bluuebunny/crossref_metadata_2025_split huggingface dataset:
Agonist-selective recruitment of engineered protein probes and of GRK2 by opioid receptors in living cells
Authors: Stoeber Miriam , Jullié Damien , Li Joy , Chakraborty Soumen , Majumdar Susruta , Lambert Nevin A. , Manglik Aashish , Zastrow Mark von 
Published: December 2019

AbstractG protein-coupled receptors (GPCRs) signal through allostery, and it is increasingly clear that chemically distinct agonists can produce different receptor-based effects. It has been proposed that agonists selectively promote receptors to recruit one cellular interacting partner over another, introducing allosteric ‘bias’ into the signaling system. However, the core underlying hypothesis - that different agonists drive GPCRs to engage different cytoplasmic proteins in living cells - remains untested due to the complexity of downstream readouts through which receptor-proximal interactions are typically inferred. Here we describe a scalable cell-based assay to overcome this challenge, based on the use of engineered GPCR-interacting proteins as orthogonal biosensors that are disconnected from endogenous transduction mechanisms. Focusing on opioid receptors, we directly demonstrate differences between protein probe recruitment produced by chemically distinct opioid ligands in living cells. We then show how the selective recruitment applies to GRK2, a biologically relevant opioid receptor regulator protein, through discrete interactions of GRK2 with receptors or with G protein beta-gamma subunits which are differentially promoted by agonists.
Functional reorganization of brain networks across the human menstrual cycle
Authors: Pritschet Laura , Santander Tyler , Taylor Caitlin M. , Layher Evan , Yu Shuying , Miller Michael B. , Grafton Scott T. , Jacobs Emily G. 
Published: December 2019

AbstractThe brain is an endocrine organ, sensitive to the rhythmic changes in sex hormone production that occurs in most mammalian species. In rodents and nonhuman primates, estrogen and progesterone’s impact on the brain is evident across a range of spatiotemporal scales. Yet, the influence of sex hormones on the functional architecture of the human brain is largely unknown. In this dense-sampling, deep phenotyping study, we examine the extent to which endogenous fluctuations in sex hormones alter intrinsic brain networks at rest in a woman who underwent brain imaging and venipuncture for 30 consecutive days. Standardized regression analyses illustrate estrogen and progesterone’s widespread associations with functional connectivity. Time-lagged analyses examined the temporal directionality of these relationships and suggest that cortical network dynamics (particularly in the Default Mode and Dorsal Attention Networks, whose hubs are densely populated with estrogen receptors) are preceded—and perhaps driven—by hormonal fluctuations. A similar pattern of associations was observed in a follow-up study one year later. Together, these results reveal the rhythmic nature in which brain networks reorganize across the human menstrual cycle. Neuroimaging studies that densely sample the individual connectome have begun to transform our understanding of the brain’s functional organization. As these results indicate, taking endocrine factors into account is critical for fully understanding the intrinsic dynamics of the human brain.HighlightsIntrinsic fluctuations in sex hormones shape the brain’s functional architecture.Estradiol facilitates tighter coherence within whole-brain functional networks.Progesterone has the opposite, reductive effect.Ovulation (via estradiol) modulates variation in topological network states.Effects are pronounced in network hubs densely populated with estrogen receptors.
An expanded analysis framework for multivariate GWAS connects inflammatory biomarkers to functional variants and disease
Authors: Ruotsalainen Sanni E. , Partanen Juulia J. , Cichonska Anna , Lin Jake , Benner Christian , Surakka Ida , FinnGen  , Reeve Mary Pat , Palta Priit , Salmi Marko , Jalkanen Sirpa , Ahola-Olli Ari , Palotie Aarno , Salomaa Veikko , Daly Mark J. , Pirinen Matti , Ripatti Samuli , Koskela Jukka 
Published: December 2019

ABSTRACTMultivariate methods are known to increase the statistical power of association detection, but they have lacked essential follow-up analysis tools necessary for understanding the biology underlying these associations. We developed a novel computational workflow for multivariate GWAS follow-up analyses, including fine-mapping and identification of the subset of traits driving associations (driver traits). Many follow-up tools require univariate regression coefficients which are lacking from multivariate results. Our method overcomes this problem by using Canonical Correlation Analysis to turn each multivariate association into its optimal univariate Linear Combination Phenotype (LCP). This enables an LCP-GWAS, which in turn generates the statistics required for follow-up analyses. We implemented our method on 12 highly correlated inflammatory biomarkers in a Finnish population-based study. Altogether, we identified 11 associations, four of which (F5, ABO, C1orf140 and PDGFRB) were not detected by biomarker-specific analyses. Fine-mapping identified 19 signals within the 11 loci and driver trait analysis determined the traits contributing to the associations. A phenome-wide association study on the 19 putative causal variants from the signals in 176,899 individuals from the FinnGen study revealed 53 disease associations (p < 1×10-4). Several reported pQTLs in the 11 loci provided orthogonal evidence for the biologically relevant functions of the putative causal variants. Our novel multivariate analysis workflow provides a powerful addition to standard univariate GWAS analyses by enabling multivariate GWAS follow-up and thus promoting the advancement of powerful multivariate methods in genomics.
The role of frequent engagement in alliances in firm likelihood to patent
Authors: Filiou Despoina , Tusselmann Heinz , Green Lawrence 
Published: December 2019

