bluuebunny/crossref_metadata_2025_split huggingface dataset:
NUFEB: A Massively Parallel Simulator for Individual-based Modelling of Microbial Communities
Authors: Li Bowen , Taniguchi Denis , Gedara Jayathilake Pahala , Gogulancea Valentina , Gonzalez-Cabaleiro Rebeca , Chen Jinju , McGough Andrew Stephen , Ofiteru Irina Dana , Curtis Thomas P , Zuliani Paolo 
Published: May 2019

AbstractWe present NUFEB, a flexible, efficient, and open source software for simulating the 3D dynamics of microbial communities. The tool is based on the Individual-based Modelling (IbM) approach, where microbes are represented as discrete units and their behaviour changes over time due to a variety of processes. This approach allows us to study population behaviours that emerge from the interaction between individuals and their environment. NUFEB is built on top of the classical molecular dynamics simulator LAMMPS, which we extended with IbM features. A wide range of biological, physical and chemical processes are implemented to explicitly model microbial systems. NUFEB is fully parallelised and allows for the simulation of large numbers of microbes (107individuals and beyond). The parallelisation is based on a domain decomposition scheme that divides the domain into multiple sub-domains which are distributed to different processors. NUFEB also offers a collection of post-processing routines for the visualisation and analysis of simulation output. In this article, we give an overview of NUFEB’s functionalities and implementation details. We provide examples that illustrate the type of microbial systems NUFEB can be used to model and simulate.Author summaryIndividual-based Models (IbM) are one of the most promising frameworks to study microbial communities, as they can explicitly describe the behaviour of each cell. The development of a general-purpose IbM solver should focus on efficiency and flexibility due to the unique characteristics of microbial systems. However, available tools for these purposes present significant limitations. Most of them only facilitate serial computing for single simulation, or only focus on biological processes, but do not model mechanical and chemical processes in detail. In this work, we introduce the IbM solver NUFEB that addresses these shortcoming. The tool facilitates the modelling of much needed biological, chemical, physical and individual microbes in detail, and offers the flexibility of model extension and customisation. NUFEB is also fully parallelised and allows for the simulation of large complex microbial system. In this paper, we first give an overview of NUFEB’s functionalities and implementation details. Then, we use NUFEB to model and simulate a biofilm system with fluid dynamics, and a large and complex biofilm system with multiple microbial functional groups and multiple nutrients.This is aPLOS Computational BiologySoftware paper.
A cellular atlas of the developing meninges reveals meningeal fibroblast diversity and function
Authors: DeSisto John , O’Rourke Rebecca , Bonney Stephanie , Jones Hannah E. , Guimiot Fabien , Jones Kenneth L. , Siegenthaler Julie A. 
Published: May 2019

AbstractThe meninges, a multilayered structure that encases the CNS, is composed mostly of fibroblasts, along with vascular and immune cells. Meningeal fibroblasts are a vital source of signals that control neuronal migration and neurogenesis yet strikingly little is known about their development. We used single cell RNA sequencing to generate a cellular atlas of embryonic meningeal fibroblasts in control andFoxc1-KOmice in which severe CNS defects arise from failed meningeal fibroblast development. We report unique transcriptional signatures for dura, arachnoid and pial fibroblasts and identify S100a6 as the first unique marker of the pial layer. We describe a new meningeal fibroblast subtype marked by µ-Crystallin expression and show these cell types and markers are conserved in human fetal meninges. Our analysis demonstrates layer specific production of extracellular matrix components, transporter expression, and synthesis of secreted factors. Lastly, the cellular atlas ofFoxc1-KOmeninges provides insight into their severe phenotype, confirming a massive loss in arachnoid and dura fibroblasts andFoxc1-KOpial fibroblasts are so altered that they cluster as a different cell type based on gene expression. These studies provide an unprecedented view of meningeal fibroblast development, highlighting unexpected fibroblast diversity and function, while providing mechanistic insights into the meninges role in CNS development.
Clonal replacement of tumor-specific T cells following PD-1 blockade
Authors: Yost Kathryn E. , Satpathy Ansuman T. , Wells Daniel K. , Qi Yanyan , Wang Chunlin , Kageyama Robin , McNamara Katherine , Granja Jeffrey M. , Sarin Kavita Y. , Brown Ryanne A. , Gupta Rohit K. , Curtis Christina , Bucktrout Samantha L. , Davis Mark M. , Chang Anne Lynn S. , Chang Howard Y. 
Published: May 2019

