bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene dosage effects of polyA track engineered hypomorphs
Authors: Powell Geralle , Pavlovic-Djuranovic Slavica , Djuranovic Sergej 
Published: February 2021

ABSTRACTThe manipulation of gene activity through the creation of hypomorphic mutants has been a long-standing tool in examining gene function. Our previous studies have indicated that hypomorphic mutants could be created by inserting cis-regulatory sequences composed of consecutive adenosine nucleotides called polyA tracks. Here we use polyA tracks to create hypomorphic mutants and functional characterization of membrane, secretory and endogenous proteins. Insertion of polyA tracks into the sequences of interleukin-2 and membrane protein CD20 results in a programmable reduction of mRNA stability and attenuation of protein expression regardless of the presence of signaling sequence. Likewise, CRISPR/Cas9 targeted insertion of polyA tracks in the coding sequence of endogenous human genesAUF1andTP53results in a programmable reduction of targeted protein and mRNA levels. Functional analyses of AUF1 engineered hypomorphs indicate a direct correlation betweenAUF1gene levels and the stability of AUF1-regulated mRNAs. Hypomorphs of TP53 affect the expression of the target genes differentially depending upon the severity of the hypomorphic mutation. Finally, decreases in TP53 protein affect the same cellular pathways in polyA track engineered cells as in cancer cells, indicating these variants’ biological relevance. These results highlight this technology’s power to create predictable, stable hypomorphs in recombinant or endogenous genes in combination with CRISPR/Cas9 engineering tools.
Bfimpute: A Bayesian factorization method to recover single-cell RNA sequencing data
Authors: Wen Zi-Hang , Langsam Jeremy L. , Zhang Lu , Shen Wenjun , Zhou Xin 
Published: February 2021

AbstractSingle-cell RNA-seq (scRNA-seq) offers opportunities to study gene expression of tens of thousands of single cells simultaneously, to investigate cell-to-cell variation, and to reconstruct cell-type-specific gene regulatory networks. Recovering dropout events in a sparse gene expression matrix for scRNA-seq data is a long-standing matrix completion problem. We introduce Bfimpute, a Bayesian factorization imputation algorithm that reconstructs two latent gene and cell matrices to impute final gene expression matrix within each cell group, with or without the aid of cell type labels or bulk data. Bfimpute achieves better accuracy than other six publicly notable scRNA-seq imputation methods on simulated and real scRNA-seq data, as measured by several different evaluation metrics. Bfimpute can also flexibly integrate any gene or cell related information that users provide to increase the performance. Availability: Bfimpute is implemented in R and is freely available athttps://github.com/maiziezhoulab/Bfimpute.
Optimized CRISPR tools and site-directed transgenesis inCulex quinquefasciatusmosquitoes for gene drive development
Authors: Feng Xuechun , Del Amo Víctor López , Mameli Enzo , Lee Megan , Bishop Alena L. , Perrimon Norbert , Gantz Valentino M. 
Published: February 2021

ABSTRACTCulexmosquitoes are a global vector for multiple human and animal diseases, including West Nile virus, lymphatic filariasis, and avian malaria, posing a constant threat to public health, livestock, companion animals, and endangered birds. While rising insecticide resistance has threatened the control ofCulexmosquitoes, advances in CRISPR genome-editing tools have fostered the development of alternative genetic strategies such as gene drive systems to fight disease vectors. However, though gene-drive technology has quickly progressed in other mosquitoes, advances have been lacking inCulex. Here, we developed aCulex-specific Cas9/gRNA expression toolkit and used site-directed homology-based transgenesis to generate and validate aCulex quinquefasciatusCas9-expressing line. We showed that gRNA scaffold variants improve transgenesis efficiency in bothCulexandDrosophilaand boost gene-drive performance in the fruit fly. These findings support future technology development to controlCulexmosquitoes and provide valuable insight for improving these tools in other species.
Bacterial diversity of chronic middle ear lesions revealed by high-throughput sequencing
Authors: Gu Xingzhi , Cheng Xiuqing , Abulajiang Tuoheti , Huang Xiaoban 
Published: February 2021