Purpose
The purpose of this paper is to explore the role of alliance experience in firm innovation; it argues that, while cumulative alliance experience has a marginally diminishing contribution to likelihood of firm innovation over time, frequent engagement in alliances and an expanding alliance portfolio inhabit an enhancing role. This reveals new dimensions to the role of alliance experience as an antecedent to firm learning in managing alliances and to the development of alliance capabilities.

Design/methodology/approach
The paper estimates a range of models identifying the relationship between alliance experience and firm innovation. The panel data sample captures the full range of firms active in the UK bio-pharmaceuticals sector during the early stages of its development observing them from 1991 to 2001. An exploratory case study analysis is employed to shed light on the nuanced factors linking frequent engagement in alliances to the development of practices for efficient alliance management.

Findings
The paper shows that cumulative alliance experience has a marginally diminishing contribution to likelihood of firm innovation over time, while frequent engagement in alliances and the ensuing expansion of alliance portfolios enhance firm innovation. The exploratory case analysis demonstrates a link between frequent engagement in alliances and the development of processes for alliance management that could collectively reflect alliance capabilities.

Originality/value
Contribution derives from a longitudinal analysis of an original panel data set that maps the UK bio-pharmaceuticals sector over the initial period of its development. The paper sheds light on factors that can compel firms to form alliance capabilities, and extends a currently thin body of work on the foundations and antecedents to alliance and alliance portfolio capabilities.
News shocks modeling on monetary policies using dynamic stochastic general equilibrium (DSGE) model
Authors: Zarei Shapoor , Marzban Hussain , Samadi Ali H. , Javaheri Ahmad Sadraei 
Published: December 2019

Purpose
The purpose of this paper is to investigate the effects of news shocks on monetary policies using the dynamic stochastic general equilibrium (DSGE) model. To this end, two kinds of news shocks (known as technology and consumer preferences) are defined according to Khan and Tsoukalas’ (2012) approach.

Design/methodology/approach
In order to construct and simulate the DSGE model to approaching the real conditions in a case study, consumption habits in the utility function were concerned based on the assumption of the zero-value obtained from multiplying the inflation by the real interest rate in the Fisher’s equation, whereas the real interest rates in the long run were appointed as negative remark in simulating the monetary policy models. The estimation and simulation results for the research models indicated that monetary policies using the interest rate instrument identified the news shocks less frequently than monetary policies using the monetary base instrument.

Findings
The approximate value of the social loss function in the optimal commitment and discretionary monetary policies suggests that the optimal commitment policy is estimated to be lower in both cases. Due to value of the social loss function in optimal monetary policies with nominal interest rate instrument in the presence of news shocks, this could be claimed that monetary policy with interest rate instrument is more appropriate than the monetary policy with a monetary base instrument.

Originality/value
The approximate value of the social loss function in the optimal commitment and discretionary monetary policies suggests that the optimal commitment policy is estimated to be lower in both cases.
Employers’ perception of employability skills among built-environment graduates
Authors: Aliu John , Aigbavboa Clinton Ohis 
Published: December 2019

Purpose
Universities have become training centres or “academic hubs” where skilled labour for societal and global consumptions are continuously produced. More so, the quality of teaching (pedagogy) provided by universities is essential in enhancing the skills, expertise and competencies of students who are required to meet the needs of the construction industry after graduation. Hence, the purpose of this study is to assess employers’ level of satisfaction with the employability skills of built-environment graduates in Nigeria.

Design/methodology/approach
A quantitative approach was adopted for this study with close-ended questionnaires administered to respondents drawn from professionals in the Nigerian construction industry. Out of 150 questionnaires disseminated, 131 were completed and 126 were usable, signifying an 87% response rate. Data from this research were analysed using descriptive and exploratory factor analysis.

Findings
Employers are seemingly satisfied with the sound academic record of built-environment graduates. They also affirmed their contentment with graduates’ willingness to learn and the way they achieve tasks with positive results. However, they expressed their dissatisfaction with the graduates’ prior work experience, communication skills and technical competencies in handling industry tasks effectively.

