bluuebunny/crossref_metadata_2025 huggingface dataset:
Urantide Improves Cardiac Function, Modulates Systemic Cytokine Response, and Increases Survival in A Murine Model of Endotoxic Shock
Authors: Clavier Thomas , Besnier Emmanuel , Maucotel Julie , Arabo Arnaud , Desrues Laurence , El Amki Mohamad , Perzo Nicolas , Richard Vincent , Tamion Fabienne , Gandolfo Pierrick , Dubois Martine , Castel Hélène , Compère Vincent
Published: October 2019

Introduction:

Urotensin II is a potent vasoactive peptide activating the the G protein-coupled urotensin II receptor UT, and is involved in systemic inflammation and cardiovascular functions. The aim of our work was to study the impact of the UT antagonist urantide on survival, systemic inflammation, and cardiac function during endotoxic shock.

Methods:

C57Bl/6 mice were intraperitoneally injected with lipopolysaccharide (LPS) and then randomized to be injected either by urantide or NaCl 0.9% 3, 6, and 9 h (H3, H6, H9) after LPS. The effect of urantide on the survival rate, the levels of cytokines in plasma at H6, H9, H12, the expression level of nuclear factor-kappa B (NF-κB-p65) in liver and kidney (at H12), and the cardiac function by trans-thoracic echocardiography from H0 to H9 was evaluated.

Results:

Urantide treatment improved survival (88.9% vs. 30% on day 6, P < 0.05). This was associated with changes in cytokine expression: a decrease in IL-6 (2,485 [2,280–2,751] pg/mL vs. 3,330 [3,119–3,680] pg/mL, P < 0.01) at H6, in IL-3 (1.0 [0.40–2.0] pg/mL vs. 5.8 [3.0–7.7] pg/mL, P < 0.01), and IL-1β (651 [491–1,135] pg/mL vs. 1,601 [906–3,010] pg/mL, P < 0.05) at H12 after LPS administration. Urantide decreased the proportion of cytosolic NF-κB-p65 in liver (1.3 [0.9–1.9] vs. 3.2 [2.3–4], P < 0.01) and kidney (0.3 [0.3–0.4] vs. 0.6 [0.5–1.1], P < 0.01). Urantide improved cardiac function (left ventricular fractional shortening: 24.8 [21.5–38.9] vs. 12.0 [8.7–17.6] %, P < 0.01 and cardiac output: 30.3 [25.9–39.8] vs. 15.1 [13.0–16.9] mL/min, P < 0.0001).

Conclusion:

These results show a beneficial curative role of UT antagonism on cytokine response (especially IL-3), cardiac dysfunction, and survival during endotoxic shock in mice, highlighting a potential new therapeutic target for septic patients.
Leveraging a Public Health Framework and Community Advisory Board to Innovate Workplace Violence Intervention Strategies
Authors: Gillespie Gordon Lee , Fisher Bonnie , Kennebeck Stephanie , Smith Carolyn , Griffith Dulcey , Matern Amanda , Richey Linda , Pendleton Jeffrey C. , Cubbage Paula , Martsolf Donna
Published: October 2019

Even with extensive evidence documenting the incidence, risk factors, and negative outcomes of workplace violence (WPV) against emergency department (ED) employees, there is a lack of intervention strategies reported that could be subjected to a clinical trial in the ED setting. The purpose of this article is to report the outcomes of a novel process adapted from the Framework for Program Evaluation in Public Health for soliciting intervention strategies from a WPV Community Advisory Board (CAB) organized by the U.S. Occupational Safety and Health Administration's WPV prevention guidelines. Ten professionals comprising both practitioners and researchers from a variety of disciplines ultimately constituted the WPV CAB. In total, 127 strategies to address WPV in ED settings organized by the Occupational Safety and Health Administration's WPV guideline elements were recommended. The use of a CAB and the Framework was shown to be effective for generating WPV intervention strategies.
Living Donor Kidney Transplantation Should Be Promoted Among “Elderly” Patients
Authors: Laging Mirjam , Kal-van Gestel Judith A. , Weimar Willem , Roodnat Joke I.
Published: October 2019

Background.

Age criteria for kidney transplantation have been liberalized over the years resulting in more waitlisted elderly patients. What are the prospects of elderly patients on the waiting list?

Methods.

Between 2000 and 2013, 2622 patients had been waitlisted. Waiting time was defined as the period between dialysis onset and being delisted. Patients were categorized according to age upon listing: <25; 25–44; 45–54; 55–64; and >64 years. Furthermore, the influence of ABO blood type and panel reactive antibodies on outflow patterns was studied.

Results.

At the end of observation (November 2017), 1957 (75%) patients had been transplanted, 333 (13%) had been delisted without a transplantation, 271 (10%) had died, and 61 (2%) were still waiting. When comparing the age categories, outflow patterns were completely different. The percentage of patients transplanted decreased with increasing age, while the percentage of patients that had been delisted or had died increased with increasing age, especially in the population without living donor. Within 6 years, 93% of the population <25 years had received a (primarily living) donor kidney. In the populations >55 years, 39% received a living donor kidney, while >50% of patients without a living donor had been delisted/died. Multivariable analysis showed that the influence of age, ABO blood type, and panel reactive antibodies on outflow patterns was significant, but the magnitude of the influence of the latter 2 was only modest compared with that of age.

