bluuebunny/crossref_metadata_2025 huggingface dataset:
Profile-likelihood Bayesian model averaging for two-sample summary data Mendelian randomization in the presence of horizontal pleiotropy
Authors: Shapland Chin Yang , Zhao Qingyuan , Bowden Jack
Published: February 2020

Two-sample summary data Mendelian randomisation is a popular method for assessing causality in epidemiology, by using genetic variants as instrumental variables. If genes exert pleiotropic effects on the outcome not entirely through the exposure of interest, this can lead to heterogeneous and (potentially) biased estimates of causal effect. We investigate the use of Bayesian model averaging to preferentially search the space of models with the highest posterior likelihood. We develop a Metropolis-Hasting algorithm to perform the search using the recently developed Robust Adjusted Profile Likelihood of Zhao et al as the basis for defining a posterior distribution that efficiently accounts for pleiotropic and weak instrument bias. We demonstrate how our general modelling approach can be extended from a standard one-parameter causal model to a two-parameter model, which allows a large proportion of SNPs to violate the Instrument Strength Independent of Direct Effect assumption. We use Monte Carlo simulations to illustrate our methods and compare it to several related approaches. We finish by applying our approach in practice to investigate the causal role of cholesterol on the development age-related macular degeneration.
Integrating multimodal data sets into a mathematical framework to describe and predict therapeutic resistance in cancer
Authors: Johnson Kaitlyn , Howard Grant R. , Morgan Daylin , Brenner Eric A. , Gardner Andrea L. , Durrett Russell E. , Mo William , Al’Khafaji Aziz , Sontag Eduardo D. , Jarrett Angela M. , Yankeelov Thomas E. , Brock Amy
Published: February 2020

A significant challenge in the field of biomedicine is the development of methods to integrate the multitude of dispersed data sets into comprehensive frameworks to be used to generate optimal clinical decisions. Recent technological advances in single cell analysis allow for high-dimensional molecular characterization of cells and populations, but to date, few mathematical models have attempted to integrate measurements from the single cell scale with other data types. Here, we present a framework that actionizes static outputs from a machine learning model and leverages these as measurements of state variables in a dynamic mechanistic model of treatment response. We apply this framework to breast cancer cells to integrate single cell transcriptomic data with longitudinal population-size data. We demonstrate that the explicit inclusion of the transcriptomic information in the parameter estimation is critical for identification of the model parameters and enables accurate prediction of new treatment regimens. Inclusion of the transcriptomic data improves predictive accuracy in new treatment response dynamics with a concordance correlation coefficient (CCC) of 0.89 compared to a prediction accuracy of CCC = 0.79 without integration of the single cell RNA sequencing (scRNA-seq) data directly into the model calibration. To the best our knowledge, this is the first work that explicitly integrates single cell clonally-resolved transcriptome datasets with longitudinal treatment response data into a mechanistic mathematical model of drug resistance dynamics. We anticipate this approach to be a first step that demonstrates the feasibility of incorporating multimodal data sets into identifiable mathematical models to develop optimized treatment regimens from data.
How many bird and mammal extinctions has recent conservation action prevented?
Authors: Bolam Friederike C. , Mair Louise , Angelico Marco , Brooks Thomas M. , Burgman Mark , Hermes Claudia , Hoffmann Michael , Martin Rob W. , McGowan Philip J.K. , Rodrigues Ana S.L. , Rondinini Carlo , Wheatley Hannah , Bedolla-Guzmán Yuliana , Calzada Javier , Child Matthew F. , Cranswick Peter A. , Dickman Christopher R. , Fessl Birgit , Fisher Diana O. , Garnett Stephen T. , Groombridge Jim J. , Johnson Christopher N. , Kennerley Rosalind J. , King Sarah R.B. , Lamoreux John F. , Lees Alexander C. , Lens Luc , Mahood Simon P. , Mallon David P. , Meijaard Erik , Méndez-Sánchez Federico , Percequillo Alexandre Reis , Regan Tracey J. , Renjifo Luis Miguel , Rivers Malin C. , Roach Nicolette S. , Roxburgh Lizanne , Safford Roger J. , Salaman Paul , Squires Tom , Vázquez-Domínguez Ella , Visconti Piero , Westrip James R.S. , Woinarski John C.Z. , Young Richard P. , Butchart Stuart H.M.
Published: February 2020

Aichi Target 12 of the Convention on Biological Diversity (CBD) aims to ‘prevent extinctions of known threatened species’. To measure its success, we used a Delphi expert elicitation method to estimate the number of bird and mammal species whose extinctions were prevented by conservation action in 1993 - 2020 (the lifetime of the CBD) and 2010 - 2020 (the timing of Aichi Target 12). We found that conservation prevented 21–32 bird and 7–16 mammal extinctions since 1993, and 9–18 bird and 2–7 mammal extinctions since 2010. Many remain highly threatened, and may still become extinct in the near future. Nonetheless, given that ten bird and five mammal species did go extinct (or are strongly suspected to) since 1993, extinction rates would have been 2.9–4.2 times greater without conservation action. While policy commitments have fostered significant conservation achievements, future biodiversity action needs to be scaled up to avert additional extinctions.
Antiviral and Virucidal activities of sulphated polysaccharides against Japanese Encephalitis Virus
Authors: Rothan Hussin A. , Yusof Rohana
Published: February 2020

Background

Japanese encephalitis virus (JEV), a member of the family Flaviviridae, causes severe neurological disorders in humans. JEV infections represent one of the most widely spread mosquito-borne diseases, and therefore, it has been considered as an endemic disease. An effective antiviral drug is still unavailable to treat JEV, and current drugs only provide supportive treatment to alleviate the symptoms and stabilize patients’ conditions. This study was designed to evaluate the antiviral activity of the sulphated polysaccharides “Carrageenan,” a linear sulphated polysaccharide that is extracted from red edible seaweeds against JEV replication in vitro.

