bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reconstructing the history of polygenic scores using coalescent trees
Authors: Edge Michael D. , Coop Graham 
Published: August 2018

1AbstractGenome-wide association studies (GWAS) have revealed that many traits are highly polygenic, in that their within-population variance is governed in part by small-effect variants at many genetic loci. Standard population-genetic methods for inferring evolutionary history are ill-suited for polygenic traits—when there are many variants of small effect, signatures of natural selection are spread across the genome and subtle at any one locus. In the last several years, several methods have emerged for detecting the action of natural selection on polygenic scores, sums of genotypes weighted by GWAS effect sizes. However, most existing methods do not reveal the timing or strength of selection. Here, we present a set of methods for estimating the historical time course of a population-mean polygenic score using local coalescent trees at GWAS loci. These time courses are estimated by using coalescent theory to relate the branch lengths of trees to allele-frequency change. The resulting time course can be tested for evidence of natural selection. We present theory and simulations supporting our procedures, as well as estimated time courses of polygenic scores for human height. Because of its grounding in coalescent theory, the framework presented here can be extended to a variety of demographic scenarios, and its usefulness will increase as both GWAS and ancestral recombination graph (ARG) inference continue to progress.
Interleukin-1 receptor antagonist mediates type I interferon-driven susceptibility to Mycobacterium tuberculosis
Authors: Ji Daisy X. , Chen Katherine J. , Mukaida Naofumi , Kramnik Igor , Darwin K. Heran , Vance Russell E. 
Published: August 2018

AbstractThe bacterium Mycobacterium tuberculosis (Mtb) causes tuberculosis (TB) and is responsible for more human mortality than any other single pathogen1. Although ~1.7 billion people are infected with Mtb2, most infections are asymptomatic. Progression to active disease occurs in ~10% of infected individuals and is predicted by an elevated type I interferon (IFN) response3–8. Type I IFNs are vital for antiviral immunity, but whether or how they mediate susceptibility to Mtb has been difficult to study, in part because the standard C57BL/6 (B6) mouse model does not recapitulate the IFN-driven disease that appears to occur in humans3–5,8. Here we examined B6. Sst1S congenic mice that carry the C3H “sensitive” allele of the Sst1 locus that renders them highly susceptible to Mtb infections9,10. We found that B6.Sst1S mice exhibit markedly increased type I IFN signaling, and that type I IFNs were required for the enhanced susceptibility of B6. Sst1S mice to Mtb. Type I IFNs affect the expression of hundreds of genes, several of which have previously been implicated in susceptibility to bacterial infections11,12. Nevertheless, we found that heterozygous deficiency in just a single IFN target gene, IL-1 receptor antagonist (IL-1Ra), is sufficient to reverse IFN-driven susceptibility to Mtb. As even a partial reduction in IL-1Ra levels led to significant protection, we hypothesized that IL-1Ra may be a plausible target for host-directed anti-TB therapy. Indeed, antibody-mediated neutralization of IL-1Ra provided therapeutic benefit to Mtb-infected B6. Sst1S mice. Our results illustrate how the diversity of inbred mouse strains can be exploited to better model human TB, and demonstrate that IL-1Ra is an important mediator of type I IFN-driven susceptibility to Mtb infections in vivo.
Evidence against the microbicidal action of neutrophil extracellular traps (NETs)
Authors: Semplici F. , Segal A. W. 
Published: August 2018

AbstractNeutrophil extracellular traps (NETs) are fibrillary structures composed of extruded nuclear chromatin decorated with granule proteins (mostly neutrophil elastase, cathepsin G and myeloperoxidase). It has been reported that NETs are able to kill bacteria and fungi based upon the observation that smaller number of organisms are obtained in plating assays after they are incubated with NETs than if the DNA is pre-digested with DNase. It is possible that the microbial killing is apparent rather than real, and occurs because the organisms are aggregated on the DNA structure, and that the plating assay results were simply misinterpreted. The present study shows that digestion of DNA after incubation of NETs with the microbes restores their numbers to preincubation levels indicating that the apparent killing is an artefact of the assay.
The Role of Gdf5 Regulatory Regions on Development of Hip Morphology and Susceptibility to Osteoarthritis and Dislocation
Authors: Kiapour Ata M. , Cao Jiaxue , Young Mariel , Capellini Terence D. 
Published: August 2018

