bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinase activity simultaneously determines the constitutive and the orthosteric gating in α4β1/3δ GABAA receptors in hippocampal granule cells
Authors: Dalby Nils Ole , Leurs Ulrike , Falk-Petersen Christina Birkedahl , Scholze Petra , Krall Jacob , Frølund Bente , Wellendorph Petrine 
Published: May 2018

AbstractA subset of the GABAA receptors expressed in recombinant systems and neurons is known to exhibit both constitutive- and agonist-induced gating. Two such receptors are the δ-subunit containing GABAA receptors α4β1δ and α4β3δ, which are expressed in adult rodent hippocampal dentate gyrus granule cells (DGGCs). Here we show that the GABAA receptor mediated tonic current recorded in the presence of tetrodotoxin in adult rodent DGGCs is almost exclusively mediated by constitutively active δ-subunit containing GABAA receptors and that the constitutive current is absent in recordings at 24 °C or in recordings at 34 °C including an intracellular inhibitor of protein kinase C. These factors simultaneously govern the efficacy of an orthosteric agonist at α4β1/3δ receptors, Thio-THIP, in a reciprocal manner. In the absence of constitutive receptor activity, the efficacy of Thio-THIP was increased approximately four-fold relative to recording conditions that favors constitutive activity. Further, only under conditions of an absent constitutive current, the classified neutral antagonist gabazine (GBZ) alone, induced a tonic current in DGGCs (EC50 2.1 μM). This effect of GBZ was not seen in recording conditions of high constitutive activity, was inhibited by picrotoxin (PTX), potentiated by DS2, completely absent in δ-/- mice and reduced in β1-/- mice, but could not be replicated in human α4β1/3δ receptors expressed recombinantly in HEK cells. We hypothesize that specific intracellular components in neurons interact with receptors to determine constitutive gating and receptor responsiveness to orthosteric ligands.Significance statementThe presented data highlight how recording conditions for whole cell patch clamp analysis of α4β1/3δ GABAA receptors can mask important pharmacological effects. Specifically, orthosteric agonists appear with reduced efficacy, and other ligands, here exemplified with the well-known antagonist GBZ, are misinterpreted as being inactive/neutral, although they could have effect in constitutively silent receptors. Unmasking of potential hidden effects are easily done using recording conditions of reduced kinase activity in a relevant neuronal context. It follows that in pathologies with changes in phosphorylation level of δ-subunit containing GABAA receptors, the efficacy of an agonist of these receptors, measured by whole-cell recordings in vitro, will not match the efficacy of the same agonist in an unperturbed neuron in vivo.
Analyzing Dwell Times with the Generalized Method of Moments
Authors: Piatt Sadie , Price Allen C. 
Published: May 2018

AbstractThe Generalized Method of Moments (GMM) is a statistical method for the analysis of samples from random processes. First developed for the analysis of econometric data, the method is here formulated to extract hidden kinetic parameters from measurements of single molecule dwell times. Our method is based on the analysis of cumulants of the measured dwell times. We develop a general form of an objective function whose minimization can return estimates of decay parameters for any number of intermediates directly from the data. We test the performance of our technique using both simulated and experimental data. We also compare the performance of our method to nonlinear least-squares minimization (NL-LSQM), a commonly-used technique for analysis of single molecule dwell times. Our findings indicate that the GMM performs comparably to NL-LSQM over most of the parameter range we explore. It offers some benefits compared with NL-LSQM in that it does not require binning, exhibits slightly lower bias and variance with small sample sizes (N<20), and is somewhat superior in identifying fast decay times with these same low count data sets. Our results show that the GMM can be a useful tool and complements standard approaches to analysis of single molecule dwell times.
Expression and purification of a functional heteromeric GABAAreceptor for structural studies
Authors: Claxton Derek P , Gouaux Eric 
Published: May 2018

