bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterocyclic sterol probes for live monitoring of sterol trafficking and lysosomal storage disorders
Authors: Králová Jarmila , Jurášek Michal , Krčová Lucie , Dolenský Bohumil , Novotný Ivan , Dušek Michal , Rottnerová Zdeňka , Kahle Michal , Drašar Pavel , Bartůněk Petr , Král Vladimír 
Published: February 2018

AbstractThe monitoring of intracellular cholesterol homeostasis and trafficking is of great importance because their imbalance leads to many pathologies. Reliable tools for cholesterol detection are in demand. This study presents the design and synthesis of fluorescent probes for cholesterol recognition and demonstrates their selectivity by a variety of methods. The construction of dedicated library of 14 probes was based on heterocyclic (pyridine)-sterol derivatives with various attached fluorophores. The most promising probe, a P1-BODIPY conjugate FP-5, was analyzed in detail and showed an intensive labeling of cellular membranes followed by intracellular redistribution into various cholesterol rich organelles and vesicles. FP-5 displayed a stronger signal, with faster kinetics, than the commercial TF-Chol probe. In addition, cells with pharmacologically disrupted cholesterol transport, or with a genetic mutation of cholesterol transporting protein NPC1, exhibited strong and fast FP-5 labeling in the endo/lysosomal compartment, co-localizing with filipin staining of cholesterol. Hence, FP-5 has high potential as a new probe for monitoring cholesterol trafficking and its disorders.Significance statementCholesterol is a vital steroid molecule with many important functions in animal cells. Although its dysregulation is associated with an expanding list of clinically important pathologies, the study of its role is limited by a lack of reliable tools for live intracellular monitoring. This study demonstrates the applicability of a novel class of heterocyclic sterol probes. These probes exhibit fast cellular uptake with effective fluorescence labeling of sterol species in a variety of living cells, without a need for artificial carriers. When applied to Niemann-Pick disease type C1 cells, they identified massive accumulation of cholesterol in the endosome/lysosome compartment. Thus, several probes from the same series can also be used for visualizing lysosomal storage disorders and sterol transporting pathologies.
Tdrd6a regulates the aggregation of Buc into functional subcellular compartments that drive germ cell specification
Authors: Roovers Elke F. , Kaaij Lucas J.T. , Redl Stefan , Bronkhorst Alfred W. , Wiebrands Kay , de Jesus Domingues António M. , Huang Hsin-Yi , Han Chung-Ting , Salvenmoser Willi , Grün Dominic , Butter Falk , van Oudenaarden Alexander , Ketting René F. 
Published: February 2018

SummaryIn recent years, it has become clear that phase separation represents an important class of subcellular compartmentalization. However, relatively little is known about how the formation or disassembly of such compartments is regulated. In zebrafish, the Balbiani body (Bb) and the germ plasm (Gp) are phase-separated structures essential for germ cell specification and home to many germ cell-specific mRNAs and proteins. Throughout development, these structures range from a single large aggregate (Bb), to a dispersed state and back to relatively large assemblies (Gp). Formation of the Bb requires Bucky ball (Buc), a protein with prion-like properties. We found that the multi-tudor domain-containing protein Tdrd6a interacts directly with Buc, affecting its mobility and aggregation properties. Importantly, lack of this regulatory interaction leads to significant defects in germ cell development. Our work presents a new mechanism for how prion-like protein-aggregations can be regulated and highlights the biological relevance of such regulatory events.
Bayesian phylodynamic inference with complex models
Authors: Volz Erik M. , Siveroni Igor 
Published: February 2018

AbstractPopulation genetic modeling can enhance Bayesian phylogenetic inference by providing a realistic prior on the distribution of branch lengths and times of common ancestry.The parameters of a population genetic model may also have intrinsic importance, and simultaneous estimation of a phylogeny and model parameters has enabled phylodynamic inference of population growth rates, reproduction numbers, and effective population size through time. Phylodynamic inference based on pathogen genetic sequence data has emerged as useful supplement to epidemic surveillance, however commonly-used mechanistic models that are typically fitted to non-genetic surveillance data are rarely fitted to pathogen genetic data due to a dearth of software tools, and the theory required to conduct such inference has been developed only recently. We present a framework for coalescent-based phylogenetic and phylodynamic inference which enables highly-flexible modeling of demographic and epidemiological processes. This approach builds upon previous structured coalescent approaches and includes enhancements for computational speed, accuracy, and stability. A flexible markup language is described for translating parametric demographic or epidemiological models into a structured coalescent model enabling simultaneous estimation of demographic or epidemiological parameters and time-scaled phylogenies. We demonstrate the utility of these approaches by fitting compartmental epidemiological models to Ebola virus and Influenza A virus sequence data, demonstrating how important features of these epidemics, such as the reproduction number and epidemic curves, can be gleaned from genetic data. These approaches are provided as an open-source packagePhyDynfor the BEAST phylogenetics platform.
Matching drug transcriptional signatures to rare losses disrupting synaptic gene networks identifies known and novel candidate drugs for schizophrenia
Authors: Merico Daniele , Wang Xiao , Yuen Ryan K. C. , Scherer Stephen W. , Bassett Anne S. 
Published: February 2018