Methods and Results

Viral inactivation, attachment, and post-infection assays were used to determine the mode of inhibition of Carrageenan. Virus titters after each application were evaluated by plaque formation assay. MTT assay was used to determine the 50% cytotoxic concentration (CC50), and ELISA-like cell-based assay and immunostaining and immunostaining techniques were used to evaluate the 50% effective concentration (EC50). This study showed that Carrageenan inhibited JEV at an EC50 of 15 μg/mL in a dose-dependent manner with CC50 more than 200 μg/mL in healthy human liver cells (WRL68). The mode of inhibition assay showed that the antiviral effects of Carrageenan are mainly due to their ability to inhibit the early stages of virus infection such as the viral attachment and the cellular entry stages.

Conclusion

Our investigation showed that Carrageenan could be considered as a potent antiviral agent to JEV infection. Further experimental and clinical studies are needed to investigate the potential applications of Carrageenan for clinical intervention against JEV infection.
iGenomics: Comprehensive DNA Sequence Analysis on your Smartphone
Authors: Palatnick Aspyn , Zhou Bin , Ghedin Elodie , Schatz Michael C.
Published: February 2020

Following the miniaturization of integrated circuitry and other computer hardware over the past several decades, DNA sequencing is following a similar path. Leading this trend is the Oxford Nanopore sequencing platform, which currently offers the hand-held MinION instrument and even smaller instruments on the near horizon. This technology has been used in several important applications, including the analysis of genomes of major pathogens in remote stations around the world. However, despite the simplicity of the sequencer, an equally simple and portable analysis platform is not yet available.

iGenomics is the first comprehensive mobile genome analysis application, with capabilities to align reads, call variants, and visualize the results entirely on an iOS device. Implemented in Objective-C using the FM-index, banded dynamic programming, and other high-performance bioinformatics techniques, iGenomics is optimized to run in a mobile environment. We benchmark iGenomics using a variety of real and simulated Nanopore sequencing datasets and show that iGenomics has performance comparable to the popular BWA-MEM/Samtools/IGV suite, without needing a laptop or server cluster. iGenomics is available open-source (https://github.com/stuckinaboot/iGenomics) and for free on Apple’s App Store (https://apps.apple.com/us/app/igenomics-mobile-dna-analysis/id1495719841).
A footprint of plant eco-geographic adaptation on the composition of the barley rhizosphere bacterial microbiota
Authors: Terrazas Rodrigo Alegria , Balbirnie-Cumming Katharin , Morris Jenny , Hedley Pete E , Russell Joanne , Paterson Eric , Baggs Elizabeth M , Fridman Eyal , Bulgarelli Davide
Published: February 2020

The microbiota thriving in the rhizosphere, the thin layer of soil surrounding plant roots, plays a critical role in plant’s adaptation to the environment. Domestication and breeding selection have progressively differentiated the microbiota of modern crops from the ones of their wild ancestors. However, the impact of eco-geographical constraints faced by domesticated plants and crop wild relatives on recruitment and maintenance of the rhizosphere microbiota remains to be fully elucidated. Here we performed a comparative 16S rRNA gene survey of the rhizosphere of 4 domesticated and 20 wild barley (Hordeum vulgare) genotypes grown in an agricultural soil under controlled environmental conditions. We demonstrated the enrichment of individual bacteria mirrored the distinct eco-geographical constraints faced by their host plants. Unexpectedly, Elite varieties exerted a stronger genotype effect on the rhizosphere microbiota when compared with wild barley genotypes adapted to desert environments with a preferential enrichment for members of Actinobacteria. Finally, in wild barley genotypes, we discovered a limited, but significant, correlation between microbiota diversity and host genomic diversity. Our results revealed a footprint of the host’s adaptation to the environment on the assembly of the bacteria thriving at the root-soil interface. In the tested conditions, this recruitment cue layered atop of the distinct evolutionary trajectories of wild and domesticated plants and, at least in part, is encoded by the barley genome. This knowledge will be critical to design experimental approaches aimed at elucidating the recruitment cues of the barley microbiota across a range of soil types.
Next-generation cytosine base editors with minimized unguided DNA and RNA off-target events and high on-target activity
Authors: Yu Yi , Leete Thomas , Born David A. , Young Lauren , Barrera Luis A. , Lee Seung-Joo , Rees Holly A. , Ciaramella Giuseppe , Gaudelli Nicole M.
Published: February 2020

