bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct and common features of numerical and structural chromosomal instability across different cancer types
Authors: Zhang Xiaoxiao , Kschischo Maik 
Published: October 2021

AbstractA large proportion of tumours is characterised by numerical or structural chromosomal instability (CIN), defined as an increased rate of gaining or losing whole chromosomes (W-CIN) or of accumulating structural aberrations (S-CIN). Both W-CIN and S-CIN are associated with tumourigenesis, cancer progression, treatment resistance and clinical outcome. Although W-CIN and S-CIN can co-occur, they are initiated by different molecular events. By analysing tumour genomic data from 33 cancer types, we show that the majority of tumours with high levels of W-CIN underwent whole genome doubling, whereas S-CIN levels are strongly associated with homologous recombination deficiency. Both CIN phenotypes are prognostic in several cancer types. Most drugs are less efficient in high-CIN cell lines, but we also report compounds and drugs which should be investigated as targets for W-CIN or S-CIN. By analysing associations between CIN and bio-molecular entities with pathway and gene expression levels, we complement gene signatures of CIN and report that the drug resistance geneCKS1Bis strongly associated with S-CIN. Finally, we propose a potential copy number-dependent mechanism to activate thePI3Kpathway in high-S-CIN tumours.1.Simple summaryMany cancer cells are chromosomally unstable, a phenotype describing a tendency for accumulating chromosomal aberrations. Entire chromosomes tend to be gained or lost, which is called whole chromosome instability (W-CIN). Structural chromosomal instability (S-CIN) describes an increased rate of gaining, losing or translocating smaller parts of chromosomes. Here, we analyse data from 33 cancer types to find differences and commonalities between W-CIN and S-CIN. We find that W-CIN is strongly linked to whole genome doubling (WGD), whereas S-CIN is associated with a specific DNA damage repair pathway. Both W-CIN and S-CIN are difficult to target using currently available compounds and have distinct prognostic values. The activity of the drug resistance geneCKS1Bis associated with S-CIN, which merits further investigation. In addition, we identify a potential copy number-based mechanism promoting signalling of the importantPI3Kcancer pathway in high-S-CIN tumours.
Whole Organism Profiling of the Timp Gene Family
Authors: Peeney David , Fan Yu , Gurung Sadeechya , Lazaroff Carolyn , Ratnayake Shashikala , Warner Andrew , Karim Baktiar , Meerzaman Daoud , Stetler-Stevenson William G. 
Published: October 2021

AbstractTissue inhibitor of metalloproteinases (TIMPs/Timps) are an endogenous family of widely expressed matrisome-associated proteins that were initially identified as inhibitors of matrix metalloproteinase activity (Metzincin family proteases). Consequently, TIMPs are often considered simply as protease inhibitors by many investigators. However, an evolving list of new metalloproteinase-independent functions for TIMP family members suggests that this concept is outdated. These novel TIMP functions include direct agonism/antagonism of multiple transmembrane receptors, as well as functional interactions with matrisome targets. While the family was fully identified over two decades ago, there has yet to be an in-depth study describing the expression of TIMPs in normal tissues of adult mammals. An understanding of the tissues and cell-types that express TIMPs 1 through 4, in both normal and disease states are important to contextualize the growing functional capabilities of TIMP proteins, which are often dismissed as non-canonical. Using publicly available single cell RNA sequencing data from the Tabula Muris Consortium, we analyzed approximately 100,000 murine cells across eighteen tissues from non-diseased organs, representing seventy-three annotated cell types, to define the diversity in Timp gene expression across healthy tissues. We describe the unique expression profiles across tissues and organ-specific cell types that all four Timp genes display. Within annotated cell-types, we identify clear and discrete cluster-specific patterns of Timp expression, particularly in cells of stromal and endothelial origins. RNA in-situ hybridization across four organs expands on the scRNA sequencing analysis, revealing novel compartments associated with individual Timp expression. These analyses provide evidence of the biological significance of Timp expression in the identified cell sub-types, which are consistent with novel roles in normal tissue homeostasis and changing roles in disease progression. This understanding of the tissues, specific cell types and microenvironment conditions in which Timp genes are expressed adds important physiological context to the growing array of novel functions for TIMP proteins.
Predicting the Influence of Axon Myelination on Sound Localization Precision Using a Spiking Neural Network Model of Auditory Brainstem
Authors: Li Ben-Zheng , Pun Sio Hang , Vai Mang I , Lei Tim C. , Klug Achim 
Published: October 2021

