bluuebunny/crossref_metadata_2025 huggingface dataset:
SpiderLearner: An ensemble approach to Gaussian graphical model estimation
Authors: Shutta Katherine H. , Balzer Laura B. , Scholtens Denise M. , Balasubramanian Raji
Published: July 2021

Multivariate biological data are often modeled using networks in which nodes represent a biological variable (e.g., genes) and edges represent associations (e.g., coexpression). A Gaussian graphical model (GGM), or partial correlation network, is an undirected graphical model in which a weighted edge between two nodes represents the magnitude of their partial correlation, and the absence of an edge indicates zero partial correlation. A GGM provides a roadmap of direct dependencies between variables, providing a valuable systems-level perspective. Many methods exist for estimating GGMs; estimated GGMs are typically highly sensitive to choice of method, posing an outstanding statistical challenge. We address this challenge by developing SpiderLearner, a tool that combines a range of candidate GGM estimation methods to construct an ensemble estimate as a weighted average of results from each candidate. In simulation studies, SpiderLearner performs better than or comparably to the best of the candidate methods. We apply SpiderLearner to estimate a GGM for gene expression in a publicly available dataset of 260 ovarian cancer patients. Using the community structure of the GGM, we develop a network-based risk score which we validate in six independent datasets. The risk score requires only seven genes, each of which has important biological function. Our method is flexible, extensible, and has demonstrated potential to identifyde novobiomarkers for complex diseases. An open-source implementation of our method is available athttps://github.com/katehoffshutta/SpiderLearner.
A modular protein subunit vaccine candidate produced in yeast confers protection against SARS-CoV-2 in non-human primates
Authors: Dalvie Neil C. , Tostanoski Lisa H. , Rodriguez-Aponte Sergio A , Kaur Kawaljit , Bajoria Sakshi , Kumru Ozan S. , Martinot Amanda J. , Chandrashekar Abishek , McMahan Katherine , Mercado Noe B. , Yu Jingyou , Chang Aiquan , Giffin Victoria M. , Nampanya Felix , Patel Shivani , Bowman Lesley , Naranjo Christopher A. , Yun Dongsoo , Flinchbaugh Zach , Pessaint Laurent , Brown Renita , Velasco Jason , Teow Elyse , Cook Anthony , Andersen Hanne , Lewis Mark G. , Camp Danielle L. , Silverman Judith Maxwell , Kleanthous Harry , Joshi Sangeeta B. , Volkin David B. , Biswas Sumi , Love J. Christopher , Barouch Dan H.
Published: July 2021

Vaccines against SARS-CoV-2 have been distributed at massive scale in developed countries, and have been effective at preventing COVID-19. Access to vaccines is limited, however, in low- and middle-income countries (LMICs) due to insufficient supply, high costs, and cold storage requirements. New vaccines that can be produced in existing manufacturing facilities in LMICs, can be manufactured at low cost, and use widely available, proven, safe adjuvants like alum, would improve global immunity against SARS-CoV-2. One such protein subunit vaccine is produced by the Serum Institute of India Pvt. Ltd. and is currently in clinical testing. Two protein components, the SARS-CoV-2 receptor binding domain (RBD) and hepatitis B surface antigen virus-like particles (VLPs), are each produced in yeast, which would enable a low-cost, high-volume manufacturing process. Here, we describe the design and preclinical testing of the RBD-VLP vaccine in cynomolgus macaques. We observed titers of neutralizing antibodies (>104) above the range of protection for other licensed vaccines in non-human primates. Interestingly, addition of a second adjuvant (CpG1018) appeared to improve the cellular response while reducing the humoral response. We challenged animals with SARS-CoV-2, and observed a ~3.4 and ~2.9 log10reduction in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, compared to sham controls. These results inform the design and formulation of current clinical COVID-19 vaccine candidates like the one described here, and future designs of RBD-based vaccines against variants of SARS-CoV-2 or other betacoronaviruses.
Chromosome-level genome assembly of a human fungal pathogen reveals synteny among geographically distinct species
Authors: Voorhies Mark , Cohen Shirli , Shea Terrance P. , Petrus Semar , Muñoz José F. , Poplawski Shane , Goldman William E. , Michael Todd P. , Cuomo Christina A. , Sil Anita , Beyhan Sinem
Published: July 2021

Histoplasma capsulatum, a dimorphic fungal pathogen, is the most common cause of fungal respiratory infections in immunocompetent hosts. Histoplasma is endemic in the Ohio and Mississippi River Valleys in the United States and also distributed worldwide. Previous studies revealed at least eight clades, each specific to a geographic location: North American classes 1 and 2 (NAm 1 and NAm 2), Latin American groups A and B (LAm A and LAm B), Eurasian, Netherlands, Australian and African, and an additional distinct lineage (H81) comprised of Panamanian isolates. Previously assembled Histoplasma genomes are highly fragmented, with the highly repetitive G217B (NAm 2) strain, which has been used for most whole genome-scale transcriptome studies, assembled into over 250 contigs. In this study, we set out to fully assemble the repeat regions and characterize the large-scale genome architecture of Histoplasma species. We re-sequenced five Histoplasma strains (WU24 (NAm 1), G217B (NAm 2), H88 (African), G186AR (Panama), and G184AR (Panama)) using Oxford Nanopore Technologies long-read sequencing technology. Here we report chromosomal-level assemblies for all five strains, which exhibit extensive synteny among the geographically distant Histoplasma isolates. The new assemblies revealed that RYP2, a major regulator of morphology and virulence, is duplicated in G186AR. In addition, we mapped previously generated transcriptome datasets onto the newly assembled chromosomes. Our analyses revealed that the expression of transposons and transposon-embedded genes are upregulated in yeast phase compared to mycelial phase in G217B and H88 strains. This study provides an important resource for fungal researchers and further highlights the importance of chromosomal-level assemblies in analyzing high-throughput datasets.

