bluuebunny/crossref_metadata_2025_split huggingface dataset:
The geometric determinants of programmed antibody migration and binding on multi-antigen substrates
Authors: Hoffecker Ian T. , Shaw Alan , Sorokina Viktoria , Smyrlaki Ioanna , Högberg Björn 
Published: October 2020

AbstractViruses and bacteria commonly exhibit spatial repetition of surface molecules that directly interface with the host immune system. However the complex interaction of patterned surfaces with multivalent immune molecules such as immunoglobulins and B-cell receptors is poorly understood, and standard characterization typically emphasizes the monovalent affinity. We developed a mechanistic model of multivalent antibody-antigen interactions as well as a pipeline for constructing such models from a minimal dataset of patterned surface plasmon resonance experiments in which antigen pattern geometries are precisely defined using DNA origami nanostructures. We modeled the change in binding enhancement due to multivalence and spatial tolerance,i.e. the strain-dependent interconversion of bound antibodies from monovalently bound to bivalently bound states at varying antigen separation distances. The parameterized model enables mechanisticpost hoccharacterization of binding behavior in patterned surface plasmon resonance experiments as well asde novosimulation of transient dynamics and equilibrium properties of arbitrary pattern geometries. Simulation on lattices shows that antigen spacing is a spatial control parameter that can be tuned to determine antibody residence time and migration speed. We found that gradients in antigen spacing are predicted to drive persistent, directed antibody migration toward favorable spacing. These results indicate that antigen pattern geometry can influence antibody interactions, a phenomenon that could be significant during the coevolution of pathogens and immunity in processes like pathogen neutralization or affinity maturation.
Defocus-dependent Thon-ring fading
Authors: Glaeser Robert M. , Hagen Wim J.H. , Han Bong-Gyoon , Henderson Richard , McMullan Greg , Russo Christopher J. 
Published: October 2020

ABSTRACTThe brightness of modern Schottky field-emission guns can produce electron beams that have very high spatial coherence, especially for the weak-illumination conditions that are used for single-particle electron cryo-microscopy in structural biology. Even so, many users have observed defocus-dependent Thon-ring fading that has led them to restrict their data collection strategy to imaging with relatively small defocus values. In this paper, we reproduce the observation of defocus-dependent Thon-ring fading and produce a quantitative analysis and clear explanation of its causes. We demonstrate that a major cause is the delocalization of high-resolution Fourier components outside the field of view of the camera. We also show that it is important to make a correction for linear magnification anisotropy, even if it is quite small, before circular averaging of the Thon rings, as is also true before merging data from particles in many orientations. Under the conditions used in this paper, which are typical of those used in single-particle electron cryomicroscopy, fading of the Thon rings due to source coherence is negligible. The principal conclusion is that much higher values of defocus can be used than is currently thought to be possible. This increased understanding should give electron microscopists the confidence to use higher amounts of defocus to allow, for example, better visibility of their particles and Ewald sphere correction.
Deep computational analysis of human cancer and non-cancer tissues details dysregulation of eIF4F components and their interactions in human cancers
Authors: Wu Su , Wagner Gerhard 
Published: October 2020

SUMMARYEukaryotic translation initiation complex (eIF4F) plays roles so diverse in human cancers as to complicate development of an overarching understanding of eIF4F’s functional and regulatory impacts across tumor types. Our analysis of large public data sets yielded several useful findings.EIF4G1frequently gains gene copies and is overexpressed to achieve characteristic stoichiometries withEIF4EandEIF4A1in cancers. Varied expressions amongEIF4Fcomponents distinguish malignant from healthy tissues, regardless of tissue or cancer types.EIF4G1expression in particular correlates with poor prognosis. Tumors dysregulate biological “house-keeping” pathways typically regulated by cap-dependent initiation in healthy tissues, yet strengthen regulation of cancer-specific pathways in cap-independent contexts. In lung adenocarcinoma, altered interactions among eIF4F subunits are mechanistically linked to eIF4G1 phosphorylation. Tumors may select between cap-dependent and -independent mechanisms, through eIF4G1’s adaptable interactions with eIF4F subunits. Collectively, these results are an important advance towards a general model of translation initiation in cancer.
The genomic formation of First American ancestors in East and Northeast Asia
Authors: Ning Chao , Fernandes Daniel , Changmai Piya , Flegontova Olga , Yüncü Eren , Maier Robert , Altınışık N. Ezgi , Kassian Alexei S. , Krause Johannes , Lalueza-Fox Carles , Manica Andrea , Potter Ben A. , Robbeets Martine , Sirak Kendra , Siska Veronika , Vajda Edward J. , Vyazov Leonid A. , Wang Ke , Wang Lixin , Wu Xiyan , Xiao Xiaoming , Zhang Fan , Reich David , Schiffels Stephan , Pinhasi Ron , Cui Yinqiu , Flegontov Pavel 
Published: October 2020

