bluuebunny/crossref_metadata_2025_split huggingface dataset:
Segmentation-Enhanced CycleGAN
Authors: Januszewski Michał , Jain Viren 
Published: February 2019

AbstractAlgorithmic reconstruction of neurons from volume electron microscopy data traditionally requires training machine learning models on dataset-specific ground truth annotations that are expensive and tedious to acquire. We enhanced the training procedure of an unsupervised image-to-image translation method with additional components derived from an automated neuron segmentation approach. We show that this method, Segmentation-Enhanced CycleGAN (SECGAN), enables near perfect reconstruction accuracy on a benchmark connectomics segmentation dataset despite operating in a “zero-shot” setting in which the segmentation model was trained using only volumetric labels from a different dataset and imaging method. By reducing or eliminating the need for novel ground truth annotations, SECGANs alleviate one of the main practical burdens involved in pursuing automated reconstruction of volume electron microscopy data.
Variation in filamentous growth and response to quorum-sensing compounds in environmental isolates ofSaccharomyces cerevisiae
Authors: Lenhart B. Adam , Meeks Brianna , Murphy Helen A. 
Published: February 2019

AbstractIn fungi, filamentous growth is a major developmental transition that occurs in response to environmental cues. In diploidSaccharomyces cerevisiae, it is known as pseudohyphal growth and presumed to be a foraging mechanism. Rather than normal unicellular growth, multicellular filaments composed of elongated, attached cells spread over and into surfaces. This morphogenetic switch can be induced through quorum sensing with the aromatic alcohols phenylethanol and tryptophol. Most research investigating pseudohyphal growth has been conducted in a single lab background, Σ1278b. To investigate the natural variation in this phenotype and its induction, we assayed the diverse 100-genomes collection of environmentalS. cerevisiaeisolates. Using computational image analysis, we quantified the production of pseudohyphae and observed a large amount of variation. Unlike ecological niche, population membership was associated with pseudohyphal growth, with the West African population having the most. Surprisingly, most strains showed little or no response to exogenous phenylethanol or tryptophol. We also investigated the amount of natural genetic variation in pseudohyphal growth using a mapping population derived from a single, highly-heterozygous clinical isolate that contained as much phenotypic variation as the environmental panel. A bulk-segregant analysis uncovered five major peaks with candidate loci that have been implicated in the Σ1278b background. Our results indicate that the filamentous growth response is a generalized, highly variable phenotype in natural populations, while response to quorum sensing molecules is surprisingly rare. These findings highlight the importance of coupling studies in tractable lab strains with natural isolates in order to understand the relevance and distribution of well-studied traits.
Sequencing and Imputation in GWAS: Cost-Effective Strategies to Increase Power and Genomic Coverage Across Diverse Populations
Authors: Quick Corbin , Anugu Pramod , Musani Solomon , Weiss Scott T. , Burchard Esteban G. , White Marquitta J. , Keys Kevin L. ,   NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Cucca Francesco , Sidore Carlo , Boehnke Michael , Fuchsberger Christian 
Published: February 2019

ABSTRACTA key aim for current genome-wide association studies (GWAS) is to interrogate the full spectrum of genetic variation underlying human traits, including rare variants, across populations. Deep whole-genome sequencing is the gold standard to capture the full spectrum of genetic variation, but remains prohibitively expensive for large samples. Array genotyping interrogates a sparser set of variants, which can be used as a scaffold for genotype imputation to capture variation across a wider set of variants. However, imputation coverage and accuracy depend crucially on the reference panel size and genetic distance from the target population.Here, we consider a strategy in which a subset of study participants is sequenced and the rest array-genotyped and imputed using a reference panel that comprises the sequenced study participants and individuals from an external reference panel. We systematically assess how imputation quality and statistical power for association depend on the number of individuals sequenced and included in the reference panel for two admixed populations (African and Latino Americans) and two European population isolates (Sardinians and Finns). We develop a framework to identify powerful and cost-effective GWAS designs in these populations given current sequencing and array genotyping costs. For populations that are well-represented in current reference panels, we find that array genotyping alone is cost-effective and well-powered to detect both common- and rare-variant associations. For poorly represented populations, we find that sequencing a subset of study participants to improve imputation is often more cost-effective than array genotyping alone, and can substantially increase genomic coverage and power.
Biochemical characterization of the methylmercaptopropionate:cob(I)alamin methyltransferase fromMethanosarcina acetivorans
Authors: Fu He , Goettge Michelle N. , Metcalf William W. 
Published: February 2019