Importance

Histoplasma species are dimorphic fungi causing significant morbidity and mortality worldwide. These fungi grow as mold in the soil and as budding yeast within the human host. Histoplasma can be isolated from soil in diverse regions, including North America, South America, Africa and Europe. Phylogenetically distinct species of Histoplasma have been isolated and sequenced. However, for the commonly used strains, genome assemblies have been fragmented, leading to underutilization of genome-scale data. This study provides chromosome-level assemblies of the commonly used Histoplasma strains using long-read sequencing technology. Comparative analysis of these genomes shows largely conserved gene order within the chromosomes. Mapping existing transcriptome data on these new assemblies reveals clustering of transcriptionally co-regulated genes. Results of this study highlight the importance of obtaining chromosome-level assemblies in understanding the biology of human fungal pathogens.
Specific phenotypic, genomic, and fitness evolutionary trajectories toward antibiotic resistance induced by pesticide co-stressors in Escherichia coli
Authors: Xing Yue , Kang Xiaoxi , Zhang Siwei , Men Yujie
Published: July 2021

To explore how co-occurring non-antibiotic environmental stressors affect evolutionary trajectories toward antibiotic resistance, we exposed susceptible Escherichia coli K-12 populations to environmentally relevant levels of pesticides and streptomycin for 500 generations. The coexposure substantially changed the phenotypic, genotypic, and fitness evolution trajectories, resulting in much stronger streptomycin resistance (>15-fold increase) of the populations. Antibiotic target modification mutations in rpsL and rsmG, which emerged and dominated at late stages of evolution, conferred the strong resistance even with less than 1% abundance, while the off-target mutations in nuoG, nuoL, glnE, and yaiW dominated at early stages only led to mild resistance (2.5 – 6-fold increase). Moreover, the strongly resistant mutants exhibited lower fitness costs even without the selective pressure and had lower minimal selection concentrations than the mildly resistant ones. Removal of the selective pressure did not reverse the strong resistance of coexposed populations at a later evolutionary stage. The findings suggest higher risks of the selection and propagation of strong antibiotic resistance in environments potentially impacted by antibiotics and pesticides.
The Polarization Dependence of 2D IR Cross-Peaks Distinguishes Parallel-Stranded and Antiparallel-Stranded DNA G-quadruplexes
Authors: Price David A. , Wedamulla Poornima , Hill Tayler D. , Loth Taylor M. , Moran Sean D.
Published: July 2021

Guanine-rich nucleic acid sequences have a tendency to form four-stranded non-canonical motifs known as G-quadruplexes. These motifs may adopt a wide range of structures characterized by size, strand orientation, guanine base conformation, and fold topology. Using three K+-bound model systems, we show that vibrational coupling between guanine C6=O and ring modes varies between parallel-stranded and antiparallel-stranded G-quadruplexes, and that such structures can be distinguished by comparison of polarization dependent cross-peaks in their two-dimensional infrared (2D IR) spectra. Combined with previously defined vibrational frequency trends, this analysis reveals key features of a 30-nucleotide unimolecular variant of the Bcl-2 proximal promoter that are consistent with its reported structure. This study shows that 2D IR spectroscopy is a convenient method for analyzing G-quadruplex structures that can be applied to complex sequences where traditional high-resolution methods are limited by solubility and disorder.
Rapid sequence evolution is associated with genetic incompatibilities in the plastid Clp complex
Authors: Abdel-Ghany Salah E. , LaManna Lisa M. , Svab Zora , Harroun Haleakala T. , Maliga Pal , Sloan Daniel B.
Published: July 2021

