bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional non-coding SNPs in human endothelial cells fine-map vascular trait associations
Authors: Toropainen Anu , Stolze Lindsey K. , Örd Tiit , Whalen Michael , Martí Torrell Paula , Link Verena M. , Kaikkonen Minna U , Romanoski Casey 
Published: August 2021

AbstractFunctional consequences of genetic variation in the non-coding human genome are difficult to ascertain despite demonstrated associations to common, complex disease traits. To elucidate properties of functional non-coding SNPs with effects in human endothelial cells (EC), we utilized molecular Quantitative Trait Locus (molQTL) analysis for transcription factor binding, chromatin accessibility, and H3K27 acetylation to nominate a set of likely functional non-coding SNPs. Together with information from genome-wide association studies for vascular disease traits, we tested the ability of 34,344 variants to perturb enhancer function in ECs using the highly multiplexed STARR-seq assay. Of these, 5,592 variants validated, whose enriched attributes included: 1) mutations to TF binding motifs for ETS or AP1 that are regulators of EC state, 2) location in accessible and H3K27ac-marked EC chromatin, and 3) molQTLs associations whereby alleles associate with differences in chromatin accessibility and TF binding across genetically diverse ECs. Next, using pro-inflammatory IL1B as an activator of cell state, we observed robust evidence (>50%) of context-specific SNP effects, underscoring the prevalence of non-coding gene-by-environment (GxE) effects. Lastly, using these cumulative data, we fine-mapped vascular disease loci and highlight evidence suggesting mechanisms by which non-coding SNPs at two loci affect risk for Pulse Pressure/Large Artery Stroke, and Abdominal Aortic Aneurysm through respective effects on transcriptional regulation of POU4F1 and LDAH. Together, we highlight the attributes and context dependence of functional non-coding SNPs, and provide new mechanisms underlying vascular disease risk.
Two-dimensional multiplexed assay for rapid and deep SARS-CoV-2 serology profiling and for machine learning prediction of neutralization capacity
Authors: Koide Akiko , Panchenko Tatyana , Wang Chan , Thannickal Sara A. , Romero Larizbeth A. , Teng Kai Wen , Li Francesca-Zhoufan , Akkappedi Padma , Corrado Alexis D. , Caro Jessica , Diefenbach Catherine , Samanovic Marie I. , Mulligan Mark J. , Hattori Takamitsu , Stapleford Kenneth A. , Li Huilin , Koide Shohei 
Published: August 2021

SUMMARYAntibody responses serve as the primary protection against SARS-CoV-2 infection through neutralization of viral entry into cells. We have developed a two-dimensional multiplex bead binding assay (2D-MBBA) that quantifies multiple antibody isotypes against multiple antigens from a single measurement. Here, we applied our assay to profile IgG, IgM and IgA levels against the spike antigen, its receptor-binding domain and natural and designed mutants. Machine learning algorithms trained on the 2D-MBBA data substantially improve the prediction of neutralization capacity against the authentic SARS-CoV-2 virus of serum samples of convalescent patients. The algorithms also helped identify a set of antibody isotype–antigen datasets that contributed to the prediction, which included those targeting regions outside the receptor-binding interface of the spike protein. We applied the assay to profile samples from vaccinated, immune-compromised patients, which revealed differences in the antibody profiles between convalescent and vaccinated samples. Our approach can rapidly provide deep antibody profiles and neutralization prediction from essentially a drop of blood without the need of BSL-3 access and provides insights into the nature of neutralizing antibodies. It may be further developed for evaluating neutralizing capacity for new variants and future pathogens.
Transcranial magnetic stimulation of the occipital cortex interferes with foot movements in acquired but not congenitally blind individuals
Authors: Ikegami Tsuyoshi , Miura Gen , Hirashima Masaya , Naito Eiichi , Hirose Satoshi 
Published: August 2021