AbstractThe multi-subunit GABA-gated chloride channels of the Cys-loop receptor family, known as GABAAreceptors, function as the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system. In addition to their role in controlling synaptic tone, these receptors are the targets of a vast array of therapeutic compounds that potentiate channel gating. Importantly, functional activity and pharmacological efficacy of GABAAreceptors is coupled directly to the subunit composition. However, the absence of high resolution structural information precludes an explicit determination of the molecular mechanism of ligand binding to ion channel gating and modulation. Efforts to obtain this data are hindered largely by the lack of heterologous expression and purification protocols for high expressing receptor constructs. To address this issue, we describe a unique approach to identify bona fide functional GABAAreceptor subunit combinations by using theXenopusoocyte as an expression host in combination with fluorescence detection size exclusion chromatography. The results demonstrate that formation of a defined pentameric species is dependent on subunit composition. Furthermore, receptor subunits can tolerate large truncations in non-conserved M3/M4 cytoplasmic loop, although removal of N-linked glycosylation sites is negatively correlated with expression level. Additionally, we report methods to improve GABAAreceptor expression in mammalian cell culture that employ recombinant baculovirus transduction. From these methods we have identified a well-behaving minimal functional construct for the α1/β1 GABAAreceptor subtype that can be purified in milligram quantities while retaining high affinity agonist binding activity.
Developing competencies to lead innovation in Indian manufacturing: an education model
Authors: Datta Partha Priya 
Published: May 2018

PurposeThis paper aims to explore the implementation of an innovation in an executive education programme in the context of the Indian manufacturing industry. This paper presents an understanding of a conceptual framework for delivering a unique manufacturing leadership programme, explaining the different linkages between government, industry and academia for changing the mindset of participants and growth of a nation by developing highly skilful employees to lead India’s manufacturing industry.Design/methodology/approachThe paper reports a single case study of an innovative manufacturing leadership development programme. Primary data were obtained from focus group studies and interviews. Documentary evidence in the form of reports, student work, course curriculum and meeting minutes was studied. The individual participants in the programme are used as units of analysis to explore systems of innovation, at individual levels. The analysis was carried out by applying theoretical models to explain the design, delivery and development of the programme over the years.FindingsThe findings from this research are an exploration of factors for sustaining the value of a system of innovation with special focus on a subsystem of knowledge creation and competence building. Institutional change is found to be a key input to the innovation process in terms of a collaborative mindset between three different academic institutes well known in different areas of expertise. Building an innovative coordination mechanism and curriculum combining academics with practical learning helped in changing the mindset of the students and faculty of the programme. This is linked to the development of country through leadership development by mindset change in mentors and students. The findings show that the studied programme has grown in terms of creating demand (in the form of increased applicants), guaranteeing 100 per cent placement with an average 50 per cent increase in salary and accelerated career in terms of role in the organisation. This was possible through continuous improvement practices for making local changes to the programme from time to time and building a community of practice in collaboration with industry.Originality/valueThe value of this research lies in highlighting the importance of international cooperation in speeding up the process of transferring management and technological knowledge from academia to industry. The framework developed for implementing a system of learning for creating a national system of innovation in manufacturing can be generalised to develop more such programmes in emerging nations for addressing skill challenges to lead future innovative projects.
Academy–industry linking capabilities as a determinant of innovation
Authors: Garcia-Montijo Leslie , Perez-Soltero Alonso 
Published: May 2018

Purpose
The purpose of this paper is to analyze the importance of the linkage between academia and industry from a business perspective. The analysis focuses on the impact generated from these collaboration programs to promote innovation. Data for the analysis was obtained through a measurement instrument, which allows evaluating multiple dimensions of capacity of absorption as determinants of the innovation.

Design/methodology/approach
The methodology consisted of the implementation of the measurement instrument for the managers in the companies who were involved in the collaborative projects. From the answers obtained, an analysis of strengths and weaknesses was performed, categorized by absorptive capacity dimensions, satisfaction with linkage relationship and innovative impact. In addition, a comparative exercise is presented with the purpose of learning the position of the Postgraduate Program in Industrial Engineering in México, and finally, an analysis of Spearman’s coefficient was performed to verify whether the linkage influenced innovation for this case study.