The plastid caseinolytic protease (Clp) complex plays essential roles in maintaining protein homeostasis and comprises both plastid-encoded and nuclear-encoded subunits. Despite the Clp complex being retained across green plants with highly conserved protein sequences in most species, examples of extremely accelerated amino acid substitution rates have been identified in numerous angiosperms. The causes of these accelerations have been the subject of extensive speculation but still remain unclear. To distinguish among prevailing hypotheses and begin to understand the functional consequences of rapid sequence divergence in Clp subunits, we used plastome transformation to replace the native clpP1 gene in tobacco (Nicotiana tabacum) with counterparts from another angiosperm genus (Silene) that exhibits a wide range in rates of Clp protein sequence evolution. We found that antibiotic-mediated selection could drive a transgenic clpP1 replacement from a slowly evolving donor species (S. latifolia) to homoplasmy but that clpP1 copies from Silene species with accelerated evolutionary rates remained heteroplasmic, meaning that they could not functionally replace the essential tobacco clpP1 gene. These results suggest that observed cases of rapid Clp sequence evolution are a source of epistatic incompatibilities that must be ameliorated by coevolutionary responses between plastid and nuclear subunits.
Differential effects of early or late exposure to prenatal maternal immune activation on mouse embryonic neurodevelopment
Authors: Guma Elisa , Bordeleau Maude , Snook Emily , Desrosiers-Grégoire Gabriel , González Ibáñez Fernando , Picard Katherine , Spring Shoshana , Lerch Jason P. , Nieman Brian J. , Devenyi Gabriel A. , Tremblay Marie-Eve , Chakravarty M. Mallar
Published: July 2021

Exposure to maternal immune activation (MIA) in utero is a risk factor for neurodevelopmental and psychiatric disorders. MIA-induced deficits in adolescent and adult offspring have been well characterized, however, less is known about the effects of MIA-exposure on embryo development. To address this gap, we performed high-resolution ex vivo magnetic resonance imaging (MRI) to investigate the effects of early (gestational day [GD]9) and late (GD17) MIA-exposure on embryo (GD18) brain structure. We identify striking neuroanatomical changes in the embryo brain, particularly in the late exposed offspring. We further examined hippocampal neuroanatomy using electron microscopy and identified differential effects due to MIA-timing. An increase in apoptotic cell density was observed in the GD9 exposed offspring, while an increase in the density of dark neurons and glia, putative markers for increased neuroinflammation and oxidative stress, was observed in GD17 exposed offspring, particularly in females. Overall, our findings integrate imaging techniques across different scales to identify differential impact of MIA-timing on the earliest stages of neurodevelopment.
Population model of Temnothorax albipennis as a distributed dynamical system: I. self-consistent threshold is an emergent property in combination of quorum sensing and chemical perception of limited resource
Authors: Qiu Siwei
Published: July 2021

House hunting of ant, such as Temnothorax albipennis, has been shown to be a distributed dynamical system. Such a system includes agent-based algorithm [1], with agents in different roles including nest exploration, nest assessment, quorum sensing, and brood item transportation. Such an algorithm, if used properly, can be applied on artificial intelligent system, like robotic swarms. Despite of its complexity, we are focusing on the quorum sensing mechanism, which is also observed in bacteria model. In bacterial model, multiple biochemical networks co-exist within each cell, including binding of autoinducer and cognate receptors, and phosphorylation-dephosphorylation cycle. In ant hunting, we also have ant commitment to the nest, mimicking binding between autoinducer and cognate receptors. We also have assessment ant specific to one nest and information exchange between two assessment ants corresponding to different nests, which is similar process to the phosphorylation-dephosphorylation cycle in bacteria quorum sensing network. Due to the similarity between the two models, we borrow the idea from bacteria quorum sensing to clarify the definition of quorum threshold through biological plausible mechanism related to limited resource model. We further made use of the contraction analysis to explore the trade-off between decision split and decision consensus within ant population. Our work provides new generation model for understanding how ant adapt to the changing environment during quorum sensing.
CIITA induces expression of MHC-I and MHC-II in transmissible cancers
Authors: Ong Chrissie E. B. , Cheng Yuanyuan , Siddle Hannah V. , Lyons A. Bruce , Woods Gregory M. , Flies Andrew S.
Published: July 2021

MHC-I and MHC-II molecules are critical components of antigen presentation and T cell immunity to pathogens and cancer. The two monoclonal transmissible devil facial tumours (DFT1, DFT2) exploit MHC-I pathways to overcome immunological anti-tumour and allogeneic barriers. This exploitation underpins the ongoing transmission of DFT cells across the wild Tasmanian devil population. We have previously shown that constitutive expression of NLRC5 can induce stable upregulation of MHC-I on DFT1 and DFT2 cells, but unlike IFNG-treated cells, NLRC5 does not upregulate PDL1. MHC-II expression is crucial for CD4+T cell activation and is primarily confined to haematopoietic antigen presenting cells. Transcriptomic analysis of DFT1 and DFT2 cell lines showed that several genes of the MHC-I and MHC-II pathways were upregulated in response to constitutive overexpression of the class II transactivator (CIITA) gene. This was further supported by upregulation of MHC-I protein on DFT1 and DFT2 cells, but interestingly MHC-II protein was upregulated only on DFT1 cells. The functional significance of the MHC upregulation on DFT cells was shown using serum from devils with natural or immunotherapy-induced DFT1 regressions; binding of serum IgG was stronger in CIITA-transfected cells than wild type cells, but was less than binding to NLRC5 transfected cells. This new insight into regulation of MHC-I and MHC-II in cells that naturally overcome allogeneic barriers can inform vaccine, immunotherapy, and tissue transplant strategies for human and veterinary medicine.
A cost-effective and efficient approach for generating and assembling reagents for conducting real-time PCR
Authors: Mote Ridim D , Laxmikant V Shinde , Singh Surya Bansi , Tiwari Mahak , Hemant  , Srivastava Juhi , Tripathi Vidisha , Seshadri Vasudevan , Majumdar Amitabha , Subramanyam Deepa
Published: July 2021

