bluuebunny/crossref_metadata_2025_split huggingface dataset:
The transcription factor STAT5 binds to distinct super-enhancer sites and controlsLrrc32expression in a prominent autoimmune and allergic disease risk locus
Authors: Hennighausen Lothar , Lee Hye Kyung 
Published: June 2020

SummaryGenetic variants associated with diseases are enriched in genomic sequences linked to regulatory regions, such as enhancers, super-enhancers and possibly repressors, that control nearby and distant genes. A known allergic and autoimmune risk locus at chromosome 11q13.51,2is associated with theLRRC32gene, which encodes GARP, a protein critical for TGF-β delivery3. This region coincides with a candidate enhancer that was predicted by the presence of activating chromatin marks and contains a polymorphism significantly associated with GARP expression on CD4+CD127-CD25+Tregcells4. In the mouse, binding of the cytokine-induced transcription factor STAT5 was detected at two sites within the expansive candidate enhancer region and a 2.3 kb deletion resulted in reducedLrrc32expression4. However, a clear definition of the enhancer units controlled by STAT5 and a functional understanding of STAT5 in the regulation ofLrrc32are needed. Here we use high-resolution ChIP-seq and identify three STAT5 binding sites within theLrrc32super-enhancer, one shared between Tregcells and mammary epithelium and one specific to each respective cell type. Using mice that express only 10% of normal STAT5 levels we demonstrate the defining contribution of STAT5 in the activation of theLrrc32super-enhancer.
Trade-offs and design principles in the spatial organization of catalytic particles
Authors: Hinzpeter Florian , Tostevin Filipe , Buchner Alexander , Gerland Ulrich 
Published: June 2020

AbstractSpatial organization of catalytic particles is ubiquitous in biological systems across different length scales, from enzyme complexes to metabolically coupled cells. Despite the different scales, these systems share common features of localized reactions with partially hindered diffusive transport, determined by the collective arrangement of the catalysts. Yet it remains largely unexplored how different arrangements affect the interplay between the reaction and transport dynamics, which ultimately determines the flux through the reaction pathway. Here we show that two fundamental trade-offs arise, the first between efficient inter-catalyst transport and depletion of substrate, and the second between steric confinement of intermediate products and accessibility of catalysts to substrate. We use a model reaction pathway to characterize the general design principles for the arrangement of catalysts that emerge from the interplay of these trade-offs. We find that the question of optimal catalyst arrangements generalizes the famous Thomson problem of electrostatics.
Metal-Organic Framework Encapsulated Whole-Cell Vaccines Enhance Humoral Immunity against Bacterial Infection
Authors: Luzuriaga Michael A. , Herbert Fabian C. , Brohlin Olivia R. , Gadhvi Jashkaran , Howlett Thomas , Shahrivarkevishahi Arezoo , Wijesundara Yalini H. , Venkitapathi Sundharamani , Veera Kavya , Ehrman Ryanne , Benjamin Candace E. , Popal Sarah , Burton Michael D. , Ingersoll Molly A. , De Nisco Nicole J. , Gassensmith Jeremiah J. 
Published: June 2020

AbstractThe increasing rate of resistance of bacterial infection against antibiotics requires next generation approaches to fight potential pandemic spread. The development of vaccines against pathogenic bacteria has been difficult owing, in part, to the genetic diversity of bacteria. Hence, there are many potential target antigens and littlea prioriknowledge of which antigen/s will elicit protective immunity. The painstaking process of selecting appropriate antigens could be avoided with whole-cell bacteria; however, whole-cell formulations typically fail to produce long-term and durable immune responses. These complications are one reason why no vaccine against any type of pathogenicE. colihas been successfully clinically translated. As a proof of principle, we demonstrate a method to enhance the immunogenicity of a model pathogenicE. colistrain by forming a slow releasing depot. TheE. colistrain CFT073 was biomimetically mineralized within a metal-organic framework (MOF). This process encapsulates the bacteria within 30 minutes in water and at ambient temperatures. Vaccination with this new formulation substantially enhances antibody production and results in significantly enhanced survival in a mouse model of bacteremia compared to standard inactivated formulations.
Ionophore antibiotic X-206 is a potent and selective inhibitor of SARS-CoV-2 infectionin vitro
Authors: Svenningsen Esben B. , Thyrsted Jacob , Blay-Cadanet Julia , Liu Han , Lin Shaoquan , Villameriel Jaime Moyano , Olagnier David , Idorn Manja , Paludan Søren R. , Holm Christian K. , Poulsen Thomas B. 
Published: June 2020

