bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacterial pore-forming proteins induce non-monotonic dynamics due to lipid ejection and crowding
Authors: Ilangumaran Ponmalar Ilanila , Ayappa K. G. , Basu J. K. 
Published: November 2020

ABSTRACTDeveloping alternate strategies against pore forming toxin (PFT) mediated bacterial virulence factors require an understanding of the target cellular response to combat rising antimicrobial resistance. Membrane-bound protein complexes involving PFTs, released by virulent bacteria are known to form pores leading to host cell lysis. However, membrane disruption and related lipid mediated active repair processes during attack by PFTs remain largely unexplored. We report counter intuitive and non-monotonic variations in lipid diffusion, measured using confocal fluorescence correlation spectroscopy, due to interplay of lipid ejection and crowding by membrane bound oligomers of a prototypical cholesterol dependent cytolysin, Listeriolysin O (LLO). The observed protein concentration dependent dynamical cross-over is correlated with transitions of LLO oligomeric state populations from rings to arc-like pore complexes, predicted using a proposed two-state free area based diffusion model. At low PFT concentrations, a hitherto unexplored regime of increased lipid diffusivity is attributed to lipid ejection events due to a preponderance of ring-like pore states. At higher protein concentrations where membrane inserted arc-like pores dominate, lipid ejection is less efficient and the ensuing crowding results in a lowering of lipid diffusion. These variations in lipid dynamics are corroborated by macroscopic rheological response measurements of PFT bound vesicles. Our study correlates PFT oligomeric state transitions, membrane remodelling and mechanical property variations, providing unique insights into developing strategies to combat virulent bacterial pathogens responsible for several infectious diseases.SIGNIFICANCEDeveloping alternate strategies against pore forming toxin (PFT) mediated bacterial virulence factors requires understanding target cellular responses and cellular defence strategies to combat rising antimicrobial resistant strains. While it is well understood that PFTs exist in a wide variety of oligomeric states, the underlying membrane response to these states is unexplored. Using confocal fluorescence correlation spectroscopy and a membrane free area based model we relate non-monotonic variations in the lipid diffusivity arising from an interplay of lipid ejection events and membrane crowding due to variations in concentration of membrane bound listeriolysin O. Our observations have a direct bearing on understanding cellular defense and repair mechanisms effective during initial stages of bacterial infection and intrinsically connected to the underlying membrane fluidity.
Dengue virus protease activity modulated by dynamics of protease cofactor
Authors: Lee W H , Liu W , Fan J , Yang D 
Published: November 2020

AbstractThe viral protease domain (NS3pro) of dengue virus is essential for virus replication and its cofactor NS2B is indispensable for the proteolytic function. Although several NS3pro-NS2B complex structures have been obtained, the dynamic property of the complex remains poorly understood. Using NMR relaxation techniques, here we found that NS3pro-NS2B exists in both closed and open conformations which are in dynamic equilibrium on a sub-millisecond timescale in aqueous solution. Our structural information indicates that the C-terminal region of NS2B is disordered in the open conformation but folded in the closed conformation. Using mutagenesis, we showed that the closed-open conformational equilibrium can be shifted by changing NS2B stability. Moreover, we revealed that the proteolytic activity of NS3pro-NS2B correlates well with the population of the closed conformation. Our results suggest that the closed-open conformational equilibrium can be used by both nature and man to control the replication of dengue virus.Statement of SignificanceThe dengue virus protease is an attractive target for drug development against dengue fever as it is essential for virus replication. However, its structure-based drug development has been unsuccessful due to the shallow substrate-binding pocket. The study presented here demonstrates for the first time that the protease activity can be reduced dramatically by shifting the closed-open conformational equilibrium of the protease in complex with its cofactor from the majority of a closed conformation to the majority of an open conformation. Moreover, our work clarifies the structure of the open conformation which has been elusive for a long time. Our results also suggest an alternative method for designing protease inhibitors based on the closed-open conformational equilibrium.
Rapid generation of potent antibodies by autonomous hypermutation in yeast
Authors: Wellner Alon , McMahon Conor , Gilman Morgan S. A. , Clements Jonathan R. , Clark Sarah , Nguyen Kianna M. , Ho Ming H. , Shin Jung-Eun , Feldman Jared , Hauser Blake M. , Caradonna Timothy M. , Wingler Laura M. , Schmidt Aaron G. , Marks Debora S. , Abraham Jonathan , Kruse Andrew C. , Liu Chang C. 
Published: November 2020