AbstractResearch has shown that the occipital cortex can be reorganized and repurposed for nonvisual perception and cognitive functions following visual loss in blind individuals. However, no studies have directly examined the involvement of the visual cortex in motor function. Here, we show that a rhythmic foot movement performed by acquired blind individuals can be disrupted by transcranial magnetic stimulation (TMS) to their primary and secondary visual cortex (V1/V2). This disruptive effect was absent for congenitally blind or sighted individuals. As a control, TMS to the neck muscles of acquired blind individuals confirms that this disruptive effect was not caused solely by the sensory (tactile/auditory) sensations accompanying the stimulation. Our results provide the direct evidence that functional repurposing of the human visual cortex is not restricted to perception and cognitive functions but also extends to motor function. Moreover, our findings suggest the nessecity of the visual experience before visual loss for the functional reorganization of the visual cortex for motor function.
Cell type-specific biotin labeling in vivo resolves regional neuronal proteomic differences in mouse brain
Authors: Rayaprolu Sruti , Bitarafan Sara , Betarbet Ranjita , Sunna Sydney , Cheng Lihong , Xiao Hailian , Bagchi Pritha , Duong Duc M. , Nelson Ruth , Goettemoeller Annie M. , Oláh Viktor János , Rowan Matt , Levey Allan I. , Wood Levi B. , Seyfried Nicholas T. , Rangaraju Srikant 
Published: August 2021

ABSTRACTIsolation and proteomic profiling of brain cell types, particularly neurons, pose several technical challenges which limit our ability to resolve distinct cellular phenotypes in neurological diseases. Therefore, we generated a novel mouse line that enables cell type-specific expression of a biotin ligase, TurboID, via Cre-lox strategy for in vivo proximity-dependent biotinylation of proteins. Using adenoviral-based and transgenic approaches, we show striking protein biotinylation in neuronal cell bodies and axons throughout the mouse brain. We quantified more than 2,000 neuron-derived proteins following enrichment that mapped to numerous subcellular compartments. Synaptic, transmembrane transporters, ion channel subunits, and disease-relevant druggable targets were among the most significantly enriched proteins. Remarkably, we resolved brain region-specific proteomic profiles of Camk2a neurons with distinct functional molecular signatures and disease associations that may underlie regional neuronal vulnerability. Leveraging the neuronal specificity of this in vivo biotinylation strategy, we used an antibody-based approach to uncover regionally unique patterns of neuron-derived signaling phospho-proteins and cytokines, particularly in the cortex and cerebellum. Our work provides a proteomic framework to investigate cell type-specific mechanisms driving physiological and pathological states of the brain as well as complex tissues beyond the brain.
Controlling reversible cell differentiation for labor division in microbial consortia
Authors: Salzano Davide , Fiore Davide , di Bernardo Mario 
Published: August 2021

SUMMARYWe address the problem of regulating and keeping at a desired balance the relative numbers between cells exhibiting a different phenotype within a monostrain microbial consortium. We propose a strategy based on the use of external control inputs, assuming each cell in the community is endowed with a reversible, bistable memory mechanism. Specifically, we provide a general analytical framework to guide the design of external feedback control strategies aimed at balancing the ratio between cells whose memory is stabilized at either one of two equilibria associated to different cell phenotypes. We demonstrate the stability and robustness properties of the control laws proposed and validate them in silico by means of a realistic agent-based implementation enabling cooperative bioproduction in microbial consortia. The proposed control framework may be used to allow long term coexistence of different populations, with both industrial and biotechnological applications.
Cytokinin-CLAVATA crosstalk is an ancient mechanism regulating shoot meristem homeostasis in land plants
Authors: Cammarata Joseph , Farfan Christopher Morales , Scanlon Michael , Roeder Adrienne HK 
Published: August 2021