ABSTRACTGiven GDF5 involvement in hip development, and osteoarthritis (OA) and developmental hip dysplasia (DDH) risk, here we sought to assess the role(s) of GDF5 and its regulatory sequence on the development of hip morphology linked to injury risk. The brachypodism (bp) mouse, which harbors a Gdf5 inactivating mutation, was used to survey how Gdf5 loss of function impacts the development of hip morphology. Two transgenic Gdf5 reporter BAC lines were used to assess the spatiotemporal expression of Gdf5 regulatory sequences. Each BAC line was also used to assess the functional roles of upstream and downstream sequence on hip morphology. bp/bp mice had shorter femora with smaller femoral heads and necks as well as larger alpha angles, smaller anterior offsets, and smaller acetabula, compared to bp/+ mice (p<0.04). Regulatory sequences downstream of Gdf5 drove strong prenatal (E17) expression and low postnatal (6 months) expression across regions of femoral head and acetabulum. Conversely, upstream regulatory sequences drove very low expression at E17 and no detectable expression at 6 months. Importantly, downstream, but not upstream Gdf5 regulatory sequences fully restored all the key morphologic features disrupted in bp/bp mice. Hip morphology is profoundly affected by Gdf5 absence, and downstream regulatory sequences mediate its effects by controlling Gdf5 expression during development. This downstream region contains numerous enhancers harboring risk variants related to hip OA, DDH, and dislocation. We posit that subtle alterations to morphology driven by changes in downstream regulatory sequence underlie this locus’ role in hip injury risk.
Qualitative modeling of signaling networks in replicative senescence by selecting optimal node and arc sets
Authors: Sakellaropoulos Theodore , Binenbaum Ilona , Lefaki Maria , Chatziioannou Aristotelis , Chondrogianni Niki , Alexopoulos Leonidas G. 
Published: August 2018

AbstractSignaling networks are an important tool of modern systems biology and drug development. Here, we present a new methodology to qualitatively model signaling networks by combining experimental data and prior knowledge about protein connectivity. Unlike other methods, our approach does not focus solely on selecting which reactions are involved but also on whether a protein is present. This allows the user to model more complicated experiments and incorporate more knowledge into the model. To demonstrate the capabilities of our method we compared the signaling networks of young and replicative senescent human primary HFL-1 fibroblasts, whose differences are expected to be due mainly to changes in the expression of the proteins rather than the reactions involved. The resulting networks indicate that, compared to young cells, aged cells are not as responsive to insulin stimulation and activate pathways that establish and maintain senescence.Author summaryCells have developed a complex network of biochemical reactions to monitor their environment and react to changes. Although multiple pathways, tuned to identify specific stimuli, have been discovered, it is generally understood that the signaling process typically involves multiple pathways and is context depended. Consequently, reconstructing the signaling network utilized by cells at any given moment is not a trivial task. In this article, we report on a novel logic-based method for identifying signaling network by combining experimental data with prior knowledge about the connectivity of the involved proteins. Unlike other methods proposed so far, our method uses data to evaluate the presence or absence of reactions and proteins alike. We reconstructed and compared the signaling network of human primary HFL-1 fibroblasts as they undergo replicative senescence in the presence of 6 different stimuli. The resulting networks indicate that, compared to young cells, senescent cells are not responsive to insulin stimulation and activate pathways that are known to establish and maintain senescence.
Inference of phenotype-relevant transcriptional regulatory networks elucidates cancer type-specific regulatory mechanisms in a pan-cancer study
Authors: Emad Amin , Sinha Saurabh 
Published: August 2018

ABSTRACTReconstruction of transcriptional regulatory networks (TRNs) is a powerful approach to unravel the gene expression programs involved in healthy and disease states of a cell. However, these networks are usually reconstructed independent of the phenotypic properties of the samples and therefore cannot identify regulatory mechanisms that are related to a phenotypic outcome of interest. In this study, we developed a new method called InPheRNo to identify ‘phenotype-relevant’ transcriptional regulatory networks. This method is based on a probabilistic graphical model whose conditional probability distributions model the simultaneous effects of multiple transcription factors (TFs) on their target genes as well as the statistical relationship between target gene expression and phenotype. Extensive comparison of InPheRNo with related approaches using primary tumor samples of 18 cancer types from The Cancer Genome Atlas revealed that InPheRNo can accurately reconstruct cancer type-relevant TRNs and identify cancer driver TFs. In addition, survival analysis revealed that the activity level of TFs with many target genes could distinguish patients with good prognosis from those with poor prognosis.
The influence of the cultural entrepreneur on the performance of cultural and creative firms
Authors: Orihuela-Gallardo Francisca , Fernández-Alles Mariluz , Ruiz-Navarro José 
Published: August 2018