Abstract/introductory paragraph

Cytosine base editors (CBEs) are molecular machines which enable efficient and programmable reversion of T•A to C•G point mutations in the human genome without induction of DNA double strand breaks1, 2. Recently, the foundational cytosine base editor (CBE) ‘BE3’, containing rAPOBEC1, was reported to induce unguided, genomic DNA3, 4and cellular RNA5cytosine deamination when expressed in living cells. To mitigate spurious off-target events, we developed a sensitive, high-throughput cellular assay to select next-generation CBEs that display reduced spurious deamination profiles relative to rAPOBEC1-based CBEs, whilst maintaining equivalent or superior on-target editing frequencies. We screened 153 CBEs containing cytidine deaminase enzymes with diverse sequences and identified four novel CBEs with the most promising on/off target ratios. These spurious-deamination-minimized CBEs (BE4 with either RrA3F, AmAPOBEC1, SsAPOBEC3B, or PpAPOBEC1) were further optimized for superior on- and off-target DNA editing profiles through structure-guided mutagenesis of the deaminase domain. These next-generation CBEs display comparable overall DNA on-target editing frequencies, whilst eliciting a 10- to 49-fold reduction in C-to-U edits in the transcriptome of treated cells, and up to a 33-fold overall reduction in unguided off-target DNA deamination relative to BE4 containing rAPOBEC1. Taken together, these next-generation CBEs represent a new collection of base editing tools for applications in which minimization of spurious deamination is desirable and high on-target activity is required.
The genome sequence of the Jean-Talon strain, an archeological tetraploid beer yeast from Québec
Authors: Fijarczyk Anna , Hénault Mathieu , Marsit Souhir , Charron Guillaume , Fischborn Tobias , Nicole-Labrie Luc , Landry Christian R
Published: February 2020

The genome sequences of archeological yeast isolates can reveal insights about the history of human baking, brewing and winemaking activities and migration around the globe. A yeast strain called Jean-Talon was recently isolated from the vaults of the Intendant’s Palace of Nouvelle France on a historical site in Québec City. This site has been occupied by various breweries, starting from the end of the 17th century and until the middle of the 20th century. We sequenced the genome of the Jean-Talon strain with short and long reads and reanalyzed the genomes of hundreds of yeast strains to identify its species of origin and determine how it relates to other domesticated and wild strains. The Jean-Talon strain is a tetraploid strain with numerous aneuploidies, is partially sterile and most closely related to beer strains from the beer and bakery genetic groups and industrial strains from the United Kingdom and Belgium. We conclude from this that the Jean-Talon strain most likely derives from recent brewing activities that took place in the same location and not from wild yeast that could have been domesticated by the original brewers of the Nouvelle France on the site.
Kupffer Cell Release of Platelet Activating Factor Drives Dose Limiting Toxicities of Nucleic Acid Nanocarriers
Authors: Jackson Meredith A. , Patel Shrusti S. , Yu Fang , Cottam Matthew A. , Glass Evan B. , Dollinger Bryan R. , Hoogenboezem Ella N. , Patil Prarthana , Liu Danielle D. , Kelly Isom B. , Bedingfield Sean K. , King Allyson R. , Miles Rachel E. , Hasty Alyssa M. , Giorgio Todd D. , Duvall Craig L.
Published: February 2020

In vivonanocarrier-associated toxicity is a significant and poorly understood hurdle to clinical translation of siRNA nanomedicines. In this work, we demonstrate that platelet activating factor (PAF), an inflammatory lipid mediator, plays a key role in nanocarrier-associated toxicities, and that prophylactic inhibition of the PAF receptor (PAFR) completely prevents these toxicities. High-dose intravenous injection of siRNA-polymer nano-complexes (si-NPs) elicited acute, shock-like symptoms (vasodilation and vascular leak) in mice and caused a three-fold increase in blood PAF levels. PAFR inhibition completely prevented these toxicities, indicating PAF activity is a primary driver of systemic si-NP toxicity. Pre-treatment with clodronate liposomes fully abrogated si-NP-associated increases in blood PAF and consequent toxicities, suggesting that nanoparticle uptake by Kupffer macrophages is the source of PAF. Assessment of varied si-NP chemistries further confirmed that toxicity level correlated to relative uptake of the carrier by liver Kupffer cells and that this toxicity mechanism is dependent on the endosome disruptive function of the carrier. Finally, the PAF toxicity mechanism was shown to be generalizable to commercial delivery reagentin vivo-jetPEI®and an MC3 lipid nanoparticle formulated to match an FDA-approved siRNA nanomedicine. Greater sensitivity to the PAF mechanism occurs in 4T1 tumor-bearing mice, a mammary tumor model known to exhibit increased circulating leukocytes and potential to respond to inflammatory insult. These results establish Kupffer cell release of PAF as a key mediator ofin vivonucleic acid nanocarrier toxicity and identify PAFR inhibition as an effective prophylactic strategy to increase maximum tolerated dose and reduce nanocarrier-associated adverse events.