AbstractPlant shoots grow from stem cells within Shoot Apical Meristems (SAMs), which produce lateral organs while maintaining the stem cell pool. In the model flowering plant Arabidopsis, the CLAVATA (CLV) pathway functions antagonistically with cytokinin signaling to control the size of the multicellular SAM via negative regulation of the stem cell organizer WUSCHEL (WUS). Although comprising just a single cell, the SAM of the model moss Physcomitrium patens (formerly Physcomitrella) performs equivalent functions during stem cell maintenance and organogenesis, despite the absence of WUS-mediated stem cell organization. Our previous work showed that the stem cell-delimiting function of the CLV pathway receptors CLAVATA1 (CLV1) and RECEPTOR-LIKE PROTEIN KINASE2 (RPK2) is conserved in the moss P. patens. Here, we use P. patens to assess whether CLV-cytokinin crosstalk is also an evolutionarily conserved feature of stem cell regulation. Genetic analyses reveal that CLV1 and RPK2 regulate SAM proliferation via separate pathways in moss. Surprisingly, cytokinin receptor mutants also form ectopic stem cells in the absence of cytokinin signaling. Through modeling, we identified regulatory network archtectures that recapitulated the stem cell phenotypes of clv1 and rpk2 mutants, cytokinin application, cytokinin receptor mutations, and higher-order combinations of these perturbations. These models predict that CLV1 and RPK2 act through separate pathways wherein CLV1 represses cytokinin-mediated stem cell initiation and RPK2 inhibits this process via a separate, cytokinin-independent pathway. Our analysis suggests that crosstalk between CLV1 and cytokinin signaling is an evolutionarily conserved feature of SAM homeostasis that preceded the role of WUS in stem cell organization.
The structural coverage of the human proteome before and after AlphaFold
Authors: Porta-Pardo Eduard , Ruiz-Serra Victoria , Valentini Samuel , Valencia Alfonso 
Published: August 2021

AbstractThe protein structure field is experiencing a revolution. From the increased throughput of techniques to determine experimental structures, to developments such as cryo-EM that allow us to find the structures of large protein complexes or, more recently, the development of artificial intelligence tools, such as AlphaFold, that can predict with high accuracy the folding of proteins for which the availability of homology templates is limited.Here we quantify the effect of the recently released AlphaFold database of protein structural models in our knowledge on human proteins. Our results indicate that our current baseline for structural coverage of 48%, considering experimentally-derived or template-based homology models, elevates up to 76% when including AlphaFold predictions. At the same time the fraction of dark proteome is reduced from 26% to just 10% when AlphaFold models are considered. Furthermore, although the coverage of disease-associated genes and mutations was near complete before AlphaFold release (69% of Clinvar pathogenic mutations and 88% of oncogenic mutations), AlphaFold models still provide an additional coverage of 3% to 13% of these critically important sets of biomedical genes and mutations. Finally, we show how the contribution of AlphaFold models to the structural coverage of non-human organisms, including important pathogenic bacteria, is significantly larger than that of the human proteome.Overall, our results show that the sequence-structure gap of human proteins has almost disappeared, an outstanding success of direct consequences for the knowledge on the human genome and the derived medical applications.
Long-range cortical synchronization supports abrupt visual learning
Authors: Csorba Bennett A. , Krause Matthew R. , Zanos Theodoros P. , Pack Christopher C. 
Published: August 2021

SUMMARYVisual plasticity declines sharply after the critical period, yet we easily learn to recognize new faces and places even as adults. Such learning is often characterized by a “moment of insight”, an abrupt and dramatic improvement in recognition. The mechanisms that support abrupt learning are unknown, but one hypothesis is that they involve changes in synchronization between brain regions. To test this hypothesis, we used a behavioral task in which non-human primates rapidly learned to recognize novel images and to associate them with specific responses. Simultaneous recordings from inferotemporal and prefrontal cortices revealed a transient synchronization of neural activity between these areas that peaked around the moment of insight. Synchronization was strongest between inferotemporal sites that encoded images and reward-sensitive prefrontal sites. Moreover, its magnitude intensified gradually over image exposures, suggesting that abrupt learning culminates from the search for informative signals within a circuit linking sensory information to task demands.
ELECTRE tree: a machine learning approach to infer ELECTRE Tri-B parameters
Authors: Montenegro de Barros Gabriela Montenegro , Pereira Valdecy , Roboredo Marcos Costa 
Published: August 2021