Real-time PCR is a widely used technique for quantification of gene expression. However, commercially available kits for real-time PCR are very expensive. The ongoing coronavirus pandemic has severely hampered the economy in a number of developing countries, resulting in a reduction in available research funding. The fallout of this will result in limiting educational institutes and small enterprises from using cutting edge biological techniques such as real-time PCR. Here, we report a cost-effective approach for preparing and assembling cDNA synthesis and real-time PCR mastermixes with similar efficiencies as commercially available kits. Our results thus demonstrate an alternative to commercially available kits.
Bioimage postprocessing based on discrete wavelet transform and Lucy-Richardson deconvolution methods
Authors: Bai Haoxin , Che Bingchen , Zhao Tianyun , Zhao Wei , Wang Kaige , Zhang Ce , Bai Jintao
Published: July 2021

Accompanied with the increasing requirements of probing micro/nanoscopic structures of biological samples, a variety of image processing algorithms have been developed for visualization or to facilitate data analysis. However, it remains challenging to enhance both the signal-to-noise ratio and image resolution using a single algorithm. In this investigation, we propose an approach utilizing discrete wavelet transform (DWT) in combination with Lucy-Richardson (LR) deconvolution (DWDC). Our results demonstrate that the signal-to-noise ratio and resolution of live cell’s microtubule network are considerably improved, allowing recognition of features as small as 120 nm. Notably, the approach is independent of imaging system and shows robustness in processing fibrous structures, e.g. the cytoskeleton networks.
A Ca2+ wave generates a force during cell extrusion in zebrafish
Authors: Yamada Sohei , Bessho Yasumasa , Fujita Yasuyuki , Hosokawa Yoichiroh , Matsui Takaaki
Published: July 2021

When oncogenic transformed or damaged cells appear within an epithelial sheet, they are apically extruded by surrounding cells. Recently, using cultured mammalian epithelial cells and zebrafish embryonic epithelial cells, we found that a calcium (Ca2+) wave propagates from RasV12-transformed cells and laser-irradiated damaged cells to surrounding cells and promotes apical extrusion by inducing polarized movements of the surrounding cells. In mammalian cell cultures, we reported that the inositol trisphosphate (IP3) receptor, gap junctions, and the mechanosensitive Ca2+ channel TRPC1 are involved in Ca2+ wave-mediated polarized movements. However, which molecules regulate Ca2+ wave-mediated polarized movements in zebrafish and whether the Ca2+ wave can generate a force remain unknown. In this study, we aimed to answer these questions. By performing pharmacological and gene knockout experiments, we showed that a Ca2+ wave induced by the IP3 receptor and trpc1 led to formation of cryptic-lamellipodia and polarized movements of surrounding cells toward extruding cells in zebrafish. By using an in vivo force measurement method, we found that the Ca2+ wave generated approximately 1 kPa of force toward extruding cells. Our results reveal a previously unidentified molecular mechanism underlying the Ca2+ wave in zebrafish and demonstrate that the Ca2+ wave generates a force during cell extrusion.
Conversion rate to the secondary conformation state in the binding mode of SARS-CoV-2 spike protein to human ACE2 may predict infectivity efficacy of the underlying virus mutant
Authors: Sevenich Marc M. , van den Heuvel Joop , Gering Ian , Mohrlüder Jeannine , Willbold Dieter
Published: July 2021

Since its outbreak in 2019 SARS-CoV-2 has spread with high transmission efficiency across the world, putting health care as well as economic systems under pressure [1, 2]. During the course of the pandemic, the originally identified SARS-CoV-2 variant has been widely replaced by various mutant versions, which showed enhanced fitness due to increased infection and transmission rates [3, 4]. In order to find an explanation, why SARS-CoV-2 and its emerging mutated versions showed enhanced transfection efficiency as compared to SARS-CoV 2002, an improved binding affinity of the spike protein to human ACE has been proposed by crystal structure analysis and was identified in cell culture models [5-7]. Kinetic analysis of the interaction of various spike protein constructs with the human ACE2 was considered to be best described by a Langmuir based 1:1 stoichiometric interaction. However, we demonstrate in this report that the SARS-CoV-2 spike protein interaction with ACE2 is best described by a two-step interaction, which is defined by an initial binding event followed by a slower secondary rate transition that enhances the stability of the complex by a factor of ∼190 with an overall KD of 0.20 nM. In addition, we show that the secondary rate transition is not only present in SARS-CoV-2 wt but is also found in B.1.1.7 where its transition rate is five-fold increased.
Allele-resolved single-cell multi-omics uncovers the dynamics and transcriptional kinetics of X-chromosome upregulation
Authors: Lentini Antonio , Cheng Huaitao , Noble JC , Papanicolaou Natali , Coucoravas Christos , Andrews Nathanael , Deng Qiaolin , Enge Martin , Reinius Björn
Published: July 2021