Research limitations/implications
Data was collected from construction professions across two cities – Abuja and Lagos. Because of the limited budget allocated for this study, other regions were not considered. Because of time and financial implications, it was extremely impossible to visit all 36 states. It is, therefore, impossible to generalise the results of this research to the larger population. In generalising the results on a larger scale, the study would have to factor in a more diverse sample to ensure it is more representative. A more diverse sample may mitigate any possible bias that may arise from a self-administered questionnaire.

Practical implications
From the survey results obtained from the respondents, it was observed that general knowledge about local and global trends, management skills, teamwork skills, work experience, communication skills, critical thinking skills, numeracy skills and civic responsibility are among the major non-academic skills lacking among built-environment graduates. This places significant pressures on universities in Nigeria to revisit and revamp its curricula in developing these skills among students who require them to thrive in the construction industry.

Originality/value
Although the subject of employability has been adequately discussed across various fields (accountancy, psychology, management, business, marketing, etc.), there exist limited research studies in the built-environment context, a gap, which this study aims to fill. This study also provides several approaches through which employability skills can be developed.
Housing not for all
Authors: Nasarre-Aznar Sergio , Simón-Moreno Héctor 
Published: December 2019

PurposeThis study aims to explore the current situation of universal accessibility to multi-unit buildings in three European countries (Spain, Germany and Sweden), in view of the lack of effective European rules on this topic, with the aim to identify which legal frameworks and policies may be useful to favour it.Design/methodology/approachThe results presented in this work are based on empirical data gathered from three surveys conducted in three representative countries of different housing models (Spain, Germany and Sweden). These surveys addressed the grade of accessibility at each point of the route that a person with mobility difficulties, with a physical deficiency or aged +70, has to do to access to their home from a public street or road.FindingsThe current paper shows that, in the end, there is still a long way to go in terms of universal accessibility to multi-unit buildings in, at least, three European Union Member States as, according to this study’s findings, the percentage of universally accessible multi-unit buildings is limited to 0.6 per cent in Spain, 2.5 per cent in Sweden and 1.5 per cent in Germany. The study also identifies successful legal frameworks and policies among the studied countries that may be useful to achieve a true universal accessibility to flats located in multi-unit buildings.Research limitations/implicationsThe legal frameworks and policies identified in this paper in terms of promoting universal accessibility to housing located in multi-unit buildings may provide guidance to other researchers and policymakers when addressing this topic, thus helping them to reach an egalitarian and inclusive society.Originality/valueThis paper goes one step further than previous works as it is based on up to date empirical data concerning accessibility and it identifies successful legal frameworks and policies in a comparative perspective.
An innovative and integrated approach based on SERVQUAL, QFD and FMEA for service quality improvement
Authors: Altuntas Serkan , Kansu Semih 
Published: December 2019

Purpose
The purpose of this paper is to propose an innovative and integrated approach based on service quality measurement (SERVQUAL), quality function deployment (QFD) and failure modes and effects analysis (FMEA) for service quality improvement.

Design/methodology/approach
The SERVQUAL scale is used for service quality measurement, QFD is used for service design and FMEA is used to prevent possible failures during service delivery.

Findings
A case study in a public hospital in Turkey is performed to show how the proposed approach works in practice. The results of the study show that the proposed approach can be used effectively to assess service quality in practice.

Originality/value
Service quality has become an important issue for service enterprises facing a fiercely competitive environment to provide sustainability. This is the first study that applies an integrated methodology based on SERVQUAL scale, QFD and FMEA to service quality improvement.
Coopetitive dynamics and inter-organizational knowledge flow among venture capital firms
Authors: Sindakis Stavros , Aggarwal Sakshi , Chen Charles 
Published: December 2019

Purpose
The purpose of this paper is to analyze important theoretical work conducted in the research streams of coopetition dynamics and knowledge flows in the area of start-up entrepreneurship. The authors see in practice that venture capital (VC) firms are a highly essential component of the environment that gives birth to entrepreneurial ventures, helping them to grow profoundly. Interorganizational collaborations facilitate VC firms to be a beneficial partner because except for providing funding, they also possess knowledge-based resources to support the new business.

Design/methodology/approach
A systematic review of the literature was conducted, using relevant keywords and academic databases. Then, the backward search was implemented to examine the references of the selected papers, and finally, the forward search to explore the citations of the selected papers. After the selection of papers, they were classified according to their content. A thorough search of the extant literature was done in Scopus and Google Scholar using a combination of keywords such as coopetition, knowledge flows, VC firms, interorganizational and inter-firm knowledge dynamics.

Findings
This paper highlights the capability of venture capitalists and provides insights as to how knowledge transfer and sharing between VC firms affect new venture’s growth and prosperity.