AbstractPandemic spread of emerging human pathogenic viruses such as the current SARS-CoV-2, poses both an immediate and future challenge to human health and society. Currently, effective treatment of infection with SARS-CoV-2 is limited and broad spectrum antiviral therapies to meet other emerging pandemics are absent leaving the World population largely unprotected. Here, we have identified distinct members of the family of polyether ionophore antibiotics with potent ability to inhibit SARS-CoV-2 replication and cytopathogenicity in cells. Several compounds from this class displayed more than 100-fold selectivity between viral-induced cytopathogenicity and inhibition of cell viability, however the compound X-206 displayed >500-fold selectivity and was furthermore able to inhibit viral replication even at sub-nM levels. The antiviral mechanism of the polyether ionophores is currently not understood in detail. We demonstrate, through unbiased bioactivity profiling, that their effects on the host cells differ from those of cationic amphiphiles such as hydroxychloroquine. Collectively, our data suggest that polyether ionophore antibiotics should be subject to further investigations as potential broad-spectrum antiviral agents.
3D microarchitecture of the human tuberculous granuloma
Authors: Wells Gordon , Glasgow Joel N. , Nargan Kievershen , Lumamba Kapongo , Madansein Rajhmun , Maharaj Kameel , Hunter Robert L. , Naidoo Threnesan , Ramdial Pratista , Coetzer Llelani , le Roux Stephan , du Plessis Anton , Steyn Adrie J.C. 
Published: June 2020

AbstractOur current understanding of the pathophysiology of human pulmonary TB is limited by the paucity of human TB lung tissue for study and reliance on 2D analytical methods. Here, to overcome the limitations of conventional 2D histopathology, we used high-resolution 3D X-ray imaging (µCT/nCT) to characterize necrotic lesions within human tuberculous lung tissues in relation to the airways and vasculature. We observed marked heterogeneity in the 3D structure and volume of lesions. Also, 3D imaging of large human TB lung sections provides unanticipated new insight into the spatial organization of TB lesions in relation to airways and the vascular system. Contrary to the current dogma depicting granulomas as simple spherical structures, we show that TB lesions exhibit complex, cylindrical, branched-type morphologies, which are connected to, and shaped by, the small airways. Our results highlight the likelihood that a single structurally complex lesion could be wrongly viewed as multiple independent lesions when evaluated in 2D. These findings have strong implications for understanding the pathophysiology and evolution of TB disease and suggest that aerosolized drug delivery strategies for TB should be reconsidered.
The changing mouse embryo transcriptome at whole tissue and single-cell resolution
Authors: He Peng , Williams Brian A. , Trout Diane , Marinov Georgi K. , Amrhein Henry , Berghella Libera , Goh Say-Tar , Plajzer-Frick Ingrid , Afzal Veena , Pennacchio Len A. , Dickel Diane E. , Visel Axel , Ren Bing , Hardison Ross C. , Zhang Yu , Wold Barbara J. 
Published: June 2020

