bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cofilin is required for polarization of tension in stress fiber networks during migration
Authors: Lee Stacey , Kumar Sanjay 
Published: May 2020

ABSTRACT
Cell migration is associated with the establishment of defined leading and trailing edges, which in turn requires polarization of contractile forces. While the actomyosin stress fiber (SF) network plays a critical role in enforcing this polarity, precisely how this asymmetry is established remains unclear. Here, we provide evidence for a model in which the actin-severing protein cofilin (specifically cofilin-1) participates in symmetry breakage by removing low-tension actomyosin filaments during transverse arc assembly. Cofilin knockdown (KD) produces a non-polarized SF architecture that cannot be rescued with chemokines or asymmetric matrix patterns. Whereas cofilin KD increases whole-cell prestress, it decreases prestress within single SFs, implying an accumulation of low-tension SFs. This notion is supported by time-lapse imaging, which reveals weakly contractile and incompletely fused transverse arcs. Confocal and super-resolution imaging further associate this failed fusion with the presence of crosslinker-rich, tropomyosin-devoid nodes at the junctions of multiple transverse arc fragments and dorsal SFs. These results support a model in which cofilin facilitates the formation of high-tension transverse arcs, thereby promoting mechanical asymmetry.
A subset of flavaglines inhibits KRAS nanoclustering and activation
Authors: Yurugi Hajime , Zhuang Yinyin , Siddiqui Farid A. , Liang Hong , Rosigkeit Sebastian , Zeng Yongpeng , Abou-Hamdan Hussein , Bockamp Ernesto , Zhou Yong , Abankwa Daniel , Zhao Wenting , Désaubry Laurent , Rajalingam Krishnaraj 
Published: May 2020

ABSTRACT
The RAS oncogenes are frequently mutated in human cancers and among the three isoforms (KRAS, HRAS and NRAS), KRAS is the most frequently mutated oncogene. Here, we demonstrate that a subset of flavaglines, a class of natural anti-tumour drugs and chemical ligands of prohibitins, inhibit RAS GTP loading and oncogene activation in cells at nanomolar concentrations. Treatment with rocaglamide, the first discovered flavagline, inhibited the nanoclustering of KRAS, but not HRAS and NRAS, at specific phospholipid-enriched plasma membrane domains. We further demonstrate that plasma membrane-associated prohibitins directly interact with KRAS, phosphatidylserine and phosphatidic acid, and these interactions are disrupted by rocaglamide but not by the structurally related flavagline FL1. Depletion of prohibitin-1 phenocopied the rocaglamide-mediated effects on KRAS activation and stability. We also demonstrate that flavaglines inhibit the oncogenic growth of KRAS-mutated cells and that treatment with rocaglamide reduces non-small-cell lung carcinoma (NSCLC) tumour nodules in autochthonous KRAS-driven mouse models without severe side effects. Our data suggest that it will be promising to further develop flavagline derivatives as specific KRAS inhibitors for clinical applications.
Predição de casos e óbitos de COVID-19 em Mato Grosso e no Brasil
Authors: Espinosa Mariano Martinez , Oliveira Elaine Cristina de , Melo Juliano Silva , Damaceno Roney Dias , Terças-Trettel Ana Cláudia Pereira 
Published: May 2020

Objetivos: prever a tendência epidemiológica de casos e óbitos do COVID-19 no Brasil e, especificamente, em Mato Grosso, por meio do modelo estatístico duplo exponencial. Métodos: para a realização deste trabalho, foram utilizados dados de casos e óbitos do COVID-19 fornecidos pelo Ministério da Saúde do Brasil e Secretaria de Estado de Saúde de Mato Grosso, e, para realizar as previsões com esses dados, foi utilizada a técnica estatística de séries temporais, considerando o modelo exponencial duplo, e para o processamento dos dados, foi utilizado o programa MINITAB V 17. Resultados: os resultados mostram que os valores ajustados pelo modelo exponencial duplo transformado dos casos e óbitos estão muito próximos dos valores observados de COVID-19 noBrasil e, principalmente, em Mato Grosso, no período considerado, indicando que esse modelo é adequado para os dados em estudo, o qual foi verificado, prevendo alguns valores com seus respectivos intervalos de confiança de 95%. Conclusões: a possibilidade de se estimar, pautado em análises estatísticas, o número de casos e óbitos de COVID-19 que ocorrerá no Brasil e no estado de Mato Grosso poderá instrumentalizar os gestores para o planejamento deações estratégicas de prevenção, monitoramento e controle da pandemia.
Recent advances in understanding the neonatal microbiome
Authors: Dalby Matthew J. , Hall Lindsay J. 
Published: May 2020