AbstractImmunotherapies that block inhibitory checkpoint receptors on T cells have transformed the clinical care of cancer patients. However, which tumor-specific T cells are mobilized following checkpoint blockade remains unclear. Here, we performed paired single-cell RNA- and T cell receptor (TCR)-sequencing on 79,046 cells from site-matched tumors from patients with basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) pre- and post-anti-PD-1 therapy. Tracking TCR clones and transcriptional phenotypes revealed a coupling of tumor-recognition, clonal expansion, and T cell dysfunction: the T cell response to treatment was accompanied by clonal expansions of CD8+CD39+T cells, which co-expressed markers of chronic T cell activation and exhaustion. However, this expansion did not derive from pre-existing tumor infiltrating T cell clones; rather, it comprised novel clonotypes, which were not previously observed in the same tumor. Clonal replacement of T cells was preferentially observed in exhausted CD8+T cells, compared to other distinct T cell phenotypes, and was evident in BCC and SCC patients. These results, enabled by single-cell multi-omic profiling of clinical samples, demonstrate that pre-existing tumor-specific T cells may be limited in their capacity for re-invigoration, and that the T cell response to checkpoint blockade relies on the expansion of a distinct repertoire of T cell clones that may have just recently entered the tumor.
A definition of song from human music universals observed in primate calls
Authors: Schruth David , Templeton Christopher N. , Holman Darryl J. 
Published: May 2019

AbstractMusical behavior is likely as old as our species with song originating as early as 60 million years ago in the primate order. Early singing likely evolved into the music of modern humans via multiple selective events, but efforts to disentangle these influences have been stifled by challenges to precisely define this behavior in a broadly applicable way. Detailed here is a method to quantify the elaborateness of acoustic displays using published spectrograms (n=832 calls) culled from the literature on primate vocalizations. Each spectrogram was scored by five trained analysts via visual assessments along six musically relevant acoustic parameters:tone, interval, transposition, repetition, rhythm, andsyllabic variation. Principal Components Analysis (PCA) was used to reduce this multivariate assessment into a simplified measure of musical elaborateness. The resulting “acoustic reappearance diversity” index simultaneously captures syllabic variation and spectral/temporal redundancy in a single continuous variable. The potential utility of this index is demonstrated by applying it to several social and habitat-based theories of acoustic display origins. Our results confirm that primate species living in small, monogamous groups have song-like calls, while forest habitat had a less pronounced association.
Phlebotomus papatasisand fly salivary protein diversity and immune response potential in Egypt and Jordan populations
Authors: Flanley Catherine M. , Ramalho-Ortigao Marcelo , Coutinho-Abreu Iliano V. , Mukbel Rami , Hanafi Hanafi A. , El-Hossary Shabaan S. , Fawaz Emadeldin Y. , Hoel David F. , Bray Alexander W. , Stayback Gwen , Shoue Douglas A. , Kamhawi Shaden , Emrich Scott , McDowell Mary Ann 
Published: May 2019