AbstractSpatial hearing allows animals to rapidly detect and localize auditory events in the surrounding environment. The auditory brainstem plays a central role in processing and extracting binaural spatial cues through microsecond-precise binaural integration, especially for detecting interaural time differences (ITDs) of low-frequency sounds at the medial superior olive (MSO). A series of mechanisms exist in the underlying neural circuits for preserving accurate action potential timing across multiple fibers, synapses and nuclei along this pathway. One of these is the myelination of afferent fibers that ensures reliable and temporally precise action potential propagation in the axon. There are several reports of fine-tuned myelination patterns in the MSO circuit, but how specifically myelination influences the precision of sound localization remains incompletely understood. Here we present a spiking neural network model of the auditory brainstem with myelinated axons to investigate whether different axon myelination thicknesses alter the sound localization process. Our model demonstrates that axon myelin thickness along the contralateral pathways can substantially modulate ITD detection. Furthermore, optimal ITD sensitivity is reached when the MSO receives contralateral inhibition via thicker myelinated axons compared to contralateral excitation, a result that is consistent with previously reported experimental observations. Our results suggest specific roles of axon myelination for extracting temporal dynamics in ITD perception, especially in the pathway of the contralateral inhibition.
The Pathogenic R5L Mutation Disrupts Formation of Tau Complexes on the Microtubule by Altering Local N-Terminal Structure
Authors: Cario Alisa , Savastano Adriana , Wood Neil B. , Liu Zhu , Previs Michael J. , Hendricks Adam G. , Zweckstetter Markus , Berger Christopher L. 
Published: October 2021

AbstractThe microtubule-associated protein (MAP) Tau is an intrinsically disordered protein (IDP) primarily expressed in axons, where it functions to regulate microtubule dynamics, modulate motor protein motility, and participate in signaling cascades. Tau misregulation and point mutations are linked to neurodegenerative diseases, including Progressive Supranuclear Palsy (PSP), Pick’s Disease and Alzheimer’s disease. Many disease-associated mutations in Tau occur in the C-terminal microtubule-binding domain of the protein. Effects of C-terminal mutations in Tau have led to the widely accepted disease-state theory that missense mutations in Tau reduce microtubule-binding affinity or increase Tau propensity to aggregate. Here, we investigate the effect of an N-terminal disease-associated mutation in Tau, R5L, on Tau-microtubule interactions using an in vitro reconstituted system. Contrary to the canonical disease-state theory, we determine the R5L mutation does not reduce Tau affinity for the microtubule using Total Internal Reflection Fluorescence (TIRF) Microscopy. Rather, the R5L mutation decreases the ability of Tau to form larger order complexes, or Tau patches, at high concentrations of Tau. Using Nuclear Magnetic Resonance (NMR), we show that the R5L mutation results in a local structural change that reduces interactions of the projection domain in the presence of microtubules. Altogether, these results challenge both the current paradigm of how mutations in Tau lead to disease and the role of the projection domain in modulating Tau behavior on the microtubule surface.Significance StatementThe microtubule-associated protein Tau is strongly linked to a number of neurological diseases. Disease onset is typically associated with weakened interaction with the microtubule, but this widely accepted model is based on hyperphosphorylation or mutations within the C-terminal microtubule-binding domain of Tau. Here, we find an N-terminal disease-associated mutation in Tau, R5L, does not reduce Tau affinity for microtubules, but instead modifies the N-terminal structure, altering Tau’s behavior and ability to condense on the microtubule surface. Our findings challenge the current paradigms of both how mutations in Tau lead to disease and the functional role of the N-terminal region of Tau.
Propofol modulates functional connectivity signatures of sustained attention
Authors: Chamberlain Taylor , Rosenberg Monica D. 
Published: October 2021