ABSTRACTSchizophrenia is a complex neuropsychiatric disorder. The etiology is not fully understood, but genetics plays an important role. Pathway analysis of genetic variants have suggested a central role for neuronal synaptic processes. Currently available antipsychotic medications successfully control positive symptoms (hallucinations and delusions) largely by inhibiting the dopamine D2 receptors; however, these drugs have more limited impact on negative symptoms (social withdrawal, flat affections, anhedonia) and cognitive deterioration. Drug development efforts have focused on a wide range of neurotransmitter systems and other agents, with conflicting or inconclusive results. New drug development paradigms are needed. A recent analysis, using common variant association results to match drugs based on their transcriptional perturbation signature, found drugs enriched in known antipsychotics plus novel candidates.We followed a similar approach, but started our analysis from a synaptic gene network implicated by rare copy number loss variants. We found that a significant number of antipsychotics (p-value = 0.0002) and other psychoactive drugs (p-value = 0.0004) upregulate synaptic network genes. Based on global gene expression similarity, active drugs formed two main clusters: one with many known antipsychotics and antidepressants, the other with various drug categories including two nootropics. We specifically recommend further examination of nootropics with limited side effects (meclofenoxate, piracetam and vinpocetine) for combination therapy with antipsychotics to improve cognitive performance. Detailed experimental follow-up is required to further evaluate other candidate drugs lacking an official nervous system indication, although, for at least a few of these, psychoactive effects have been reported in the literature.
Information vs knowledge
Authors: Du Rietz Sabina 
Published: February 2018

Purpose
The purpose of this paper is to offer a new and more elaborate view of the relationship between information and knowledge in accountability settings.

Design/methodology/approach
The study investigates how knowledge is accomplished when accountability is demanded. The “knowing-in-practice” perspective (Lave, 1988; Orlikowski, 2002; Pentland, 1992) is introduced to theorise knowledge as the ability to purposefully go on with practice and information as a resource that may contribute to this knowledge. Empirically, the study investigates Nordic investors’ engagement with companies addressing environmental, social, and governance issues.

Findings
The findings illustrate how information may contribute to knowledge in an accountability setting. Whether or not the information contributes to knowledge in the accountability setting depends on the information’s origin, convergence with other accounts, and use in contradicting and disproving executives’ information. The analysis also shows how knowledge in accountability settings may be achieved without information – for example, by enacting theories.

Research limitations/implications
The study suggests that research should more carefully distinguish between knowledge and information. According to the perspective used here, knowledge is the ability to purposefully go on with practice. Information is one of many resources that can contribute to knowledge.

Practical implications
This study provides insight into the relationship between accounting systems and the practice of demanding accountability. Such understanding is valuable when designing accounts-based governance and civil regulation, such as for addressing sustainability issues, as in this study.

Originality/value
The study challenges the view of knowledge as a representation or factual commodity, and provides a new and more elaborate view of the relationship between information and knowledge in accountability settings by introducing the knowing-in-practice perspective to the accounting literature.
From the Big Five to the Big Four? Exploring extinction accounting for the rhinoceros
Authors: Atkins Jill , Maroun Warren , Atkins Barry Colin , Barone Elisabetta 
Published: February 2018

Purpose
The purpose of this paper is to explore a possible framework for extinction accounting which builds on but also extends significantly the existing GRI guidelines relating to species identified by the International Union for the Conservation of Nature Red List as under threat of extinction.

Design/methodology/approach
The paper analyses disclosures relating to rhinoceros conservation and protection produced by top South African-listed companies in order to assess the current state of “extinction accounting”. Following this analysis, the authors explore and discuss a potential framework for extinction accounting which may be used by companies to demonstrate their accountability for species and disclose the ways in which they are working alone, and in partnerships, to prevent species extinction.