The neonatal developmental window represents a key time for establishment of the gut microbiota. First contact with these microbes within the infant gastrointestinal tract signifies the start of a critical mutualistic relationship, which is central for short- and longer-term health. Recent research has provided insights into the origin of these microbial pioneers, how they are maintained within the gut environment, and how factors such as antibiotics or preterm birth may disrupt the succession of beneficial microbes. The acquisition, colonisation, and maintenance of the early life microbiota, and subsequent interactions with the host is a rapidly developing research area. In this review we explore some of these key topics which have been illuminated by recent research, and we highlight some of the important unresolved questions which currently limit our overall understanding of the neonatal gut microbiome.
The Benefits and Risks of Iron interventionS in Children (BRISC) trial: Statistical analysis plan
Authors: Braat Sabine , Larson Leila , Simpson Julie A. , Hasan Mohammed Imrul , Hamadani Jena Derakhshani , Hossain Sheikh Jamal , Shiraji Shamima , Bhuiyan Mohammad Saiful Alam , Biggs Beverley-Ann , Pasricha Sant-Rayn 
Published: May 2020

Background: The Benefits and Risks of Iron interventionS in Children (BRISC) trial will evaluate the impact of universal supplementation with iron supplements or iron-containing multiple micronutrient powders (MNPs) compared with placebo given for 3 months on child development, growth, morbidity, laboratory indices of anaemia, iron deficiency, and inflammation at end of intervention and after a further 9 months post intervention in children aged 8 months living in rural Bangladesh. This paper describes the statistical analysis plan. Methods: BRISC is a multi-site, three-arm, double-dummy blinded, parallel group, randomised control superiority trial in 3300 children. The statistical analysis plan was developed by the trial statistician in consultation with the trial steering committee and trial management committee based on the protocol, data collection forms, and study outcomes available in the blinded study database. Conclusion: This detailed statistical analysis plan published prior to unblinding the allocated treatments will support the statistical analyses and reporting of the BRISC trial to be undertaken after unblinding. It allows for transparency as well as reproducibility of statistical analyses and reporting. Registration: Australian New Zealand Clinical Trials Registry ACTRN12617000660381 (registered on 8 May 2017); World Health Organization Universal Trial Number U1111-1196-1125.
Case Report: Peptic ulcer disease following short-term use of nonsteroidal anti-inflammatory drugs in a 3-year-old child
Authors: Ciubotaru Alin Dumitru , Leferman Carmen-Ecaterina 
Published: May 2020

