bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid Cortical Adaptation and the Role of Thalamic Synchrony During Wakefulness
Authors: Wright Nathaniel C. , Borden Peter Y. , Liew Yi Juin , Bolus Michael F. , Stoy William M. , Forest Craig R. , Stanley Garrett B. 
Published: October 2020

AbstractRapid sensory adaptation is observed across all sensory systems, and strongly shapes sensory percepts in complex sensory environments. Yet despite its ubiquity and likely necessity for survival, the mechanistic basis is poorly understood. A wide range of primarily in-vitro and anesthetized studies have demonstrated the emergence of adaptation at the level of primary sensory cortex, with only modest signatures in earlier stages of processing. The nature of rapid adaptation and how it shapes sensory representations during wakefulness, and thus the potential role in perceptual adaptation, is underexplored, as are the mechanisms that underlie this phenomenon. To address these knowledge gaps, we recorded spiking activity in primary somatosensory cortex (S1) and the upstream ventral posteromedial (VPm) thalamic nucleus in the vibrissa pathway of awake male and female mice, and quantified responses to whisker stimuli delivered in isolation and embedded in an adapting sensory background. We found that cortical sensory responses were indeed adapted by persistent sensory stimulation; putative excitatory neurons were profoundly adapted, and inhibitory neurons only modestly so. Further optogenetic manipulation experiments and network modeling suggest this largely reflects adaptive changes in synchronous thalamic firing combined with robust engagement of feedforward inhibition, with little contribution from synaptic depression. Taken together, these results suggest that cortical adaptation in the regime explored here results from changes in the timing of thalamic input, and the way in which this differentially impacts cortical excitation and feedforward inhibition, pointing to a prominent role of thalamic gating in rapid adaptation of primary sensory cortex.Significance StatementRapid adaptation of sensory activity strongly shapes representations of sensory inputs across all sensory pathways over the timescale of seconds, and has profound effects on sensory perception. Despite its ubiquity and theoretical role in the efficient encoding of complex sensory environments, the mechanistic basis is poorly understood, particularly during wakefulness. In this study in the vibrissa pathway of awake mice, we show that cortical representations of sensory inputs are strongly shaped by rapid adaptation, and that this is mediated primarily by adaptive gating of the thalamic inputs to primary sensory cortex and the differential way in which these inputs engage cortical sub-populations of neurons.
Mechanistic model of nutrient uptake explains dichotomy between marine oligotrophic and copiotrophic bacteria
Authors: Norris Noele , Levine Naomi M. , Fernandez Vicente I. , Stocker Roman 
Published: October 2020

AbstractMarine heterotrophic bacteria use a spectrum of nutrient uptake strategies, from that of copiotrophs—which dominate in nutrient-rich environments—to that of oligotrophs—which dominate in nutrient-poor environments. While copiotrophs possess numerous phosphotransferase systems (PTS), oligotrophs lack PTS and rely on ATP-binding cassette (ABC) transporters, which use binding proteins. Here we present a molecular-level model that explains the dichotomy between oligotrophs and copiotrophs as the consequence of trade-offs between PTS and ABC transport. When we approximate ABC transport in Michaelis–Menten form, we find, contrary to the canonical formulation, that its half-saturation concentrationKMis not a constant but instead a function of binding protein abundance. Thus, oligotrophs can attain nanomolarKMvalues using binding proteins with micromolar dissociation constants and while closely matching transport and metabolic capacities. However, this requires large periplasms and high abundances of binding proteins, whose slow diffusion limits uptake rate. We conclude that the use of binding proteins is critical for oligotrophic survival yet severely constrains maximal growth rates, thus fundamentally shaping the divergent evolution of oligotrophs and copiotrophs.
Structural basis for the initiation of COPII vesicle biogenesis
Authors: Joiner Aaron M.N. , Fromme J. Christopher 
Published: October 2020