AbstractChronic otitis media is a common middle ear disease in otolaryngology and head and neck surgery. Bacterial infection is considered the main cause of disease, but relying on conventional bacterial cultures can be problematic for identification of specific pathogens. Current research suggests that bacteria in microbial communities can only be identified by rDNA sequencing of bacteria.This prospective study utilized broad-range PCR amplification of 16S rRNA genes with clone analysis to compare bacterial diversity in lesions from 6 patients with chronic suppurative otitis media (CSOM) and 10 patients with cholesteatoma of middle ear lesions. Bacteria were analyzed at the phylum, order, family, genus, and species levels. Bacterial species abundance and species diversity were greater in cholesteatoma of the middle ear lesions than in CSOM lesions. At all bacterial taxonomic levels, the epithelial tissue of middle ear cholesteatoma was complex in terms of bacterial diversity, covering a large number of Gram-positive and Gram-negative bacteria, likely related to bacterial microbiome formation. In contrast, bacteriology of the CSOM lesions was relatively simple at all taxonomic levels, with all sequences characterized as belonging to Gram-negative bacteria. These results suggest that persistent infection of middle ear cholesteatoma may be a microbial flora disorder, which is related to conditional pathogenic bacteria, rather than a single bacterial infectious disease. Findings from the study may have implications in the selection of antimicrobial agents for the treatment of chronic otitis media.
Comparative proteome signatures of trace samples by multiplexed Data-Independent Acquisition
Authors: Ctortecka Claudia , Krššáková Gabriela , Stejskal Karel , Penninger Josef M. , Mendjan Sasha , Mechtler Karl , Stadlmann Johannes 
Published: February 2021

AbstractSingle cell transcriptomics has revolutionized our understanding of basic biology and disease. Since transcript levels often do not correlate with protein expression, it is crucial to complement transcriptomics approaches with proteome analyses at single cell resolution. Despite continuous technological improvements in sensitivity, mass spectrometry-based single cell proteomics ultimately faces the challenge of reproducibly comparing the protein expression profiles of thousands of individual cells. Here, we combine two hitherto opposing analytical strategies, DIA and Tandem-Mass-Tag (TMT)-multiplexing, to generate highly reproducible, quantitative proteome signatures from ultra-low input samples. While conventional, data-dependent shotgun proteomics (DDA) of ultra-low input samples critically suffers from the accumulation of missing values with increasing sample-cohort size, data-independent acquisition (DIA) strategies do usually not take full advantage of isotope-encoded sample multiplexing. We developed a novel, identification-independent proteomics data-analysis pipeline that allows to quantitatively compare DIA-TMT proteome signatures across hundreds of samples independent of their biological origin, and to identify cell types and single protein knockouts. We validate our approach using integrative data analysis of different human cell lines and standard database searches for knockouts of defined proteins. These data establish a novel and reproducible approach to markedly expand the numbers of proteins one detects from ultra-low input samples, such as single cells.
Cholinergic calcium responses in cultured antennal lobe neurons of the migratory locust
Authors: Bergmann Gregor A. , Bicker Gerd 
Published: February 2021

AbstractLocusts are advantageous organisms to elucidate mechanisms of olfactory coding at the systems level. Sensory input is provided by the olfactory receptor neurons of the antenna, which send their axons into the antennal lobe. So far, cellular properties of neurons isolated from the circuitry of the olfactory system, such as transmitter-induced calcium responses, have not been studied. Biochemical and immunocytochemical investigations have provided evidence for acetylcholine as classical transmitter of olfactory receptor neurons. Here, we characterize cell cultured projection and local interneurons of the antennal lobe by cytosolic calcium imaging to cholinergic stimulation. We bulk loaded the indicator dye Cal-520 AM in dissociated culture and recorded calcium transients after applying cholinergic agonists and antagonists. The majority of projection and local neurons respond with increases in calcium levels to activation of both nicotinic and muscarinic receptors. In local interneurons, we reveal interactions lasting over minutes between intracellular signaling pathways, mediated by muscarinic and nicotinic receptor stimulation. The present investigation is pioneer in showing that Cal-520 AM readily loadsLocusta migratorianeurons, making it a valuable tool for future research in locust neurophysiology, neuropharmacology, and neurodevelopment.
BMP signaling interferes with optic chiasm formation and retinal ganglion cell pathfinding in zebrafish
Authors: Knickmeyer Max D. , Mateo Juan L. , Heermann Stephan 
Published: February 2021

AbstractDecussation of axonal tracts is an important hallmark of vertebrate neuroanatomy resulting in one brain hemisphere controlling the contralateral side of the body and also computing the sensory information originating from that respective side. Here, we show that BMP interferes with optic chiasm formation and RGC pathfinding in zebrafish.Experimental induction of BMP4 at 15 hpf results in a complete ipsilateral projection of RGC axons and failure of commissural connections of the forebrain in part being the result of an interaction with shh signaling, transcriptional regulation of midline guidance cues and an affected optic stalk morphogenesis.Experimental induction of BMP4 at 24 hpf, resulting in only a mild repression of forebrain shh ligand expression but in a broad expression of pax2a in the diencephalon, does not per se prevent RGC axons from crossing the midline. It nevertheless shows severe pathologies of RGC projections e.g. the fasciculation of RGC axons with the ipsilateral optic tract resulting in the innervation of one tectum by two eyes or the projection of RGC axons in the direction of the contralateral eye.
A sociological view toward the economic and technological development zones in China
Authors: Yan Zheng Joseph , Zámborský Peter , Liang Hongji 
Published: February 2021

