bluuebunny/crossref_metadata_2025_split huggingface dataset:
The fundamental principles of reproducibility
Authors: Gundersen Odd Erik 
Published: March 2021

Reproducibility is a confused terminology. In this paper, I take a fundamental view on reproducibility rooted in the scientific method. The scientific method is analysed and characterized in order to develop the terminology required to define reproducibility. Furthermore, the literature on reproducibility and replication is surveyed, and experiments are modelled as tasks and problem solving methods. Machine learning is used to exemplify the described approach. Based on the analysis, reproducibility is defined and three different degrees of reproducibility as well as four types of reproducibility are specified.This article is part of the theme issue ‘Reliability and reproducibility in computational science: implementing verification, validation and uncertainty quantificationin silico’.
VECMAtk: a scalable verification, validation and uncertainty quantification toolkit for scientific simulations
Authors: Groen D. , Arabnejad H. , Jancauskas V. , Edeling W. N. , Jansson F. , Richardson R. A. , Lakhlili J. , Veen L. , Bosak B. , Kopta P. , Wright D. W. , Monnier N. , Karlshoefer P. , Suleimenova D. , Sinclair R. , Vassaux M. , Nikishova A. , Bieniek M. , Luk Onnie O. , Kulczewski M. , Raffin E. , Crommelin D. , Hoenen O. , Coster D. P. , Piontek T. , Coveney P. V. 
Published: March 2021

We present the VECMA toolkit (VECMAtk), a flexible software environment for single and multiscale simulations that introduces directly applicable and reusable procedures for verification, validation (V&V), sensitivity analysis (SA) and uncertainty quantication (UQ). It enables users to verify key aspects of their applications, systematically compare and validate the simulation outputs against observational or benchmark data, and run simulations conveniently on any platform from the desktop to current multi-petascale computers. In this sequel to our paper on VECMAtk which we presented last year [1] we focus on a range of functional and performance improvements that we have introduced, cover newly introduced components, and applications examples from seven different domains such as conflict modelling and environmental sciences. We also present several implemented patterns for UQ/SA and V&V, and guide the reader through one example concerning COVID-19 modelling in detail.This article is part of the theme issue ‘Reliability and reproducibility in computational science: implementing verification, validation and uncertainty quantificationin silico’.
Whole-exome sequencing in 16,511 individuals reveals a role of the HTRA1 protease and its substrate EGFL8 in brain white matter hyperintensities
Authors: Malik Rainer , Beaufort Nathalie , Frerich Simon , Gesierich Benno , Georgakis Marios K , Rannikmäe Kristiina , Ferguson Amy C , Haffner Christof , Traylor Matthew , Ehrmann Michael , Sudlow Cathie LM , Dichgans Martin 
Published: March 2021

ABSTRACTWhite matter hyperintensities (WMH) are among the most common radiological abnormalities in the ageing population and an established risk factor for stroke and dementia. While common variant association studies have revealed multiple genetic loci with an influence on WMH volume, the contribution of rare variants to WMH burden in the general population remains largely unexplored. We conducted a comprehensive analysis of WMH burden in the UK Biobank using publicly available whole-exome sequencing data (N=16,511) and found a splice-site variant in GBE1, encoding 1,4-alpha-glucan branching enzyme 1, to be associated with lower white matter burden on an exome-wide level (c.691+2T>C, beta=-0.74, se=0.13, p=9.7E-9). Applying whole-exome gene-based burden tests, we found damaging missense and loss-of-function variants in HTRA1 to associate with increased WMH volume (p=5.5E-6, FDR=0.04). HTRA1 encodes a secreted serine protease implicated in familial forms of small vessel disease. Domain-specific burden tests revealed that the association with WMH volume was restricted to rare variants in the protease domain (amino acids 204-364; beta=0.79, se=0.14, p=9.4E-8). The frequency of such variants in the UK Biobank population was 1 in 450. WMH volume was brought forward by approximately 11 years in carriers of a rare protease domain variant. A comparison with the effect size of established risk factors for WMH burden revealed that the presence of a rare variant in the HTRA1 protease domain corresponded to a larger effect than meeting the criteria for hypertension (beta=0.26, se=0.02, p=2.9E-59) or being in the upper 99.8% percentile of the distribution of a polygenic risk score based on common genetic variants (beta=0.44, se=0.14, p=0.002). In biochemical experiments, most (6/9) of the identified protease domain variants resulted in a markedly reduced protease activity. We further found EGFL8, which showed suggestive evidence for association with WMH volume (p=1.5E-4, FDR=0.22) in gene burden tests, to be a direct substrate of HTRA1 and to be preferentially expressed in cerebral arterioles and arteries. In a phenome-wide association study (PheWAS) mapping ICD-10 diagnoses to 741 standardized Phecodes, rare variants in the HTRA1 protease domain were associated with multiple neurological and non-neurological conditions including migraine with aura (OR=12.24, 95%CI [2.54-35.25], p=8.3E-5). Collectively, these findings highlight an important role of rare genetic variation and of the HTRA1 protease in determining WMH burden in the general population.
Some Mathematics for the Method of Pooled PCR Test
Authors: Otsu Nobuyuki ,   Honorable Researcher of AIST
Published: March 2021