Findings
There is a positive correlation between linkage and innovation. An unexpected finding was the level of satisfaction of the companies that collaborated with the academy and the real situation of each dimension to determine the improvements in the policies and mechanisms of linkage.

Research limitations/implications
One of the main challenges of this paper was to identify and contact the managers of the projects. These projects have been performed and completed in several companies from 2011 to date. Over this time, some managers have changed their employment status and even their places of residence. Therefore, establishing contact and performing interviews with the managers directly linked to each project was a complex process.

Originality/value
This is the first paper that demonstrates and measures the relationship between linkage and innovation through an instrument of absorptive capacity, which determines the behavior of each dimension where strengths and weaknesses of collaboration relationships are detected and determines the punctual impact on innovation from the perspective of the businessmen involved.
Supply chain management scholar’s research impact: moderated mediation analysis
Authors: Zhang Yucheng , Wu Yenchun Jim , Goh Mark , Liu Xinhong 
Published: May 2018

PurposeThe purpose of this paper is to draw on social capital theory to develop a model to explain the determinants of a supply chain management scholar’s academic research impact.Design/methodology/approachDrawing from a database of 450 supply chain management scholars in different countries collected from ResearchGate and the World Bank, the bootstrapping method was applied on the moderated mediation analysis.FindingsAnalysis of the mediating role of a scholar’s social capital suggests that social capital theory has a strong explanatory power on the relationship between a scholar’s research skill and academic impact. To account for the boundary effect at the country-level, the authors further examine if this mechanism differs by country in the supply chain management research context.Research limitations/implicationsThe findings from this study are from a single research area, which limits the generalizability of the study. Although the data are collected from different sources, including ResearchGate and the World Bank, it is cross-sectional in nature. The variables in this model do not have strong causal relationships.Practical implicationsThe results suggest that supply chain management scholars can reap the benefits of their social capital. Specifically, scholars can enhance their academic impact by increasing their social capital.Originality/valueThe results provide a reference for supply chain management scholars keen on enhancing their academic research impact. It also provides a reference to explain why country-level differences can influence these scholars.
Personal digital archiving for journalists: a “private” solution to a public problem
Authors: King Rachel 
Published: May 2018

Purpose
The purpose of this paper is to encourage librarians to teach digital archiving practices to journalists as a way of giving journalists the skills they need to save their work for future use and to facilitate the preservation of journalism for posterity.

Design/methodology/approach
The author has reviewed the personal digital archiving literature and analyzed how it might be specifically tailored to the unique needs of journalists.

Findings
Daily journalism has traditionally been preserved by libraries in the form of newspapers and magazines housed in library periodicals departments. Now that nearly all journalism is published online and libraries generally only have access via temporary subscriptions, libraries are prevented from doing any kind of traditional preservation work (e.g. storing copies locally). In the future, this lack of local preservation may lead to a shortage of early twenty-first century primary source material for historians.

Research limitations/implications
The needs of journalists do vary greatly based on the nature and format of their work and its publication venue, making it difficult to offer a single set of standards or recommendations.

Originality/value
While personal digital archiving advocates have generally interpreted the word “personal” to be synonymous with “private,” this paper points to the need to expand the concept to include professional activities, particularly in light of the prevalence of telecommuting and freelance work arrangements, and the lack of support and training received by remote workers and independent contractors.
Cultural sensitivity: an antecedent of the image gap of tourist destinations
Authors: Beerli-Palacio Asunción , Martín-Santana Josefa D. 
Published: May 2018

Purpose
This paper aims to analyse the influence of the cultural sensitivity of tourists on the change in image that occurs for tourist destinations prior to and after a visit; understanding cultural sensitivity as the recognition of and respect for different beliefs, values and customs.