PurposeThe purpose of this paper is to analyse the influence of the profile of cultural entrepreneurs (CE), in terms of their demographic characteristics and resources, on the performance of cultural and creative firms (CCFs).Design/methodology/approachDeparting from demographic theory and resource-based view, two hypotheses have been formulated and empirically tested, using a multiple regression model, with a sample of 80 Spanish CCFs. The CCF performance has been measured through two objective (employment growth and profitability) and one subjective/perceptual measurements (satisfaction of the CE with the attainment of objectives).FindingsWith respect to the demographic variables, a negative relationship between the CE’s age and employment growth, and a partial positive influence of the CE’s prior experience on employment growth and the subjective measurement of performance have been found. Regarding to the CE’s resources, the empirical evidence shows that there is no direct relationship between the CE’s possession of any resources studied − financial, knowledge and social connections − and CCF performance.Originality/valueThis work makes three important contributions as it analyses the CE and focuses on CCF management, a topic little discussed in the entrepreneurship literature. Second, there is an analysis of some of the variables pertaining to the entrepreneur’s demographic profile that have been applied to top management teams and in a more or less isolated way in the entrepreneurship area. And, finally, a multidimensional measurement is used to explain the CCF performance.
Optimization of the carbon nanotubes synthesis in arc discharge systems
Authors: Raniszewski Grzegorz 
Published: August 2018

Purpose
The purpose of this paper is to focus on the influence of electromagnetic field during the arc discharge carbon nanotubes synthesis. It proposes modeling of electromagnetic field distribution to calculate forces in the area of arcing. The paper presents the influence of this field on the final product of the synthesis.

Design/methodology/approach
A short literature review of the arc discharge systems supported by electromagnetic field is presented. The technical solution of the coil placement is discussed. An experimental research is described. The research system constructed preceded by a series of measurements and modeling is analyzed.

Findings
The paper describes the significant meaning of the electromagnetic field during the synthesis. The electromagnetic field forces the slow rotation of the carbon plasma column where carbon nanotubes are formed. It leads to the improvement in yield.

Research limitations/implications
Because the research is limited to one type of geometry of the reactor, the results may vary in different reactors. However, the influence of the electromagnetic field is confirmed. Therefore, researchers are encouraged to investigate the influence of the electromagnetic coil in the applied systems.

Practical implications
The systems with a coil inside the reactor require the application of complex cooling systems or/and additional screens. The work proposes a technical solution based on the coil placed outside the reactor. Therefore, it simplifies the construction and increases the yield.

Social implications
The high yield of the high-quality nanotubes opens new technical possibilities for electronics and electrical engineering.

Originality/value
The paper identifies a connection between the electromagnetic field, the arc discharge movement, plasma jet, carbon nanotubes containing deposit and the yield.
Tackling everyday risks through climate adaptive organic farming
Authors: Rahmawati Hepi , Lestari Anastasia Maylinda Titi 
Published: August 2018

Purpose
With the shifting patterns of rain and dry periods as a result of global climate change, the people of Gunungkidul have to deal with extreme conditions, such as crop failure, ponds and artificial lakes drying up at an alarming rate due to high evaporation. The paper aims to discuss these issues.

Design/methodology/approach
Participatory disaster and risks assessment and action planning were carried out to identify how communities perceive risks and identify priorities of actions. Farmers agreed to implement climate adaptive farming which combines organic farming, biological pest control and drought-resistant seedlings from local varieties.

Findings
The processes to adaptation required collective actions, paradigm shift and it also constitutes trial and error processes. Acceptance to innovation is mostly one of the major challenges. Working with “contact” farmers and “advance” farmers is the key to the community organizing strategy for innovation and adaptation.

Research limitations/implications
This case study is limited to the adaptation program funded by Indonesia Climate Change Trust Fund in four farmer groups in Purwosari Sub-District, GunungKidul district and Yogyakarta province, Indonesia.

Practical implications
Trainings and direct assistance to climate adaptive farming have benefitted the farmers that they are able to increase the farming production and reduce the risk of crop failure.

Social implications
The demonstration plot has strengthened farmer groups’ social modalities by working together to shift from traditional into adaptive farming.

Originality/value
This case study described how farmers have shifted from traditional practice into climate adaptive farming.
Barriers to the adoption of value management in developing countries
Authors: Aghimien Douglas Omoregie , Oke Ayodeji Emmanuel , Aigbavboa Clinton Ohis 
Published: August 2018

Purpose
The purpose of this paper is to determine the barriers to the adoption of value management (VM) in the construction industry of developing countries with a view to providing possible measures in avoiding these barriers and increasing the usage of the system within the construction industry.

Design/methodology/approach
The level of knowledge and adoption of VM practices, as well as the barriers to its adoption in the construction industry were assessed through a survey design. Construction professionals were sampled from the six geo-political zones in Nigeria through the use of a structured questionnaire. Factor analysis was conducted on data gathered on the barriers of VM.