AbstractAt the time of the worldwide COVID-19 disaster, the author learned about the pooled (RT-) PCR test from the news. From the common sense of individual tests, the idea of mixing multiple samples seems taboo, however in fact many samples can be tested with a smaller number of tests by the method. As a retired researcher of mathematical engineering, the author was deeply interested in the idea and absorbed in the mathematical formulation and intensive analysis of the method.Later, he found that the original basic equation was already proposed in the old (1943) treatise [1] and so many related research works have been done and available as materials on the web [2], although many of those seem to be based on qualitative or intuitive analysis. In that sense, some of the analysis here seems to be already known in the field, but some results might be novel, such as boundary conditions, derivation of limit values, estimation of infection rate and adaptive optimization scheme of pool test, strict extension to multi-stage pool test, and explicit derivation of asymptotic approximate solutions of optimal pooling number and achieved efficiency measure, etc.In any case, he decided to put it together here as a material rather than a formal treatise, hoping that the results here would be useful for deeper mathematical insights into and better understanding of the pool inspection, and also in its actual practice.
Transcriptome and Functions of Granulocytic Myeloid-Derived Suppressor Cells Determine their Association with Disease Severity of COVID-19
Authors: Dean Matthew J. , Ochoa Juan B. , Sanchez-Pino Maria , Zabaleta Jovanny , Garai Jone , Del Valle Luis , Wyczechowska Dorota , Buckner Lyndsey , Philbrook Phaethon , Majumder Rinku , Heide Richard Vander , Dunkenberger Logan , Thylur Ramesh , Nossaman Robert , Roberts W. Mark , Chapple Andrew , Collins Jack , Luke Brian , Johnson Randall , Koul Hari , Rees Christopher A. , Morris Claudia R. , Garcia-Diaz Julia , Ochoa Augusto C. 
Published: March 2021

ABSTRACTCOVID-19 ranges from asymptomatic in 35% of cases to severe in 20% of patients. Differences in the type and degree of inflammation appear to determine the severity of the disease. Recent reports show an increase in circulating monocytic-myeloid-derived suppressor cells (M-MDSC) in severe COVID 19, that deplete arginine but are not associated with respiratory complications. Our data shows that differences in the type, function and transcriptome of Granulocytic-MDSC (G-MDSC) may in part explain the severity COVID-19, in particular the association with pulmonary complications. Large infiltrates by Arginase 1+ G-MDSC (Arg+G-MDSC), expressing NOX-1 and NOX-2 (important for production of reactive oxygen species) were found in the lungs of patients who died from COVID-19 complications. Increased circulating Arg+G-MDSC depleted arginine, which impaired T cell receptor and endothelial cell function. Transcriptomic signatures of G-MDSC from patients with different stages of COVID-19, revealed that asymptomatic patients had increased expression of pathways and genes associated with type I interferon (IFN), while patients with severe COVID-19 had increased expression of genes associated with arginase production, and granulocyte degranulation and function. These results suggest that asymptomatic patients develop a protective type I IFN response, while patients with severe COVID-19 have an increased inflammatory response that depletes arginine, impairs T cell and endothelial cell function, and causes extensive pulmonary damage. Therefore, inhibition of arginase-1 and/or replenishment of arginine may be important in preventing/treating severe COVID-19.
Adolescent ethanol exposure decreases cholinergic markers, blunts behaviorally-evoked acetylcholine and increases in apical dendritic branching within the orbital frontal cortex
Authors: Kipp BT , Nunes PT , Galaj E , Hitchcock B , Nasra T , Poynor KR , Heide SK , Reitz NL , Savage LM 
Published: March 2021