Design/methodology/approach
A structural equations model is carried out with a representative sample of 411 tourists from Tenerife (Canary Islands).

Findings
Cultural sensitivity directly and positively influences the gap in the global image of the destination, so greater cultural sensitivity improves the post-visit image compared to the pre-visit image at a global level. Likewise, there are significant differences in cultural sensitivity according to the sociodemographic characteristics of tourists.

Research limitations
Although this study is based on a single case (Tenerife) and the generalisation of the results must be treated tentatively, the developed model could be applied in other destinations.

Practical implications
This study contributes to a better understanding of the influence of cultural sensitivity on the image gap in tourist destinations, as there is still little empirical evidence on the subject.

Originality/value
The results of this study represent an advance in the literature, as there are few studies in the tourism marketing literature that studied the effect of the cultural sensitivity on the image of a tourist destination.
The effect of online and offline experiential marketing on brand equity in the hotel sector
Authors: Castañeda García José Alberto , Del Valle Galindo Andrea , Martínez Suárez Rocío 
Published: May 2018

Propose
This paper aims to measure the relationship between online experiential marketing (during the purchasing process involving information search and booking) and offline experiential marketing (during the stay) with hotel brand equity. In addition, the study attempts to determine if there is a significant link between the online hotel experience and the subsequent offline hotel stay experience.

Desing/methodology/approach
A self-report survey was conducted in a series of four-star hotels in Granada city. The questionnaire was focused on measuring online experience, offline experience and brand equity. For the analysis of the data, a structural equations model was developed.

Findings
The results suggest that the experience during the hotel stay, contrary to that of the online purchase process, has an influence on hotel brand equity. Nonetheless, the online experience has a significant impact on the hotel stay experience.

Practical implications
This study is of particular utility for hotel management given that, although it is a sector that for several years has integrated experiential marketing in its service strategy, there is little research analyzing the impact of such actions on the variables that are of interest to the hotel.

Originality/value
There are no hotel sector studies that have jointly analyzed the role of the online and offline tourist experience and its role in contributing to brand equity. Recognizing the previous notions will allow hotels to identify where to focus marketing efforts so as to increase brand equity.
Novel mutations in Chinese Han patients with tuberous sclerosis complex: Case series and review of the published work
Authors: Zheng Li‐Yun , LEE Yu‐Wei , Han Yang , Tang Li‐Li , Cheng Yu‐Yan , Dou Jin‐Fa , Zhou Fu‐Sheng , Zheng Xiao‐Dong , Wang Hong‐Yan , Wang Pei‐Guang , Gao Min 
Published: May 2018

AbstractTuberous sclerosis complex (TSC) is an autosomal dominant genetic disease characterized by hamartomas in multiple organ systems. This study was performed in one familial and two sporadic cases with TSC. Two novel mutations (c.1884_1887delAAAG and c.5266A>G) and two previously reported mutations (c.4258_4261delTCAG and c.1960G>C) were identified by direct DNA sequencing. Of the four mutations, c.1884_1887delAAAG and c.1960G>C were found in a family and identified in the same allele by TA cloning sequencing. However, c.1960G>C was reported to be non‐pathogenic. Furthermore, correlations between genotypes and phenotypes of Chinese Han patients since 2014 were performed by paired χ2‐tests in our published work review, which has not been reported. The results showed that patients with TSC2 mutations had a higher frequency of mental retardation and there were no significant differences of seizures and skin lesions with TSC1 mutations. Genetically, they had a higher frequency of familial inheritance.
Development of a Caregiver‐Reported Experience Measure for Pediatric Hospital‐to‐Home Transitions
Authors: Desai Arti D. , Jacob‐Files Elizabeth A. , Lowry Sarah J. , Opel Douglas J. , Mangione‐Smith Rita , Britto Maria T. , Howard Waylon J. 
Published: May 2018