Research limitations/implications
This paper attempts to provide new perspectives and explore the significance of interorganizational coopetition and knowledge transfer and sharing between VC firms when they take part in the support and development of new ventures (e.g. start-ups). A theoretical model is proposed via the coopetition dynamics and inter-firm knowledge flows in the VC sector framework.

Originality/value
This paper adds to the existing theoretical knowledge and underlines the topic of interorganizational coopetition and knowledge flows between VC firms. This is the first attempt, on the one hand, to link inter-firm knowledge flows and new venture development, while on the other to examine the dynamics between VC firms and the collective contribution for the growth of start-ups.
Mediating knowledge across health ecosystems: a qualitative field study
Authors: Maženytė Brigita , Petraitė Monika 
Published: December 2019

Purpose
Knowledge sharing across health ecosystems is extremely fuzzy because of knowledge asymmetries, barriers and diverse types and sources of knowledge, all of which together affect patient decision making and value creation. The purpose of this study is to identify core knowledge mediators across ecosystem with the focus on a patient as a central decision maker in their own health management to ensure smooth knowledge flows across actors.

Design/methodology/approach
To understand the knowledge flows in the health ecosystem, a phenomenological approach was applied in this study. Based on case study research. The analysis is based on the patient-centric approach and draws on qualitative, semi-structured interviews. Moreover, a knowledge-creating community approach (Paavola et al., 2004) is applied in which various stakeholders create and share knowledge of clinical and social domain, which together contribute to patient value creation.

Findings
Knowledge socialization and development starts within very close and trusted community members. Trust, validity, reliability and responsibility of knowledge have emerged as full mediators for knowledge absorption. Thus, health communities and knowledge ecosystems need safe places for “unverified” knowledge to ensure that the important trends and unresolved questions are not missed.

Originality/value
This study proposes a new health knowledge management approach for communities, which is more than clinical decisions and formal medical knowledge and embraces varieties of knowledge and information sources and types. At the end, the identified barriers and mediators can be used for serving the main goal of patient value increase because it responds to the need for a systematic approach in encouraging patients to play a more active role in their own health management.
Demotivation in academic reading during teacher training
Authors: Muñoz Carla , Valenzuela Jorge 
Published: December 2019

BackgroundIn this study, we analyse the process of academic reading demotivation in elementary preservice teachers. Academic reading motivation is conceptualised from the Expectancy‐Value Theory, with the respective eponymous dimensions as well as interest, attainment, utility, and cost as subcomponents for task value.MethodsThese motivational variables were measured by the Escala Motivacional por la Lectura Académica (Academic Reading Motivation Scale). Analysis focused on confirming the demotivation process organised by four different educational motivation profile types (clusters), as well as by cohorts. Participants were a total of 785 elementary preservice teachers from seven Chilean universities, both public and private, from six regions of Chile, enrolled in the first, third and last years of their programme. This population was tested, with a subsample (n = 295) retested the following year.ResultsResults show a concentration of negative motivational changes in the “school motivation” group, as well as changes during the first years of the programme. The more affected dimensions are utility and cost. There is no evidence for changes in feeling of competence for academic reading (expectancy).ConclusionsWe conclude the importance of focusing efforts on avoiding these negative motivational changes in students that demonstrate three key characteristics: they want to become primary teachers, they are engaged in their studies, and finally, they want to work in the school system.
Component skills that underpin listening comprehension and reading comprehension in learners with English as first and additional language
Authors: Babayiğit Selma , Shapiro Laura 
Published: December 2019

AimsThe primary aim of this study is to augment our understanding of the component skills that underpin second‐language learners' text comprehension by examining the direct and indirect roles of vocabulary knowledge and grammatical skills in second‐language learners' listening and reading comprehension.MethodsOur sample included 134 learners with English as an additional language (EAL) and 74 with English as first language (EL1) (Mage = 123.76, SD = 5.02 months).ResultsOur path analyses underscored the central role of English vocabulary and grammar in EAL learners' text comprehension. Both made independent and direct contributions to EAL learners' listening and reading comprehension levels. There were also indirect relations between vocabulary and grammar, and reading comprehension through listening comprehension. Similar results were observed for the EL1 group. We also found an association between weaknesses in EAL learners' vocabulary and grammatical skills and their underperformance on listening comprehension and reading comprehension.ConclusionsEAL learners' oral language, listening comprehension, and reading comprehension development should be examined in tandem and beyond the primary‐school years to clarify the long‐term implications of the observed EAL gap at primary‐school levels. Finally, our findings suggest that both vocabulary knowledge and grammatical skills need to be targeted to support children's listening and reading comprehension. This is important for both EAL and EL1 learners but particularly for the former whose English oral language skills may lag behind those of their EL1 peers.