PurposeThis paper presents an algorithm that can elicitate (infer) all or any combination of elimination and choice expressing reality (ELECTRE) Tri-B parameters. For example, a decision maker can maintain the values for indifference, preference and veto thresholds, and the study’s algorithm can find the criteria weights, reference profiles and the lambda cutting level. The study’s approach is inspired by a machine learning ensemble technique, the random forest, and for that, the authors named the study’s approach as ELECTRE tree algorithm.Design/methodology/approachFirst, the authors generate a set of ELECTRE Tri-B models, where each model solves a random sample of criteria and alternates. Each sample is made with replacement, having at least two criteria and between 10% and 25% of alternates. Each model has its parameters optimized by a genetic algorithm (GA) that can use an ordered cluster or an assignment example as a reference to the optimization. Finally, after the optimization phase, two procedures can be performed; the first one will merge all models, finding in this way the elicitated parameters and in the second procedure, each alternate is classified (voted) by each separated model, and the majority vote decides the final class.FindingsThe authors have noted that concerning the voting procedure, nonlinear decision boundaries are generated and they can be suitable in analyzing problems of the same nature. In contrast, the merged model generates linear decision boundaries.Originality/valueThe elicitation of ELECTRE Tri-B parameters is made by an ensemble technique that is composed of a set of multicriteria models that are engaged in generating robust solutions.
BIM research vs BIM practice: a bibliometric-qualitative analysis from China
Authors: Ding Zhikun , Zheng Kairui , Tan Yi 
Published: August 2021

PurposeUnderstanding the frontier difference between building information modeling (BIM) research and practice is a top priority to guarantee the engineering significance and feasibility of academic achievements, yet such research gap has not been well-explored. The purpose of this paper is to provide an objective and accurate analysis of BIM knowledge using 551 published BIM-related papers and 68 documents of frontier BIM projects in China.Design/methodology/approachThis paper adopts the mixed method, combining the bibliometrics method with the qualitative method. Bibliometrics was used to analyze 551 BIM-related literatures from China with Citespace 5.0. Qualitative research was used to analyze 68 project documents from China with Nvivo. Finally, the analysis results are compared to obtain the final conclusion.FindingsThe analysis results of the collected BIM-related papers, given by bibliometrics analysis, show that the subject categories of engineering, civil engineering, and construction and building technology, and 8 key research clusters are extremely important for development of BIM knowledge. The analysis results of the collected project documents, given by qualitative analysis, indicate that visualization, aided management, intelligent construction, simulation and analysis are the hot applications of BIM practice.Originality/valueThrough comparison, certain research gaps between the research and practice community in China was identified, which are useful for identification of research trends and practice frontier in BIM community. This study offers useful and new insights to summarize the status quo of BIM and can be used as a reference to integrate future BIM developments.
Using social distancing technology in hotels: a social exchange perspective
Authors: Morosan Cristian , DeFranco Agnes 
Published: August 2021

Purpose
As social distancing procedures can be facilitated by various hotel technologies, the purpose of this paper is to investigate the extent to which consumers develop perceptions of value regarding the use of certain hotel technologies for social distancing in hotels.

Design/methodology/approach
Drawing from the social exchange theory, this study conceptualized the benefits of using technologies for social distancing, health risks, social rewards and privacy concerns as antecedents of value of using technologies for social distancing in hotels. The structural model was validated by using data from more than 1,000 nationwide US consumers.

Findings
Benefits and consumers’ privacy concerns of using technologies for social distancing in hotels were the strongest predictors of value. Social rewards also had a significant but relatively lower effect on value. Health risks was found to have no influence on value.