AbstractSustained attention is a critical cognitive function reflected in an individual’s whole-brain pattern of fMRI functional connectivity. However sustained attention is not a purely static trait. Rather, attention waxes and wanes over time. Do functional brain networks that underlie individual differences in sustained attention also underlie changes in attentional state? To investigate, we replicate the finding that a validated connectome-based model of individual differences in sustained attention tracks pharmacologically induced changes in attentional state. Specifically, preregistered analyses revealed that participants exhibited functional connectivity signatures of stronger attention when awake than when under deep sedation with the anesthetic agent propofol. Furthermore, this effect was relatively specific to the predefined sustained attention networks: propofol administration modulated strength of the sustained attention networks more than it modulated strength of canonical resting-state networks and a network defined to predict fluid intelligence, and the functional connections most affected by propofol sedation overlapped with the sustained attention networks. Thus, propofol modulates functional connectivity signatures of sustained attention within individuals. More broadly these findings underscore the utility of pharmacological intervention in testing both the generalizability and specificity of network-based models of cognitive function.
Hepatocyte Cell Cycle Progression Depends on a Transcriptional Repressor Cascade Downstream of Wnt Signaling
Authors: Jin Yinhua , Anbarchian Teni , Wu Peng , Sarkar Abby , Fish Matt , Nusse Roel 
Published: October 2021

AbstractCell proliferation is tightly controlled by inhibitors that block cell cycle progression until growth signals relieve this inhibition. In several tissues including the liver, transcriptional repressors such as E2F7 and E2F8 function as inhibitors of mitosis and promote polyploidy, but how growth factors release these mitotic inhibitors to facilitate cell cycle progression is unknown. We describe here a newly identified mechanism of cell division control in which Wnt/βcatenin signaling in the postnatal liver maintains active hepatocyte proliferation through Tbx3, a Wnt target gene. TBX3 directly represses transcription of E2f7 and E2f8, promoting a low ploidy state and cell cycle progression. This sequential transcriptional repressor cascade, initiated by Wnts, provides a new paradigm for exploring how a commonly active developmental signal impacts cell cycle completion.
Microbial community dispersal in sourdough
Authors: von Gastrow Lucas , Amelot Rémy , Segond Diego , Guézennec Stéphane , Valence Florence , Sicard Delphine 
Published: October 2021

AbstractUnderstanding how microbes disperse in ecosystems is critical to understand the dynamics and evolution of microbial communities. However, microbial dispersal is difficult to study because of uncertainty about the vectors that may contribute to their migration. This applies to both microbial communities in natural and human-associated environments. Here, we studied microbial dispersal among French sourdoughs and flours used to make bread. Sourdough is a naturally fermented mixture of flour and water. It hosts a community of bacteria and yeasts whose origins are only partially known. We analyzed whether flour is a carrier of sourdough yeast and bacteria and studied whether microbial migration occurs between sourdoughs. The microbial community of a collection of 46 sourdough samples, as well as that of the flour from which each was made, was studied by 16S rDNA and ITS1 metabarcoding. No sourdough yeast species were detected in the flours. Sourdough lactic acid bacteria (LAB) were found in only five flour samples, and they did not have the same amplicon sequence variant (ASV) as found in the corresponding sourdough. The species shared between the sourdough and flour samples are commonly found on plants and are not known to be alive in sourdough. Thus, the flour microorganisms did not appear to grow in the sourdough microbial community. Dispersal between sourdoughs was also studied. Sourdoughs shared no yeast ASV, except in few cases where groups of three to five bakers shared some. These results suggest that there is little migration between sourdoughs, except in a few situations where bakers may exchange sourdough or be vectors of yeast dispersal themselves.
Sensorless localization of a minimally-actuated robotic system for automated pallet de-strapping
Authors: Khalifeh Nour El-Hoda , Youssef Rudy , Fadel Farah , Khalil Roy , Shammas Elie , Daher Naseem , Elhajj Imad H. , Irrenhauser Thomas , Niedermeier Michael N. , Poss Christian 
Published: October 2021

