bluuebunny/crossref_metadata_2025_split huggingface dataset:
The PAX3 and 7 homeodomains have evolved unique determinants that influence DNA-binding, structure and communication with the paired domain
Authors: Corry Gareth N. , Sykes Brian D. , Underhill D. Alan 
Published: July 2019

ABSTRACTThe PAX (paired box) family is a collection of metazoan transcription factors defined by the paired domain, which confers sequence-specific DNA-binding. Ancestral PAX proteins also contained a homeodomain, which can communicate with the paired domain to modulate DNA-binding. In the present study, we sought to identify determinants of this functional interaction using the paralogous PAX3 and 7 proteins. First, we evaluated a group of heterologous paired domains and homeodomains for the ability to bind DNA cooperatively through formation of a ternary complex (paired domain:homeodomain:DNA). This revealed that capacity for ternary complex formation was unique to the PAX3 and 7 homeodomains and therefore not simply a consequence of DNA-binding. We also found PAX3 and 7 were distinguished by an extended region of conservation N-terminal to the homeodomain (NTE). Phylogenetic analyses established the NTE was restricted to PAX3/7 orthologs of segmented metazoans, indicating it arose in a bilaterian precursor prior to separation of deuterostomes and protostomes. In DNA-binding assays, presence of the NTE caused a decrease in monomeric binding by the PAX3 homeodomain that reflected a lack of secondary structure in 1D-1H-NMR. Nevertheless, this inhibitory effect could be overcome by homeodomain dimerization or cooperative binding with the paired domain, establishing that protein interactions could induce homeodomain folding in the presence of the NTE. Strikingly, the PAX7 counterpart did not impair homeodomain binding, revealing inherent differences that could account for its distinct target profile in vivo. Collectively, these findings identify critical determinants of PAX3 and 7 activity, which contribute to their functional diversification.
Unexpected opposing biological effect of genetic risk factors for Parkinson’s disease
Authors: Keatinge Marcus , Gegg Matthew E. , Watson Lisa , Mortiboys Heather , Li Nan , Dunning Mark , Ailani Deepak , Bui Hai , van Rens Astrid , Lefeber Dirk J. , MacDonald Ryan B. , Schapira Anthony H.V. , Bandmann Oliver 
Published: July 2019

AbstractThe additive effect of genetic risk variants on overall disease risk is a plausible but frequently unproven hypothesis. To test this hypothesis, we assessed the biological effect of combined glucocerebrosidase (GCase) and acid sphingomyelinase (ASM) deficiency. Variants in both glucocerebrosidase1 (GBA1) and sphingomyelinase (SMPD1) are genetic risk factors for Parkinson’s disease. Unexpectedly, ASM deficiency resulted in normalized behaviour and prolonged survival in gba1−/−;smpd1−/− double-mutant zebrafish compared to gba1−/−. RNAseq-based pathway analysis confirmed a profound rescue of neuronal function and intracellular homeostasis. We identified complete reciprocal rescue of mitochondrial respiratory chain function and abolished lipid membrane oxidation in gba1−/−;smpd1−/− compared to gba1−/− or smpd1−/− as the underlying rescue mechanism. Complementing in vitro experiments demonstrated an unexpected reduction of α-synuclein levels in human cell lines with combined GCase and ASM deficiency. Our study highlights the importance of functional validation for any putative interactions between genetic risk factors and their overall effect on disease-relevant mechanisms rather than readily assuming an additive effect.SummaryThe additive effect of genetic risk variants on disease risk is a popular but typically unproven hypothesis. We investigated this hypothesis mechanistically for Parkinson’s disease risk factors and provide evidence of an unexpected rescue effect on neuronal function and survival.
Incorporating polygenic scores in the twin model to estimate genotype-environment covariance: exploration of statistical power
Authors: Dolan Conor V. , Huijskens Roel C. A. , Minică Camelia C. , Neale Michael C. , Boomsma Dorret I. 
Published: July 2019

AbstractThe assumption in the twin model that genotypic and environmental variables are uncorrelated is primarily made to ensure parameter identification, not because researchers necessarily think that these variables are uncorrelated. Although the biasing effects of such correlations are well understood, it would be useful to be able to estimate these parameters in the twin model. Here we consider the possibility of relaxing this assumption by adding polygenic score to the (univariate) twin model. We demonstrated numerically and analytically this extension renders the additive genetic (A) – unshared environmental correlation (E) and the additive genetic (A) - shared environmental (C) correlations simultaneously identified. We studied the statistical power to detect A-C and A-E correlations in the ACE model, and to detect A-E correlation in the AE model. The results showed that the power to detect these covariance terms, given 1000 MZ and 1000 DZ twin pairs (α=0.05), depends greatly on the parameter settings of the model. We show fixing the estimated percentage of variance in the outcome trait that is due to the polygenic scores greatly increases statistical power.
3D modelling of a frame assembly using deep learning and the Chu–Liu–Edmonds Algorithm
Authors: Cao Hao , Mo Rong , Wan Neng 
Published: July 2019

Purpose
The proposed method is to generate the 3 D model of frame assemblies based on their topological model automatedly. It was a very demanding task and there was no appropriate automated method to facilitate this work.