PurposeThis paper aims to introduce a sociological view to analyze the Economic and Technological Development Zones (ETDZs) in China. The ETDZs are established to foster concentrated regional economic development. Currently, there are 219 national level ETDZs throughout the country, and they account for more than 10% of China’s total GDP. Given the scale of the Chinese economy, the economic significance of the ETDZs indicates an important phenomenon for better understanding.Design/methodology/approachThis paper conceptualizes the Chinese ETDZs with sociology concepts of place, institutional logics and habitus.FindingsThe sociological view centers on how the ETDZs can naturally evolve with the participation of firms. The authors show that firms operating in the ETDZs can unintentionally alter the dynamics of the policy environment. A process model of place, logics and practice is developed to encapsulate these ideas.Originality/valueConventional research on the connections between Chinese Government policies and business operations has been largely conducted under a political economy view which outlines a top-down logic (policymaking, followed by firms’ strategic response). The authors move away from this dogma by introducing a sociological view of the ETDZs. This new view highlights that a government-initiated policy environment in China can also evolve when firms are seeking to blend into the regulatory system, instead of trying to shape the coercive arrangements to suit their best interests.
Responsiveness of residential construction-production progress to house price dynamics
Authors: Ma Le , Liu Henry , Sing Michael 
Published: February 2021

PurposeThis study aims to address the gap by empirically exploring how residential construction-production progress, which includes project commencement, under-construction and project completion, responds dynamically to fluctuations in house prices.Design/methodology/approachA vector autoregressive model and an impulse response function are applied to simulate and analyse the circle of the stage-responsiveness of residential construction to residential property price dynamics in the state of Victoria, Australia. The quarterly numbers of dwelling units commenced, under-construction and completed are used as the proxy for the residential construction activities at three stages over the construction progress.FindingsThe analysis indicates that the dynamics are essentially transmitted throughout the construction process and can substantially impact the pace of production progress. The findings from this study provide an empirical base that should be useful in developing price-elasticity and production theories applicable to the context of residential property construction.Research limitations/implicationsThe findings described above have been generated basically by examining the case of Victoria, Australia at a macro level. The generalisation of the research output needs to be verified further by future researchers using data collected from other regions/countries. Nevertheless, the reliability of the conclusions with particular practical implications can be substantially improved by future researchers by analysing more markets and production proxies at the activity level.Practical implicationsBased on new empirical findings, this research argues that building activity (i.e. under construction) played as a gateway between the construction and housing sectors, via which the inter-responsiveness of the housing supply in terms of construction activities and housing prices are transmitted.Originality/valueThis research firstly attempts to explore the inter-responsiveness between the real estate and construction sectors. A simulated circle of the stage-responsiveness of residential construction to residential property price dynamics is proposed, which can serve as a significant foundation for developing the theory of construction production.
Application of Lean Six Sigma framework for improving manufacturing efficiency: a case study in Indian context
Authors: Sharma Astha , Bhanot Neeraj , Gupta Ajay , Trehan Rajeev 
Published: February 2021

PurposeThis study aims to utilize DMAIC methodology along with value stream mapping and other Lean Six Sigma tools in a major automobile light manufacturing industry to reduce defect rates and increase production capacity in their manufacturing line. The study also proposes a modified framework based on lean principles and FlexSim to identify and reduce waste in the selected industry.Design/methodology/approachA Lean Six Sigma modified framework has been deployed with DMAIC to reduce the defect rate and increase the production rate. Various tools like value stream mapping, brainstorming, Pareto charts, 5S, kanban, etc. have been used at different phases of DMAIC targeting wastes and inventory in the production line. Also, a simulation model has been utilized for the automobile light manufacturing industry to improve the machine utilization time with varying batch sizes.FindingsThe results of the study indicated a 53% reduction in defect rates. Thus, there would be an expected improvement in sigma value from 3.78 to 3.89 and a reduction in defects per million opportunities (DPMO) from 11,244 to 8,493. Additionally, simulation model using FlexSim was developed, and the optimum ordering batch size of raw material was obtained. It was also analyzed that idle time for various stations could be reduced by up to 30%.Practical implicationsThe utilized framework helps identify defects for managers to increase production efficiency. The workers, operators and supervisors on the production line also need to be trained regularly for identifying the areas of improvement.Originality/valueThe modified Lean Six Sigma framework used in this study includes FlexSim simulation to make the framework robust, which has not been used with LSS tools in the literature studied. Also, the LSS finds very less application in the manufacturing domain, considering which this study tends to add value in existing literature taking a case of an automobile light manufacturing industry.
Firm capability assessment via the BSC and DEA
Authors: Lin Chinho , Ting Shu-Fang , Lee Leslie , Lin Sheng-Tun 
Published: February 2021