AbstractThe predominant approach for antibody generation remains animal immunization, which can yield exceptionally selective and potent antibody clones owing to the powerful evolutionary process of somatic hypermutation. However, animal immunization is inherently slow, has poor compatibility with certain antigens (e.g., integral membrane proteins), and suffers from self-tolerance and immunodominance, which limit the functional spectrum of antibodies that can be obtained. Here, we describeAutonomousHypermutation yEast surfAceDisplay (AHEAD), a synthetic recombinant antibody generation technology that imitates somatic hypermutation inside engineered yeast. In AHEAD, antibody fragments are encoded on an error-prone orthogonal DNA replication system, resulting inSaccharomyces cerevisiaepopulations that continuously mutate surface-displayed antibody repertoires. Simple cycles of yeast culturing and enrichment for antigen binding drive the evolution of high-affinity antibody clones in a readily parallelizable process that takes as little as 2 weeks. We applied AHEAD to generate nanobodies against the SARS-CoV-2 S glycoprotein, a GPCR, and other targets. The SARS-CoV-2 nanobodies, concurrently evolved from an open-source naïve nanobody library in 8 independent experiments, reached subnanomolar affinities through the sequential fixation of multiple mutations over 3-8 AHEAD cycles that saw ∼580-fold and ∼925-fold improvements in binding affinities and pseudovirus neutralization potencies, respectively. These experiments highlight the defining speed, parallelizability, and effectiveness of AHEAD and provide a template for streamlined antibody generation at large with salient utility in rapid response to current and future viral outbreaks.
Straight eye for the queer ad: attitudes, skepticism, inferences of manipulative intent and willingness to buy
Authors: Cheah Isaac , Teah Min , Lee Sean , Davies Zachary 
Published: November 2020

PurposeThis study aims to provide a conceptual framework to investigate the effects of consumer attitudes toward brands and attitudes toward a series of fashion oriented print advertisements with and without homosexual themes, on consumer willingness to buy from brands. The influence of consumer skepticism and inferences of manipulative intent (IMI) as moderators between these variables is also investigated. This study also closes various research gaps identified within the literature.Design/methodology/approachA self-administered survey instrument was designed using established scales to collect data through an online questionnaire. Fashion advertisements namely one advertisement representing homosexual content and one heterosexual advertisement were used in the study within subjects (e.g. male and female) design. Statistical techniques, specifically factor analysis, regressions and multiple regressions are used to analyze the data.FindingsThe findings indicate significant and positive relationships between attitude toward the brand and advertisement as well as willingness to buy for both males and females. The moderation analyses noted that consumer skepticism enhanced the relationship between attitude toward the brand and attitude toward the advertisement, but weakened the relationship between attitude toward the advertisement and willingness to buy, only for the female cohort. Similarly, a weakening effect of IMI was noted on the relationship between attitude toward the advertisement and willingness to buy.Research limitations/implicationsThe current study contributes to the literature on homosexual imagery in advertising. In applying the persuasion knowledge model, the current study demonstrates the applicability of the model to homosexual themes in fashion advertising while accounting for the effects of consumer skepticism and IMI.Practical implicationsThe current research highlights the importance of accounting for gender differences when introducing homosexual themes in fashion advertisements. Heterosexual males and females differ in their attitudes toward homosexual themes in fashion advertising, as well as how skeptical they are with regards to the motives of the advertiser. While a great deal of acceptance is already present in today's society, these differences still need to be accounted for in future fashion advertising campaigns.Originality/valueThe present study represents an examination of consumer responses to a series of fashion advertisements in Australia and provides useful implications to marketers of fashion products. The study further contributes to the literature on consumer skepticism and IMI with regards to cause-related advertising.
Consumers' willingness to adopt genetically modified foods
Authors: Fozouni Ardekani Zahra , Akbari Morteza , Pino Giovanni , Zúñiga Miguel Ángel , Azadi Hossein 
Published: November 2020

PurposeThis study investigates consumers' willingness to adopt genetically modified foods (GM) and the role of innovation and behavioral determinants.Design/methodology/approachA new integrated model that expands the Health Belief Model (HBM) into the Innovation Diffusion Theory (IDT) was developed and examined. A total of 241 consumers were selected from the capital of Iran, Tehran, through a multistage random sampling. The data were analyzed using SEM-PLS modeling.FindingsThe extended HBM model was able to predict about 84% of the variance changes in consumers' willingness to adopt GM foods. The effects of net benefit and perceived compatibility on the willingness were also significant. In addition, the mediating effect of compatibility on the relationship between net benefit/self-efficacy and willingness to adopt GM foods was also significant.Originality/valueThis study contributes to the literature by developing the HBM into the IDT to assess consumers' willingness to adopt GM foods.
The model of evidence-based benchmarking: a more robust approach to benchmarking
Authors: Kulikowski Konrad 
Published: November 2020