AbstractIn mammalian embryogenesis differential gene expression gradually builds the identity and complexity of each tissue and organ system. We systematically quantified mouse polyA-RNA from embryo day E10.5 to birth, sampling 17 whole tissues, enhanced with single-cell measurements for the developing limb. The resulting developmental transcriptome is globally structured by dynamic cytodifferentiation, body-axis and cell-proliferation gene sets, characterized by their promoters’ transcription factor (TF) motif codes. We decomposed the tissue-level transcriptome using scRNA-seq and found that neurogenesis and haematopoiesis dominate at both the gene and cellular levels, jointly accounting for 1/3 of differential gene expression and over 40% of identified cell types. Integrating promoter sequence motifs with companion ENCODE epigenomic profiles identified a promoter de-repression mechanism unique to neuronal expression clusters and attributable to known and novel repressors. Focusing on the developing limb, scRNA-seq identified 25 known and candidate novel cell types, including progenitor and differentiating states with computationally inferred lineage relationships. We extracted cell type TF networks and complementary sets of candidate enhancer elements by de-convolving whole-tissue IDEAS epigenome chromatin state models. These ENCODE reference data, computed network components and IDEAS chromatin segmentations, are companion resources to the matching epigenomic developmental matrix, available for researchers to further mine and integrate.
Improving representations of genomic sequence motifs in convolutional networks with exponential activations
Authors: Koo Peter K. , Ploenzke Matt 
Published: June 2020

ABSTRACTDeep convolutional neural networks (CNNs) trained on regulatory genomic sequences tend to build representations in a distributed manner, making it a challenge to extract learned features that are biologically meaningful, such as sequence motifs. Here we perform a comprehensive analysis on synthetic sequences to investigate the role that CNN activations have on model interpretability. We show that employing an exponential activation to first layer filters consistently leads to interpretable and robust representations of motifs compared to other commonly used activations. Strikingly, we demonstrate that CNNs with better test performance do not necessarily imply more interpretable representations with attribution methods. We find that CNNs with exponential activations significantly improve the efficacy of recovering biologically meaningful representations with attribution methods. We demonstrate these results generalise to real DNA sequences across severalin vivodatasets. Together, this work demonstrates how a small modification to existing CNNs, i.e. setting exponential activations in the first layer, can significantly improve the robustness and interpretabilty of learned representations directly in convolutional filters and indirectly with attribution methods.
Transcriptional networks are dynamically regulated during cell cycle progression in human Pluripotent Stem Cells
Authors: Osnato Anna , Brown Stephanie , Vallier Ludovic 
Published: June 2020

SummaryCell cycle progression follows a precise sequence of events marked by different phases and checkpoints which are associated with specific chromatin organisation. Whilst these changes have been extensively studied, their consequences on transcriptional networks remain to be fully uncovered, especially in dynamic model systems such as stem cells. Here, we take advantage of the FUCCI reporter system to show that chromatin accessibility, gene expression and key transcription factors binding change during cell cycle progression in human Embryonic Stem Cells (hESCs). These analyses reveal that core pluripotency factors such as OCT4, NANOG and SOX2 but also chromatin remodelers such as CTCF and RING1B bind the genome at specific phases of the cell cycle. Importantly, this binding pattern allows differentiation in the G1 phase while preserving pluripotency in the S/G2/M. Our results highlight the importance of studying transcriptional and epigenetic regulations in the dynamic context of the cell cycle.
Global epistasis emerges from a generic model of a complex trait
Authors: Reddy Gautam , Desai Michael M. 
Published: June 2020

AbstractEpistasis between mutations can make adaptation contingent on evolutionary history. Yet despite widespread “microscopic” epistasis between the mutations involved, microbial evolution experiments show consistent patterns of fitness increase between replicate lines. Recent work shows that this consistency is driven in part by global patterns of diminishing-returns and increasing-costs epistasis, which make mutations systematically less beneficial (or more deleterious) on fitter genetic backgrounds. However, the mechanistic basis of this “global” epistasis remains unknown. Here we show that diminishing-returns and increasing-costs epistasis emerge generically as a consequence of pervasive microscopic epistasis. Our model predicts a specific quantitative relationship between the magnitude of global epistasis and the stochastic effects of microscopic epistasis, which we confirm by re-analyzing existing data. We further show that the distribution of fitness effects takes on a universal form when epistasis is widespread, and introduce a novel fitness landscape model to show how phenotypic evolution can be repeatable despite sequence-level stochasticity.
Measurement and assessment of accounting research, impact and engagement
Authors: O'Connell Brendan Thomas , De Lange Paul , Martin-Sardesai Ann , Agyemang Gloria 
Published: June 2020