Conclusions.

“Elderly” (not only >64 y but even 55–64 y) received a living donor kidney transplantation less often. Moreover, they cannot bear the waiting time for a deceased donor kidney, resulting in delisting without a transplant in more than half the population of patients without a living donor. Promoting living donor kidney transplantation is the only modification that improves transplantation and decreases delisting/death on the waiting list in this population.
Fear effects associated with predator presence and habitat structure interact to alter herbivory on coral reefs
Authors: Bauman Andrew G. , Seah Jovena C. L. , Januchowski-Hartley Fraser A. , Hoey Andrew S. , Fong Jenny , Todd Peter A.
Published: October 2019

Non-consumptive fear effects are an important determinant of foraging decisions by consumers across a range of ecosystems. However, how fear effects associated with the presence of predators interact with those associated with habitat structure remain unclear. Here, we used predator fish models (Plectropomus leopardus) and experimental patches of the macroalgaSargassum ilicifoliumof varying densities to investigate how predator- and habitat-associated fear effects influence herbivory on coral reefs. We found the removal of macroalgal biomass (i.e. herbivory) was shaped by the interaction between predator- and habitat-associated fear effects. Rates of macroalgal removal declined with increasing macroalgal density, likely due to increased visual occlusion by denser macroalgae patches and reduced ability of herbivorous fishes to detect the predators. The presence of the predator model reduced herbivory within low macroalgal density plots, but not within medium- and high-density macroalgal plots. Our results suggest that fear effects due to predator presence were greatest at low macroalgal density, yet these effects were lost at higher densities possibly due to greater predation risk associated with habitat structure and/or the inability of herbivorous fishes to detect the predator model.
Intergenerational transmission of longevity is not affected by other familial factors: Evidence from 16,905 Dutch families from Zeeland, 1812-1962
Authors: Mourits R.J. , van den Berg N.M.A. , Rodríguez-Girondo M. , Mandemakers K. , Slagboom P.E. , Beekman M. , Janssens A.A.P.O.
Published: October 2019

Studies have shown that long-lived individuals seem to pass their survival advantage on to their offspring. Offspring of long-lived parents had a lifelong survival advantage over individuals without long-lived parents, making them more likely to become long-lived themselves. We test whether the survival advantage enjoyed by offspring of long-lived individuals is explained by environmental factors. 101,577 individuals from 16,905 families in the 1812-1886 Zeeland cohort were followed over time. To prevent that certain families were overrepresented in our data, disjoint family trees were selected. Offspring was included if the age at death of both parents was known. Our analyses show that multiple familial resources are associated with survival within the first 5 years of life, with stronger maternal than paternal effects. However, between ages 5 and 100 both parents contribute equally to offspring’s survival chances. After age 5, offspring of long-lived fathers and long-lived mothers had a 16-19% lower chance of dying at any given point in time than individuals without long-lived parents. This survival advantage is most likely genetic in nature, as it could not be explained by other, tested familial resources and is transmitted equally by fathers and mothers.
Gap junction coding innexin inLymnaea stagnalis: sequence analysis and characterization in tissues and the central nervous system
Authors: Mersman Brittany A. , Jolly Sonia N. , Lin Zhenguo , Xu Fenglian
Published: October 2019

Connections between neurons called synapses are the key components underlying all nervous system functions of animals and humans. However, important genetic information on the formation and plasticity of one type, the electrical (gap junction-mediated) synapse, is severely understudied, especially in invertebrates. In the present study, we set forth to identify and characterize the gap junction-encoding gene innexin in the central nervous system (CNS) of the mollusc pond snailLymnaea stagnalis(L. stagnalis). With PCR, 3’ and 5’ RACE, and BLAST searches, we identified eight innexin genes in theL. stagnalisnervous system namedLst Inx1-8. Phylogenetic analysis revealed that theL. stagnalisinnexin genes originated from a single copy in the common ancestor of molluscan species by multiple gene duplication events and have been maintained inL. stagnalissince they were generated. The paralogous innexin genes demonstrate distinct expression patterns among tissues. In addition, one paralog,Lst Inx1, exhibits heterogeneity in cells and ganglia, suggesting the occurrence of functional diversification after gene duplication. These results introduce possibilities to study an intriguing potential relationship between innexin paralog expression and cell-specific functional outputs such as heterogenic ability to form channels and exhibit synapse plasticity. TheL. stagnalisCNS contains large neurons and a functionally defined network for behaviors; with the introduction ofL. stagnalisin the gap junction field, we are providing novel opportunities to combine genetic research with direct investigation of functional outcomes at the cellular, synaptic, and behavioral levels.