X-chromosome inactivation (XCI) and upregulation (XCU) are the major opposing chromosome-wide modes of gene regulation that collectively achieve dosage compensation in mammals, but the regulatory link between the two remains elusive. Here, we use allele-resolved single-cell RNA-seq combined with chromatin accessibility profiling to finely dissect the separate effects of XCI and XCU on RNA levels during mouse development. We uncover that balanced X dosage is flexibly attained through expression tuning by XCU in a sex- and lineage-specific manner along varying degrees of XCI and across developmental and cellular states. Male blastomeres achieve XCU upon zygotic genome activation while females experience two distinct waves of XCU, upon imprinted- and random XCI, and ablation of Xist impedes female XCU. Contrary to widely established models of mammalian dosage compensation, naïve female embryonic cells carrying two active X chromosomes do not exhibit upregulation but express both alleles at basal level, yet collectively exceeding the RNA output of a single hyperactive allele. We show, in vivo and in vitro, that XCU is kinetically driven by X-specific modulation of transcriptional burst frequency, coinciding with increased compartmentalization of the hyperactive allele. Altogether, our data provide unprecedented insights into the dynamics of mammalian XCU, prompting a revised model of the chain in events of allelic regulation by XCU and XCI in unitedly achieving stable cellular levels of X-chromosome transcripts.
ECM dimensionality tunes actin tension to modulate the endoplasmic reticulum and spheroid phenotype
Authors: Kai FuiBoon , Ou Guanqing , Tourdot Richard W. , Stashko Connor , Gaietta Guido , Swift Mark F. , Volkmann Niels , Long Alexandra F. , Han Yulong , Huang Hector H. , Northey Jason J. , Leidal Andrew M. , Viasnoff Virgile , Bryant David M. , Guo Wei , Wiita Arun P. , Guo Ming , Dumont Sophie , Hanein Dorit , Radhakrishnan Ravi , Weaver Valerie M.
Published: July 2021

Primary tissue organoids and cell spheroids recapitulate tissue physiology with remarkable fidelity. We investigated how engagement with a three dimensional laminin-rich extracellular matrix supports the polarized, stress resilient spheroid phenotype of mammary epithelial cells. Cells within a three dimensional laminin-rich extracellular matrix decreased and redistributed the actin crosslinker filamin to reduce their cortical actin tension. Cells with low cortical actin tension had increased plasma membrane protrusions that promoted negative plasma membrane curvature and fostered protein associations with the plasma membrane, consistent with efficient protein secretion. By contrast, cells engaging a laminin-rich extracellular matrix in two dimensions had high filamin-dependent cortical actin tension, exhibited compromised endoplasmic reticulum function including increased expression of PKR-like Endoplasmic Reticulum Kinase signaling effectors, and had compromised protein secretion. Cells with low filamin-mediated cortical actin tension and reduced endoplasmic reticulum stress response signaling secreted, and assembled, a polarized endogenous basement membrane and survived better, and their spheroids were more resistant to exogenous stress. The findings implicate filamin-dependent cortical actin tension in endoplasmic reticulum function and highlight a role for mechanics in organoid homeostasis.
Autoimmune regulator act in synergism with thymocyte adhesion in the control of lncRNAs in medullary thymic epithelial cells
Authors: Duarte Max Jordan , Mascarenhas Romário S. , Assis Amanda Freire , Tanaka Pedro Paranhos , Speck-Hernandez Cesar A. , Passos Geraldo Aleixo
Published: July 2021

The autoimmune regulator (Aire) gene in medullary thymic epithelial cells (mTECs) encodes the AIRE protein, which interacts with its partners within the nucleus. This “Aire complex” induces stalled RNA Pol II on chromatin to proceed with transcription elongation of a large set of messenger RNAs and microRNAs. Considering that RNA Pol II also transcribes long noncoding RNAs (lncRNAs), we hypothesized that Aire might be implicated in the upstream control of this RNA species. To test this, we employed a loss-of-function approach in which Aire knockout mTECs were compared to Aire wild-type mTECs for lncRNA transcriptional profiling both in vitro and in vivo model systems. RNA sequencing enables the differential expression profiling of lncRNAs when these cells adhere in vitro to thymocytes or do not adhere to them as a way to test the effect of cell adhesion. Sets of lncRNAs that are unique and that are shared in vitro and in vivo were identified. Among these, we found the Aire-dependent lncRNAs as for example, Platr28, Ifi30, Morrbid, Malat1, and Xist. This finding represents the first evidence that Aire mediates the transcription of lncRNAs in mTECs. Microarray hybridizations enabled us to observe that temporal thymocyte adhesion modulates the expression levels of such lncRNAs as Morrbid, Xist, and Fbxl12o after 36h of adhesion. This finding shows the existence of a synergistic mechanism involving a link between thymocyte adhesion, Aire, and lncRNAs in mTECs that might be important for immune self-representation.
A Gradient-based Spectral Explainability Method for EEG Deep Learning Classifiers
Authors: Ellis Charles A. , Sendi Mohammad S.E. , Miller Robyn L. , Calhoun Vince D.
Published: July 2021