Findings
Corporate disclosures relating to rhinoceros may be interpreted as emancipatory. The authors identify several disclosure themes dealing with rhinoceros in integrated and sustainability reports of large South African companies and on their websites. Contrary to initial expectations, there is evidence to suggest corporate awareness of the importance of addressing the risk of this species becoming extinct.

Research limitations/implications
The authors have relied on public corporate disclosures and would like to extend the work further to include interview data for a further paper.

Practical implications
An extinction accounting framework may be applied to corporate accounting and accountability for any species under threat of extinction. The framework may also be considered for use as a tool for institutional investors as well as NGO engagement and dialogue with stakeholder companies.

Social implications
The rhinoceros has, from the analysis, significant cultural, heritage, eco-tourism and intrinsic value. Developing and implementing an emancipatory extinction accounting framework to prevent extinction will have a substantial social and environmental impact.

Originality/value
This is the first attempt to the knowledge to explore accounting for extinction and a possible extinction accounting framework. It is also the first attempt to investigate accounting and accountability for the rhinoceros.
ACSESim: Agile and Lean software development in practice
Authors: Maritz Andries , Hamdulay Fatima 
Published: February 2018

Subject area
Agile software development, Knowledge workers and Lean thinking as a management system

Study level/applicability
The case lends itself to students of business management, or aspiring consultants, who have been exposed to operations management in general and Lean thinking specifically. It is an advanced case study, assuming prior knowledge in these subjects and approaches the subject matter from an organisational development point of view, rather than a pure operations point of view. It is thus well suited to an elective on operational excellence on an MBA or in executive education courses in Lean thinking

Case overview
The case starts with Mark, manager of a software development team, hearing that he will have budget for two new developers who will join his team in the coming year. While the extra help could be useful, he was considering what the impact of new people would be on the productivity of the team, which he felt was already stretched. Mark continues to consider the entire development chain and how code changes were implemented to ACSESim’s (the company’s primary product) graphical user interfaces. Having recently been acquired by an American company, he was also under pressure to start to adopt some of the parent company’s systems, which would constitute a fairly disruptive, but necessary, change, particularly for future collaborations with other developers in the parent company. With two new developers, experience taught Mark that development could slow down owing to training efforts. To minimise disruption, he was wondering about how to get the new developers up-to-speed quickly and streamline their operations within a changing corporate environment. The case highlights the different mechanisms that were in place at ACSESim, including the use of issue trackers; Kanban boards; version control software; automated systems; stand-up meetings, etc. Each of these mechanisms is discussed briefly and shows the value they added to the development practices that were in place. This also allows students to understand Agile practices and what Lean thinking might mean in a knowledge work environment and then to consider what the proposed changes might mean and how they could be deployed.

Expected learning outcomes
To gain an understanding of how Lean and Agile principles can be applied in a software development environment and Lean knowledge work in general To consider the best way to manage new hires so that they can become productive in a Lean or Agile software development environment, whilst dealing with pressures to migrate to new systems.

Supplementary materials
Teaching notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code
CSS: 9: Operations and Logistics.
Keeping up with growing complexity of managing global operations
Authors: Ferdows Kasra 
Published: February 2018

PurposeThe purpose of this paper is to argue that operations management (OM) scholars ought to be among the thought leaders in research into the design and management of global production networks, but too few of them currently are. It suggests possible reasons for what is holding them back and calls for ideas for removing the obstacles.Design/methodology/approachThis paper is a viewpoint. Nevertheless, it reports results of an indicative survey and uses example cases to illustrate and support its arguments.FindingsThe survey confirms the conclusions from previous studies that the number of publications specifically in leading OM journals focusing on management of global operations is small. Relatively high levels of detail and dynamic complexity and hysteresis of variables affecting the management of global operations are identified as the major hurdles. Applying analytical modeling, a popular research methodology among OM scholars, may be of limited use as it mandates making too many simplifying assumptions. Empirical research is also difficult because it is time consuming and requires access to often sensitive data and may require longitudinal studies. These are tough problems with no clear solutions.Originality/valueThe paper urges OM scholars to take on the broad and strategic problems in management of global operations. That would not only change how the OM discipline is viewed, but it would also benefit the firm, the economy, and the society.
Measuring supply chain performance: a lifecycle framework and a case study
Authors: Maestrini Vieri , Luzzini Davide , Caniato Federico , Maccarrone Paolo , Ronchi Stefano 
Published: February 2018