Significance

Non-viral nucleic acid nanocarriers can enablein vivogene therapy, but their potential interaction with innate immune cells can cause dose-limiting toxicities. Nanoparticle toxicities are currently poorly understood, making it difficult to identify relevant design criteria for maximizing nanoparticle safety. This work connects nanoparticle-associated toxicities to the release of platelet activating factor (PAF) by liver Kupffer cells. Small molecule inhibition of the PAF receptor (PAFR) completely prevents severe adverse events associated with high doses of multiple polymer-based formulations and a lipid nanoparticle matching the composition of the first clinically-approved siRNA nanomedicine. This study identifies PAF as a toxicity biomarker for future nanomedicine discovery programs. Further, PAFR inhibition should be explored as a strategy to expand the therapeutic index of nanomedicines.
Amyloid fibril structure of islet amyloid polypeptide by cryo-electron microscopy reveals similarities with amyloid beta
Authors: Röder Christine , Kupreichyk Tatsiana , Gremer Lothar , Schäfer Luisa U. , Pothula Karunakar R. , Ravelli Raimond B. G. , Willbold Dieter , Hoyer Wolfgang , Schröder Gunnar F.
Published: February 2020

A critical role of the hormone islet amyloid polypeptide (IAPP) is vividly discussed for Type 2 Diabetes (T2D), where amyloid deposits in pancreatic islets consisting of fibrillar IAPP have been associated with beta cell loss. Here, we applied cryo-electron microscopy to elucidate the structure of IAPP fibrils prepared at physiological pH and reconstructed densities of three dominant polymorphs. An atomic model of the main polymorph comprising residues 13 – 37 in a density map of 4.2 Å resolution reveals two S-shaped, intertwined protofilaments. The segment 21-NNFGAIL-27, which is essential for IAPP amyloidogenicity, forms the protofilament interface together with tyrosine 37 and the amidated C-terminus. The main IAPP fibril polymorph resembles polymorphs of the Alzheimer disease (AD)-associated amyloid-β peptide (Aβ), which is striking in light of the epidemiological link between T2D and AD and reports on IAPP-Aβ cross-seedingin vivo. The results structurally link the early-onset T2D IAPP genetic polymorphism S20G with the early-onset AD Arctic mutation E22G of Aβ, rationalize previous data on IAPP fibrils, help to elucidate mechanisms of amyloid formation and toxicity, and support the design of fibril growth inhibitors as well as imaging probes for early detection of IAPP fibrils.
Co-transcriptional splicing regulates 3’ end cleavage during mammalian erythropoiesis
Authors: Reimer Kirsten A. , Mimoso Claudia , Adelman Karen , Neugebauer Karla M.
Published: February 2020

Pre-mRNA processing steps are tightly coordinated with transcription in many organisms. To determine how co-transcriptional splicing is integrated with transcription elongation and 3’ end formation in mammalian cells, we performed long-read sequencing of individual nascent RNAs and PRO-seq during mouse erythropoiesis. Splicing was not accompanied by transcriptional pausing and was detected when RNA polymerase II (Pol II) was within 75 – 300 nucleotides of 3’ splice sites (3’SSs), often during transcription of the downstream exon. Interestingly, several hundred introns displayed abundant splicing intermediates, suggesting that splicing delays can take place between the two catalytic steps. Overall, splicing efficiencies were correlated among introns within the same transcript, and intron retention was associated with inefficient 3’ end cleavage. Remarkably, a thalassemia patient-derived mutation introducing a cryptic 3’SS improves both splicing and 3’ end cleavage of individual β-globin transcripts, demonstrating functional coupling between the two co-transcriptional processes as a determinant of productive gene output.
Combination of antifungal drugs and protease inhibitors preventCandida albicansbiofilm formation and disrupt mature biofilms
Authors: Lohse Matthew B. , Gulati Megha , Craik Charles S. , Johnson Alexander D. , Nobile Clarissa J.
Published: February 2020

Biofilms formed by the fungal pathogenCandida albicansare resistant to many of the antifungal agents commonly used in the clinic. Previous reports suggest that protease inhibitors, specifically inhibitors of aspartyl proteases, could be effective antibiofilm agents. We screened three protease inhibitor libraries, containing a total of 80 compounds for the abilities to preventC. albicansbiofilm formation and to disrupt mature biofilms. The compounds were screened individually and in the presence of subinhibitory concentrations of the most commonly prescribed antifungal agents forCandidainfections: fluconazole, amphotericin B, or caspofungin. Although few of the compounds affected biofilms on their own, seven aspartyl protease inhibitors inhibited biofilm formation when combined with amphotericin B or caspofungin. Furthermore, nine aspartyl protease inhibitors disrupted mature biofilms when combined with caspofungin. These results suggest that the combination of standard antifungal agents together with specific protease inhibitors may be useful in the prevention and treatment ofC. albicansbiofilm infections.