ABSTRACTMethanogenesis from methylated substrates is initiated by substrate specific methyltransferases that generate the central metabolic intermediate methyl-coenzyme M. This reaction involves a methyl-corrinoid protein intermediate and one or two cognate methyltransferases. Based on genetic data, theMethanosarcina acetivoransMtpC (corrinoid protein) and MtpA (methyltransferase) proteins were suggested to catalyze the methylmercaptopropionate(MMPA):Coenzyme M (CoM) methyl transfer reaction without a second methyltransferase. To test this, MtpA was purified after overexpression in its native host and characterized biochemically. MtpA catalyzes a robust methyl transfer reaction using free methylcob(III)alamin as the donor and mercaptopropionate (MPA) as the acceptor, withkcatof 0.315 s-1and apparentKmfor MPA of 12 μM. CoM did not serve as a methyl acceptor, thus a second, unidentified methyltransferase is required to catalyze the full MMPA:CoM methyl transfer reaction. The physiologically relevant methylation of cob(I)alamin with MMPA, which is thermodynamically unfavorable, could also be demonstrated, but only at high substrate concentrations. Methylation of cob(I)alamin with methanol, dimethylsulfide, dimethylamine and methyl-CoM was not observed, even at high substrate concentrations. Although the corrinoid protein MtpC was poorly expressed alone, a stable MtpA/MtpC complex was obtained when both proteins were co-expressed. Biochemical characterization of this complex was not feasible because the corrinoid cofactor of this complex was in the inactive Co(II) state and could not be reactivated by incubation with strong reductants. The MtsF protein, comprised of both corrinoid and methyltransferase domains, co-purifies with the MtpA/MtpC, suggesting that it may be involved in MMPA metabolism.IMPORTANCEMMPA is an environmentally significant molecule produced by degradation of the abundant marine metabolite dimethylsulfoniopropionate, which plays a significant role in the biogeochemical cycles of both carbon and sulfur, with ramifications for ecosystem productivity and climate homeostasis. Detailed knowledge of the mechanisms for MMPA production and consumption is key to understanding steady state levels of this compound in the biosphere. Unfortunately, the biochemistry required for MMPA catabolism under anoxic conditions is poorly characterized. The data reported here validate the suggestion that the MtpA protein catalyzes the first step in methanogenic catabolism of MMPA. However, the enzyme does not catalyze a proposed second step required to produce the key intermediate methyl-CoM. Therefore, additional enzymes required for methanogenic MMPA catabolism await discovery.
Automated high-throughput heart rate measurement in medaka and zebrafish embryos under physiological conditions
Authors: Gierten Jakob , Pylatiuk Christian , Hammouda Omar , Schock Christian , Stegmaier Johannes , Wittbrodt Joachim , Gehrig Jochen , Loosli Felix 
Published: February 2019

AbstractRationaleAccurate and efficient quantification of heartbeats in small fish models is an important readout to study cardiovascular biology, disease states and pharmacology at large scale. However, dependence on anesthesia, laborious sample orientation or requirement for fluorescent reporters have hampered the establishment of high-throughput heartbeat analysis.ObjectiveTo overcome these limitations, we aimed to develop a high-throughput assay with automated heart rate scoring in medaka (Oryzias latipes) and zebrafish (Danio rerio) embryos under physiological conditions designed for genetic screens and drug discovery and validation.Methods and ResultsWe established an efficient screening assay employing automated label-free heart rate determination of randomly oriented, non-anesthetized specimen in microtiter plates. Automatically acquired bright-field data feeds into an easy-to-useHeartBeatsoftware, a MATLAB algorithm with graphical user interface developed for automated quantification of heart rate and rhythm. Sensitivity of the assay and algorithm was demonstrated by profiling heart rates during entire embryonic development. Our analysis pipeline revealed acute temperature changes triggering rapid adaption of heart rates, which has implications for standardization of experimental layout. The approach is scalable and allows scoring of multiple embryos per well resulting in a throughput of >500 embryos per 96-well plate. In a proof of principle screen for compound testing, our assay captured concentration-dependent effects of nifedipine and terfenadine over time.ConclusionA novel workflow andHeartBeatsoftware provide efficient means for reliable and direct quantification of heart rate and rhythm of small fish in a physiological environment. Importantly, confounding factors such as anesthetics or laborious mounting are eliminated. We provide detailed profiles of embryonic heart rate dynamics in medaka and zebrafish as reference for future assay development. Ease of sample handling, automated imaging, physiological conditions and software-assisted analysis now facilitate various large-scale applications ranging from phenotypic screening, interrogation of gene functions to cardiovascular drug development pipelines.
Measles vaccine virus RNA in children more than 100 days after vaccination
Authors: McMahon Jamie , Mackay Ian M , Lambert Stephen B 
Published: February 2019