The automated feature extraction capabilities of deep learning classifiers have promoted their broader application to EEG analysis. In contrast to earlier machine learning studies that used extracted features and traditional explainability approaches, explainability for classifiers trained on raw data is particularly challenging. As such, studies have begun to present methods that provide insight into the spectral features learned by deep learning classifiers trained on raw EEG. These approaches have two key shortcomings. (1) They involve perturbation, which can create out-of-distribution samples that cause inaccurate explanations. (2) They are global, not local. Local explainability approaches can be used to examine how demographic and clinical variables affected the patterns learned by the classifier. In our study, we present a novel local spectral explainability approach. We apply it to a convolutional neural network trained for automated sleep stage classification. We apply layer-wise relevance propagation to identify the relative importance of the features in the raw EEG and subsequently examine the frequency domain of the explanations to determine the importance of each canonical frequency band locally and globally. We then perform a statistical analysis to determine whether age and sex affected the patterns learned by the classifier for each frequency band and sleep stage. Results showed that δ, β, and γ were the overall most important frequency bands. In addition, age and sex significantly affected the patterns learned by the classifier for most sleep stages and frequency bands. Our study presents a novel spectral explainability approach that could substantially increase the level of insight into classifiers trained on raw EEG.
Modeling microRNA-driven post-transcriptional regulation by using exon-intron split analysis (EISA) in pigs
Authors: Mármol-Sánchez Emilio , Cirera Susanna , Zingaretti Laura M. , Jacobsen Mette Juul , Ramayo-Caldas Yuliaxis , Jørgensen Claus B. , Fredholm Merete , Cardoso Tainã Figueiredo , Quintanilla Raquel , Amills Marcel
Published: July 2021

The contribution of microRNAs (miRNAs) to mRNA regulation has often been explored bypost hocselection of downregulated genes and determining whether they harbor binding sites for miRNAs of interest. This approach, however, does not discriminate whether these mRNAs are also downregulated at the transcriptional level. Here, we have characterized the transcriptional and post-transcriptional changes of mRNA expression in two porcine tissues:gluteus mediusmuscle of fasted and fed Duroc gilts and adipose tissue of lean and obese Duroc-Göttingen minipigs. Exon-intron split analysis (EISA) of RNA-seq data allowed us to identify downregulated mRNAs with high post-transcriptional signals in fed or obese states, and we assessed whether they harbor binding sites for upregulated miRNAs in any of these two physiological states. We found 26 downregulated mRNAs with high post-transcriptional signals in the muscle of fed gilts and 21 of these were predicted targets of upregulated miRNAs also in the fed state. For adipose tissue, 44 downregulated mRNAs in obese minipigs displayed high post-transcriptional signals, and 25 of these were predicted targets of miRNAs upregulated in the obese state. These results suggest that the contribution of miRNAs to mRNA repression is more prominent in the skeletal muscle system. Finally, we identified several genes that may play relevant roles in the energy homeostasis of the pig skeletal muscle (DKK2andPDK4) and adipose (SESN3andESRRG) tissues. By differentiating transcriptional from post-transcriptional changes in mRNA expression, EISA provides a valuable view about the regulation of gene expression, complementary to canonical differential expression analyses.
Emergence of a geometric pattern of cell fates from tissue-scale mechanics in the Drosophila eye
Authors: Gallagher Kevin D. , Mani Madhav , Carthew Richard W.
Published: July 2021

Pattern formation of biological structures involves the arrangement of different types of cells in an ordered spatial configuration. In this study, we investigate the mechanism of patterning the Drosophila eye into a precise triangular grid of photoreceptor clusters called ommatidia. Previous studies had led to a long-standing biochemical model whereby a reaction-diffusion process is templated by recently formed ommatidia to propagate a molecular prepattern across the eye epithelium. Here, we find that the templating mechanism is instead, mechanical in origin; newly born columns of ommatidia serve as a template to spatially pattern cell flows that move the cells in the epithelium into position to form each new column of ommatidia. Cell flow is generated by a pressure gradient that is caused by a narrow zone of cell dilation precisely positioned behind the growing wavefront of ommatidia. The newly formed lattice grid of ommatidia cells are immobile, deflecting and focusing the flow of other cells. Thus, the self-organization of a regular pattern of cell fates in an epithelium is mechanically driven.
Accounting for (public) value(s): reconsidering publicness in accounting research and practice
Authors: Bracci Enrico , Saliterer Iris , Sicilia Mariafrancesca , Steccolini Ileana
Published: July 2021

Purpose

This paper aims to highlight the importance of (public) value(s) and publicness in accounting and accountability research. It pinpoints a range of issues that scholars need to contemplate when reconsidering publicness in accounting research and practice.

Design/methodology/approach

The paper adopts an interdisciplinary literature review associated with a conceptual discussion of the actual and future challenges of public service accounting and accountability in considering public value(s).

Findings

The paper illustrates the centrality of (public) value(s) at the individual, organizational and societal levels in shaping and being shaped by calculative practices, and shows that looking at the interconnections between values and accounting is a fruitful research avenue. Moreover, it highlights the power of embracing interdisciplinary approaches to illuminate these interconnections and relate them to complex and current phenomena.