Importance

Candida albicansis one of the most common pathogens of humans.C. albicansforms biofilms, structured communities of cells several hundred microns thick, on both biotic and abiotic surfaces. These biofilms are typically resistant to antifungal drugs at the concentrations that are normally effective against free-floating cells, thus requiring treatment with higher drug concentrations that often have significant side effects. Here, we show that certain combinations of existing antifungal agents with protease inhibitors, including several drugs already commonly used to treat HIV patients, are effective at inhibiting biofilm formation byC. albicansand/or at disrupting matureC. albicansbiofilms.
Metagenomic analysis of the cow, sheep, reindeer and red deer rumen
Authors: Glendinning Laura , Genç Buğra , Wallace R John , Watson Mick
Published: February 2020

The rumen microbiota comprises a community of microorganisms which specialise in the degradation of complex carbohydrates from plant-based feed. These microbes play a highly important role in ruminant nutrition and could also act as sources of industrially useful enzymes. In this study, we performed a metagenomic analysis of samples taken from the ruminal contents of cattle (Bos Taurus), sheep (Ovis aries), reindeer (Rangifer tarandus) and red deer (Cervus elaphus). We constructed 391 metagenome-assembled genomes originating from 16 microbial phyla. We compared our genomes to other publically available microbial genomes and found that they contained 279 novel species. We also found significant differences between the microbiota of different ruminant species in terms of the abundance of microbial taxonomies, carbohydrate-active enzyme genes and KEGG orthologs. However, we found that the vast majority of carbohydrate-active enzymes were present in all of our sample types, which may indicate that there is a core set of these enzymes which are present across ruminants and are independent of diet and environmental conditions. We present a dataset of rumen-derived genomes which in combination with other publicly-available rumen genomes can be used as a reference dataset in future metagenomic studies.

Data Summary

The paired-read fastq files supporting the conclusions of this article are available in the European Nucleotide Archive repository (https://www.ebi.ac.uk/ena/browser/view/PRJEB34458). The RUG fasta files supporting the conclusions of this article are available in the Edinburgh DataShare repository (https://doi.org/10.7488/ds/2640).
A time-resolved multi-omic atlas of the developing mouse liver
Authors: Gong Tongqing , Zhang Chunchao , Ni Xiaotian , Li Xianju , Li Jin'e , Liu Mingwei , Zhan Dongdong , Xia Xia , Song Lei , Zhou Quan , Ding Chen , Qin Jun , Wang Yi
Published: February 2020

Liver organogenesis and development are composed of a series of complex, well-orchestrated events. Identifying key factors and pathways governing liver development will help elucidate the physiological and pathological processes including those of cancer. We conducted multidimensional omics measurements including protein, mRNA, and transcription factor (TF) DNA-binding activity for mouse liver tissues collected from embryonic day 12.5 (E12.5) to postnatal week 8 (W8), encompassing major developmental stages. These data sets reveal dynamic changes of core liver functions and canonical signaling pathways governing development at both mRNA and protein levels. The TF DNA-binding activity data set highlights the importance of TF activity in early embryonic development. A comparison between mouse liver development and human hepatocellular carcinoma (HCC) proteomic profiles reveal that more aggressive tumors are characterized with the activation of early embryonic development pathways, whereas less aggressive ones maintain liver function–related pathways that are elevated in the mature liver. This work offers a panoramic view of mouse liver development and provides a rich resource to explore in-depth functional characterization.
TraDIS-Xpress: a high-resolution whole-genome assay identifies novel mechanisms of triclosan action and resistance
Authors: Yasir Muhammad , Turner A. Keith , Bastkowski Sarah , Baker David , Page Andrew J. , Telatin Andrea , Phan Minh-Duy , Monahan Leigh , Savva George M. , Darling Aaron , Webber Mark A. , Charles Ian G.
Published: February 2020

Understanding the genetic basis for a phenotype is a central goal in biological research. Much has been learnt about bacterial genomes by creating large mutant libraries and looking for conditionally important genes. However, current genome-wide methods are largely unable to assay essential genes which are not amenable to disruption. To overcome this limitation, we developed a new version of “TraDIS” (transposon directed insertion-site sequencing) that we term “TraDIS-Xpress” that combines an inducible promoter into the transposon cassette. This allows controlled overexpression and repression of all genes owing to saturation of inserts adjacent to all open reading frames as well as conventional inactivation. We applied TraDIS-Xpress to identify responses to the biocide triclosan across a range of concentrations. Triclosan is endemic in modern life, but there is uncertainty about its mode of action with a concentration-dependent switch from bacteriostatic to bactericidal action unexplained. Our results show a concentration-dependent response to triclosan with different genes important in survival between static and cidal exposures. These genes include those previously reported to have a role in triclosan resistance as well as a new set of genes, including essential genes. Novel genes identified as being sensitive to triclosan exposure include those involved in barrier function, small molecule uptake, and integrity of transcription and translation. We anticipate the approach we show here, by allowing comparisons across multiple experimental conditions of TraDIS data, and including essential genes, will be a starting point for future work examining how different drug conditions impact bacterial survival mechanisms.
Concentrated protein solutions investigated using acoustic levitation and small-angle X-ray scattering
Authors: Sønderby Pernille , Söderberg Christopher , Frankær Christian G. , Peters Günther , Bukrinski Jens T. , Labrador Ana , Plivelic Tomás S. , Harris Pernille
Published: February 2020