AbstractDuring adolescence, heavy binge-like ethanol consumption can lead to frontocortical structural and functional impairments. These impairments are likely driven by adolescence being a critical time point for maturation of brain regions associated with higher-order cognitive functioning. Rodent models of heavy binge-like ethanol exposure show consistent disruptions to the typical development of the prefrontal cortex (PFC). All deep cortical layers receive cholinergic projections that originate from the Nucleus basalis of Meynert (NbM) complex. These cholinergic projections are highly involved in learning, memory, and attention. Adolescent intermittent ethanol exposure (AIE) induces cholinergic dysfunction as a result of an epigenetic suppression of the genes that drive the cholinergic phenotype. The current study used a model of AIE to assess structural and functional changes to the frontal cortex and NbM following binge-like ethanol exposure in adolescence. Western blot analysis revealed long-term disruptions of the cholinergic circuit following AIE: choline acetyltransferase (ChAT) was suppressed in the NbM and vesicular acetylcholine transporter (VAChT) was suppressed in the orbitofrontal cortex (OFC). In vivo microdialysis for acetylcholine efflux during a spatial memory task determined changes in cholinergic modulation within the PFC following AIE. However, AIE spared performance on the spatial memory task and on an operant reversal task. In a second study, Golgi-Cox staining determined that AIE increased apical dendritic complexity in the OFC, with sex influencing whether the increase in branching occurred near or away from the soma. Spine density or maturity was not affected, likely compensating for a disruption in neurotransmitter function following AIE.Significance StatementAdolescent ethanol exposure decreases cholinergic markers in the basal forebrain to orbital frontal cortical circuit, which lead to a massive suppression of behaviorally-activated tonic release acetylcholine and sex-dependent increases in dendritic branching. We concluded that cholinergic dysfunction is a contributor to cognitive impairments associated with heavy alcohol exposure during adolescence.Data SharingThe data that support the findings of this study are available from the corresponding author upon reasonable request.
ModPhred: an integrative toolkit for the analysis and storage of nanopore sequencing DNA and RNA modification data
Authors: Pryszcz Leszek P. , Novoa Eva Maria 
Published: March 2021

SUMMARYMotivationDNA and RNA modifications can now be identified using Nanopore sequencing. However, we currently lack a flexible software to efficiently encode, store, analyze and visualize DNA and RNA modification data.ResultsHere we presentModPhred, a versatile toolkit that facilitates DNA and RNA modification analysis from nanopore sequencing reads in a user-friendly manner.ModPhredintegrates probabilistic DNA and RNA modification information within the FASTQ and BAM file formats, can be used to encode multiple types of modifications simultaneously, and its output can be easily coupled to genomic track viewers, facilitating the visualization and analysis of DNA and RNA modification information in individual reads in a simple and computationally efficient manner.Availability and ImplementationModPhredis available athttps://github.com/novoalab/modPhred, is implemented in Python3, and is released under an MIT license.Supplementary DataSupplementary Data are available atBioinformaticsonline.
Identification of Blood Based Bio-Marker for Huntington’s disease using in-silico gene expression analysis
Authors: Chakraborty Souvik 
Published: March 2021