AbstractThe first stage of the eukaryotic secretory pathway is the packaging of cargo proteins into COPII vesicles exiting the endoplasmic reticulum (ER). The cytoplasmic COPII vesicle coat machinery is recruited to the ER membrane by the activated, GTP-bound, form of the conserved Sar1 GTPase. Activation of Sar1 on the surface of the ER by Sec12, a membrane-anchored GEF (guanine nucleotide exchange factor), is therefore the initiating step of the secretory pathway. Here we report the structure of the complex between Sar1 and the cytoplasmic GEF domain of Sec12, both fromSaccharomyces cerevisiae. This structure, representing the key nucleotide-free activation intermediate, reveals how the potassium ion-binding K-loop disrupts the nucleotide binding site of Sar1. We describe an unexpected orientation of the GEF domain relative to the membrane surface and propose a mechanism for how Sec12 facilitates membrane insertion of the amphipathic helix exposed by Sar1 upon GTP-binding.
An exploratory analysis of the current chemical regulations and guidelines from the perspective of endocrine disrupting chemicals using public resources
Authors: Shanmugam Karthikeyan Bagavathy , Ravichandran Janani , Aparna S. R. , Samal Areejit 
Published: October 2020

AbstractThe regulatory assessment of endocrine disrupting chemicals (EDCs) is complex due to the lack of a standardized definition of EDCs and validated testing criteria. In spite of these challenges, there is growing scientific interest in EDCs which has resulted in the rapid expansion of published literature on endocrine disruption upon chemical exposure. Here, we explore how academic research leading to curated knowledgebases can inform current chemical regulations on EDCs. To this end, we present an updated knowledgebase, DEDuCT 2.0, containing 792 potential EDCs with supporting evidence from 2218 research articles. Thereafter, we study the distribution of potential EDCs across several chemical lists that reflect guidelines for use or regulations. Further, to understand the scale of possible exposure to the potential EDCs present in chemical lists, we compare them with high production volume chemicals. Notably, we find many potential EDCs are in use across various product categories such as ‘Food additives and Food contact materials’ and ‘Cosmetics and household products’. Several of these EDCs are also produced or manufactured in high volume across the world. Lastly, we illustrate using an example how diverse information in curated knowledgebases such as DEDuCT 2.0 can be helpful in the risk assessment of EDCs. In sum, we highlight the need to bridge the gap between academic and regulatory aspects of chemical safety, as a step towards the better management of environment and health hazards such as EDCs.
ES-62 suppression of arthritis reflects epigenetic rewiring of synovial fibroblasts to a joint-protective phenotype
Authors: Corbet Marlene , Pineda Miguel A , Yang Kun , Tarafdar Anuradha , McGrath Sarah , Nakagawa Rinako , Lumb Felicity E , Harnett William , Harnett Margaret M 
Published: October 2020

AbstractThe parasitic worm product, ES-62 protects against collagen-induced arthritis, a mouse model of rheumatoid arthritis (RA) by suppressing the synovial fibroblast (SF) responses perpetuating inflammation and driving joint destruction. Such SF responses are shaped during disease progression by the inflammatory microenvironment of the joint that promotes remodelling of their epigenetic landscape, inducing an “aggressive” pathogenic SF phenotype. Critically, exposure to ES-62 in vivo induces a stably imprinted “safe” phenotype that exhibits responses more typical of healthy SFs. Surprisingly however, DNA methylome analysis reveals that rather than simply preventing the pathogenic rewiring of SFs, ES-62 induces further epigenetic remodelling, including targeting genes associated with ciliogenesis and differentiation, to program a distinct “protective” phenotype. Such unique behaviour signposts potential DNA methylation signatures predictive of pathogenesis and its resolution and hence, candidate mechanisms by which novel therapeutic interventions could prevent SFs from perpetuating joint inflammation and destruction in RA.
Time-dependent synergy for multi-agent anticancer therapy
Authors: Fujarewicz Krzysztof , Łakomiec Krzysztof 
Published: October 2020