An acoustically levitated droplet has been used to collect synchrotron SAXS data on human serum albumin protein solutions up to a protein concentration of 400 mg ml−1. A careful selection of experiments allows for fast data collection of a large amount of data, spanning a protein concentration/solvent concentration space with limited sample consumption (down to 3 µL per experiment) and few measurements. The data analysis shows data of high quality that are reproducible and comparable with data from standard flow-through capillary-based experiments. Furthermore, using this methodology, it is possible to achieve concentrations that would not be accessible by conventional cells. The protein concentration and ionic strength parameter space diagram may be covered easily and the amount of protein sample is significantly reduced (by a factor of 100 in this work). Used in routine measurements, the benefits in terms of protein cost and time spent are very significant.
X-ray free-electron laser wavefront sensing using the fractional Talbot effect
Authors: Liu Yanwei , Seaberg Matthew , Feng Yiping , Li Kenan , Ding Yuantao , Marcus Gabriel , Fritz David , Shi Xianbo , Grizolli Walan , Assoufid Lahsen , Walter Peter , Sakdinawat Anne
Published: February 2020

Wavefront sensing at X-ray free-electron lasers is important for quantitatively understanding the fundamental properties of the laser, for aligning X-ray instruments and for conducting scientific experimental analysis. A fractional Talbot wavefront sensor has been developed. This wavefront sensor enables measurements over a wide range of energies, as is common on X-ray instruments, with simplified mechanical requirements and is compatible with the high average power pulses expected in upcoming X-ray free-electron laser upgrades. Single-shot measurements were performed at 500 eV, 1000 eV and 1500 eV at the Linac Coherent Light Source. These measurements were applied to study both mirror alignment and the effects of undulator tapering schemes on source properties. The beamline focal plane position was tracked to an uncertainty of 0.12 mm, and the source location for various undulator tapering schemes to an uncertainty of 1 m, demonstrating excellent sensitivity. These findings pave the way to use the fractional Talbot wavefront sensor as a routine, robust and sensitive tool at X-ray free-electron lasers as well as other high-brightness X-ray sources.
Multicultural attitudes and cultural intelligence of preschool teachers
Authors: Peköz Çağrı , Gürşimşek Ayşe Işık
Published: February 2020

Purpose

The purpose of this paper is to investigate the preschool teachers’ cultural intelligence, their attitudes towards multicultural education and the correlation between these two variables.

Design/methodology/approach

The sample consisted of 203 preschool teachers working in preschool classes within primary schools administrated by the Ministry of Education in Turkish Republic of Northern Cyprus (TRNC). Data were collected from the teachers by cultural intelligence scale (CQS), teacher multicultural attitude survey (TMAS) and demographic information form.

Findings

The analysis revealed that cultural intelligence and attitudes towards multicultural education did not differ according to teaching experience in a foreign country. Significant differences were found in metacognition, motivation and behaviour sub-dimension scores, cultural intelligence total scores and multicultural education attitude scores because of having a friend in foreign country, cognition sub-dimension scores because of having a non-Turkish-speaking student (NTSS) in class and cultural intelligence total scores because of knowing a foreign language. Significant relation was found between cultural intelligence scores and multicultural education attitude scores of the participants.

Originality/value

Despite the increasing cultural diversity in the country, there are no official regulations or efforts to establish arrangements for multicultural education in TRNC. Thus, this research is valuable for clarifying the situation in TRNC, determining the requirements and providing insights for future scientific work and implications.
Design for maintenance: new algorithmic approach
Authors: Adjoul Oussama , Benfriha Khaled , Aoussat Améziane
Published: February 2020

Purpose

This paper proposes a new simultaneous optimization model of the industrial systems design and maintenance. This model aims to help the designer in searching for technical solutions and the product architecture by integrating the maintenance issues from the design stage. The goal is to reduce the life-cycle cost (LCC) of the studied system.

Design/methodology/approach

Literature indicates that the different approaches used in the design for maintenance (DFM) methods are limited to the simultaneous characterization of the reliability and the maintainability of a multicomponent system as well as the modeling of the dynamic maintenance. This article proposes to go further in the optimization of the product, by simultaneously characterizing the design, in terms of reliability and maintainability, as well as the dynamic planning of the maintenance operations. This combinatorial characterization is performed by a two-level hybrid algorithm based on the genetic algorithms.

Findings

The proposed tool offers, depending on the life-cycle expectation, the desired availability, the desired business model (sales or rental), simulations in terms of the LCCs, and so an optimal product architecture.

Research limitations/implications

In this article, the term “design” is limited to reliability properties, possible redundancies, component accessibility (maintainability), and levels of monitoring information.

Originality/value

This work is distinguished by the use of a hybrid optimization algorithm (two-level computation) using genetic algorithms. The first level is to identify an optimal design configuration that takes into account the LCC criterion. The second level consists in proposing a dynamic and optimal maintenance plan based on the maintenance-free operating period (MFOP) concept that takes into account certain criteria, such as replacement costs or the reliability of the system.
When brands use CEOs and employees as spokespersons
Authors: Zeitoun Valérie , Michel Geraldine , Fleck Nathalie
Published: February 2020

Purpose

This paper aims to clarify the persuasion mechanism of chief executive officers (CEOs) and employees as endorsers of brand advertising and helps discern consumer attitudes toward internal endorsement.

Design/methodology/approach

The exploratory character of the present research required a qualitative approach combining focus groups and face-to-face interviews considered as both meaningful and complementary.

Findings

The findings suggest that while the celebrity endorsement ensures familiarity and likability, internal endorsement supports credibility and congruity with an important role of storytelling. Moreover, employee endorsements induce an internalization process based on the real-self, while the endorser CEO induces admiration grounded in the ideal self. More fundamentally, the study reveals how the internal endorsement modifies the meaning transfer model and involves a process of meaning translation, which affects the corporate brand image rather than the product brand image.