Summary Statement

By characterizing the gap junction gene innexin inLymnaea stagnalis, we open opportunities for novel studies on the regulation, plasticity, and evolutionary function of electrical synapses throughout the animal kingdom.
Selecting the most important self-assessed features for predicting conversion to Mild Cognitive Impairment with Random Forest and Permutation-based methods
Authors: Gómez-Ramírez Jaime , Ávila-Villanueva Marina , Fernández-Blázquez Miguel Ángel
Published: October 2019

Alzheimer’s Disease (AD) is a complex, multifactorial and comorbid condition. The asymptomatic behavior in the early stages makes the identification of the disease onset particularly challenging. Mild cognitive impairment (MCI) is an intermediary stage between the expected decline of normal aging and the pathological decline associated with dementia. The identification of risk factors for MCI is thus sorely needed. Self-reported personal information such as age, education, income level, sleep, diet, physical exercise, etc. are called to play a key role not only in the early identification of MCI but also in the design of personalized interventions and the promotion of patients empowerment. In this study we leverage onThe Vallecas Project, a large longitudinal study on healthy aging in Spain, to identify the most important self-reported features for future conversion to MCI. Using machine learning (random forest) and permutation-based methods we select the set of most important self-reported variables for MCI conversion which includes among others, subjective cognitive decline, educational level, working experience, social life, and diet. Subjective cognitive decline stands as the most important feature for future conversion to MCI across different feature selection techniques.
Including measures of high gamma power can improve the decoding of natural speech from EEG
Authors: Synigal Shyanthony R. , Teoh Emily S. , Lalor Edmund C.
Published: October 2019

The human auditory system is adept at extracting information from speech in both single-speaker and multi-speaker situations. This involves neural processing at the rapid temporal scales seen in natural speech. Non-invasive brain imaging (electro-/magnetoencephalography [EEG/MEG]) signatures of such processing have shown that the phase of neural activity below 16 Hz tracks the dynamics of speech, whereas invasive brain imaging (electrocorticography [ECoG]) has shown that such rapid processing is even more strongly reflected in the power of neural activity at high frequencies (around 70-150 Hz; known as high gamma). The aim of this study was to determine if high gamma power in scalp recorded EEG carries useful stimulus-related information, despite its reputation for having a poor signal to noise ratio. Furthermore, we aimed to assess whether any such information might be complementary to that reflected in well-established low frequency EEG indices of speech processing. We used linear regression to investigate speech envelope and attention decoding in EEG at low frequencies, in high gamma power, and in both signals combined. While low frequency speech tracking was evident for almost all subjects as expected, high gamma power also showed robust speech tracking in a minority of subjects. This same pattern was true for attention decoding using a separate group of subjects who undertook a cocktail party attention experiment. For the subjects who showed speech tracking in high gamma power, the spatiotemporal characteristics of that high gamma tracking differed from that of low-frequency EEG. Furthermore, combining the two neural measures led to improved measures of speech tracking for several subjects. Overall, this indicates that high gamma power EEG can carry useful information regarding speech processing and attentional selection in some subjects and combining it with low frequency EEG can improve the mapping between natural speech and the resulting neural responses.
Model-based assessments of differential introgression and linked natural selection during divergence and speciation
Authors: Sethuraman Arun , Sousa Vitor , Hey Jody
Published: October 2019

Demographic changes such as fluctuating population size and differential introgression can mask the effects of natural selection, and affect rates of genome evolution, local adaptation, reproductive isolation, and eventual speciation. Besides identifying differentially introgressing genes (and genomic regions) that are “labeled” to be retroactively causal to adaptive evolution and speciation, there is significant impetus to understand, and perhaps estimate the underlying demography that affects current genomic diversity. Using model-based likelihood methods to directly estimate, and decouple the effects of differential intogression and demography across genomic loci offers an ideal solution to detect differential introgression, and population demography and build hypotheses around its underlying evolutionary processes. We describe a computationally efficient parallelized implementation of mixture-model based isolation with migration (IM) analyses to assign loci to classes based on their shared coalescent histories (population sizes, or migration rates). We apply this method to several genomic data sets (great apes - chimpanzees and bonobos, Anopheles mosquitoes, threespine sticklebacks, Mullerian mimics of Heliconius butterflies, mice, European rabbits, and fruitflies), that have been previously characterized (perhaps erroneously) using genome-wide scans of differentiation. We show that we cannot reject a model of differential introgression, or linked selection across a majority of species analyzed, with two species showing the combined effects of differential introgression and linked natural selection across multiple, non-independent genomic loci.
Prey partitioning between sympatric canid species revealed by DNA metabarcoding
Authors: Shi Yue , Hoareau Yves , Reese Ellie , Wasser Samuel K.
Published: October 2019