Originality/value

The paper’s originality lies in the reconsideration of (public) value(s) for public service accounting scholars, providing a critical reflection and setting new research avenues.
Financial ratios and efficiency in Malaysian listed companies
Authors: Alarussi Ali Saleh Ahmed
Published: July 2021

Purpose

This paper examines the financial ratios that may have a significant effect on the efficiency in Malaysian listed companies. Nine financial ratios measure seven variables which are firm visibility, tangibility, working capital, leverage, liquidity, productivity and profitability.

Design/methodology/approach

Data are collected from 108 public listed companies in Malaysia. The data extracted from companies' annual reports for three years 2012–2014. STATA software analysis is used to examine these relationships.

Findings

The results show each of tangibility and liquidity have negative relationships with efficiency ratio. In against of that, profitability, working capital and productively positively link to efficiency. Leverage which is measured by two ratios – Debt ratio and Debt equity ratio – shows mix results. Debt ratio shows a positive but not significant relationship with efficiency ratio and Debt equity ratio shows a negative significant relationship with efficiency ratio.

Practical implications

The results benefit companies, investors, economists and governments regulators in Malaysia-to understand the efficiency determinants, so help to make the right decision to enhance the efficiency level in companies which leads to enhance the amount of investments which in turn, enhance the country's economy in general.

Originality/value

This study differs than previous studies number of aspects: first the study covers a three years' period between 2012 and 2014, this period presents the movement of Malaysian current into depreciation with more than 45 percent of its value. Second, in the Malaysia context, this study examines new variables such as firm visibility, tangibility, and productivity. Third, the results of this study will help managers, shareholders, investors, regulators and other parties to make right decisions that will enhance the level of firm efficiency which enhances the investments and the economy of Malaysia.
A curriculum guide model to the next normal in developing construction supervisory training programmes
Authors: Manoharan Kesavan , Dissanayake Pujitha B.G. , Pathirana Chintha , Deegahawature Dharsana , Silva K.D. Renuka Ruchira
Published: July 2021

Purpose

This study aims to develop a curriculum guide model to upgrade the construction supervision practices, considering evolving challenges and thereby the next normal of the industry.

Design/methodology/approach

Both qualitative and quantitative research designs were adopted to identify productivity-related challenges that can be addressed through effective supervision in construction. Meetings, discussions, workshops and surveys were conducted among construction experts to systematically develop the competencies of construction supervision. The necessary mapping models were used to identify the level of outcomes for each competency element along with the learning domains and programme outcomes.

Findings

A curriculum guide model consisting of 64 competency elements has been introduced with corresponding assessment weightages and mapping outcomes. Using this model, a new training programme has been designed and tested with weightage percentages on learning domains.

Research limitations/implications

Although the scope of the study is limited to Sri Lanka, the findings can be interpreted for critical learning in other developing countries too.

Practical implications

The study outcomes are expected to make a high impact on improving the standards of vocational training education in the country, thereby upgrading the current industry practices.

Originality/value

The developed guide model is expected to be a valuable tool for training providers/organisations in upgrading their programmes/practices with the scope of productivity improvement. The obtained mapping outcomes are significant for the evolving next normal situations in teaching, learning and assessment methods with regard to construction supervision practices.
Design and implementation of artificial magnetic conductor surface as decoupling structure in microstrip antenna arrays
Authors: Shaik Khader Zelani , P. Siddaiah , Prasad K. Satya
Published: July 2021

Purpose

Millimeter wave spectrum represents new opportunities to add capacity and faster speeds for next-generation services as fifth generation (5G) applications. In its Spectrum Frontiers proceeding, the Federal Communications Commision decided to focus on spectrum bands where the most spectrums are potentially available. A low profile antenna array with new decoupling structure is proposed and expected to resonate at higher frequency bands, i.e. millimeter wave frequencies, which are suitable for 5G applications.

Design/methodology/approach

The presented antenna contains artificial magnetic conductor (AMC) surface as decoupling structure. The proposed antenna array with novel AMC surface is operating at 29.1GHz and proven to be decoupling structure and capable of enhancing the isolation by reducing mutual coupling as 8.7dB between the array elements. It is evident that, and overall gain is improved as 10.1% by incorporating 1x2 Array with AMC Method. Mutual coupling between the elements of 1 × 2 antenna array is decreased by 39.12%.

Findings

The proposed structure is designed and simulated using HFSS software and the results are obtained in terms of return loss, gain, voltage standing wave ratio (VSWR) and mutual coupling. The S-Parameters of each stage of design is tabulated and compared with each other to prove the decoupling capability of AMC surface in antenna arrays.

Originality/value

The proposed structure is designed and simulated using HFSS software, and the results are obtained in terms of return loss, gain, VSWR and mutual coupling. The S-Parameters of each stage of design is tabulated and compared with each other to prove the decoupling capability of AMC surface in antenna arrays.
Exploring user experience of learning management system
Authors: Maslov Ilia , Nikou Shahrokh , Hansen Preben
Published: July 2021

Purpose

This paper aims to explore the perspectives of university students on the learning management system (LMS) and determine factors that influence user experience and the outcomes of e-learning.