AbstractA synergy between two therapeutic agents occurs when the effect of using both is greater than the sum of the effects of using each of them separately. There are several methods of detecting synergies in the literature, but they do not take into account the relationship between the times in which the factors act. In the article, we propose and justify the use of second-order sensitivity analysis as a potential tool for the detection and visualization of this type of synergy. We test and illustrate the proposed approach using four exemplary models of combined radio-chemotherapy of cancer.
Protein-bound molybdenum cofactor is bioavailable and rescues molybdenum cofactor-deficientC. elegans
Authors: Warnhoff Kurt , Hercher Thomas W. , Mendel Ralf R. , Ruvkun Gary 
Published: October 2020

AbstractThe molybdenum cofactor (Moco) is a 520 dalton prosthetic group that is synthesized in all domains of life. In animals, four oxidases (among them sulfite oxidase) use Moco as a prosthetic group. Moco is essential in animals; humans with mutations in genes that encode Moco-biosynthetic enzymes display lethal neurological and developmental defects. Moco supplementation seems a logical therapy, however the instability of Moco has precluded biochemical and cell biological studies of Moco transport and bioavailability. The nematodeCaenorhabditis eleganscan take up Moco from its bacterial diet and transport it to cells and tissues that express Moco-requiring enzymes, suggesting a system for Moco uptake and distribution. Here we show that protein-bound Moco is the stable, bioavailable species of Moco taken up byC. elegansfrom its diet and is an effective dietary supplement, rescuing aC.elegansmodel of Moco deficiency. We demonstrate that diverse Moco:protein complexes are stable and bioavailable, suggesting a new strategy for the production and delivery of therapeutically active Moco to treat human Moco deficiency.
ATF6 aggravates angiogenesis-osteogenesis coupling during ankylosing spondylitis by mediating FGF2 expression in chondrocytes
Authors: Ma Mengjun , Li Hongyu , Wang Peng , Yang Wen , Mi Rujia , Jiang Yuhang , Lu Yixuan , Shen Xin , Sui Pengfei , Wu Yanfeng , Shen Huiyong 
Published: October 2020

SummaryAlthough angiogenesis-osteogenesis coupling is important in ankylosing spondylitis (AS), therapeutic agents targeting the vasculature remain elusive. Here, we identified activating transcription factor 6 (ATF6) as an important regulator of angiogenesis in AS patients. Firstly, we found that ATF6 and fibroblast growth factor 2 (FGF2) levels were higher in SKG mice and AS patient cartilage. The pro-angiogenic ability of human chondrocytes was enhanced through activated ATF6-FGF2 axis following long-term stimulation with inflammatory factors, e.g. TNF-α, IFN-γ or IL-17.Mechanistically, ATF6 interacted with theFGF2promotor and promoted its transcription. Treatment with the ATF6 inhibitor Ceapin-A7 inhibited angiogenesisin vitroand angiogenesis-osteogenesis couplingin vivo. ATF6 may aggravate angiogenesis-osteogenesis coupling during AS by mediating FGF2 transcription in chondrocytes, implying that ATF6 represents a promising therapeutic target for AS.
An inverse modelling study on the local volume changes during early morphoelastic growth of the fetal human brain
Authors: Wang Z. , Martin B. , Weickenmeier J. , Garikipati K. 
Published: October 2020

AbstractWe take a data-driven approach to deducing the local volume changes accompanying early development of the fetal human brain. Our approach uses fetal brain atlas MRI data for the geometric changes in representative cases. Using a nonlinear continuum mechanics model of morphoelastic growth, we invert the deformation obtained from MRI registration to arrive at a field for the growth deformation gradient tensor. Our field inversion uses a combination of direct and adjoint methods for computing gradients of the objective function while constraining the optimization by the physics of morphoelastic growth. We thus infer a growth deformation gradient field that obeys the laws of morphoelastic growth. The errors between the MRI data and the forward displacement solution driven by the inverted growth deformation gradient field are found to be smaller than the reference displacement by well over an order of magnitude, and can be driven even lower. The results thus reproduce the three-dimensional growth during the early development of the fetal brain with controllable error. Our findings confirm that early growth is dominated by in plane cortical expansion rather than thickness increase.
Wide and Deep Learning for Automatic Cell Type Identification
Authors: Wilson Christopher M. , Fridley Brooke L. , Conejo-Garcia José , Wang Xuefeng , Yu Xiaoqing 
Published: October 2020

