed a mathematical model that reproduces reported clinical efficacies for nine biological drugs (dupilumab, lebrikizumab, tralokinumab, secukinumab, fezakinumab, nemolizumab, tezepelumab, GBR 830, and recombinant interferon‐gamma) by describing system‐level AD pathogenesis. Using this model, we simulated the clinical efficacy of hypothetical therapies on virtual patients.ResultsOur model reproduced reported time courses of %improved EASI and EASI‐75 of the nine drugs. The global sensitivity analysis and model simulation indicated the baseline level of IL‐13 could stratify dupilumab good responders. Model simulation on the efficacies of hypothetical therapies revealed that simultaneous inhibition of IL‐13 and IL‐22 was effective, whereas application of the nine biologic drugs was ineffective, for dupilumab poor responders (EASI‐75 at 24 weeks: 21.6% vs. max. 1.9%).ConclusionOur model identified IL‐13 as a potential predictive biomarker to stratify dupilumab good responders, and simultaneous inhibition of IL‐13 and IL‐22 as a promising drug therapy for dupilumab poor responders. This model will serve as a computational platform for model‐informed drug development for precision medicine, as it allows evaluation of the effects of new potential drug targets and the mechanisms behind patient variability in drug response.