AbstractHuntington’s disease (HD) is an autosomal dominant neurodegenerative disorder with profound phenotypic characters. HD is at present incurable and there are several trials going on to find a cure. HD is caused when there is a mutation in the Huntingtin gene which is found to be associated with axonal transport. Diagnosis is based on the signs and symptoms of the patients but by that time the psychomotor problems have already reached the level from where reversing the disease is impossible. Blood based biomarkers can be used for the diagnosis of the disease at an early stage. In this study several gene expression study data were analyzed and there were 329 Differentially Expressed Genes (DEGs) in all the three chosen datasets. Protein protein interaction network was created using STRING and CytoHubba plug-in was used to identify top ten hub genes which are CXCL8, PSMC6, UBE2D1, UBE2D1, CD27, UBE2D3, SF3B1, CASP3, EIF4E, BIRC2 and PTEN. Online software Enrichr was used for Gene Ontology and KEGG pathway enrichment analysis to find out the biological process, molecular function, cellular component and the pathways that were enriched in HD. This study finds out that those genes which were present in all the three datasets namely FNDC3A, BCLAF1 and ALCAM were not the hub genes. So further studies are required for identifying a potential biomarker of HD.
Somatic DNA demethylation generates tissue-specific methylation states and impacts flowering time
Authors: Williams Ben P. , Bechen Lindsey A. , Pohlmann Deborah A. , Gehring Mary 
Published: March 2021

AbstractCytosine methylation is a reversible epigenetic modification to DNA. In plants, removal of cytosine methylation is accomplished by the four members of the DME family of 5-methylcytosine DNA glycosylases. Demethylation by DME is critical for seed development. Consequently, determining the function of the entire gene family in somatic tissues by mutant analysis has not been possible. Here, we bypassed the reproductive defects ofdmemutants to create somatic quadruple homozygous mutants of the entire DME family.dme; ros1; dml2; dml3(drdd) leaves exhibit hypermethylated genomes compared to both wild-type plants andrddtriple mutants, indicating functional redundancy among all four demethylases. Targets of demethylation include regions co-targeted by RNA-directed DNA methylation and, surprisingly, CG gene body methylation, indicating dynamic methylation at these little-understood sites. Additionally, many tissue-specific methylation differences are absent indrdd, suggesting a role for active demethylation in generating divergent epigenetic states across wild-type tissues. Furthermore,drddplants display a striking early flowering phenotype, which is associated with 5’ hypermethylation and transcriptional down-regulation ofFLOWERING LOCUS C. Active DNA demethylation is therefore required for proper methylation patterning across somatic tissues and defines the epigenetic landscape of both intergenic and coding regions.
The too-much-of-a-good-thing effect of new ventures' opportunity development on innovation strategy under the Chinese context
Authors: Yin Miaomiao , Zhou Bingyu 
Published: March 2021

PurposeThe purpose of this research is to reveal how to improve the quality of entrepreneurship by exploring the key factor, opportunity development, impacting the innovation strategy of new ventures. It also introduces political and business ties as moderating variables to reveal the uniqueness of entrepreneurial activities in the Chinese context.Design/methodology/approachEmpirical data from 215 entrepreneurs and top executives in Chinese new ventures were gathered through a survey and the statistical method used is the regression model.FindingsThe empirical results indicate that: (1) new ventures' opportunity creation positively impacts innovation strategy, while opportunity discovery has a curvilinear (invertedU-shape) impact on innovation strategy; (2) the relationship between opportunity development and innovation strategy is moderated by political and business ties.Originality/valueThis research analyzes and compares the effect of opportunity discovery and opportunity creation on new ventures' innovation strategy. This research further offers an in-depth understanding of the influence mechanism between opportunity development and innovation strategy among Chinese new ventures. Further, the results provide practical guidance for new ventures to develop innovation strategies and for Chinese governments to make entrepreneurial policies.
Profiling gifters via a psychographic segmentation analysis: insights for retailers
Authors: Quach Xuan , Lee Seung Hwan (Mark) 
Published: March 2021