Design/methodology/approach
The proposed method includes two stages. The first stage is decisive. In this stage, a deep learning network and the Chu–Liu–Edmonds algorithm are used to recognize contact relations among parts. Based on this recognition, the authors perform a geometrical computation in the second stage to finalize the 3 D model.

Findings
The authors verify the feasibility of the proposed method using a case study and find that the classification rate of the deep learning network for part contact relations is higher than 75 per cent. Furthermore, more accurate results could be achieved with modification by the Chu–Liu–Edmonds algorithm. The proposed method has lower computational complexity compared with traditional heuristic methods, and its results are more consistent with existing designs.

Research limitations/implications
The paper introduces machine learning method into assembly modelling issue. The proposed method divides the assembly modelling into two steps and solves the assemble relation creatively.

Practical implications
Frame assemblies are fundamental to many areas. The proposed method could automate frame assembly modelling in a viable way. It could benefit design and manufacture process significantly.

Originality/value
The proposed method expands the application of machine learning into a new field. It would be more useful than simple machine learning in industry. The proposed method is better than general heuristic algorithms. It outputs identical results when the inputs are the same. Meanwhile, the algorithmic complexity in worst situation is better than general heuristic algorithms.
Fast tolerance-aware design optimization of miniaturized microstrip couplers using variable-fidelity EM simulations and response features
Authors: Koziel Slawomir , Bekasiewicz Adrian 
Published: July 2019

Purpose
This paper aims to investigate the strategy for low-cost yield optimization of miniaturized microstrip couplers using variable-fidelity electromagnetic (EM) simulations.

Design/methodology/approach
Usefulness of data-driven models constructed from structure frequency responses formulated in the form of suitably defined characteristic points for statistical analysis is investigated. Reformulation of the characteristics leads to a less nonlinear functional landscape and reduces the number of training samples required for accurate modeling. Further reduction of the cost associated with construction of the data-driven model, is achieved using variable-fidelity methods. Numerical case study is provided demonstrating feasibility of the feature-based modeling for low cost statistical analysis and yield optimization.

Findings
It is possible, through reformulation of the structure frequency responses in the form of suitably defined feature points, to reduce the number of training samples required for its data-driven modeling. The approximation model can be used as an accurate evaluation engine for a low-cost Monte Carlo analysis. Yield optimization can be realized through minimization of yield within the data-driven model bounds and subsequent model re-set around the optimized design.

Research limitations/implications
The investigated technique exceeds capabilities of conventional Monte Carlo-based approaches for statistical analysis in terms of computational cost without compromising its accuracy with respect to the conventional EM-based Monte Carlo.

Originality/value
The proposed tolerance-aware design approach proved useful for rapid yield optimization of compact microstrip couplers represented using EM-simulation models, which is extremely challenging when using conventional approaches due to tremendous number of EM evaluations required for statistical analysis.
Some advances in high-performance finite element methods
Authors: Cen Song , Wu Cheng Jin , Li Zhi , Shang Yan , Li Chenfeng 
Published: July 2019

PurposeThe purpose of this paper is to give a review on the newest developments of high-performance finite element methods (FEMs), and exhibit the recent contributions achieved by the authors’ group, especially showing some breakthroughs against inherent difficulties existing in the traditional FEM for a long time.Design/methodology/approachThree kinds of new FEMs are emphasized and introduced, including the hybrid stress-function element method, the hybrid displacement-function element method for Mindlin–Reissner plate and the improved unsymmetric FEM. The distinguished feature of these three methods is that they all apply the fundamental analytical solutions of elasticity expressed in different coordinates as their trial functions.FindingsThe new FEMs show advantages from both analytical and numerical approaches. All the models exhibit outstanding capacity for resisting various severe mesh distortions, and even perform well when other models cannot work. Some difficulties in the history of FEM are also broken through, such as the limitations defined by MacNeal’s theorem and the edge-effect problems of Mindlin–Reissner plate.Originality/valueThese contributions possess high value for solving the difficulties in engineering computations, and promote the progress of FEM.
A three-layer mechanical model for the analysis of effects of pia matter on cortical folding
Authors: Wang Linlin , Yao Jianyao , Ning Huiming , Wu Liangke , Sun Dongyang , Hu Ning 
Published: July 2019