PurposeThe purpose of this paper is to examine prominent issues and knowledge contributions from research exploring measurement and assessment of accounting research, impact and engagement. This paper also provides an overview of the other papers presented in this AAAJ Special Issue and draws from their findings to scope out future impactful research opportunities in this area.Design/methodology/approachConsists of a review and examination of the prior literature and the other papers published in this AAAJ Special Issue.FindingsThe paper identifies and summarises three key research themes in the extant literature: research productivity of accounting academics; the rise of the “Corporate University” and commodification of research; and, the benefits and limitations of Research Assessment Exercises. It draws upon work within these research themes to set out four broad areas for future impactful research.Research limitations/implicationsThe value of this paper rests with collating and synthesising several important research themes on the nature and impact of measurement and assessment of accounting research, impact and engagement, and in prompting future extensions of this work through setting out areas for further innovative research in the area.Practical implicationsThe research examined in this paper and the future research avenues proposed are highly relevant to university academics, administrators and regulators/policymakers. They also offer important insights into matters of accounting measurement, accountability, and control more generally.Originality/valueThis paper adds to vibrant existing streams of research in the area by bringing together authors from different areas of accounting research for this AAAJ Special Issue. In scoping out an agenda for impactful research in the nature and impact of measurement and assessment of accounting research, impact and engagement, this paper also draws attention to underexplored issues pertaining to areas such as the “lived experience” of academics in the corporatised university and envisioning what a future “optimal” system of measurement and assessment of research quality might look like?
Enhancing classroom instruction with online news
Authors: Ekstrand Michael D. , Wright Katherine Landau , Pera Maria Soledad 
Published: June 2020

PurposeThis paper investigates how school teachers look for informational texts for their classrooms. Access to current, varied and authentic informational texts improves learning outcomes for K-12 students, but many teachers lack resources to expand and update readings. The Web offers freely available resources, but finding suitable ones is time-consuming. This research lays the groundwork for building tools to ease that burden.Design/methodology/approachThis paper reports qualitative findings from a study in two stages: (1) a set of semistructured interviews, based on the critical incident technique, eliciting teachers' information-seeking practices and challenges; and (2) observations of teachers using a prototype teaching-oriented news search tool under a think-aloud protocol.FindingsTeachers articulated different objectives and ways of using readings in their classrooms, goals and self-reported practices varied by experience level. Teachers struggled to formulate queries that are likely to return readings on specific course topics, instead searching directly for abstract topics. Experience differences did not translate into observable differences in search skill or success in the lab study.Originality/valueThere is limited work on teachers' information-seeking practices, particularly on how teachers look for texts for classroom use. This paper describes how teachers look for information in this context, setting the stage for future development and research on how to support this use case. Understanding and supporting teachers looking for information is a rich area for future research, due to the complexity of the information need and the fact that teachers are not looking for information for themselves.
Beyond the horizon of words: silent landscape experience within spiritual retreat tourism
Authors: Mourtazina Ellina 
Published: June 2020

Purpose
The purpose of this paper is to explore the notion and function of silent landscape in a touristic experience by presenting the findings of a study on silent retreats in a Buddhist meditation retreat center in Northern India.

Design/methodology/approach
This study adopted a sensory ethnography approach applied through interviews and participant observation methods conducted during and after nine retreats in a meditation center.

Findings
This study suggests that silent landscapes are not only backdrops of touristic experiences but can be considered as inter-subjective performative and resourceful milieu of engagement that intertwine intimate embodied experiences with broader social and cultural values.