AbstractCell type classification is an important problem in cancer research, especially with the advent of single cell technologies. Correctly identifying cells within the tumor microenvironment can provide oncologists with a snapshot of how a patient’s immune system is reacting to the tumor. Wide deep learning (WDL) is an approach to construct a cell-classification prediction model that can learn patterns within high-dimensional data (deep) and ensure that biologically relevant features (wide) remain in the final model. In this paper, we demonstrate that the use of regularization can prevent overfitting and adding a wide component to a neural network can result in a model with better predictive performance. In particular, we observed that a combination of dropout andℓ2regularization can lead to a validation loss function that does not depend on the number of training iterations and does not experience a significant decrease in prediction accuracy compared to models withℓ1, dropout, or no regularization. Additionally, we show WDL can have superior classification accuracy when the training and testing of a model is completed data on that arise from the same cancer type, but from different platforms. More specifically, WDL compared to traditional deep learning models can substantially increase the overall cell type prediction accuracy (41 to 90%) and T-cell sub-types (CD4: 0 to 76%, and CD8: 61 to 96%) when the models were trained using melanoma data obtained from the 10X platform and tested on basal cell carcinoma data obtained using SMART-seq.
A history of university income in the United Kingdom and Australia, 1922–2017
Authors: Pietsch Tamson 
Published: October 2020

PurposeThe purpose of this paper is to create comparable time series data on university income in Australia and the UK that might be used as a resource for those seeking to understand the changing funding profile of universities in the two countries and for those seeking to investigate how such data were produced and utilised.Design/methodology/approachA statistical analysis of university income from all sources in the UK and Australia.FindingsThe article produces a new time series for Australia and a comparable time series for the UK. It suggests some of the ways these data related to broader patterns of economic change, sketches the possibility of strategic influence, and outlines some of their limitations.Originality/valueThis is the first study to systematically create a time series on Australian university income across the twentieth century and present it alongside a comparable dataset for the UK.
Investigating consumer behaviour for environmental, sustainable and social apparel
Authors: Byrd Kerri , Su Jin 
Published: October 2020

PurposeThe purpose of this study is to investigate consumers' perceptions of and consumer behaviour towards apparel labels and environmental, sustainable and social apparel.Design/methodology/approachQuantitative research was conducted, and empirical data were collected from 399 US consumers.FindingsFindings indicate that consumers expressed positive sentiments towards apparel sustainability, yet they lacked knowledge about socially and environmental practices within the apparel industry. Overall, it is apparent that the respondents have an interest in environmental and social labelling; but they are not aware of brands that sell these types of garments nor their validity. It was also found that consumers may not have much knowledge regarding environmental, sustainable and social apparel or their meanings.Originality/valueBy surveying the consumers about their perspectives on apparel labels and environmental, sustainable and social apparel, valuable market information was obtained. Sustainably and ethically produced garments are of demand as transparency in the apparel industry grows. Brands looking to become more transparent about their production methods will need to find new ways to reach their target market by accurately labelling products and educating their consumers about these label claims.
The development of inter-regional and intra-regional cooperation frameworks for multi-hazard early warning systems in South and South-East Asia
Authors: Borg Ruben Paul , Borg Axisa Glorianne , Ophiyandri Taufika , Hakam Abdul 
Published: October 2020

Purpose
This paper aims to provide a framework for building resilience to coastal hazards with reference to Asian nations at the local, intra-regional and inter-regional levels. This framework provides a roadmap that will enable higher education institutions in the region to play a significant role in educating and training new leaders for disaster risk reduction (DRR) and in working directly with local communities to implement plans.