Originality/value

The present paper reveals that CEOs and employees can be strong levers for gilding the corporate brand image compared to the celebrities who enhance the product brand image. Moreover, the authors show that the CEO is a character who can be admired without the threat of upward comparison at the opposite of celebrities. Finally, this research highlights the specific role of employees bringing authenticity because of their anchorage in real life.
Internet of things in the archives: novel tools for environmental monitoring of archival collections
Authors: Maceli Monica
Published: February 2020

Purpose

Cultural heritage archives rely on environmental monitoring devices, such as dataloggers or more complex networked systems, to ensure collection preservation through collecting temperature, humidity, light and/or air quality measures. Existing systems are often costly, inflexible and do not use a modern, internet of things (IoT) approach. This paper aims to determine the suitability of currently popular general-purpose IoT devices, standards and technologies to the environmental monitoring needs of archivists, as well as identify any challenges.

Design/methodology/approach

This paper describes an exploratory study detailing the design, construction and usability testing of a do-it-yourself datalogger and data dashboard system, which seeks to manage previously identified trade-offs in cost, required technical skill and maintainability.

Findings

The environmental monitoring system presented met archivists’ needs well and was generally noted to be easy-to-use, efficient and an improvement on existing systems. This suggests that an IoT approach can support archivists’ needs in this area.

Research limitations/implications

Potential limitations of this study include lack of archival staff with sufficient technical training to maintain such a system and the rapid pace of IoT evolution yielding unstable and constantly changing technologies.

Practical implications

The system design presented in this work provides a blueprint for cultural heritage organizations desiring a fuller-featured, lower cost environmental monitoring system for archival collections.

Originality/value

This research takes a novel user-centered, open-source, IoT approach to construct an environmental monitoring system that is designed directly from archivists’ requirements and is extensible for future needs.
University social responsibility: perceptions and advances
Authors: Sousa Júlio César Rodrigues de , Siqueira Elisabete Stradiotto , Binotto Erlaine , Nobre Liana Holanda Nepomuceno
Published: February 2020

Purpose

The purpose of this paper is to analyze the perception of professors, students, administrative staff and academic directors about social responsibility in four universities of Rio Grande do Norte (RN) – Brazil.

Design/methodology/approach

The research was carried out in four universities in RN, Brazil. A survey was conducted with 1,318 students, 118 members of the administrative team, 104 professors and 29 academic directors, to whom a Likert-type questionnaire was applied, with 65 items allocated in seven dimensions as follows: organizational governance, human rights, work practices, environment, legal practices, consumer issues and community involvement and development. Exploratory factorial analysis and Cronbach’s alpha were the statistics used to analyze the data.

Findings

The research showed difficulties in assessing social responsibility aspects because of the lack of discussion and little socialization and debate of the data. Concerning everyday issues such as student service, environment issues, working conditions and local development is an exception because they have explicit opinions and often negative perceptions.

Research limitations/implications

The data used were self-reported they were subjected to bias, such as self-attribution and selective perception by community members. The lack of a theoretical model of social responsibility to study a non-profit organization. This study offers a theoretical contribution to analyzing six variables in non-profit organizations.

Practical implications

The data collection instrument also contribute to Brazilian universities can meet the evaluation criteria of higher education institutions in Brazil by Law 10.861/04, which established the national higher education evaluation system.

Social implications

This contribution allowed the authors to understand, which of them find the most consensus among stakeholders and which are the most contradictory, as well as to promote improvements in the implementation of social responsibility policies. The proposal of the instrument results in concrete actions for the adoption of the university, to accelerate the implementation of ISO 26000 in its statutes.

Originality/value

The study on social responsibility at universities of RN, Brazil, under dimensions of organizational governance, human rights, work practices, environment, legal practices, consumer issues, and community involvement and development is innovative and supports other universities to think their processes and better contribute in training new generations of citizens and professionals.
Knowledge sharing and the theory of planned behavior: a meta-analysis review
Authors: Afshar Jalili Yasha , Ghaleh Samaneh
Published: February 2020

Purpose

The purpose of this paper is to summarize the application of the theory of planned behavior (TPB) in predicting knowledge sharing behavior (KSB) based on a systematic literature review.

Design/methodology/approach

A meta-analysis was applied as a research methodology, and 47 studies were included in this study with a total population of 15,528 people (mean = 353). The authors summarized previous studies which used the TPB for predicting (KSB).

Findings

Findings reveal that KSB is determined jointly by knowledge-sharing intention (KSI) and perceived behavioral control (PBC). Intention itself is a function of attitude toward knowledge sharing, subjective norm surrounding knowledge sharing and PBC to perform KSB.

Practical implications

The primary implication of this meta-analysis is to deeply interpret the essence of KSB r and its determinants, in which managers can foster the conduction of this valuable behavior in their organizations. However, as a limitation, a remarkable threat to validity in the existing literature is a potential “cooperation bias” in which participants likely overestimate their knowledge sharing intention and knowledge sharing behavior. In future studies, this limitation can be addressed by measuring actual KSB.