Design/methodology/approach

This paper employs a mixed-method approach. For qualitative data, 20 semi-structure interviews were conducted. Moreover, for quantitative data, a short survey was developed and distributed among the potential respondents.

Findings

The results showed that students, particularly in programs where courses are mainly offered online, are dependent on such learning platforms. Moreover, the use of modular object-oriented dynamic learning environment (Moodle) as an application of LMS was rated positively, and e-learning was considered as an effective sustainable learning solution in current conditions.

Originality/value

The authors have illustrated empirically how the notion of UX of the LMS provides a means of exploring both students' participation in e-learning and their intention towards using such learning platforms.
Non-compliance behavior of de-risking force the EU to enhance anti-money laundering regulation
Authors: Rose Kalle Johannes
Published: July 2021

Purpose

Recent research shows that because of money-laundering risks, there has been an increase in the off-boarding of certain types of corporate clients in the financial sector. This phenomenon known as “de-risking” has been argued to have a negative impact on society, because it increases the possible risk of money laundering. The purpose of this paper is to analyze whether the de-risking strategy of financial institutions results in an expansion of the regulatory framework concerning anti-money laundering focusing on off-boarding of clients and, if so, is there a way to avoid further regulation by changing present behavior.

Design/methodology/approach

This paper applies functional methods to law and economics to achieve higher efficiency in combating money laundering.

Findings

In this paper, it is found that the continuing of de-risking by financial institutions because of the avoidance strategy of money-laundering risks will inevitably result in further regulatory demands regarding the off-boarding process of clients. The legal basis for the introduction of further regulatory intervention is that some of the de-risking constitutes a direct contradiction to the aim of the present regulatory framework, making the behavior non-compliant to the regulation.

Originality/value

There has been very little research concerning de-risking related to money laundering. The present research has focused on the effect on society and not the relationship between the financial institutions and the regulator. This paper raises an important and present problem, as the behavior of the financial institutions constitute a response from the regulator that is contradicting the thoughts behind the behavior of the financial institutions. It is found that the paper is highly relevant if an expansion of regulation is to be hindered.
The commons institution of Antarctica: a roadmap to governance of mankind resources
Authors: Arvanitidis Paschalis , Almyriotou Aikaterini
Published: July 2021

Purpose

This paper aims to draw on Ostrom’s commons theory to analyse the governance regime of Antarctic as a commons institution. Antarctic is a peculiar territorial space on Earth, which due to its unique characteristics constitutes a global common resource that very much resembles outer space resources. On these grounds, the paper highlights successful, and less successful, arrangements developed in the Antarctic commons to be considered as a blueprint or roadmap towards the governance of outer space resources as a commons.

Design/methodology/approach

The paper uses first, the social-ecological system (SES) framework to outline the characteristics of Antarctic as a commons institution, and second, Ostrom’s design principles to assess the commons institution of Antarctic. The Antarctic commons institution is used next, as an analogy to reflect on the challenges outer space global resource face and the way it could be managed.

Findings

The paper concludes that Antarctic enjoys a functional, credible and successful commons institution that should reinforce the twofold governance structure it exhibits. Similar cases of global common resources, such as these of outer space, that seek to establish a similar commons institution should take into account issues related the benefits spectrum and the credible commitment of actors to engage in different levels of the governance regime. What matters is not necessarily the form of the regime but rather how the commons as an institution functions, whether it fulfils the needs and interests of the driving actors and, on these grounds, how credible these arrangements are in the eyes of the committed members.

Research limitations/implications

Both Antarctica and outer space are rather unique cases and domains of multiple resources.

Practical implications

The paper provides an analogy to consider sustainable appropriation of global resources (“global commons”) for peace and prosperity to all.

Originality/value

The paper is original, in the sense that according to the best of the authors’ knowledge, no published work has identified Antarctic as a commons institution or has used the aforementioned methodologies to analyse Antarctica as a commons and to employ their findings in providing directions for the design of appropriate governance frameworks for other resources that exhibit the characteristics of global commons, such as these of the outer space.
The future of food tourism in a post-COVID-19 world: insights from New Zealand
Authors: Fountain Joanna
Published: July 2021

Purpose

This paper considers two sectors critical to New Zealand's economy and identity – food and tourism – and addresses the question: what role will – or could – food and drink play in a more resilient tourism future for the country?

Design/methodology/approach

This is largely a conceptual paper, informed by the academic literature, media commentary and recent market research.

Findings

The paper concludes that there are trends apparent in the food and tourism sectors prior to the COVID-19 pandemic that have intensified during lockdown and which are likely to influence the resetting of tourism on a more resilient and regenerative pathway. Three potential trends in food and drink tourism are identified, labelled “Getting back to basics”, “Valuing local and locals” and “Food for well-being”.

Originality/value

By synthesising recent research and academic, industry and media commentaries, this paper provides a timely assessment of a potential future role of food and drink tourism in a reimagined tourism sector for New Zealand, with this assessment offering a starting point for further discussions about a more regenerative, equitable and inclusive tourism future.