PurposeThis study proposes an objective assessment model to evaluate the performance of internal and external capabilities of firms. It facilitates firms to invest appropriate resources to cultivate the organizational capability necessary to meet the requirements of the performance indicators.Design/methodology/approachThis study integrates the concepts of resource-based theory, the organizational capability concept, and conduct a performance analysis to the four perspectives of the BSC by implementing the fuzzy set theory and data employment analysis.FindingsThe findings show that the appropriate strategies help allocate available resources and capabilities during the different product life cycle, which provides practical guidelines for firms to achieve sustaining competitive advantage.Research limitations/implicationsThe selected factors were focused on four resources and capabilities rather than all possible factors.Originality/valueAn objective assessment model was created based on internal and external competitive performance efficiency in this research field. This model facilitates the ability of the top management to make decisions for resource allocation that will enhance firm's performance.
Crime linkage practice in New Zealand
Authors: Tonkin Matt , Weeks Martin Joseph 
Published: February 2021

Purpose
The purpose of this paper is to understand (i) how crime linkage is currently performed with residential burglaries in New Zealand, (ii) the factors that promote/hinder accurate crime linkage and (iii)whether computerised decision-support tools might assist crime linkage practice.

Design/methodology/approach
A total of 39 New Zealand Police staff completed a questionnaire/interview/focus group relating to the process, challenges, products and uses of crime linkage with residential burglary in New Zealand. These data (alongside four redacted crime linkage reports) were subjected to thematic analysis.

Findings
The data clearly indicated wide variation in crime linkage process, methods and products (Theme 1). Furthermore, a number of factors were identified that impacted on crime linkage practice (Theme 2).

Research limitations/implications
Future research should develop computerised crime linkage decision-support tools and evaluate their ability to enhance crime linkage practice. Also, researchers should explore the use of crime linkage in court proceedings.

Practical implications
To overcome the barriers identified in the current study, greater training in and understanding of crime linkage is needed. Moreover, efforts to enhance the quality of crime data recorded by the police will only serve to enhance crime linkage practice.

Social implications
By enhancing crime linkage practice, opportunities to reduce crime, protect the public and deliver justice for victims will be maximised.

Originality/value
The practice of crime linkage is under-researched, which makes it difficult to determine if/how existing empirical research can be used to support ongoing police investigations. The current project fills that gap by providing a national overview of crime linkage practice in New Zealand, a country where crime linkage is regularly conducted by the police, but no published linkage research exists.
Risk-adjusted banks' resource-utilization and investment efficiencies: does intellectual capital matter?
Authors: Kweh Qian Long , Lu Wen-Min , Tone Kaoru , Nourani Mohammad 
Published: February 2021

PurposeThe purpose of this study is twofold. First, this research estimates banks' efficiencies from the perspectives of resource utilization and investment after incorporating risk measures as an exogenous input in the investment-efficiency stage. Second, the current study examines the relationship between intellectual capital (IC) and banks' efficiencies.Design/methodology/approachFirst, this study uses a dynamic network data envelopment analysis approach in investigating the efficiencies of 24 Taiwanese banks in 2007–2018 from two perspectives. Second, this research utilizes various regression techniques, namely, ordinary least squares (OLS), robust least squares and truncated regression, to gauge the impact of IC on banks' efficiencies. Typically, IC is determined based on a monetary value-based measure and value-added intellectual coefficient (VAICTM).FindingsResource-utilization (investment) efficiencies were observed as 0.941 (0.964), thereby contributing to the mean overall efficiency of the sample banks at 0.952. However, the related efficiency changes decline over the sample period, thereby suggesting that the average banks' efficiencies hardly increase. Regression analyses show a significantly positive relationship between IC and banks' overall resource-utilization and investment efficiencies.Research limitations/implicationsOverall, this study suggests that researchers should consider risks when estimating banks' efficiencies owing to their connection to banks' investment performance. From banks' dynamic two-stage efficiencies, this study demonstrated that investments in IC will bring improved future economic benefits.Originality/valueDifferent from prior studies, this study improves banks' efficiency evaluation models by incorporating risk measures and assuming weighted periods for the 2007–2008 global financial crisis. Moreover, the use of monetary value-based measure of IC provides consistent results as the commonly-used VAICTM does.