PurposeThis paper aims to investigate the effects of the pia matter on cerebral cortical folding.Design/methodology/approachA three-layer buckling simulation model composited by the white matter, gray matter and the pia matter is adopted to analyze the effect of the pia matter on cortical folding. The volume growth of brain tissues is simulated using thermal expansion. The effects of the pia matter growth rate, thickness and stiffness on cortical folding is investigated.FindingsThe simulation results show that all of these three aforementioned factors of pia matter have obvious effects on cerebral cortical folding. Especially, the thickening of the pia matter may lead to cortical folding malformation such as polymicrogyria, which is in good agreement with the recent reported anatomical findings.Originality/valueThe three-layer model in this paper composited by the white matter, gray matter and the pia matter is different from the usually used two-layer model only composited by the white matter and gray matter. This three-layer model has successfully validated the effect of the pia matter on cerebral cortical folding. The simulation results can explain the anatomical findings very well.
Numerical study of crystal growth kinetics influence on prediction of different dendritic zones and macro-segregation in binary alloy solidification
Authors: Seredyński Mirosław , Banaszek Jerzy 
Published: July 2019

Purpose
Proper selection of the stability parameter determines the accuracy of dendrite tip kinetics at a single crystal scale. Recently developed sophisticated phase field modelling of a single grain evolution provides evidence that this parameter is not constant during the process. Nevertheless, in the commonly used micro-macroscopic simulations of alloy solidification, it is a common practice to use a constant value of the stability parameter, resulting from the marginal stability theory. This paper aims to address the issue of how this inaccuracy in modelling crystal growth kinetics can influence numerically predicted zones of columnar and equiaxed dendrites and the macro-segregation formation.

Design/methodology/approach
Using the original authors’ micro-macroscopic computer simulation model of binary alloy solidification, the calculations have been performed for the Kurz-Giovanola-Trivedi (KGT) crystal growth kinetics with two different values of the stability parameter, and for two different compositions of Al-Cu alloys. The computational model is based on single domain-based formulation of transport equations, which are discretized on control-volume mesh. To identify zones of different grain structures, developing within the two-phase liquid-solid region, an envelope of columnar dendrite tips is tracked on a fixed non-orthogonal, triangular control volume grid. The models of porous and slurry media are used, along with the concept of the switching function, to account for diverse flow resistances in the columnar and equiaxed crystal zones. The numerical predictions are carefully studied to address the question of how the chosen stability parameter influences macroscopic structures of a cast, the most important issue from the engineering point of view.

Findings
The carried-out comprehensive numerical analysis shows that the value of the stability parameter of the KGT-constrained dendrite growth model does not have a direct significant impact on the macrosegregation formation. It, however, visibly influences the undercooling along the front, separating different dendritic structures and the size of the undercooled melt region where the equiaxed grains can develop. It also affects the amount of eutectic phase created.

Originality/value
To the best of the authors’ knowledge, this is the first attempt at estimating the influence of some inaccuracies, caused by possible ambiguities in choosing the stability constant of the KGT law, on numerically predicted macroscopic fields of solute concentration, the developing zones of columnar and equiaxed crystals and the macrosegregation patterns.
When a stigmatized brand is doing good
Authors: Choi Jihee , Seo Soobin 
Published: July 2019

PurposeThis study aims to investigate consumer responses to cause-related marketing (CRM) implemented by socially stigmatized industries, especially in fast food restaurants.Design/methodology/approachThis experimental study uses a 2 (degree of perceived fit) × 2 (complementary fit) × 2 (brand equity) between-subjects design.FindingsResults show significant interaction effects between the degree of fit and brand equity and complementary fit and brand equity on consumers’ brand evaluation. When a company with high brand equity chooses a high fit (vs low fit) or complementary fit (vs non-complimentary fit) for CRM promotion, this leads to consumers’ more positive attitude and higher intent to participate in CRM promotion.Practical implicationsThis study provides practical implications for designing effective CRM promotion in the stigmatized industry such as fast food restaurants and casino.Originality/valueGiven the increased demand on CRM in the hospitality industry, the paper contributes to extend the realm of CRM literatures by investigating antecedents affecting consumers’ responses toward the CRM in the stigmatized companies or brands.
Responding to youth gangs in England: a public health model?
Authors: Pitts John 
Published: July 2019

Purpose
The purpose of this paper is to consider youth gangs and county lines with reference to the current drive for a public health response to these issues.