PurposeThis conceptual paper aims to propose the evidence-based benchmarking model that bridges standard benchmarking practices with evidence-based management (EBMgt) principles and lessens tensions between two opposite views of benchmarking as a useful management tool vs a management hype and fashion.Design/methodology/approachThis conceptual paper is based on the critical reasoning, analysis and integration of so far largely separated research fields of benchmarking and EBMgt. The author employs a method of conceptual model building to identify connections between standard benchmarking model and EBMgt practices and to explain how a sequence of benchmarking events supplemented by EBMgt principles might lead to more reliable managerial decision-making.FindingsThe author argues that although there are no common benchmarking procedures, it is possible to identify a standard benchmarking model that resonates in most contemporary benchmarking procedures and consists of four main phases: plan, do, check and act (PDCA). The author integrated this standard model with EBMgt practices of searching for evidence in four sources of information and a six-step critical thinking process to put forward the model of evidence-based benchmarking.Originality/valueThe proposed model is a novel, comprehensive framework that puts together so far incompatible practices of benchmarking and EBMgt. The model clears up existing conceptual confusions around “casual” benchmarking and advances contemporary understanding of benchmarking practices. The model of evidence-based benchmarking might act as a practical, heuristic tool improving the quality of the managerial decisions and thus positively influencing the bottom line of business performance.
Multidimensional research on agrometeorological disasters based on grey BP neural network
Authors: Li Bingjun , Zhang Shuhua 
Published: November 2020

PurposeThe purpose of this study to provide a reference basis for effectively managing the risk of agrometeorological disasters in Henan Province, speeding up the establishment of a scientific and reasonable system of agrometeorological disasters prevention and reduction and guaranteeing grain security.Design/methodology/approachFirstly, according to the statistical data of areas covered by natural disaster, areas affected by natural disaster, sown area of grain crops and output of grain crops from 1979 to 2018 in Henan Province, China. We have constructed an agrometeorological disaster risk assessment system for Henan province, China, which is composed of indicators such as rate covered by natural disaster, rate affected by natural disaster, disaster coefficient of variation and disaster vulnerability. The variation characteristics of agrometeorological disasters in Henan Province and their effects on agricultural production are analyzed. Secondly, the grey relational analysis method is used to analyze the relation degree between the main agrometeorological disaster factors and the output of grain crops of Henan Province. Based on the grey BP neural network, the rate covered by various natural disaster and the rate affected by various natural disaster are simulated and predicted.FindingsThe results show that: (1) the freeze injury in the study period has a greater contingency, the intensity of the disaster is also greater, followed by floods. Droughts, windstorm and hail are Henan Province normal disasters. (2) According to the degree of disaster vulnerability, the ability to resist agricultural disasters in Henan Province is weak. (3) During the study period, drought and flood are the key agrometeorological disasters affecting the grain output of Henan Province, China.Practical implicationsThe systematic analysis and evaluation of agrometeorological disasters are conducive to the sustainable development of agriculture, and at the same time, it can provide appropriate and effective measures for the assessment and reduction of economic losses and risks.Originality/valueBy calculating and analyzing the rate covered by natural disaster, the rate affected by natural disaster, disaster coefficient of variation and disaster vulnerability of crops in Henan Province of China and using grey BP neural network simulation projections for the rate covered by various natural disaster and the rate affected by various natural disaster, the risk assessment system of agrometeorological disasters in Henan is constructed, which provides a scientific basis for systematic analysis and evaluation of agrometeorological disasters.
Insider action research towards companywide sustainable product innovation: ecodesign transition framework
Authors: Brones Fabien , Zancul Eduardo , Carvalho Marly M. 
Published: November 2020

PurposeThis study discusses the application of Insider Action Research to the systematic integration of an environmental perspective into industrial product innovation processes and projects. Applying Insider Action Research, it aims at a broader integration between top-down and bottom-up and soft and hard perspectives in the intersection of ecodesign and innovation and project management disciplines.Design/methodology/approachThe research design is based on action research and specificities from Insider Action Research to capture the change and transition aspects involving two main action research cycles. The longitudinal five-year research was carried out within a Brazilian cosmetics company. The outcomes of these cycles are analysed including customisation of ecodesign tools and related application, and views of different stakeholders of the challenge for the transition.FindingsThis paper describes an action research application aiming at faster learning loops in the field of sustainable innovation management. As a second contribution, an Ecodesign Transition Framework (ETF) is proposed, combining both technical and soft sides. The proposed framework is structured in three levels (strategic, tactical and operational), with two complementary perspectives of a mature ecodesign pattern and a transition pathway.Practical implicationsThe action research led to the intended outcomes both on the applied side, with increased diffusion of ecodesign in the company, and on the research side, with the ETF formulation and application. Practitioners interested in sustainable innovation can follow the ETF procedures, challenges faced, lessons learnt and conclusions.Originality/valueThe Insider Action Research addressed the literature gap to better relate the recommendations in the field to business reality. The resulting ETF brings a novel perspective for integrating environmental considerations in the product innovation process of a company. It organises the soft issues to be considered for the necessary transition towards such integration, consolidating and advancing previous theoretical views of ecodesign, with associated new practical implications.
Abandonment of mergers and acquisitions: a review and research agenda
Authors: Kumar Deepak , Sengupta Keya 
Published: November 2020