AbstractUpward Sun River 1, an individual from a unique burial of the Denali tradition in Alaska (11500 calBP), is considered a type representative of Ancient Beringians who split from other First Americans 22000–18000 calBP in Beringia. Using a new admixture graph model-comparison approach resistant to overfitting, we show that Ancient Beringians do not form the deepest American lineage, but instead harbor ancestry from a lineage more closely related to northern North Americans than to southern North Americans. Ancient Beringians also harbor substantial admixture from a lineage that did not contribute to other Native Americans: Amur River Basin populations represented by a newly reported site in northeastern China. Relying on these results, we propose a new model for the genomic formation of First American ancestors in Asia.One Sentence SummaryAncient Beringians do not form the deepest American lineage, but harbor admixture from Amur River Basin populations.
Brain-Specific Inhibition of mTORC1 by a Dual Drug Strategy: A Novel Approach for the Treatment of Alcohol Use Disorder
Authors: Ehinger Yann , Zhang Ziyang , Phamluong Khanhky , Soneja Drishti , Shokat Kevan M. , Ron Dorit 
Published: October 2020

AbstractAlcohol Use Disorder (AUD) is a devastating psychiatric disorder affecting a large portion of the population. Unfortunately, efficacious medications to treat the disease are limited and thus AUD represents an area of unmet medical need. mTORC1 plays a crucial role in neuroadaptations underlying alcohol use. mTORC1 also contributes to alcohol craving, habit, and relapse. Thus, mTORC1 inhibitors are promising therapeutic agents to treat AUD. However, chronic inhibition of mTORC1 in the periphery produces undesirable side effects in humans, which limit their potential clinical use for the treatment of AUD. To overcome these limitations, we utilized a binary drug strategy in which mice were co-administered the mTORC1 inhibitor RapaLink-1 together with a novel small molecule (RapaBlock) to protect mTORC1 activity in the periphery. We show that the dual administration of RapaLink-1 with RapaBlock, abolishes RapaLink-1-dependent mTORC1 inhibition in the liver and blocks adverse side effects detected in humans including body weight loss, glucose intolerance and liver toxicity. Importantly, we show that co-administration of RapaLink-1 and RapaBlock inhibits alcohol-dependent mTORC1 activation in the Nucleus Accumbens and robustly moderates the level of alcohol use. Our data present a novel approach that could be used to treat individuals suffering from AUD.
The causes and challenges of low interest rates: insights from basic principles and recent literature
Authors: Wu Youchang 
Published: October 2020

PurposeWhat causes the downward trend of real interest rates in major developed economies since the 1980s? What are the challenges of the near-zero interest and inflation rates for monetary policy? What can the policymakers learn from the latest developments in the monetary and interest rate theory? This paper aims to answer these questions by reviewing both basic principles of interest rate determination and recent academic and policy debates.Design/methodology/approachThe paper critically reviews the explanations for the downward trend of real interest rates in recent decades and monetary policy options in a near-zero interest rate environment.FindingsThe decline of real interest rates is likely an outcome of multiple technological, social and economic factors including diminished productivity growth, changing demographics, elevated tail-risk concerns, time-varying convenience yields of safe assets, increased global demand for safe assets, rising wealth and income inequality, falling relative price of capital, accommodative monetary policies, and changes in industry structure that alter the investment and saving behaviors of the corporate sector. The near-zero interest rate limits the space of central banks' response to economic crises. It also challenges some conventional wisdoms of monetary theory and sparks radically new ideas about monetary policy.Originality/valueThis survey differs from the existing work by taking a broader view of both economics and finance literature. It critically assesses the economic forces driving the global decline of real interest rates through the lens of basic principles and empirical evidence and discusses the merits and limitations of each proposed explanation. The study emphasizes the importance of a better understanding of economic forces driving diverging trends of corporate investment and saving behaviors. It also discusses the implications of the neo-Fisherism and the fiscal theory of price level for monetary policy in a low interest rate environment.
Let’s not just “talk” about it: reflections on women’s career development in hospitality
Authors: Gebbels Maria , Gao Xiongbin , Cai Wenjie 
Published: October 2020

Purpose
This paper aims to provide an action-orientated reflection for promoting gender equality in hospitality, based on Bradley’s (2013) approach that considers the operation of gender in the “production” and “reproduction” spheres of social life. To that end, it reflects on women’s career development in hospitality based on the Western perspective.