AbstractMeasles vaccines have been in use since the 1960s with excellent safety and effectiveness profiles. Limited data are available on detection of measles vaccine virus (MeVV) RNA in human subjects following vaccination. Available evidence suggests MeVV RNA can be identified up to 14 days after vaccination, with detection beyond this rare. In routine diagnostic testing, we used two real-time reverse transcription-polymerase chain reaction (RT-rPCR) assays for identifying measles virus (MeV) and MeVV RNA, followed by sequence confirmation of RT-rPCR positives by a semi-nested conventional RT-PCR. We report detection and confirmation of MeVV RNA from the respiratory tract of 11 children between 100 and 800 days after most recent receipt of measles-containing vaccine. These novel preliminary findings emphasize the importance of genotyping all MeV detections and highlight the need for further work to assess whether persistent MeVV RNA represents viable virus and if transmission to close contacts can occur.
Just another Chinese city? Hong Kong’s post-1997 role to the European Union
Authors: Lai Suetyi 
Published: February 2019

Purpose
By overviewing the role of Hong Kong to the European Union (EU), the world’s largest economic bloc and a key global actor, the purpose of this paper is to understand any change in international prominence and status of Hong Kong after two decades of its sovereignty return.

Design/methodology/approach
It is based on analysis of statistics, government discourses and official documents.

Findings
Main findings are that although the function of Hong Kong as an entrepot of China–EU trade and the ranking of the city as the EU’s trade partners have both diminished, the city sustains its roles as a platform to enter Mainland China, a regional hub in Asia, a major international capital market, a diplomatic counterpart and a partner in socio-cultural aspects to the EU. This paper agrees with the EU’s view that continuous well-functioning of Hong Kong under “One Country, Two System” serves stake of the Union which is keen on helping the SAR to ensure its high autonomy. Yet, the determinants remain Hong Kong and Beijing Governments, which have been and should continue to make use of Hong Kong’s closer tie with the mainland to promote international importance of both the city and China.

Originality/value
Research on relations between Hong Kong and the EU has been few, especially so in the past decades. This paper serves as a stock-take of the most recent developments in Hong Kong–EU relation.
Teaching classics as moral and civic education
Authors: Leung Cheuk-Hang , Chan Hin Yan 
Published: February 2019

PurposeIn light of the concerns of declining value education in higher education and the debates on the role of general education in current university setting, the purpose of this paper is to discuss the relation between general education and moral and civic education by examining the effectiveness of a compulsory classics reading general education program in cultivating civic literacy in Asia-Pacific context.Design/methodology/approachMixed-method approach in the form of survey assessment and focus group studies was employed to examine the degree of students’ development in abilities and virtues relevant to civic literacy in the course.FindingsData analyses reveal a promising development on students’ civic literacy in the classics reading general education course. Statistical analysis on surveys indicated students experienced a significant development on democratic skills and critical thinking, acquisition of civic knowledge and cultivation of democratic virtues after taking the course. Focus group analysis illustrated a relation between classics reading and students’ acquisition of knowledge of socio-political institutions, cultivation of open-mindedness and sense of tolerance for diversity and willingness of seeking reasonableness and engaging in social debates.Originality/valueThis paper discusses the successful experience of a newly formulated General Education program in Hong Kong. The program is the first attempt in East Asia to launch values education through the teaching and learning of classics in Asia-Pacific context. This could be an example of launching values education at the level of undergraduate education for other local universities.
Changing Hong Kong university students’ national identity through studying abroad
Authors: Cheng Annie , Szeto Elson 
Published: February 2019

Purpose
The purpose of this paper is to explore whether there are any effects on Hong Kong university students’ national identity after short-term study abroad. If so, what sources of influence from the short-term study abroad programme contribute to the students’ change in national identity?

Design/methodology/approach
Using the case study approach, 85 students completed a questionnaire, and a small group of 12 students were invited to individual interviews for further investigation.

Findings
Results show that the students’ perceptions of national identity are multiple and complicated through the lens of four components of national identity. The responses of students’ perceptions of change in identity were pointed to three statements: “feeling prouder of being Chinese”, “Hongkongers are very different from mainland Chinese” and “no change in my views of national identity”. The influences of study abroad experiences on national identity varied, dependent on the students’ interaction with the local and non-local people, and reflection on their own identity, whether on the cultural or political differences or on national achievements.

Research limitations/implications
The findings of this study can inform educators and administrators to enhance profound short-term study abroad experience for the students. The limitation of this case study is that it is concerned with understanding how small numbers of students construct meaning from their individual experience. It is recommended that studies with larger sampling sizes be conducted to investigate students’ perceptions of their national identity before and after studying abroad.