Background: Peptic ulcer disease (PUD) affects 1-2 per 1000 people annually in the USA, the UK and Europe, and occurs less frequently in children than in adults. PUD in children occurs mainly during the second decade of development. Among risk factors, nonsteroidal anti-inflammatory drugs (NSAIDs), commonly used to manage acute febrile illness or pain in healthy children, is rarely reported to lead to PUD and upper gastrointestinal bleeding. Case presentation: We present a rare case of upper gastrointestinal bleeding following a low dose ibuprofen treatment in a 3-year-old female. The patient with a family history of peptic ulcer was admitted for fever, coffee-ground vomiting and abdominal pain. The clinical examination revealed an altered general health status with a distended and mildly tender abdomen moving normally with respiration as well as normal stool. The initial laboratory test indicated anemia with reticulocytosis. During the first hours of hospitalization, the patient had a second episode of coffee-ground vomiting. An upper digestive endoscopy with biopsy was performed in the following six hours revealing a non-bleeding gastric ulcer at 2 cm from pylorus. Helicobacter pylori testing was negative. The patient was treated with a proton pump inhibitor (esomeprazole 10 mg/day) for 2 months. There were no further gastrointestinal symptoms and hemoglobin values returned to normal, indicating resolution of her gastrointestinal bleeding. Conclusion: The short-term utilization of NSAIDs in the appropriate dosage can lead to PUD, and considering the risk factors before administration can lead to an appropriate management.
Rethinking Crowdfunding Platform Design: Mechanisms to Deter Misconduct and Improve Efficiency
Authors: Belavina Elena , Marinesi Simone , Tsoukalas Gerry 
Published: May 2020

Lacking credible rule-enforcement mechanisms to punish misconduct, existing reward-based crowdfunding platforms can leave backers exposed to two risks: entrepreneurs may run away with backers’ money (funds misappropriation), and product specifications may be misrepresented (performance opacity). We show that each of these risks can materially impact crowdfunding efficiency, and, when jointly present, they interact with each other in ways that can dampen or, more worryingly, amplify their individual adverse effects. To mitigate these risks, we propose two mechanisms based on deferred payments. The first involves stopping the campaign once the funding goal is reached and servicing any unmet demand in the aftermarket. The second involves escrowing any funds raised in excess of the goal, as insurance for backers. We show that early stopping dominates escrow and boosts platform revenues. Pairing these deferred payment designs with (costly) performance verification contingencies can bring additional gains, but doing so can flip their relative performance, with escrow coming out on top. Overall, by accounting for different timing (pre- versus post-campaign) and enforcement rules (mandatory versus optional) of the verification contingencies, we analyze a total of 10 different designs and show that two of them dominate: the early stopping design and the escrow design with mandatory ex-post verification. We conclude by providing recommendations for which design works best under different conditions and exploring the potential of crowdsourced performance checks. This paper was accepted by Terry Taylor, operations management.
Everything in Moderation: Foundations and Applications of the Satiation Model
Authors: Baucells Manel , Zhao Lin 
Published: May 2020

Models in which current utility depends solely on current consumption (a.k.a. time-separable preferences) are widely acknowledged to be unrealistic, especially when attempting to describe preferences over consumption rates. Alternatively, one may stipulate that instant utility also depends on a state, for example, some stock of past consumption. Escaping the gravitational pull of time separability, however, is difficult because (1) the behavioral axioms that characterize the state and the instant utility are not known, (2) how to elicit the preference parameters—most notably the initial level of the state and the decay rate—is not known, and (3) managerial applications where state-dependent preferences produce interesting insights and solutions are scarce. This paper makes advances on these three fronts by proposing a novel set of axioms that characterize the satiation model, a proof of concept on how to elicit all preference parameters using consumption rates, and a mixed-integer linear formulation to solve the optimal design of experiential services under satiation. Our preferences introduce a de-satiation motive, absent in separable preferences, and we explore how to optimally manage this motive. This paper was accepted by David Simchi-Levi, decision analysis.
Tacit Collusion and Voluntary Disclosure: Theory and Evidence from the U.S. Automotive Industry
Authors: Bertomeu Jeremy , Evans John Harry , Feng Mei , Tseng Ayung 
Published: May 2020

We develop a model of voluntary disclosure and production decisions and use it to establish that firms will tacitly collude by disclosing when current market demand is low and when the decision horizon is long. Low demand helps sustain tacit collusion, because deviation from tacit collusion yields only a limited increase in profit when demand is low. Similarly, longer decision horizons give firms incentive to receive the benefits of collusion over a longer period. Using monthly production forecasts issued by the Big Three U.S. automobile manufacturers, we show that the frequency, horizon, and accuracy of the production forecasts increase when demand decreases and when the firms focus more on long-term profit. Collectively, the evidence suggests that firms use voluntary disclosures to tacitly collude. This paper was accepted by Brian Bushee, accounting.
Maximizing Intervention Effectiveness
Authors: Gupta Vishal , Han Brian Rongqing , Kim Song-Hee , Paek Hyung 
Published: May 2020