Findings
The study revealed a moderate level of knowledge of VM among construction professionals. This implies that the problem of VM is not that of awareness, but readiness to adopt the system. The study also reveals that the barriers to the adoption of VM can be categorised under the general stakeholder’s barriers, training and education barriers, client barriers and government/top management barriers.

Practical implications
This study was conducted across the six geo-political zones of the country as against common practice of selecting a particular region or states to represent the entire country. The findings therefore show a true reflection of the barriers to VM adoption in the country and its recommendations can to a large extent promote the adoption of VM in the country and also other developing countries where construction projects are executed through similar method, style and approach.

Originality/value
This paper highlights the possible barriers to the adoption of VM in Nigeria construction industry and provides ways to avoiding these barriers in order to achieve better quality construction and value for money.
Lubrication regime analysis for spherical pump
Authors: Guan Dong , Hilton Harry H. , Yang Zhengwei , Jing Li , Lu Kuan 
Published: August 2018

Purpose
This paper aims to investigate the lubrication regime in spherical pump, especially under different structural parameters and operational conditions.

Design/methodology/approach
A ball-on-plane configuration is adopted to represent the contact model between spherical piston and cylinder cover. The governing equations, which include the Reynolds and elasticity equations, are solved and validated by Jin–Dowson model. Both minimum film thickness and lambda ratio (ratio of minimum fluid film thickness to combined surface roughness of the piston and cylinder cover) of the equivalent model are obtained using an established model.

Findings
The results indicate that piston diameter and radial clearance are the two main factors affecting the pump lubrication regime. Other related parameters such as rotation speed of the piston, load, viscosity of working medium, material matching and surface roughness of piston and cylinder cover also have different impacts on the lubrication regime of the spherical pump.

Originality/value
These results emphasize the importance of the design and manufacturing parameters on the tribological performance of spherical pumps and these are also helpful in improving the spherical pump lubrication regime and enlarging its life cycle. This is to certify that to the best of the authors’ knowledge, the content of this manuscript is their own work. This manuscript has only been submitted to this journal and never been published elsewhere. The authors certify that the intellectual content of this manuscript is the product of their own work and that all the assistance received in preparing this manuscript and sources has been acknowledged.
Frictional characteristic of sintered iron in high temperature
Authors: Wang Yanzhong , Guo Chao 
Published: August 2018

Purpose
This paper aims to study the change rule of sintered iron friction properties under high temperature and establish the model to predict the friction coefficient.

Design/methodology/approach
The morphological measurements of sintered iron material with four different oxidation degrees are carried out. A prediction model of friction coefficient in high temperature oxide growth stage for sintered iron material is established based on the theory of flash temperature and adhesion friction. The relationship between friction coefficient and the key parameters is found through the test fitting.

Findings
The surface topography changes with oxidative wear. The wear debris will be compacted and sintered again to form a composite oxide layer with the temperature increasing. The validity and accuracy of proposed model are tested using the friction coefficient and temperature experiments. Results are in reasonable agreement with those obtained using values of load commonly used.

Originality/value
The significance lies in the change mechanism of high temperature friction characteristic is clarified. Three friction stages related to temperature of dry friction are put forward for sintered iron, and a meaningful reference is provided by the established model for high-temperature performance design of sintered iron friction material.
Managing bioethanol supply chain resiliency: a risk-sharing model to mitigate yield uncertainty risk
Authors: Ye Fei , Hou Gang , Li Yina , Fu Shaoling 
Published: August 2018

Purpose
The purpose of this paper is to propose a risk-sharing model to coordinate the decision-making behavior of players in a cassava-based bioethanol supply chain under random yield and demand environment, so as to mitigate the yield and demand uncertainty risk and improve the bioethanol supply chain resiliency and performance.

Design/methodology/approach
The decision-making behavior under three models, namely, centralized model, decentralized model and risk-sharing model, are analyzed. An empirical test of the advantages and feasibility of the proposed risk-sharing model, as well as the test of yield uncertainty risk, risk-sharing coefficients and randomly fluctuating cassava market price on the decision-making behavior and performances are provided.

Findings
Though the proposed risk-sharing model cannot achieve the supply chain performance in the centralized model, it does help to encourage the farmers and the company to increase the supply of cassava and achieve the Pareto improvement of both players compared to the decentralized model. In particular, these improvements will be enlarged as the yield uncertainty risk is higher.

Practical implications
The findings will help decision makers in the bioethanol supply chain to understand how to mitigate the yield uncertainty risk and improve the supply chain resiliency under yield and demand uncertainty environment. It will also be conducive to ensure the supply of feedstock and the development of the bioethanol industry.

Originality/value
The proposed risk-sharing model incorporates the yield uncertainty risk, the random market demand and the hierarchical decision-making behavior structure of the bioethanol supply chain in the model.