Design/methodology/approach
A two-stage thematic analysis of a public research seminar on gender issues in tourism and hospitality were used to explore issues of women’s career development within the intertwining spheres of “production” and “reproduction”.

Findings
Three themes, namely, culture of an open dialogue, bringing men into the equation and educating the future workforce, emerged from data to propose new insights on “what can be done” about gender equality in tourism and hospitality, including practical suggestions for transformations of gender relations in organisations.

Research limitations/implications
This paper contributes new knowledge on women’s career development in the hospitality industry by proposing recommendations to address gender gaps including fostering a culture of an open dialogue based on an inclusive listening environment, recommending changes to organisational policies and culture and integrating the subject of gender into tourism and hospitality curriculum.

Originality/value
By proposing a sociological perspective of gender in hospitality employment informed by Bradley (2013), this study challenges the traditional masculinity and the long-standing gender labour division through education, organisational and daily practices thus tackling fundamental gender issues.
The relevance of financial and economic informational environment: evidence from South Asian markets
Authors: Arshad Muhammad Usman , Khan Fahad Najeeb , Ishfaq Muhammad , Shabbir Muhammad Nadir , Shah Syed Mehmood Raza 
Published: October 2020

PurposeThis study aims to explore the firm's specific, opacity and economy-specific variables to explain the variation in South Asian market returns and indicate that how the difference in adoption of accounting standards refers to the effect of the movement in stock returns.Design/methodology/approachFollowing the scope of the study, factor analysis, fixed effect, Driscoll and Kraay standard errors (DKSE) and Panel Corrected standard error (PCSE) models have been inducted to determine the influence of firm-specific, opacity and economy-specific variables on stock returns. The sample of study comprises 1,885 firms from five countries located in the South Asia region with the period 2005–2018. To ensure the reliability of data, firm-specific data have been collected from DataStream International, while an international country risk guide was used to compile the data for economy-specific variables.FindingsThis study concluded that firm-specific variables showed a consistent and significant association with stock return except for beta, accrual and momentum while earning aggressiveness was the only factor in opacity measure to capture the variation in stock return. The implementation of international accounting standards seemed to be significant and proves to be helpful to enhance the quality of accounting information.Research limitations/implicationsThe limitations of this study comprised the estimation error by avoiding the firm's observations with negative equity in case of earning opacity and majority (more than 50%) of the observation belongs to a single market as India out of final sample which leads to having biasedness in findings.Practical implicationsThis study helps the investors to consider the firms with smaller market capitalization and lower book to market ratio and avoid the momentum strategy under firm specific factors. Moreover, earning aggressiveness under opacity domain capture the variation in stock return and must be considered while investing funds.Originality/valueThe influence of adoption of international accounting standards along with firm and economy specific variable in South Asian Equity Markets return was the major contribution. Moreover, the inclusion of DKSE and PCSE models to examine the relevance of the financial and economic informational environment was also considered as a part of major contribution of this study.
Maintenance strategy selection: a combined goal programming approach and BWM-TOPSIS for paper production industry
Authors: Avakh Darestani Soroush , Palizban Tahereh , Imannezhad Rana 
Published: October 2020

PurposeCorrect and well-planned maintenance based on modern global methods directly affects efficiency, quality, direct production costs, reliability and profitability. The selection of an optimal policy for maintenance can be a good solution for industrial units. In fact, by managing constraints such as costs, working hours and human workforce causing sudden equipment failure, production and performance can increase.Design/methodology/approachTherefore, in this research a model was presented to select the best maintenance strategy at Kaghaz Kar Kasra Co of Iran. In this study, it was tried to integrate the two techniques of goal programming and the technique for order of preference by similarity to ideal solution (TOPSIS) to prioritize maintenance strategies. First, all factors affecting maintenance were identified, and based on the Best Worst Method (BWM) the degree of their importance was determined.FindingsAfter the evaluation, only 14 criteria in the 4 dimensions of cost, added value, safety and feasibility were selected. The highest points were given to the criteria of equipment cost and depreciation, equipment and personnel performance, equipment installation time and technical feasibility, respectively. In the next stage, using the TOPSIS method the item of maintenance strategy was ranked, and the 3 strategies of preventive maintenance (PM), predictive maintenance (PDM) and corrective maintenance (CM) were chosen. Modeling was performed utilizing a goal programming approach to select the optimal maintenance strategy for 13 devices. All the technical specifications, cost limits and the device time were extracted. After the model was finished and solved the best item for each device was specified.Originality/value1. Developing a goal programming model and decision-making dashboard. 2. Identifying the criteria and factors affecting the selection of the maintenance strategy for paper production Industry
Strategy communication and transition dynamics amongst managers: a public sector organization perspective
Authors: Obembe Demola , Al Mansour Jarrah , Kolade Oluwaseun 
Published: October 2020