Originality/value
Despite landscapes having been thoroughly investigated in tourist studies, this paper underlines the pertinence of mobilizing the lens of other forms of presences such as affects, embodiment, sensoriality and sonority to understand the inter-relation between tourists-selves and the surrounding world encountered during their travels.
Low-cost IoT framework for irrigation monitoring and control
Authors: Borah Siddhanta , Kumar R. , Mukherjee Subhradip 
Published: June 2020

PurposeThe purpose of this work is to make an IoT-based low-cost and power-efficient portable system to control irrigation using a threshold value algorithm and to measure soil-irrigation-related parameters such as soil moisture, soil temperature, humidity and air temperature.Design/methodology/approachThis paper presents a threshold value algorithm to optimize power consumption and to control irrigation process.FindingsThe system uses ESP-12F 8266 as the main microcontroller unit to monitor and control irrigation system. The system also consists of an actuator system that triggers automatically based on a threshold value algorithm. An open-source cloud platform is used to monitor and store all the data for future perspective. To make the system run for a long time without any human intervention, a solar panel is used as an alternate source of energy for charging the 12V lithium-ion battery. The battery takes 2.64 h for full charging considering peak intensity of sunlight. A capacitive moisture sensor is included using less expensive 555 timer and calibrated to measure water content in the soil. The 555 timer is used in astable mode of configuration to generate a signal of 572 KHz. The calibrated sensor data when compared with a standard SEN0193 moisture sensor shows an error of 3.4%. The prototype model is made to optimize the power consumption. This can be achieved by utilizing sleep mode of ESP-12F 8266. The total cost involved to make the system is 3900.55 Indian rupees and around US$54.90.Practical implicationsThe device is tested in a flower garden during winter season of Nagaland, India, for 75 days to collect all the data and to automate the irrigation process.Originality/valueThe proposed threshold value algorithm optimizes the power consumption of the device, and wastage of water is reduced up to 60% as compared to the traditional method of irrigation.
The relationship between corporate governance, corporate characteristics and agricultural credit supply: evidence from Bangladesh
Authors: Mehedi Sohel , Rahman Habibur , Jalaludin Dayana 
Published: June 2020

PurposeThe paper aims to examine the level of agricultural credit by commercial banks and the determinants that influence the commercial banks to the increased level of agricultural credit through the pressures of the institutional environment.Design/methodology/approachThe study selects seventeen sample commercial banks following the market capitalization method and investigates a total of 85 annual reports during the period from 2013 to 2017. The study conducts a pooled regression to conclude the proposed hypotheses.FindingsThe present study finding indicates that the average of agricultural credits to total credits is 2.25% among the sample commercial banks. The study finds a positive significant association between board gender diversity, foreign director, management team and agricultural credit. Furthermore, the study has found that the role of the deposit in enhancing agricultural credit is positive. On the other hand, the association between independent directors, profitability and agricultural credits is negative.Research limitations/implicationsThe study is based on secondary data with five firm-year observations of commercial banks. The study finding is based on commercial banks, so it should not be generalized to non-bank financial institutions.Practical implicationsThe study emphasizes policymakers’ attention towards the level of agricultural credit and determinants that influence the level of agricultural credit by commercial banks in emerging markets.Originality/valueThe key contribution of the study is to focus on the reformist role of the determinants in promoting the increased level of agricultural credit in the emerging markets.
Numerical study of fatigue damage under random loading using Rainflow cycle counting
Authors: Kebir Tayeb , Correia José A.F.O. , Benguediab Mohamed , Jesus Abilio M.P. De 
Published: June 2020

PurposeThe purpose of this scientific work is to simulate the fatigue damage under random loading, taking into account the mean stress effect on fatigue lifetime and using the Rainflow counting technique to assess the fatigue damage by the Ansys software. The used material is aluminum alloy 6082-T6. A comparison with literature results has confirmed this investigation in this paper.Design/methodology/approachThe study of fatigue under random loading is based on the same concepts as constant loading with the addition of damage summation. The proportion of damage caused by a stress cycle depends not only on the alternating stress but also on the mean stress.FindingsAnalysis of the fatigue damage shows that the number of relative damage due to each cycle.Originality/valueThis paper aims to simulate the fatigue damage under random loading for aluminum alloys.