Frequently, policy makers seek to roll out an intervention previously proven effective in a research study, perhaps subject to resource constraints. However, because different subpopulations may respond differently to the same treatment, there is no a priori guarantee that the intervention will be as effective in the targeted population as it was in the study. How then should policy makers target individuals to maximize intervention effectiveness? We propose a novel robust optimization approach that leverages evidence typically available in a published study. Our model can be easily optimized in minutes for realistic instances with off-the-shelf software and is flexible enough to accommodate a variety of resource and fairness constraints. We compare our approach with current practice by proving performance guarantees for both approaches, which emphasize their structural differences. We also prove an intuitive interpretation of our model in terms of regularization, penalizing differences in the demographic distribution between targeted individuals and the study population. Although the precise penalty depends on the choice of uncertainty set, we show that for special cases we can recover classical penalties from the covariate matching literature on causal inference. Finally, using real data from a large teaching hospital, we compare our approach to common practice in the particular context of reducing emergency department utilization by Medicaid patients through case management. We find that our approach can offer significant benefits over common practice, particularly when the heterogeneity in patient response to the treatment is large. This paper was accepted by Chung-Piaw Teo, optimization.
Climate Change, Consumption and Intergenerational Justice
Authors: Diprose Kristina , Valentine Gill , Vanderbeck Robert , Liu Chen , McQuaid Katie 
Published: May 2020

This book examines lived experiences and perceptions of climate change, changing consumption practices, and intra- and intergenerational justice with urban residents in China, Uganda, and the United Kingdom. The book draws on an interdisciplinary research programme called INTERSECTION, which was funded by the Arts and Humanities Research Council from 2014 to 2017. INTERSECTION was an innovative, cross-national programme that employed participatory arts and social research methods with urban residents in three cities: Jinja in Uganda, Nanjing in China, and Sheffield in the United Kingdom. Drawing together a unique dataset from these three cities -- which are very differently positioned in relation to global networks of production and consumption, (de)industrialisation and vulnerability to climate change -- the research demonstrates how people engage selectively with the ‘global storm’ and the ‘intergenerational storm’ of climate change. The research reveals a ‘human sense of climate’ that clouds its framing as an issue of either international and intergenerational justice. Its chapters focus on the global and intergenerational dimensions of climate change, local narratives of climate change, moral geographies of climate change, intergenerational perspectives on sustainable consumption, and imaging alternative futures through community based and creative research practices.
Green Economy Game: A Modular Approach for Sustainable Development Education
Authors: Gatti Junior Wilian , Kim Beaumie , Liu Liping , Lai Xingru 
Published: May 2020

In this paper, we discuss our approach to designing a board game, the Green Economy, that promotes systems thinking. We anchored our game design process on design-by-analogy and rapid prototyping concepts by taking a modular approach to overcome the trade-off between realism and simplicity. The unique feature of the Green Economy enables players to change the rules of the game during the gameplay, which gives them a partial design opportunity. The theme, sustainable development, was chosen to challenge the players’ systems thinking in sustainable development. Systems thinking enables us to understand and face the complex challenges in global and networked social structures. Our design experience demonstrates the benefit of designing dynamic game elements that involve both strategic gameplay and game (re)design through systems thinking.
Waiver in the Russian Criminal Process from the Point of View of Standards of European Court of Human Rights
Authors: CHEBOTAREVA Irina N. 
Published: May 2020