Originality/value
Considering the increasing number of Hong Kong youths who have participated in these short-term study-abroad programmes in higher education, the findings of this study are significant in terms of awakening the students’ taken-for-granted national identity, if any. The programme serves as a means of triggering the students’ feelings and emotions regarding their identity in different national, social and cultural contexts. This can inform policy makers, educational administrators and teachers to formulate an appropriate national education curriculum for the youth.
Walls all around: barriers women professionals face in high-tech careers in Bangladesh
Authors: Saifuddin Samina , Dyke Lorraine , Hossain Md Sajjad 
Published: February 2019

PurposeThe purpose of this paper is to create a nuanced understanding of the barriers women high-tech professionals face in Bangladesh. The main aim is to identify the extent to which these barriers are common across different contexts and to explore the barriers that are unique and situated in the local socio-cultural context.Design/methodology/approachIn-depth interviews with high-tech professionals were conducted to identify and explore the barriers.FindingsAlthough some of the barriers are common across different contexts, most of the barriers women professionals face arise due to the interaction between situated socio-cultural practices and gender. The dynamics of socio-cultural and patriarchal norms reinforce gender biases and gendered practices that afford men with greater control over resources and systematically limit women’s access to opportunities.Research limitations/implicationsThe study recruited 35 participants using snowball sampling. From a methodological perspective, future research could benefit from recruiting a larger, more varied sample using random sampling.Practical implicationsWomen experience barriers due to both internal organizational features and external contextual barriers. The findings suggest that some of these barriers can be removed through governmental and organizational policies and through appropriate intervention strategies delivered in partnership with governmental and non-governmental organizations.Originality/valueThe study makes a unique contribution by using a macro-social lens to analyze the meso-organizational practices and micro-individual phenomena thereby providing a holistic view of the barriers faced by women professionals in Bangladesh.
Building information modelling to support maintenance management of healthcare built assets
Authors: Wanigarathna Nadeeshani , Jones Keith , Bell Adrian , Kapogiannis Georgios 
Published: February 2019

Purpose
This paper aims to investigate how digital capabilities associated with building information modelling (BIM) can integrate a wide range of information to improve built asset management (BAM) decision-making during the in-use phase of hospital buildings.

Design/methodology/approach
A comprehensive document analysis and a participatory case study was undertaken with a regional NHS hospital to review the type of information that can be used to better inform BAM decision-making to develop a conceptual framework to improve information use during the health-care BAM process, test how the conceptual framework can be applied within a BAM division of a health-care organisation and develop a cloud-based BIM application.

Findings
BIM has the potential to facilitate better informed BAM decision-making by integrating a wide range of information related to the physical condition of built assets, resources available for BAM and the built asset’s contribution to health-care provision within an organisation. However, interdepartmental information sharing requires a significant level of time and cost investment and changes to information gathering and storing practices within the whole organisation.

Originality/value
This research demonstrated that the implementation of BIM during the in-use phase of hospital buildings is different to that in the design and construction phases. At the in-use phase, BIM needs to integrate and communicate information within and between the estates, facilities division and other departments of the organisation. This poses a significant change management task for the organisation’s information management systems. Thus, a strategically driven top-down organisational approach is needed to implement BIM for the in-use phase of hospital buildings.
Missed opportunities: two case studies of digitalization of FM in hospitals
Authors: Koch Christian , Hansen Geir Karsten , Jacobsen Kim 
Published: February 2019

Purpose
Digital practices of facility management (FM) are undergoing transformation. Several Nordic countries have ambitious hospital-building projects, driven by large public clients with long-term experience of operating complex building campuses. There is thus an opportunity for creating state-of-the-art digital FM. This paper aims to investigate the role of digital FM in new hospital projects in Scandinavia.

Design/methodology/approach
Based on a literature review, a framework of understanding of digital FM in hospital operation is established. Two longitudinal cases are presented and analysed, one for a greenfield hospital and the other for an extension of an existing hospital.

Findings
The literature highlights the importance of integration between technical digitalization, competences, organization and management of digital FM. The projects are in different phases and represent quite advanced preparations for digital FM. State-of-the-art computer-aided FM systems are prepared before operation. External consultants are involved, posing a dilemma of in-house/outsourced human resources in the future digital FM operation.

Research limitations/implications
Two case studies provide insights, but they have limited generalizability.

Practical implications
The study underscores the importance of preparation of management, organization and competences for digitalization.

Originality/value
Documented research on building information modelling (BIM) integrations in FM is still scarce. This article adds to the few empirical studies in the area. The findings illustrate that real estate administrators investing in FM software for new hospital buildings face challenges of aligning BIM models from design and construction to the FM system.