Originality/value
The study is the first to examine the role of technologies in mitigating the effects of coronavirus. Thus, it extends the information technology and hospitality literature by examining the role of these technologies in safeguarding individual and public health.
Organizational resilience and employee performance in COVID-19 pandemic: the mediating effect of emotional intelligence
Authors: Dhoopar Aastha , Sihag Priyanka , Kumar Anil , Suhag Ashok Kumar 
Published: August 2021

PurposeThe explosion of the deadly coronavirus (COVID-19) has led to an unprecedented crisis lately, which has adversely affected the performance level of professionals in the educational sector worldwide because of numerous constraints, imposition of the lockdown being one of those. Organizational resilience (OReg) and emotional intelligence (EI) discretely have been identified as indicators of employee performance (EP) over the years, but during the period of crisis, it has scarcely been analysed. Therefore, this study aims to examine the mediating role of EI on the relationship between OReg and EP in such a global pandemic.Design/methodology/approachIn total, 390 samples including teaching and non-teaching professionals working in higher educational institutions (HEIs) were collected from different HEIs located in India through online survey questionnaires. The collected data was further analysed using regression analysis, factor analysis, structural equation modelling along with bootstrapping technique, reliability and validity analysis, mediation analysis and model fit indices analysis.FindingsThe results of the study confirmed the partial mediation effect of EI on the OReg-EP relationship, and further results also exhibited that employees with a higher level of EI, contribute more positively to the OReg level, which further enhances the performance level at the workplace.Research limitations/implicationsThe samples collected for the current study pertain to the HEIs only, and therefore the present study results have limited general applicability. Furthermore, the study does not investigate the influence of time.Practical implicationsThis study would assist practitioners of HEIs in improving the resilience capabilities of the organization. EP can be improved by enhancing the levels of OReg and individual emotional intelligence, which is in line with the findings of the current study.Social implicationsIn the COVID-19 pandemic, worldwide the students are affected due to the transition to online teaching. This study will help HEI’s to cope up with the student’s loss by being flexible in approach for the retention of performance of employees by taking care of their emotional needs and focusing on their skill development by providing a learning culture in a depressing time of the pandemic so that students will not suffer due to this rapid change without any preparation or previous experience in a pandemic.Originality/valueThe current study examines the mediating effect of EI on the OReg and EP relationship for the first time in HEIs in India.
Are your international salespeople culturally intelligent? The influence of cultural intelligence on adaptive selling behavior with B2B customers
Authors: Kimber David , Guesalaga Rodrigo , Dickmann Michael 
Published: August 2021

Purpose
This study aims to investigate cultural intelligence (CQ) as an antecedent of adaptive selling behavior (ASB) and cultural distance and intrinsic motivation as moderators in this relationship.

Design/methodology/approach
This research builds on a survey to 310 US-based international sales executives (ISE) and multiple regression analysis to test the hypotheses.

Findings
The results show that CQ has a significant positive relationship with ASB, both as an aggregate construct and through its metacognitive, motivational and behavioral facets. Also, intrinsic motivation moderates such relationship, whereas cultural distance does not.

Research limitations/implications
The study includes only a sample of US-based international salespeople in the B2B context, which limits the generalizability of the findings to salespeople from other countries or other contexts.

Practical implications
The findings of this research suggest that supplier companies involved in international selling should consider the cultural intelligence of their salespeople for selection, training and coaching.

Originality/value
This study makes an important contribution to the literature on both ASB and CQ by expanding the knowledge on how to manage international salespeople effectively, considering the conditions under which CQ effects are expected and how these vary in this context.
Effect of capital flows on financial stability in middle-income countries
Authors: Ebire Kolawole , Ullah Saif , Adeleye Bosede Ngozi , Shah Muhammad Ibrahim 
Published: August 2021

Purpose
This study aims to examine the effect of various forms of capital flows on financial stability in middle-income countries from 2010 to 2017 using the World Bank economy classifications of 121 economies.

Design/methodology/approach
Panel spatial correlation consistent approach was used in this study.

Findings
The findings provide convincing evidence that in middle-income countries, capital flows are positive and significant predictors of financial stability and that financial systems in advanced economies are more stable than those of emerging and developing countries. However, outward foreign direct investments are shown to have the largest potential for ensuring financial stability.

Originality/value
Globalization has fostered financial integration of nations, which is manifested in capital flows from lower-income countries to middle-income and upper-income countries and vice versa. These flows can lead to financial instability if not properly controlled. The authors show how the various forms of capital flows affect the financial stability in middle-income countries.