Purpose
The purpose of this paper is to detail the design and prototyping of a smart automation solution for de-strapping plastic bonding straps on shipping pallets, which are loaded with multiple containers secured by a top-cover as they move on a conveyor belt.

Design/methodology/approach
The adopted design methodology to have the system perform its function entails using the least number of sensors and actuators to arrive at an economic solution from a system design viewpoint. Two prototypes of the robotic structure are designed and built, one in a research laboratory and another in an industrial plant, to perform localized cutting and grabbing of the plastic straps, with the help of a custom-designed passive localizing structure. The proposed structure is engineered to locate the plastic straps using one degree of freedom (DOF) only. An additional strap removal mechanism is designed to collect the straps and prevent them from interfering with the conveyor.

Findings
The functionality of the system is validated by performing full-process tests on the developed prototypes in a laboratory setting and under real-life operating conditions at BMW Group facilities. Testing showed that the proposed localization system meets the specified requirements and can be generalized and adapted to other industrial processes with similar requirements.

Practical implications
The proposed automated system for de-strapping pallets can be deployed in assembly or manufacturing facilities that receive parts in standard shipping pallets that are used worldwide.

Originality/value
To the best of the authors’ knowledge, this is the first mechanically smart system that is used for the automated removal of straps from shipping pallets used in assembly facilities. The two main novelties of the proposed design are the robustness of the strap localization without the need for computer vision and a large number of DOF, and the critical placement and choice of the cutting and gripping tools to minimize the number of needed actuators.
Characterizing and predicting the cross-app behavior in mobile search
Authors: Liang Shaobo 
Published: October 2021

PurposeThis paper aims to explore the users' cross-app behavior characteristics in mobile search and to predict users' cross-app behavior using multi-dimensional information.Design/methodology/approachThis paper presents a longitudinal user experiment in 15 days. This paper recruited 30 participants and collected their mobile phone log data in the whole experiment. The structured diary method was also used to collect contextual information in mobile search.FindingsThis study focused on the users' cross-app behavior in mobile search and described cross-app behavior's basic characteristics. Usage of communication app and tool apps could trigger more cross-app behavior in mobile search. The method of cross-app behavior prediction in the mobile search was proposed. Collecting users' more contextual information, such as search tasks, search motivation and other environmental information, can effectively improve the prediction accuracy of cross-app behavior in mobile search.Practical implicationsThe future research on cross-app behavior prediction should focus on context information in mobile search. Better prediction of cross-app behavior can reduce the users' interaction burden.Originality/valueThis paper contributes to research into cross-app behavior, especially in the mobile search research domain.
How managerial communication reduces perceived job insecurity of flight attendants during the COVID-19 pandemic
Authors: Charoensukmongkol Peerayuth , Suthatorn Pornprom 
Published: October 2021

PurposeThis research investigates whether and how the quality of vertical communication implemented by airline industry management can reduce perceived job insecurity of flight attendants during the coronavirus disease 2019 (COVID-19) pandemic.Design/methodology/approachThe sample of this research covers 322 flight attendants from five domestic airlines based in Thailand. An online questionnaire survey was used for data collection, and a partial least squares structural equation model was used for data analysis.FindingsThe results support the negative association between the quality of vertical communication and perceived job insecurity; moreover, this association is partially mediated by perceived role ambiguity. When considering the moderating effect of perceived organizational support on the direct linkage between the quality of vertical communication and perceived job insecurity, the quality of vertical communication only has a negative association with perceived job insecurity among employees who exhibit high levels of perceived organizational support. For those who exhibit low levels of perceived organizational support, the quality of vertical communication does not have a negative association with perceived job insecurity.Originality/valueThis study advances prior communication research by showing that in order for communication to effectively lessen the perceived job insecurity of employees, it needs to be backed by high-quality organizational support.
Impact of entrepreneurial orientation on the performance of new ventures in China: the roles of entrepreneurial bricolage and opportunity recognition
Authors: Ma Tiannv , Yang Siying 
Published: October 2021