Design/methodology/approach
Events such as the 2004 tsunami highlighted the transboundary nature of coastal hazard and the importance of regional cooperation. A framework for inter- and intra-regional cooperation was developed through focus groups organised with community participants in five Asian nations exposed to coastal risks: Sri Lanka, Maldives, Myanmar, Indonesia and the Philippines.

Findings
Different stakeholders assessed inter- and intra-regional cooperation at different levels as a means to provide a baseline scenario to develop a capacity-building roadmap for such cooperation. The discussions organised through structured face-to-face encounters considered cooperation at different scales: international, regional, national and local. The framework key areas were developed and included knowledge databases, data and resource sharing and exchange education programmes.

Originality/value
Multi-hazard early warning for more resilient coastal communities is increasingly complex in view of the discourse related to the wider economic and social environments. The research proposes a framework for inter- and intra-regional cooperation at different scales; from local to regional and to the inter-continental dimensions and even through a bottom-up approach, together with the experts’ and managing authorities’ top-down positions.
Sentiment urgency emotion conversion over time for business intelligence
Authors: Soussan Tariq , Trovati Marcello 
Published: October 2020

PurposeSocial media has become a vital part of any institute’s marketing plan. Social networks benefit businesses by allowing them to interact with their clients, grow brand exposure through offers and promotions and find new leads. It also offers vital information concerning the general emotions and sentiments directly connected to the welfare and security of the online community involved with the brand. Big organizations can make use of their social media data to generate planned and operational decisions. This paper aims to look into the conversion of sentiments and emotions over time.Design/methodology/approachIn this work, a model called sentiment urgency emotion detection (SUED) from previous work will be applied on tweets from two different periods of time, one before the start of the COVID-19 pandemic and the other after it started to monitor the conversion of sentiments and emotions over time. The model has been trained to improve its accuracy and F1 score so that the precision and percentage of correctly predicted texts is high. This model will be tuned to improve results (Soussan and Trovati, 2020a; Soussan and Trovati, 2020b) and will be applied on a general business Twitter account of one of the largest chains of supermarkets in the UK to be able to see what sentiments and emotions can be detected and how urgent they are.FindingsThis will show the effect of COVID-19 pandemic on the conversions of the sentiments, emotions and urgencies of the tweets.Originality/valueSentiments will be compared between the two periods to evaluate how sentiments and emotions vary over time taking into consideration the COVID-19 as an affective factor. In addition, SUED will be tuned to enhance results and the knowledge that is mined when turning data into decisions is crucial because it will aid stakeholders handling the institute to evaluate the topics and issues that were mostly emphasized.
Reconnecting governance configuration variables to enterprises contingency factors for optimizing productivity at the start-up level
Authors: Amedzro St-Hilaire Walter 
Published: October 2020

PurposeThe article broaches the important topic of the relationships between governance operationalizations and productivity at the start-up level. It proposes a new approach to reconnect the contingency factors to the optimization of productivity. This helps us to identify the changing characteristics that influence the determinants of decisions, actions and management of the technological projects of the mainly innovative enterprises.Design/methodology/approachThe study uses techniques that effectively solve unobserved endogeneity and heterogeneity problems in enterprises: an empirical–structural design. With this method, this study enables rich empirical conceptualization and helps with extending theory. However, there is a need to further the research by taking into account the system analysis and the complexity of the research object: one of the options might be to explore a possible follow-up of the research through drawing on ethnostatistics and qualimetrics.FindingsThe analysis reveals that the phenomenon of technological project productivity in operational governance context is thus manifested by the coexistence of the applied governance configuration variables, the contingency factors operationalization, the optimizing productivity mechanisms and this with the secular innovation and stagnation and stagnation. Ceteris paribus, the governance operationalizations have an important role in the productivity of technological projects of the innovative enterprises.Originality/valueThis research is the first to mobilize as major determinants of the operationalization of governance, the oversight of the capital, the dividend strategy and the system control, the managerial follow-up, the detection of opportunistic behaviours and the application of governing incentives (among others) as governance configuration variables in order to highlight their interactions with productivity in the innovative firm technological projects. For this reason alone, the paper will be referenced by other authors in the future.