The recovery of apex predators relies on restoring the full suite of trophic interactions within the ecosystem. Diet analysis with DNA metabarcoding technology can help deliver insights into these trophic interactions with fine-grained resolution. The recovery of wolves in Washington state offers an excellent case to study the trophic cascade impacts of the apex predators on the ecosystem and explore prey partitioning between sympatric canid species. We used DNA metabarcoding technology on scats to characterize the diet composition and its spatiotemporal variations of wolves and coyotes and quantified the diet niche overlap between these two canid species in northeastern Washington. In total, 19 different prey taxa were detected. Frequency of occurrence data showed that wolves primarily preyed upon deer (Odocoileus sp.) (47.47%) and moose (Alces alces) (42.42%). Coyotes also consumed moose (30.10%) and deer (21.36%), but snowshoe hares (Lepus americanus) were the most common prey (61.17%) in their diet. There were significant spatial variations in the wolf diet composition (p = 0.001) with wolves in the Dirty Shirt pack range consuming more moose (71.43%). Coyotes showed significant spatial and temporal dietary variations (season: p = 0.037; pack: p = 0.003; pack:season p = 0.043). Our data suggested that coyotes use ungulate carrion subsidies from wolves as food resources. DNA metabarcoding with fecal DNA provides an excellent noninvasive tool to characterize diet profile at the fine-grained level and can be applied to other carnivore species to help understand the impacts of recovery of apex predators on the local ecosystems.
Mutual information reveals a homonucleotide bias at 6 bp distance in promoters
Authors: Dannemiller James L.
Published: October 2019

Motivation

Statistical dependencies between nucleotides at different positions within a DNA sequence have been used for several purposes including distinguishing coding from noncoding regions of a genome. Coding sequences show correlations within and between codon positions. This study asked whether such correlations between positions separated by short distances might also exist in noncoding DNA. To this end, positional nucleotide dependencies were examined in the promoter regions of four eukaryotic species:Homo sapiens(Hs),Mus musculus(Mm),Drosophila melanogaster(Dm), andSaccharomyces cerevisiae(Sc). The degree of dependency between pairwise positions across a set of aligned sequences was quantified by Mutual Information (MI) and visualized using a novel heatmap method.

Results

MI in promoter sequences aligned at their putative Transcription Start Site (TSS) generally decreased with increasing distance between two positions, but also showed a prominent increase at a distance of 6 base pairs (bp) (i.e., between nucleotides atxandx+ 6 in a sequence) in the three multicellular species, but much less so inSc. This dependency at a distance of 6 bp appears to reflect anN1…N7homonucleotide bias in promoters.

Availability

R code and data files available at github/dannemil/promoters.

Contact

dannemil@rice.edu

Supplementary information

Dannemiller-supplementary-documents.zip
Benchmarking metagenomic marine microbial growth prediction from codon usage bias and peak-to-trough ratios
Authors: Long Andrew M. , Hou Shengwei , Ignacio-Espinoza J. Cesar , Fuhrman Jed A.
Published: October 2019

Growth rates are fundamental to all organisms and essential for characterizing microbial ecologies. Despite this, we do not know the instantaneous nor maximum growth rates of most naturally-occurring microorganisms. Recent reports indicate DNA replication rates can be estimated from metagenomic coverage, and maximum growth rates can be estimated from genomic characteristics. We tested these approaches with native marine bacteria (<0.6 um size fraction) as 10% inoculum grown in unamended virus-free seawater from the San Pedro Channel, California. This allowed microbial growth without grazing and with greatly reduced viral infection. At multiple time points up to 48 h, we sampled for cell abundances and metagenomic analyses. We generated 101 unique Metagenome-assembled genomes (MAGs) including α, β, and γ Proteobacteria, Flavobacteria, Actinobacteria, Verrucomicrobia, Marine Group A/SAR406, MGII archaea, and others. We tracked the growth of each as the fraction of total metagenomic reads mapped to each MAG normalized with length, completeness, and total cell counts. Some MAGs did not grow appreciably, but those we could estimate had growth rates ranging from 0.08 to 5.99 d−1; these are the first reported growth rates for several of the groups. These metagenome-determined growth rates, which often changed within experiments, were compared to (a) DNA replication estimates from the ‘peak-to-trough’ ratio (PTR) as determined by three different approaches, and (b) maximum growth rates predicted from codon usage bias (CUB). For the large majority of taxa, observed growth rates were not correlated to PTR indices (r ~ −0.26 - 0.08), with exceptions being rapidly growingOceanospirillalesandSaccharospirillaceae(r ~ 0.63 - 0.92). However, CUB was moderately well correlated to observed maximum growth rates (r = 0.57). This suggests that maximum growth rates can be reasonably well-estimated from genomic information alone, but current PTR approaches poorly predict actual growth of most marine planktonic bacteria in unamended seawater.
Computational redesign of a PETase for plastic biodegradation by the GRAPE strategy
Authors: Cui Yinglu , Chen Yanchun , Liu Xinyue , Dong Saijun , Tian Yu’e , Qiao Yuxin , Mitra Ruchira , Han Jing , Li Chunli , Han Xu , Liu Weidong , Chen Quan , Du Wenbin , Tang Shuangyan , Xiang Hua , Liu Haiyan , Wu Bian
Published: October 2019