Originality/value

This study is the first meta-analysis conducted to investigate the prediction power of the TPB for determining KSB. While there are several contradictions reported in the researches which used the TPB in the knowledge-sharing context, this research has summarized and reported the results.
What does coal mine dust lung disease look like? A radiological review following re‐identification in Queensland
Authors: McBean Rhiannon , Tatkovic Annaleis , Edwards Robert , Newbigin Katrina
Published: February 2020

Introduction

Coal mine dust lung disease (CMDLD), including the pneumoconioses, dust‐related diffuse fibrosis (DDF) and chronic obstructive pulmonary disease (COPD), are occupational lung diseases attributed to respirable coal mine dust. Following the re‐identification of CMDLD in Queensland in 2015, we undertook a case series to understand their radiological presentation.

Methods

Chest radiographs and high‐resolution computed tomography (HRCT) were retrospectively reviewed for 79 male individuals diagnosed by a respiratory physician with a CMDLD since 2015. Radiological findings were characterised as per the International Labour Office Classification System (ILO system) and the International Classification of HRCT for Occupational and Environmental Respiratory Diseases (ICOERD).

Results

Subjects with pneumoconiosis (n = 56) demonstrated widespread opacities with bilateral upper zone predominance. The majority of the lung was impacted, with 72% and 79% of zones demonstrating opacities on chest radiograph and HRCT, respectively. Most pneumoconiosis subjects (71%) demonstrated ILO category 1 disease, while 29% had advanced disease (ILO grades ≥ 2/1). A high proportion (81%) of pneumoconiosis subjects demonstrated at least one radiological feature associated with exposure to respirable crystalline silica (RCS). DDF subjects (n = 5) had radiologically severe disease (mean ILO 2/1) with lower zone‐predominant irregular opacities. Widespread emphysema, with no zone dominance, was the key radiological feature in those with COPD (n = 18).

Conclusion

Radiological findings of particular interest included the high burden of opacities observed and the presence of RCS‐associated features in the majority of subjects. Radiologists are at the front line in occupational lung disease screening/diagnosis and must be aware of the imaging spectrum.
Growth Shocks in the United States and China: Effects on Australia's Growth
Authors: Fisher Lance A. , Huh Hyeon‐seung , Kim David
Published: February 2020

This paper estimates a block recursive VAR to evaluate the relative impacts of US and Chinese GDP growth shocks on Australia's growth, controlling for the impacts of these shocks on growth in three of Australia's other major trading partners. For the sample 1984–2016, shocks to US GDP growth have a larger impact on Australian GDP growth than do shocks to Chinese GDP growth. In rolling windows through the sample, the impact of Chinese GDP shocks on Australia's growth increases substantially. For the sub‐sample 2000–2016, shocks to United States and Chinese GDP growth impact Australian GDP growth by the same magnitude.
Sense of home buffers threats to the self
Authors: Yang Ziyan , Sedikides Constantine , Yue Xitong , Cai Huajian
Published: February 2020

We hypothesised that sense of home serves as a buffer against self‐threat. In three experiments, we induced sense of home (vs. control) and assessed its buffering function to threat. Sense of home augmented openness to stereotype threat information (Experiment 1), increased performance on a spatial rotation ability test after stereotype threat (Experiment 2), and reduced the desire for high‐status products following mortality salience (Experiment 3). This “proof of concept” research establishes the buffering potential of sense of home and raises theoretical and practical implications.
Clinicopathologic features and prognostic factors in patients with renal cell carcinoma with sarcomatoid differentiation
Authors: Zhao Yuan , Chen Hong , Xie Yan , Zhang Chuanhong , Hou Yirui , Jin Mulan
Published: February 2020

Renal cell carcinoma with sarcomatoid differentiation (RCCs) is rare, accounting for 1–8% of all RCC histological subtypes. In this study, we examined 139 patients with RCCs and aimed to explore their clinicopathologic features and prognostic factors. From January 2007 to January 2019, patients who were pathologically diagnosed with RCCs were included in this retrospective study. Data on clinicopathologic features and overall survival were collected. The expression of CK, vimentin, CK7, and CD10 in the sarcomatoid regions of RCCs was detected. The Kaplan–Meier curves and log‐rank tests were used to describe the effect of clinicopathologic characteristics on overall survival. A Cox regression model was used to evaluate risk factors for prognosis. A total of 139 patients with RCCs were identified. The median age at diagnosis was 60 years. The median survival time of all patients was 39 months. The three‐ and five‐year survival rates were 50.2% and 44.0%, respectively. A high pathologic T stage (pT3 and pT4), microvascular invasion, and lymph node metastasis were significant predictors of prognosis. Pathologic T4 stage and lymph node metastasis were independent prognostic factors for overall survival in patients with RCCs. Furthermore, the expression of CD10 was a prognostic factor for overall survival. In this study, a relatively large cohort of patients with RCCs was analyzed. We summarized the clinicopathologic features of RCCs and explored the risk factors for prognosis. Our findings may provide valuable prediction for clinical strategy.
Letter: new insights on tofacitinib dose de‐escalation
Authors: Amiot Aurelien
Published: February 2020

LINKED CONTENT

This article is linked to Sands et al paper. To view this article, visit https://doi.org/10.1111/apt.15555.