PurposeThe purpose of this paper is to provide a conceptual framework of the supply chain performance measurement system (SCPMS) lifecycle (highlighting key activities of the design, implementation, use and review phases) and to investigate how the different actors involved in the SCPMS perceive the system and can act to allow for an effective adoption.Design/methodology/approachThe SCPMS lifecycle framework is developed grounding on performance measurement and supply chain (SC) management literature. To answer the two theory-building research questions, an in-depth case study involving seven firms across three tiers of the mass retail SC has been conducted.FindingsThe empirical evidence highlighted potential SCPMS benefits (including operational performance improvement, higher control, lower information overloading and higher SC integration) and criticalities/barriers to an effective adoption (lack of industry standards, lack of trust regarding data reliability, SCPMS as a tool of power, lack of interest in the system and the performance metrics). Several elements characterizing the SCPMS lifecycle could increase its effective adoption: engaging SC partners in the design phase; relying on a rigorous primary data collection and performance measures calculation; and actively exploiting the tool through a systematic discussion on performance and establishing incentive/disincentives plans.Originality/valueThe paper contributes to the conceptualization of SCPMSs and to clarify how to ensure an effective SCPMS adoption: apart from relationship-specific attributes, SCPMS lifecycle phases are suggested to have a key role.
Architectures for multichannel front-office service delivery models
Authors: Sousa Rui , Amorim Marlene 
Published: February 2018

PurposeMultichannel (MC) service providers have been adopting a wide diversity of front-office service delivery models, i.e. different ways of employing channels to support the delivery of the service activities that involve customer interaction. Despite this, we are still faced with a paucity of concepts to understand the myriad of possible choices. The purpose of this paper is to develop a theoretical framework and basic design architectures to provide a structured understanding of the diversity of operational design choices for MC front-office service delivery models, their efficacy implications, and how they fit with the provider’s service strategy.Design/methodology/approachThe study employs the analytical conceptual approach. The authors logically develop the architectures based on the operations management theory and provide corresponding empirical illustrations based on secondary sources, direct observation, and case studies.FindingsThe authors propose two theoretically meaningful dimensions to characterize and distinguish between delivery models (channel redundancy and channel span) and put forward four anchor architectures for such models: generalist, parallel, constricted, and centralized. The authors identify the operational efficacy implications (effectiveness and efficiency) of the different architectures, and develop a set of propositions and design principles for selecting appropriate architectures.Research limitations/implicationsFuture research should develop empirical measures for the dimensions underlying the architectures.Originality/valueThe study extends existing service process classifications by capturing the MC traits of front-office processes. The authors offer design principles to assist firms in selecting architectures that are aligned with their service strategy. The framework and architectures provide seminal concepts to support a wealth of future empirical studies.
How does intellectual capital affect product innovation performance? Evidence from China and India
Authors: Zhang Min , Qi Yinan , Wang Zhiqiang , Pawar Kulwant S. , Zhao Xiande 
Published: February 2018

PurposeIntellectual capital reflects the sum of existing knowledge a manufacturer is able to leverage and plays a critical role in new product development. The purpose of this paper is to empirically investigate the mechanisms through which intellectual capital enhances product innovation performance and how economic and institutional environments affect the mechanisms.Design/methodology/approachUsing a knowledge-based view and institutional theory, this study proposes a model on the relationships among intellectual capital, supplier knowledge integration, supply chain adaptability, and product innovation performance. The hypotheses are empirically tested using multiple group structural equation modelling and data collected from 300 Chinese and 200 Indian manufacturers.FindingsThe authors find that intellectual capital improves product innovation performance both directly and indirectly through supplier knowledge integration. However, the effects are different in China and India. In particular, the direct effect of intellectual capital on product innovation performance is significantly higher in China than that in India, and intellectual capital improves product innovation performance indirectly through supplier knowledge integration only in India. The authors also find that supplier knowledge integration improves product innovation performance indirectly through supply chain adaptability in both China and India.Originality/valueUsing a moderated mediation model, this study provides insights into the joint effects of intellectual capital, supplier knowledge integration, and supply chain adaptability on product innovation performance. The findings enhance current understandings of how supply chain management helps a manufacturer develop new products using existing knowledge and the influences of economic and institutional environments on knowledge and supply chain management.