The excessive use of plastics has been accompanied by severe ecologically damaging effects. The recent discovery of a PETase from Ideonella sakaiensis that decomposes poly(ethylene terephthalate) (PET) under mild conditions provides an attractive avenue for the biodegradation of plastics. However, the inherent instability of the enzyme limits its practical utilization. Here, we devised a novel computational strategy (greedy accumulated strategy for protein engineering, GRAPE). A systematic clustering analysis combined with greedy accumulation of beneficial mutations in a computationally derived library enabled the design of a variant, DuraPETase, which exhibits an apparent melting temperature that is drastically elevated by 31 °C and strikingly enhanced degradation performance toward semicrystalline PET films (23%) at mild temperatures (over two orders of magnitude improvement). The mechanism underlying the robust promotion of enzyme performance has been demonstrated via a crystal structure and molecular dynamics simulations. This work shows the capabilities of computational enzyme design to circumvent antagonistic epistatic effects and provides a valuable tool for further understanding and advancing polyester hydrolysis in the natural environment.
CD146+CD107a+ Mesenchymal Stem/Stromal Cells with Signature Attributes Correlate to Therapeutic Potency as “First Responders” to Injury and Inflammation
Authors: Bowles Annie C. , Kouroupis Dimitrios , Willman Melissa A. , Orfei Carlotta Perucca , Agarwal Ashutosh , Correa Diego
Published: October 2019

CD146+ bone marrow–derived Mesenchymal Stem/Stromal Cells (BM-MSC) play key roles in the perivascular niche, skeletogenesis and hematopoietic support, however elucidation of therapeutic potency has yet to be determined. Here, inflammatory challenge to crude BM-MSC captured a baseline of signatures including enriched expression of CD146+ with CD107a+, CXCR4+, and LepR+, transcriptional profile, enhanced secretory capacity, robust secretome and immunomodulatory function with stimulated target immune cells. These responses were significantly more pronounced in CD146+ (POS)-selected subpopulation than in the CD146- (NEG). Mechanistically, POS uniquely mediated robust immunosuppression while inducing significant frequencies of Naïve and Regulatory T cells in vitro. Moreover, POS promoted a pivotal M1-to-M2 macrophage shift in vivo, ameliorating inflammation/fibrosis of joint synovium and fat pad of the knee, failed by NEG. This study provides high-content evidence of CD146+CD107a+ BM-MSC, herein deemed ‘first responders’ to inflammation, as the underrepresented subpopulation within crude BM-MSC with innately higher secretory capacity and therapeutic potency.

HIGHLIGHTS

Signature phenotypic, transcriptional, and secretome profiles were identified and enriched in human CD146+ (POS)-selected subpopulation in response to inflammation

Inflammatory challenge consistently altered stemness (LIF) and differentiation master regulators (SOX9, RUNX2, PPARγ) in crude, POS, and NEG BM-MSC, and deduced unique expressions in POS compared to NEG

POS BM-MSC mediated the strongest immunomodulation, e.g. target immune cell suppression, Treg induction, diminished T cell differentiation

POS BM-MSC promoted the largest M1-to-M2 shift in vivo alleviating induced synovitis and infrapatellar fat pad fibrosis of the knee
Genetic colocalization atlas points to common regulatory sites and genes for hematopoietic traits and hematopoietic contributions to disease phenotypes
Authors: Thom CS , Voight BF
Published: October 2019

Background

Genetic associations link hematopoietic traits and disease end-points, but most causal variants and genes underlying these relationships are unknown. Here, we used genetic colocalization to nominate loci and genes related to shared genetic signal for hematopoietic, cardiovascular, autoimmune, neuropsychiatric and cancer phenotypes.

Results

Our findings recapitulate developmental hematopoietic lineage relationships, identify loci associating traits with causal genetic relationships, and reveal novel associations. Out of 2706 loci with genome-wide significant signal for at least 1 blood trait, we identified 1779 unique sites (66%) with shared genetic signal for 2+ hematologic traits at a false discovery rate <5%. We could assign some sites to specific developmental cell types during hematopoiesis based on affected traits, including those likely to impact hematopoietic progenitor cells and/or megakaryocyte-erythroid progenitor cells. Through an expanded analysis of 70 human traits, we define 2+ colocalizing traits at 2007 loci from an analysis of 9852 sites (20%) containing genome-wide significant signal for at least 1 GWAS trait. In addition to variants and genes underlying shared genetic signal between blood traits and disease phenotypes that had been previously related through mendelian randomization studies, we define loci and related genes underlying shared signal between eosinophil count and eczema. We also identified colocalizing signals in a number of clinically relevant coding mutations, including in sites linkingPTPN22with Crohns disease,NIPAwith coronary artery disease and platelet trait variation, and the hemochromatosis geneHFEwith altered lipid levels. Finally, we anticipate potential off-target effects on blood traits related novel therapeutic targets, includingTRAIL.