ObjectiveTo develop and test a caregiver‐reported experience measure for pediatric hospital‐to‐home transitions.Data Sources/Study SettingPrimary data were collected between 07/2014 and 05/2015 from caregivers within 2–8 weeks of their child's discharge from a tertiary care children's hospital.Study Design/Data CollectionWe used a step‐wise approach to developing the measure that included drafting de novo survey items based on caregiver interviews (n = 18), pretesting items using cognitive interviews (n = 18), and pilot testing revised items among an independent sample of caregivers (n = 500). Item reduction statistics and confirmatory factor analysis (CFA) were performed on a test sample of the pilot data to refine the measure, followed by CFA on the validation sample to test the final measure model fit.Principal FindingsOf 46 initial survey items, 19 were removed after pretesting and 19 were removed after conducting item statistics and CFA. This resulted in an eight‐item measure with two domains: transition preparation (four items) and transition support (four items). Survey items assess the quality of discharge instructions, access to needed support and resources, care coordination, and follow‐up care. Practical fit indices demonstrated an acceptable model fit: χ2 = 28.3 (df = 19); root‐mean‐square error of approximation = 0.04; comparative fit index = 0.99; and Tucker–Lewis index = 0.98.ConclusionsAn eight‐item caregiver‐reported experience measure to evaluate hospital‐to‐home transition outcomes in pediatric populations demonstrated acceptable content validity and psychometric properties.
The Mental Health Parity and Addiction Equity Act Evaluation Study: Impact on Nonquantitative Treatment Limits for Specialty Behavioral Health Care
Authors: Thalmayer Amber Gayle , Harwood Jessica M. , Friedman Sarah , Azocar Francisca , Watson L. Amy , Xu Haiyong , Ettner Susan L. 
Published: May 2018

ObjectiveTo assess frequency, type, and extent of behavioral health (BH) nonquantitative treatment limits (NQTLs) before and after implementation of the Mental Health Parity and Addiction Equity Act of 2008 (MHPAEA).Data SourcesSecondary administrative data for Optum carve‐out and carve‐in plans.Study DesignCross‐tabulations and “two‐part” regression models were estimated to assess associations of parity period with NQTLs.Data Collection/Extraction MethodsOptum provided four proprietary BH databases, including 2008–2013 data for 40 carve‐out and 385 carve‐in employers from Optum's claims processing databases and 2010 data from interviews conducted by Optum's parity compliance team with 49 carve‐out employers.Principal FindingsPreparity, carve‐out plans required preauthorization for in‐network inpatient/intermediate care; otherwise coverage was denied. Postparity, 73 percent would review later by request and half charged no penalty for late authorization. Outpatient visit authorization requirements virtually disappeared. For carve‐out out‐of‐network inpatient/intermediate care, and for carve‐ins, plans changed penalties to match medical service policies, but this did not necessarily lead to fewer requirements or lower penalties.ConclusionAfter 2011, MHPAEA was associated with the transformation of BH care management, including much less restrictive preauthorization requirements, especially for in‐network care provided by carve‐out plans.
Pancreatic panniculitis: A case series from a tertiary university hospital in Spain
Authors: Fernández‐Sartorio Clara , Combalia Andrea , Ferrando Joan , Alsina Mercè , Iranzo Pilar , Estrach Teresa , Hernández‐Ruiz Eugenia , Mascaró José M 
Published: May 2018

AbstractPancreatic panniculitis is a rare type that only occurs in 2–3% of all patients with pancreatic diseases. It is usually described in association with benign pancreatic disease and less commonly in association with pancreatic carcinoma. We describe a case of pancreatic panniculitis as the first manifestation of underlying ampullary adenocarcinoma and a new case of pancreatitis, panniculitis and polyarthritis (PPP‐Syndrome). Pancreatic panniculitis may be the cutaneous manifestation of pancreatic allograft rejection after simultaneous pancreas‐kidney transplantation.