PurposeThe purpose of this paper is to build on the research-supported view that interactions between top and middle management enhances effective implementation of organizational strategies by exploring the role of internal actors in driving organizational strategy at the intersection between strategy formulation and strategy implementation.Design/methodology/approachAdopting a social practice perspective, we undertook semi-structured interviews of 27 top and middle level managers drawn from a single case organization. Data collected were analysed using thematic analysis.FindingsDifferences in managerial perception of strategy has significant impact on implementation of strategic decisions as well as creating tensions in recursive communication practices between internal social actors. Furthermore, individual perceptions cannot only limit the extent of strategy awareness amongst key actors, the manifestations through social interaction between top and middle managers is a critical determinant of effective communication and realization of organizational strategy.Originality/valueThe research contributes to the strategy process and practice literature by exploring the dynamic interactions taking place at the intersections of strategy formulation-implementation phases of organizational strategy. It particularly highlights practical issues in top and middle manager interactions and implications for successful strategy implementation.
Why property market forecasts fail
Authors: Mooya Manya Mainza 
Published: October 2020

PurposeThe paper addresses the puzzling phenomenon of the ubiquity of economic forecasting, of which property market forecasting is but one instance, on the one hand, and the unreliability of such forecasts, on the other hand. The paper explains why property market forecasts fail, in a non-trivial sense, and why this problem is irredeemable.Design/methodology/approachThis was a conceptual paper and was based on original thought and literature review.FindingsThis paper attributes the failure of property market forecasts to the inappropriate application of the methodology of the natural sciences to the social sciences by mainstream economics. Specifically, the problem is located in the positivist philosophy and the assumptions of methodological individualism and rational choice theory underlying neoclassical economic theory.Originality/valueThe paper makes an original contribution by clearly showing why and how the methodology of the natural sciences, especially physics, has been applied to economics and property market analysis, why this is inappropriate and why it leads to failure. The paper introduces a debate that has hitherto been mostly confined to philosophy and mainstream economics into the property or real estate discipline and in a manner that is accessible to a non-philosophy audience.
An empirical examination of the relationship between benchmarking, innovation culture and organisational performance using structural equation modelling
Authors: Alosani Mohammed Saleh , Al-Dhaafri Hassan Saleh 
Published: October 2020

PurposePolice agencies are under pressure to improve their performance and provide outstanding services for the community. In response, academics and practitioners have called to adopt effective methods that help these agencies to achieve their goals. Studies reported that benchmarking has a role to improve organisational performance. However, poor evidence of using benchmarking within police agencies and very few studies examine the relationship between it and police performance. Motivated by this gap, this study aims to explore and examine this relationship under the mediating role of innovation culture.Design/methodology/approachA quantitative methodology was utilised in this study. Data used to examine the hypotheses were obtained from the departments and stations of the Dubai Police Force (DPF), and the population comprised head section officers. A total of 338 questionnaires were distributed to respondents, 252 of which were returned. The hypothesised relationships were tested with the data collected by SPSS and SmartPLS statistical software.FindingsFindings clearly show that benchmarking is directly and indirectly associated with the organisational performance of the DPF through innovation culture. Results support the notion that innovation culture facilitates the implementation of proper benchmarking projects in the DPF, which positively affects different aspects of its performance.Research limitations/implicationsThis study includes several limitations. Specifically, the generalisability of the findings should be considered. The analysis applies only to the DPF in the UAE. Thus, investigating and analysing variables in different police agencies in the UAE or internationally would be valuable.Practical implicationsSeveral recommendations are provided in relation to the obtained results to assist managers and decision makers in the DPF and other police agencies. This study includes suggestions for improving police performance by establishing an innovation culture and adopting benchmarking practices.Originality/valueAlthough several contributions indicated that benchmarking and innovation culture is a key determinant of success, the literature lacks empirical studies investigating this link in the police field. This study is the only one to date that examined this relationship in police services. Accordingly, this study seeks to bridge this gap and delivers empirical evidence and theoretical insight to better understand this relationship.