Conclusions

Our findings provide a road map for gene validation experiments and novel therapeutics related to hematopoietic development, and offer a rationale for pleiotropic interactions between hematopoietic loci and disease end-points.
STAG2 cohesin is essential for heart morphogenesis
Authors: De Koninck M. , Lapi E. , Badia-Careaga C. , Cossio I. , Giménez-Llorente D. , Rodríguez-Corsino M. , Andrada E. , Hidalgo A. , Manzanares M. , Real F. X. , Losada A.
Published: October 2019

The distinct functions of cohesin complexes carrying STAG1 or STAG2 need to be unraveled. STAG2 is commonly mutated in cancer and germline mutations have been identified in cohesinopathy patients. To better understand the underlying pathogenic mechanisms, we here report the consequence of Stag2 ablation in mice. STAG2 is largely dispensable in adults and its tissue-wide inactivation does not lead to tumors but reduces fitness and affects both hematopoiesis and intestinal homeostasis. STAG2 is also dispensable for murine embryonic fibroblasts in vitro. In contrast, null embryos die by mid gestation showing global developmental delay and heart defects. Histopathological analysis and RNA-sequencing unveiled that STAG2 is required both for proliferation and regulation of cardiac transcriptional programs and in its absence, secondary heart field progenitors fail to enter the heart tube. These results provide compelling evidence on cell- and tissue-specific roles of the two cohesin complexes and how their dysfunction contributes to disease.
Kidney organoids: accurate models or fortunate accidents
Authors: Little Melissa H. , Combes Alexander N.
Published: October 2019

There are now many reports of human kidney organoids generated via the directed differentiation of human pluripotent stem cells (PSCs) based on an existing understanding of mammalian kidney organogenesis. Such kidney organoids potentially represent tractable tools for the study of normal human development and disease with improvements in scale, structure, and functional maturation potentially providing future options for renal regeneration. The utility of such organotypic models, however, will ultimately be determined by their developmental accuracy. While initially inferred from mouse models, recent transcriptional analyses of human fetal kidney have provided greater insight into nephrogenesis. In this review, we discuss how well human kidney organoids model the human fetal kidney and how the remaining differences challenge their utility.
Electro Cell Fusion for Hybridoma Production
Authors: Greenfield Edward A.
Published: October 2019

Once a good immune response has developed in an animal and an appropriate screening procedure has been developed, the construction of hybridomas is ready to begin. The electro cell fusion (electrofusion) method uses an electrical field in the form of short, intense pulses to increase the permeability of the membrane. The resulting local perforation of the cell membrane induces the cells to fuse, forming hybridomas. Electrofusion is accomplished in three steps: Prealignment of the cells (convergence and cell contact), membrane fusion, and postalignment (rounding off the fused cells). This method has been applied successfully to hybridoma production with higher efficiency than routine polyethylene glycol fusion, allowing production of more hybrid cells.
An end-to-end learning method for industrial defect detection
Authors: Wu Yupei , Guo Di , Liu Huaping , Huang Yao
Published: October 2019

Purpose

Automatic defect detection is a fundamental and vital topic in the research field of industrial intelligence. In this work, the authors develop a more flexible deep learning method for the industrial defect detection.

Design/methodology/approach

The authors propose a unified framework for detecting defects in industrial products or planar surfaces based on an end-to-end learning strategy. A lightweight deep learning architecture for blade defect detection is specifically demonstrated. In addition, a blade defect data set is collected with the dual-arm image collection system.

Findings

Numerous experiments are conducted on the collected data set, and experimental results demonstrate that the proposed system can achieve satisfactory performance over other methods. Furthermore, the data equalization operation helps for a better defect detection result.

Originality/value

An end-to-end learning framework is established for defect detection. Although the adopted fully convolutional network has been extensively used for semantic segmentation in images, to the best knowledge of the authors, it has not been used for industrial defect detection. To remedy the difficulties of blade defect detection which has been analyzed above, the authors develop a new network architecture which integrates the residue learning to perform the efficient defect detection. A dual-arm data collection platform is constructed and extensive experimental validation are conducted.
Confidence interval prediction of ANN estimated LPT parameters
Authors: Yildirim Mustagime Tülin , Kurt Bülent
Published: October 2019

Purpose

With the condition monitoring system on airplanes, failures can be predicted before they occur. Performance deterioration of aircraft engines is monitored by parameters such as fuel flow, exhaust gas temperature, engine fan speeds, vibration, oil pressure and oil temperature. The vibration parameter allows us to easily detect any existing or possible faults. The purpose of this paper is to develop a new model to estimate the low pressure turbine (LPT) vibration parameter of an aircraft engine by using the data of an aircraft’s actual flight from flight data recorder (FDR).

Design/methodology/approach

First, statistical regression analysis is used to determine the parameters related to LPT. Then, the selected parameters were applied as an input to the developed Levenberg–Marquardt feedforward neural network and the output LPT vibration parameter was estimated with a small error. Analyses were performed on MATLAB and SPSS Statistics 22 package program. Finally, the confidence interval method is used to check the accuracy of the estimated results of artificial neural networks (ANNs).