AbstractPhlebotomus papatasisand flies inject their hosts with a myriad of pharmacologically active salivary proteins to assist with blood feeding and to modulate host defenses. These salivary proteins have been studied for their role in cutaneous leishmaniasis disease outcome with different salivary proteins attenuating or exacerbating lesion size. Studies have shown that while co-administered sand fly saliva exacerbatesLeishmania majorinfections in naïve mice, animals pre-exposed to saliva are protected, with the infection attenuated via a delayed-type hypersensitivity immune reaction. These studies highlight the potential of the salivary components to be used as a vaccine. One protein in particular,P. papatasisalivary protein 15 (PpSP15) has been intensively studied because of its ability to protect mice againstLe. majorchallenge. The number of antigenic molecules included in vaccines is restricted thus emphasizing the role of population genetics to identify molecules, like PpSP15, that are functionally significant, conserved across populations and do not experience selection. Three distinct ecotope study sites, one in Egypt (Aswan) and two in Jordan (Swaimeh and Malka), were chosen based on their elevation, rainfall, vegetation, differing reservoir species, and the presence or absence ofLe. major. The objective of this work was to analyze the genetic variability of nine of the most abundantly expressed salivary proteins including PpSP12, PpSP14, PpSP28, PpSP29, PpSP30, PpSP32, PpSP36, PpSP42, and PpSP44 and to predict their ability to elicit an immune response. Two proteins, PpSP12 and PpSP14, demonstrated low genetic variability across the three sand fly populations represented in this study, with multiple predicted MHCII epitope binding sites, identified by alleles present in the human populations from the study sites. The other seven salivary proteins revealed greater allelic variation across the same sand fly populations indicating that their use as vaccine targets may prove to be challenging.
Optimizing website quality: the case of two superstar museum websites
Authors: Garcia-Madariaga Jesús , Recuero Virto Nuria , Blasco López Maria Francisca , Aldas Manzano Joaquín 
Published: May 2019

Purpose
Studies that examine users’ perceptions of museum’s website quality are scarce. The purpouse of this paper is to propose a multi-group comparison between two superstar museums to outline the variables that define website quality regarding museum websites towards achieving e-loyalty, trust and perceived control.

Design/methodology/approach
The sample comprised 305 valid online questionnaires, collected from a panel survey using a quota-sampling technique. The proposed model was tested using partial least squares analysis multi-group comparison between Prado and Thyssen-Bornemisza museum websites.

Findings
Website quality plays a determinant role in users’ behavioural outcomes. As evidenced in the results for the first time in a museum setting, website quality has the potential of influencing e-loyalty, trust and perceived control. Besides, trust has a positive influence on e-loyalty and perceived control, on trust. The multi-group comparison revealed no significant differences between the two museum superstars, which offer highly useful insights for the correct design of these websites.

Originality/value
This research addresses a multi-group comparison using partial least squares, a quite recent technique that advances knowledge regarding this method. It contributes to knowledge museum website management and online literature by means of proposing website quality as a dimension that includes content, ease of understanding, emotion, informational fit-to-task, promotion and visual appeal and by revealing significant effects of the relationships of the proposed model. Museum managers are provided with valuable inputs to design websites in an appropriate and suitable way for their users so they will be more willing to repeat their navigation experience.
How do audit fees change? Effects of firm size and section 404(b) compliance
Authors: Lyubimov Alexey 
Published: May 2019

Purpose
The purpose of this paper is to investigate the effect of the size of the audit firm and compliance with Section 404(b) on how audit fees change over time.

Design/methodology/approach
This study uses panel data and an OLS regression to examine the relationship between audit fee changes, firms’ size and Section 404(b) compliance.

Findings
Section 404(b)-compliant companies experience a larger change in audit fees if they are audited by Big 4 firms than second-tier firms. Second-tier audit firms increase the fees primarily for the companies which do not comply with Section 404(b).

Practical implications
Regulators have been concerned with the Big 4 fee premium for four decades. This study informs regulators that the Big 4 continue increasing their fees at a higher rate than second-tier firms for their Section 404(b)-compliant clients (even though recent research shows that second-tier firms have increased quality to match the Big 4). This suggests that the Big 4 fee premium increases for this subset of clients, adding to the regulatory concerns.