PurposeThis study aims to examine how entrepreneurial orientation affects new venture performance in a dynamic environment. The authors examine whether entrepreneurial bricolage and opportunity recognition mediate the effect of entrepreneurial orientation on new venture performance and whether environmental dynamics moderate the above effects.Design/methodology/approachThis study uses questionnaires to collect data. The sample includes responses of managers from 274 new Chinese ventures. Regression analysis and bootstrapping are used to test the hypotheses.FindingsEntrepreneurial bricolage and opportunity recognition play mediating roles between entrepreneurial orientation and new venture performance. Environmental dynamism positively moderates the relationship between opportunity recognition and new venture performance.Practical implicationsIn a dynamic environment, new ventures should strengthen their entrepreneurial orientation, which would gradually improve their performance by improving their entrepreneurial bricolage and opportunity recognition ability.Originality/valueThis study innovatively explains the relationship between entrepreneurial orientation and new venture performance from the perspectives of “flexible solutions to current problems” and “discovering and grasping potential new opportunities.” It does so by using the concepts of entrepreneurial bricolage and entrepreneurial opportunity identification in the context of a dynamic environment.
Modelling the blockchain adoption barriers in the AEC industry
Authors: Xu Yongshun , Chong Heap-Yih , Chi Ming 
Published: October 2021

PurposeIn the era of digitalisation, blockchain has the potential to fundamentally change the architecture, engineering and construction (AEC) industry's workflow, trust and procurement environments. However, few studies have investigated blockchain adoption barriers in the AEC industry in detail. Therefore, the study aims to provide a comprehensive understanding of these barriers and their interdependent relationships in the context of the AEC industry.Design/methodology/approachBased on a review of the literature, industry reports and expert feedback, 11 barriers towards adopting the blockchain were identified. Then, the authors investigated the interdependencies amongst the factors by adopting a two-stage integrated interpretive structural modelling (ISM) and decision-making trial and evaluation laboratory (DEMATEL) method.FindingsThe findings show that the lack of information technology infrastructure (BC4) and legal and regulatory uncertainty (BC11) are the most prominent barriers towards blockchain adoption in the AEC industry.Practical implicationsThe research contributes in providing a clearer understanding of related barriers and potential solutions for practitioners in this area. Subsequently, the identification of adoption barriers can enable an important knowledge foundation and suggest possible solutions for adopting blockchain techniques successfully and effectively in the AEC industry.Originality/valueThe study lays an essential research foundation for the effective adoption and use of blockchain in the AEC industry.
Predicting intention to follow online restaurant community advice: a trust-integrated technology acceptance model
Authors: Shaker Aya K. , Mostafa Rasha H.A. , Elseidi Reham I. 
Published: October 2021

PurposeThis research investigates consumer intention to follow online community advice. Applying the technology acceptance model (TAM) to the context of online restaurant communities, the study empirically examines the effects of perceived usefulness, perceived ease of use, attitude and trust on the intention to follow online advice.Design/methodology/approachThe data were collected from 360 members of online restaurant communities on Facebook and analyzed using structural equation modeling (SEM).FindingsThe findings revealed that trust, perceived usefulness and attitude are key predictors of the intention to follow online restaurant community advice.Originality/valueExtant research on the influence of online reviews on consumer behavior in the restaurant industry has largely focused on the characteristics of the review, reviewers or readers. Moreover, other studies have investigated consumers' motivations to write online restaurant reviews. This study, however, takes a different approach and examines what drives consumers to follow the advice from online restaurant communities.