The research deals with the case law of European Court of Human Rights against the Russian Federation on complaints of its citizens regarding violation of Article 6 of European Convention on Human Rights in criminal proceedings when it considers waiver. The author has defined and analyzed both the standards of waiver and the Court’s approaches to the establishment of waiver and the requirements and conditions developed by it.
The author’s analysis of the decisions of European Court of Justice in respect of Russia, in which the court considered the legality of waiver in specific criminal cases when the Russian authorities claimed that the Applicant had waived his right, has led to the conclusion about misunderstanding of the Russian law executor of this legal phenomenon. As a result the defects of law enforcement are hidden behind the waiver of one’s right in the Russian criminal process.
Evaluation the Role of Media and Language Policy in the Stabilization of Interethnic Relations at the Present Stage: The Example of a Multinational Kazakhstan
Authors: KASHKINBAYEV А.Т. , GABDULINA B.А. , KUZEMBAYEVA А.О. , TAKIBAYEV M.А. , ZHANPEYISOVA К.D. 
Published: May 2020

Background: Theoretical and practical study of technologies for preventing and regulating inter-ethnic conflicts is an urgent problem for multinational Kazakhstan, which is undergoing the stage of statehood formation. The aim of the research is to analyze the place and role of democratic mass media and language policy in the system of mechanisms for improving national relations and to identify the main levers of influence on the formation of the language environment.
Objectives: The object of the research is the analysis of the influence of mass media on the improvement of interethnic relations and aspects of the formation of the language environment as a factor in the development of interethnic relations.
Method: The main research methods were expert evaluation, principles of unity and development, system and comparative analysis, socio-political and functional approaches, historical and comparative method, and content analysis.
Results: The scientific result of the study was to identify the influence of mass media and language policy on the formation of civil society in a multinational Kazakhstan.It also reveals the dynamics of the language situation in the regions of the country in terms of its impact on inter-ethnic relations and determines the role of the language factor in the structure of ethnic identity of the largest ethnic groups in Kazakhstan.
Conclusion: The results of this study can be used in the analysis of ethnopolitical situations in the regions of Kazakhstan, in the process of training journalists.
Definiowanie koncepcji hybrydyzacji rozwoju
Authors: Drobniak Adam 
Published: May 2020

Zamierzeniem artykułu jest próba zdefiniowania koncepcji hybrydyzacji rozwoju, a także zainicjowanie dyskusji, w jaki sposób podejście to może wzbogacać współczesne koncepcje rozwoju wykorzystywane w ekonomii regionalnej i geografii ekonomicznej. Artykuł ma charakter teoretyczny i bazuje na metodyce studiów literaturowych. W pierwszej części przedstawiono wprowadzenie do problematyki hybrydyzacji rozwoju w kontekście współczesnych zjawisk globalizacyjnych. W kolejnej przybliżono pojęcia związane z hybrydyzacją rozwoju. Następnie poddano analizie ujęcie sektorowe i przestrzenne hybrydyzacji oraz sformułowano propozycję ogólnego ujęcia tej koncepcji. Artykuł kończą rozważania na temat znaczenia hybrydyzacji rozwoju w kontekście wybranych współczesnych koncepcji rozwoju wykorzystywanych w ekonomii regionalnej i geografii ekonomicznej.
Czy więcej znaczy lepiej? Badania ilościowe w geografii społeczno-ekonomicznej ery Big Data
Authors: Rzeszewski Michał , Rodak Olga 
Published: May 2020

Wielkie zbiory danych typu Big Data są obecnie nieodłącznym elementem badań w wielu dziedzinach nauki – w tym w geografii społeczno-ekonomicznej. Znajdują one szereg zastosowań, zarówno wnosząc możliwość analizy nowych danych w klasycznych problemach badawczych, jak i same w sobie będąc nowym przedmiotem badań oraz pozwalając na badanie cyfrowych geografii. Jednocześnie Big Data krytykuje się za niejednorodność, brak reprezentatywności, nierówność reprezentacji czy też problemy etyczne. Z tego powodu zwracamy uwagę na szereg dylematów związanych z obecnością Big Data w praktyce badawczej, sugerując istotną rolę krytycznego podejścia do ich zastosowania w praktyce badawczej.