Findings

This study shows that the health conditions of an aircraft engine can be evaluated in terms of this paper by using confidence interval prediction of ANN-estimated LPT vibration parameters without dismantling and expert knowledge.

Practical implications

With this study, it has been shown that faults that may occur during flight can be easily detected using the data of a flight without expert evaluation.

Originality/value

The health condition of the turbofan engine was evaluated using the confidence interval prediction of ANN-estimated LPT vibration parameters.
Which Google keywords influence entrepreneurs? Empirical evidence from Vietnam
Authors: Huynh Toan Luu Duc
Published: October 2019

Purpose

This paper aims to shed light on an impact of Google keywords on the number of new businesses (and an amount of capital registered) in Vietnam, the Southeast Asian country, after the year of an entrepreneur, 2016.

Design/methodology/approach

This study uses a rich set of quantitative techniques from VAR Granger and threshold regression. The whole sample period covers the data (keywords, number of new businesses, an amount of capital invested to register) from the first week of 2016 to October 2018, which includes 144 observations in total.

Findings

The findings suggest that the relationship between Google does not persist in the long run. There is a short-run shock, might cause a change to the frequency of the other keywords rather than the number of firms (or an amount of capital). However, under the number of firms’ threshold, keywords have the both positive and negative impacts on entrepreneurs whereas a higher threshold of capital, keywords show their roles to predict an amount of money for registering firms.

Practical implications

The Vietnamese Government and executives are advised to consider the Google keywords “entrepreneur” (in Vietnamese) and “start-up”, which cause a decline in entrepreneurial movements. In addition, the current period is going to inverse from the previous one in terms of the number of firms and an amount of capital. Finally, there are two critical thresholds: 1,602 companies and 35,010m VND for the keywords' influence.

Originality/value

This study contributes empirical evidence of technological change and entrepreneurship and contributes to the existing literature by discussing how this relationship under the threshold.
Toward robotic process automation implementation: an end-to-end perspective
Authors: Santos Filipa , Pereira Rúben , Vasconcelos José Braga
Published: October 2019

Purpose

Robotic process automation (RPA) seeks to automate business processes, using software robots that interact with systems through their user interface, improving efficiency and reducing costs. However, some critical steps, such as identifying processes suitable for RPA automation, can have a tremendous impact in organizations if a wrong process is selected. Therefore, the purpose of this paper is to provide an approach for analyzing RPA development in business organizations.

Design/methodology/approach

This research presents a cohesive literature review about RPA, in order to identify RPA main concepts, which should be reported and considered in all RPA case studies. A model connecting the main elicited RPA concepts is presented as well as its evaluation and applicability grounded of past RPA case study (CS) analysis, using design science research.

Findings

The results from this research show that most of the RPA main concepts gathered in the literature review are not reported in the selected RPA CSs.

Originality/value

As RPA is a recent topic, literature lacks a synthetization of RPA main topics. This research aims to fill the gap on that, by identifying and synthesize the main topics related to RPA and proposing a model that connects the main RPA concepts, which can be used by researchers as a schema for conducting and writing RPA case studies.
Expedited optimization of antenna input characteristics with adaptive Broyden updates
Authors: Koziel Slawomir , Pietrenko-Dabrowska Anna
Published: October 2019

Purpose

A technique for accelerated design optimization of antenna input characteristics is developed and comprehensively validated using real-world wideband antenna structures. Comparative study using a conventional trust-region algorithm is provided. Investigations of the effects of the algorithm control parameters are also carried out.

Design/methodology/approach

An optimization methodology is introduced that replaces finite differentiation (FD) by a combination of FD and selectively used Broyden updating formula for antenna response Jacobian estimations. The updating formula is used for directions that are sufficiently well aligned with the design relocation that occurred in the most recent algorithm iteration. This allows for a significant reduction of the number of full-wave electromagnetic simulations necessary for the algorithm to converge; hence, it leads to the reduction of the overall design cost.

Findings

Incorporation of the updating formulas into the Jacobian estimation process in a selective manner considerably reduces the computational cost of the optimization process without compromising the design quality. The algorithm proposed in the study can be used to speed up direct optimization of the antenna structures as well as surrogate-assisted procedures involving variable-fidelity models.

Research limitations/implications

This study sets a direction for further studies on accelerating procedures for the local optimization of antenna structures. Further investigations on the effects of the control parameters on the algorithm performance are necessary along with the development of means to automate the algorithm setup for a particular antenna structure, especially from the point of view of the search space dimensionality.

Originality/value

The proposed algorithm proved useful for a reduced-cost optimization of antennas and has been demonstrated to outperform conventional algorithms. To the authors’ knowledge, this is one of the first attempts to address the problem in this manner. In particular, it goes beyond traditional approaches, especially by combining various sensitivity estimation update measures in an adaptive fashion.
Static analysis of carbon nanotube-reinforced FG shells using an efficient solid-shell element with parabolic transverse shear strain
Authors: Hajlaoui Abdessalem , Chebbi Elouni , Wali Mondher , Dammak Fakhreddine
Published: October 2019

Purpose

This paper aims to study the static behavior of carbon nanotubes (CNTs) reinforced functionally graded shells using an efficient solid-shell element with parabolic transverse shear strain. Four different types of reinforcement along the thickness are considered.