Originality/value
While prior research has established the existence of the Big 4 fee premium, little is known about how this premium changes over time. Prior research shows that audit fees increase when internal controls are weak; however, little is known about how Section 404(b) compliance (once control effectiveness is controlled) affects fee changes. This paper addresses these voids in research.
Investment in internal auditing and governance characteristics
Authors: Park Hyun-Young , Lee Ho-Young , Kim Jin Wook 
Published: May 2019

PurposeBased on 3,775 firm-year observations from 2009 to 2013 using publicly available disclosure data for Korean listed firms, this study examines whether and how firm-level governance characteristics are associated with investment in internal auditing proxied by compensation and the number of statutory internal auditors.Design/methodology/approachThe authors investigate the association between governance characteristics and investment in internal auditing proxied by compensation and the number of statutory internal auditors.FindingsThe authors find that firms with greater ownership of the largest shareholders and with a higher proportion of outside directors invest more in internal auditing. These results indicate that firms with higher incentive and demand for monitoring are more likely to invest more in internal auditing. The authors further find that the positive effect of the largest shareholder ownership (board independence) on investment in internal auditing is attenuated in firms with greater board independence (ownership of the largest shareholders) suggesting that the complementary effect of the two governance mechanisms associated with internal auditing weakens as they function simultaneously.Research limitations/implicationsThe results provide regulators and investors with a clear picture of the governance characteristics of firms associated with investment in internal auditing. The results imply that both the largest shareholders and the outside board of directors play a significant role in resource allocation in internal auditing within a firm. The effect of allocation, however, can be attenuated contingent upon the combined characteristics of governance mechanisms.Originality/valueUsing large amounts of public archival data, this study adds to the extant literature on firm characteristics associated with investment in internal auditing. This study also contributes to the literature by expanding the scope of research on executive compensation to the locus of statutory internal auditors.
Asset pricing when trading is for entertainment
Authors: Luo Jiang , Subrahmanyam Avanidhar 
Published: May 2019

Purpose
High levels of turnover in financial markets are consistent with the notion that trading, like gambling, yields direct utility to some agents. The purpose of this paper is to show that the presence of these agents attenuates covariance risk pricing and volatility, and implies a negative relation between volume and future returns. Since psychological literature indicates that the desirability of a gamble arises from the ex ante volatility of the outcome, the authors propose that agents derive greater utility from trading more volatile stocks. These stocks earn lower average returns in equilibrium, although the risk premium on the market portfolio is positive. The authors then consider a dynamic setting where agents’ utility from trading increases when they make positive profits in earlier rounds (e.g. due to an endowment effect). This leads to “bubbles,” i.e. disproportionate jumps in asset returns as a function of past prices, higher volume in up markets relative to down markets, as well as a leverage effect, wherein down markets are followed by higher volatility than up markets.

Design/methodology/approach
Analytical.

Findings
The presence of gamblers attenuates covariance risk pricing and volatility, and implies a negative relation between volume and future returns. If gamblers prefer more volatile stocks, these stocks earn lower average returns in equilibrium. If agents’ utility from trading increases when they make positive profits in earlier rounds (e.g. to an endowment effect), this leads to higher volume and lower volatility in up markets relative to down markets.

Originality/value
No paper has previously modeled agents who derive direct utility from trading.
Stressor dominance and sensitivity‐dependent antagonism: Disentangling the freshwater effects of an insecticide among co‐occurring agricultural stressors
Authors: Bray Jon P. , Nichols Sue J. , Keely‐Smith Alexandra , Thompson Ross , Bhattacharyya Saurav , Gupta Susmita , Gupta Abhik , Gao Jianfa , Wang Xianyu , Kaserzon Sarit , Mueller Jochen F. , Chou Audrey , Kefford Ben J. 
Published: May 2019

Abstract

Pesticide concentrations are correlated with regional declines in stream invertebrate diversity. Experimental studies have identified that pesticides can have strong and persistent negative effects on aquatic ecosystems. These effects may occur at concentrations orders of magnitude lower than laboratory toxicity studies predict. Synergism among stressors is one explanation for observed laboratory–field differences. However, the true effect of pesticides on stream invertebrates remains uncertain, given interactions between stressors and natural environmental conditions.