PurposeThe aim of this study is to profile types of gifters via a set of psychographic consumption traits (frugality, gratitude, market mavenism and novelty seeking) and identify differences among the groups regarding their gift-purchasing behavior.Design/methodology/approachBased on the data from 193 participants, the authors seek to identify and profile unique consumer segments (gifters) generated from the four psychographic consumption traits. Second, once the segments are established, the authors analyze how the segments differ across 16 unique gift-purchasing behaviors.FindingsThe data generated four distinct consumer segments: experiential gifters, considerate gifters, convenience gifters and astute gifters. Across the segments, there were differences in their gift consumption behavior (e.g. time/effort spent, desire for customization, gift presentation, derived joy, purchasing frequency, eco-friendliness, seeking assistance, regifting and more).Research limitations/implicationsUS-based sample was collected via an online panel in January; this may restrict the generalizability of the research, given that gift consumption customs may vary across different countries. Thus, future research should include participants from other geographic regions to increase the external validity of the research.Practical implicationsRetail managers can use this knowledge to devise marketing strategies focused on the gift-purchasing behaviors of each group.Originality/valueSegmenting clusters based on differences in consumption traits provides insights to retailers looking to build a competitive advantage, particularly in a gift purchasing context.
Surviving the aftermaths of natural disasters: the earthen vessels of Kerala, India
Authors: Menon Devaki Vadakepat , Vadakepat Vanaja Menon 
Published: March 2021

PurposeSince 2018, the two floods and droughts that struck Kerala's economy have threatened the state's sustainable earthen vessel production. Current studies allocate focus to the pottery industry's techno-social impacts and ethnography of the potter community; hence, there is a gap in understanding consumers, who are responsible for environmentally conscious behaviors, and their switch from earthen vessels to other materials adaptable to modern kitchens. This study aims to bridge gaps in understanding the reasons behind their demand shift and the challenges of earthenware consumption and production after the disasters.Design/methodology/approachThis quantitative research explored the perceptions of pottery producers and consumers in Kerala. The sample for the primary survey comprised 590 randomly selected consumers and one master artisan from each of Kerala's total of 44 registered pottery communities. Unpublished records provided the secondary data on production and sales.FindingsAn upward shift in the demand for earthen vessels after natural calamities is observed. Quality, availability and adaptability are consumer concerns. The Markov chain analysis predicts that future consumption of earthen vessels depends on improved marketing mix strategies. After natural disasters, persistent demand exists for earthen vessels, but sustainable production is challenged due to the deteriorating quality and shortage of clay along with the consequent increase in procurement costs of raw materials.Originality/valueAs the earthen vessel industry was affected by disasters very recently, this study contributes an immediate exploration of its sustainable production and consumption challenges.
Consumer attitude towards green products: revisiting the profile of green consumers using segmentation approach
Authors: Mehta Pooja , Chahal Harpreet Singh 
Published: March 2021

PurposeOver the last few decades, there has been a substantial increase in environmentally conscious consumers' willingness to switch their preferences from mainstream products to green products. Hence, it becomes essential for academicians and marketers to understand the notion, attributes and a comprehensive profile of green consumers. Since consumer attitude towards green products is not widely studied in developing countries, the present study aims at exploring the profile of green consumers in India (Punjab State) based on the same in the Indian context.Design/methodology/approachThe study used the survey method, and a sample of 400 respondents was selected from the Punjab State of India. Initially, principal component analysis was employed to reduce the dimensions. Following this, cluster analysis was applied to segment consumer market in distinctive segments. Results of cluster analysis were validated with discriminant analysis and finally, differences amongst the segments of green and non-green consumers were examined to build on the profile of green consumers.FindingsThe study segmented the consumer market based on consumer attitude towards green products. Results of the study revealed four distinct segments. “Dynamic Green”, the largest cluster, presents truly green consumers who exhibit a positive attitude towards green products. Finally, the study highlighted the attitudinal profile of green and non-green consumers and differences amongst the segments were explained.Research limitations/implicationsSimilar study should be conducted in other developing/developed countries. Furthermore, cross-cultural studies can be undertaken to contrast consumer attitude towards green products. The study may also be extended to probe the connection between consumers' attitude and actual behaviour towards green products.Originality/valueThe study examined the role of consumer attitude towards green products in identifying the distinct segment of green consumers and determining different configurations of consumer characteristics to build on the profile of green consumers.