Design/methodology/approach

Furthermore, the developed solid-shell element allows an efficient and accurate analysis of CNT-reinforced functionally graded shells under linear static conditions.

Findings

The validity and accuracy of the developed solid-shell element are illustrated through the solution of deflection and stress distribution problems of shell structures taken from the literature. The influences of some geometrical and material parameters on the static behavior of shell structures are discussed.

Originality/value

The finite element formulation is based on a modified first-order enhanced solid-shell element formulation with an imposed parabolic shear strain distribution through the shell thickness in the compatible strain part. This formulation guarantees a zero transverse shear stress on the top and bottom surfaces of the shell and the shear correction factors is no longer needed.
What debt threshold hampers economic growth in Africa?
Authors: Mensah Lord , Allotey Divine , Sarpong-Kumankoma Emmanuel , Coffie William
Published: October 2019

Purpose

This paper aims to test whether a debt threshold of public debt has any effect on economic growth in Africa.

Design/methodology/approach

The authors applied the panel autoregressive distributed models on 38 African countries with annual data from 1970 to 2015. It was established that the threshold and the trajectory of debt has an impact on economic growth.

Findings

Specifically, the authors found that public debt hampers economic growth when the depth is in the region of 20 to 80 per cent of GDP. Based on debt trajectory, this study established that increasing public debt beyond 50 to 80 per cent of GDP adversely affects economic growth in Africa. The study also finds that the persistent rise in debt also has adverse effect on economic growth in the African countries in the sample. It must be known to policymakers that the threshold of debt in developing countries, and for that matter African countries, are less than that of developed countries.

Practical implications

This study suggests threshold effects between 20 and 50 per cent; this should be a guide for policymakers in the accumulation of debt stock. Interestingly, the findings suggest some debt trajectory effect, which policymakers might consider by increasing efforts to reduce debt levels when they fall between 50 to 80 per cent of GDP. This implies that reducing such debt levels can help African countries increase their economic growth.

Originality/value

The study is unique because it seeks to add new evidence on the relationship between public debt and growth in the African region, by considering the impact of the persistent growth of public debt on economic growth.
School competition in Hong Kong: a battle of lifting school academic performance?
Authors: Chun Sing Ho Maxwell , Lu Jiafang
Published: October 2019

Purpose

Under-examination of the notion of competition between schools has created a considerable asymmetry between the reality and the literature of schooling. Therefore, the purpose of this paper is to investigate the validity of school competition and verify the propositions regarding the effects of school marketing practices in literature, particularly Direct Subsidy Scheme (DSS) and aided schools in Hong Kong.

Design/methodology/approach

It tests the relationships between student intake and school academic performance and school marketing practices. It also compares the pattern of the relationships between the DSS and aided secondary schools. Secondary data from 441 secondary schools were retrieved from a popular secondary school admission magazine in Hong Kong and from the schools’ websites.

Findings

Hierarchical regression analysis revealed that the school’s academic performance was positively related to discretionary student intake. In addition, marketing school academic performance, but not marketing school features, was positively related to student intake. At last, it was found that marketing school academic performance intensified the relationship between the school’s academic performance and student intake in aided schools but not in DSS schools. The results were interpreted as demonstrating that school competition in Hong Kong is a battle of lifting academic performance.

Originality/value

This study is potential and worthwhile in at least two ways. First, testing the relationships of student intake with academic performance and school marketing practices helps to verify the notion of school competition in the education sector, which, in turn, can bridge the gap between the practice and literature of schooling. Second, examining school competition in Hong Kong can help to identify an important contextual reality for future scholars whose research site is located in Hong Kong.
Attributes valued by students in higher education services: a lean perspective
Authors: Petrusch Anete , Vaccaro Guilherme Luís Roehe
Published: October 2019

Purpose

The purpose of this paper is to use theoretical and field evidence to discuss what the value-attributes for academic-administrative services as perceived by students in higher education institutions (HEIs) and how such organizations deliver them. An emerging framework relating value-attributes for HEIs’ administrative and academic services is presented from the perspective of students.

Design/methodology/approach

Focus group analysis with Brazilian HEI’s students supported this study. Extensive theoretical references from lean services and services theory contribute to building an emerging framework that extends the background on the subject.

Findings

The following framework of eight value-attributes for administrative services in HEIs were studied: reliability, empathy, access, responsiveness, self-service technology convenience, communication, personalization and imperceptibility. The value-attributes may receive different degrees of prioritization and improvement effort according to the type of service and strategic positioning of the organization.

Research limitations/implications

Field evidence is limited by the extent of students and organizations accessed. Implications include directing future research to produce a quantitatively validated model and as an emerging framework, to support decision-planning in the context of HEIs.

Originality/value

The study extends the literature relating the connection between lean services, services theory and higher education services. No similar study has been found in Brazilian HEIs.