PurposeThe purpose of this study is to provide a broad understanding of the pre-completion stage and subsequent abandonment of mergers and acquisitions (M&As).Design/methodology/approachA total of 117 peer-reviewed, English language articles published in scholarly journals were considered in the review. The approach includes a descriptive evaluation of the literature, coupled with content analysis. The paper uses both positivist and constructivist approaches to qualitative research. The analysis is conducted with the help of R programming and Gephi visualization software. The authors organize the work around the event of outcome/closure of deal proposal.FindingsIt is found that earlier studies sampled on domestic M&As in developed economies (DEs). However, the interest of scholars has increased in cross-border deals and emerging economies (EEs) in the last decade. Various factors interact and facilitate the completion/abandonment of good and bad deals. The authors find that complex non-linear relationships exist, and there is a need for studies with other classification techniques focusing on predictive accuracy.Research limitations/implicationsThe literature review is limited to articles available to the researcher using search terms related to M&A completion/termination. The databases accessed were: ProQuest, Scopus and Web of Science. However, backward snowballing was performed to avoid the omission of relevant articles.Originality/valueThe findings and subsequent discussions familiarize researchers and practitioners with an overview of research undertaken in the field of M&A abandonment. The authors find voids within the literature and suggest future research agendas.
Information technology and marketing: an important partnership for decades
Authors: Graesch Jan Philipp , Hensel-Börner Susanne , Henseler Jörg 
Published: November 2020

PurposeThe enabling technologies that emerged from information technology (IT) have had a considerable influence upon the development of marketing tools, and marketing has become digitalized by adopting these technologies over time. The purpose of this paper is to demonstrate the impacts of these enabling technologies on marketing tools in the past and present and to demonstrate their potential future. Furthermore, it provides guidance about the digital transformation occurring in marketing and the need to align of marketing and IT.Design/methodology/approachThis study demonstrates the impact of enabling technologies on the subsequent marketing tools developed through a content analysis of information systems and marketing conference proceedings. It offers a fresh look at marketing's digital transformation over the last 40 years. Moreover, it initially applies the findings to a general digital transformation model from another field to verify its presence in marketing.FindingsThis paper identifies four eras within the digital marketing evolution and reveals insights into a potential fifth era. This chronological structure verifies the impact of IT on marketing tools and accordingly the digital transformation within marketing. IT has made digital marketing tools possible in all four digital transformation levers: automation, customer interaction, connectivity and data.Practical implicationsThe sequencing of enabling technologies and subsequent marketing tools demonstrates the need to align marketing and IT to design new marketing tools that can be applied to customer interactions and be used to foster marketing control.Originality/valueThis study is the first to apply the digital transformation levers, namely, automation, customer interaction, connectivity and data, to the marketing discipline and contribute new insights by demonstrating the chronological development of digital transformation in marketing.
Leverage and performance: do size and crisis matter?
Authors: Danso Albert , Lartey Theophilus A. , Gyimah Daniel , Adu-Ameyaw Emmanuel 
Published: November 2020

PurposeThis paper contributes to the capital structure literature by examining the impact of financial leverage on firm performance and also the extent to which firm size and crisis matter in the leverage -performance relationship.Design/methodology/approachUsing data from 2403 Indian firms during the period 1995–2014, generating a total of 19,544 firm-year observations, panel econometric methods are employed to test the leverage-performance relationship.FindingsDrawing insights from agency theory and using Tobin's Q (TQ) as our main measure of performance, the authors uncover that financial leverage is negatively and significantly related to firm performance. The authors also observe that the impact of financial leverage on firm performance is lower for smaller firms than larger ones. Finally, the authors show that the 2007/08 financial crisis had no significant impact on the relationship between financial leverage and firm performance.Originality/valueThe paper provides fresh evidence on the impact of leverage on performance, particularly from the Indian context. This study is also among the first studies to examine the role of firm size and financial crisis in the leverage-performance relationship.