Design/methodology/approach
This viewpoint paper traces the development of gang and serious youth violence responses in England, exploring the shift from a punitive to safeguarding response to young people affected by these issues.

Findings
Drawing on the learning from both Scotland and the USA, this paper considers the relevance of a public health model to responding to youth gangs and county lines, highlighting the key facets of such an approach.

Originality/value
This paper provides a historical context to the issues surrounding previous responses to youth gangs and goes on to consider the practicalities and relevance of a public health model response.
How to detect potential sport intrapreneurs? Validation of the intrapreneurial intention scale with sport science students
Authors: González-Serrano Maria Huertas , Calabuig Moreno Ferran , Valantine Irena , Crespo Hervás Josep 
Published: July 2019

Purpose
The sport sector is a very competitive and dynamic industry, son intrapreneurial employees are needed. However, although entrepreneurial intentions in sport sciences students have been studied, less is known about intrapreneurial intentions. It is, therefore, the purpose of this paper to validate a scale to measure the intrapreneurial intentions of sports science students from two different countries.

Design/methodology/approach
A sample of 304 final-year students from the sport sector of two different countries (Spain and Lithuania) was analyzed. First, an exploratory factorial analysis of the two samples was performed separately, and then a confirmatory factorial analysis was carried out to performed. Finally, in order to check the invariance of the measuring instrument, a multi-group analysis was performed with the constraints of all factors variances and all factors loading.

Findings
The entrepreneurial intentions scale works well both in its English version in the Lithuanian sports students’ and in its Spanish version with the university sports students from Spain. Therefore, it can be said that there is a metric invariance. However, the scale presents better fit indexes, reliability and validity in its English version. Lithuanian sports students scored significantly higher on the risk-taking dimension than Spanish students.

Research limitations/implications
The scale has only been validated with final-year sport science students from two countries. It is necessary to test this scale with a larger sample of students from different fields and countries.

Practical implications
This scale can be used in both in Spanish and English versions to detect potential entrepreneurs in the sports sector, so it can help universities and employers to detect future intraentrepreneurs in the sports sector.

Social implications
Social implication of this paper is the detection of potential entrepreneurs who can improve economic, social or sports performance in organizations or sports companies.

Originality/value
A new tool to detect the potential sport intrapreneurs in university students has been created. Moreover, a cross-cultural validation of the intrapreneurial intentions scale (in English and Spanish version) with sport sciences students from two different countries has been performed.
An extension of the socioemotional wealth perspective
Authors: Saleem Irfan , Siddique Irfan , Ahmed Aqeel 
Published: July 2019

PurposeSocioemotional wealth (SEW) has emerged as the most differentiating aspect in family firms and has become the focal issue in family firm decision making. Family firms have to face the jeopardy of financial gains and socioemotional. The purpose of this paper is to investigate the different dimensions of SEW in developing the firm as corporate entrepreneurial and which dimensions engage stakeholders.Design/methodology/approachThe authors designed a survey questionnaire to obtain primary data for the study using purposive sampling method. The study conducted on the family firm using the questionnaire to investigate for corporate entrepreneurship (CE), and stakeholder engagement (SE) depended on family control and influence, family identity, binding social ties, emotional attachment and renewal of family bonds.FindingsThe study identified different SEW factors affecting CE and SE. The authors found that binding social ties and renewal of family bonds has a statistically significant impact on SE, whereas family identity and social ties have a statistically significant impact on CE.Research limitations/implicationsThe authors receive data from the CEOs with low response rate and expected to have better results with more observations. The same study been conducted in different parts of the world may give different results and a cultural bias may restrict the findings.Practical implicationsFrom the research, family firms can take twofold benefits. In short term, a family firm with better SE can generate satisfied employees with lesser turnover intentions. For long-term objectives with respect to CE, a firm can get a result in terms of market innovations through for better firm’s performance.Social implicationsSince her inception, Pakistan has emerged as a society of commodity traders and technology importers. This society can easily generate an import-driven business. Nonetheless this import-driven economy always remains under great economic distress due to limited potential for actual innovations and market disruptions. The family businesses of any emerging market like Pakistan need to learn CE and SE while safeguarding social-emotional wealth, thereby being successful as firm to become export-driven economy at large.Originality/valueThe study identifies different SEW factors that help in developing a firm as corporate entrepreneurial and stakeholder’s engagement. Findings of the study are valuable for managing the family firms in developing economies where the family structures are very vibrant and businesses have a clear dependency on family formations.