We experimentally examined multiple‐stressor effects on stream invertebrate assemblages and leaf litter breakdown using 24 independent ~900 L re‐circulating outdoor mesocosms in a semi‐orthogonal design. Two pulses of the pesticide malathion (C10H19O6PS2) were delivered at low and high concentrations (Pulse 1: low at 0.1 and high at 1 µg/L; Pulse 2: at 2.5 and 25 µg/L). These were crossed with a treatment combining stressors commonly associated with agricultural development; nitrogen, phosphorus and sediment (kaolinite).

Malathion degradation was rapid (<24 hr half‐life) in all treatments, likely because of photolysis, hydrolysis, the presence of biofilms and sorptive processes. There were significant differences in invertebrate assemblages between treatments, where malathion contributed to 48% and 87% of deviance during Pulse 1 and 2 respectively. Malathion had strong negative effects during Pulse 2, with declines occurring between control and high pesticide treatments in Ephemeroptera, Plecoptera and Trichoptera abundances (Cohen's d = 3.08), invertebrate richness (d = 3.57) and total abundance (d = 3.31).

Despite the dominant effects of malathion on invertebrates, agricultural stressors inhibited rates of leaf litter breakdown (p < 0.05), and weakly mitigated malathion toxicity in mesocosms (e.g. PERMANOVA, P ≈ 0.1). Malathion breakdown analysis indicated sediment addition reduced malathion concentrations through alkaline hydrolysis and sorption. Experimental assays on common taxa supported sediment‐malathion interactions resulted in antagonism.

Synthesis and applications. Pesticide effects were not synergistic with the stressors tested here. Indeed, sensitivity‐dependent stressor antagonisms were observed, reinforcing a mechanistic understanding of stressor effects and interactions is important. Among aquatic stressors examined, malathion had dominant effects on invertebrate assemblages, despite rapid degradation. Our results suggest that pesticide effects may be underestimated within ecosystems, where pesticides can have severe community‐wide effects, but rapid pesticide breakdown and sorptive processes may conceal causal links.
Clinical significance of CCN2/connective tissue growth factor in Behçet's disease patients
Authors: Bassyouni Iman Hamed , Mohammed Wafaa Hob Sharkawy , Taha Fatma M. , El Refai Rasha M. 
Published: May 2019

AbstractAimBehçet's disease (BD) is a chronic autoimmune vasculitic disorder of unclear pathogenesis. CCN2/CTGF (connective tissue growth factor) is one of the CCN family members which carry out pro‐angiogenic biological functions and play an important role in inflammatory and autoimmune diseases. The aim of the present study was to assess CCN2 plasma concentrations in BD patients and to analyze their association with clinical features of the disease, activity and laboratory parameters.MethodsWe included 87 BD patients and 60 healthy control subjects matched for age and gender. Demographic, clinical, disease activity and severity data were recorded. Plasma CCN2 concentrations were measured using enzyme‐linked immunosorbent assay.ResultsThe plasma concentrations of CCN2 in BD patients were significantly elevated compared to healthy controls. The mean plasma CCN2 levels in patients with major organ involvement were significantly higher than those without. Patients who received steroids or cyclophosphamide showed a significant reduction in CCN2 levels. This was confirmed by the results of multivariate analysis. Patients with active ocular disease had a significant increase in CCN2 compared to the inactive group. On the other hand, CCN2 levels were not significantly correlated with overall disease activity and severity scores.ConclusionBehçet's disease patients showed a significant increase of CCN2 levels, especially in the group of patients with major organ involvement. A significant reduction of these levels was found in patients who received steroids or cyclophosphamide. Larger studies with further investigations of the precise role of CCN2 in BD pathogenesis might lead to novel therapies for the clinical management of this disease.