bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prior vaccination with the rVSV-ZEBOV vaccine does not interfere with but improves the efficacy of postexposure antibody treatment in nonhuman primates exposed to Ebola virus
Authors: Cross Robert W. , Bornholdt Zachary A. , Prasad Abhishek N. , Geisbert Joan B. , Borisevich Viktoriya , Agans Krystle N. , Deer Daniel J. , Melody Kevin , Fenton Karla A. , Feldmann Heinz , Sprecher Armand , Zeitlin Larry , Geisbert Thomas W. 
Published: April 2020

AbstractA replication-competent, vesicular stomatitis virus vaccine expressing the Ebola virus (EBOV) glycoprotein (GP) (rVSV-ZEBOV) was successfully used during the 2013-16 EBOV epidemic1. Additionally, chimeric and human monoclonal antibodies (mAb) against the EBOV GP showed promise in animals and EBOV patients when administered therapeutically2-6. Given the large number of at-risk humans being prophylactically vaccinated with rVSV-ZEBOV, there is uncertainty regarding whether vaccination would preclude use of antibody treatments in the event of a known exposure of a recent vaccinee. To model a worst-case scenario, we performed a study using rhesus monkeys vaccinated or unvaccinated with the rVSV-ZEBOV vaccine. One day after vaccination, animals were challenged with a uniformly lethal dose of EBOV. Five vaccinated animals and five unvaccinated animals were then treated with the anti-EBOV GP mAb-based therapeutic MIL77 starting 3 days postexposure. Additionally, five vaccinated macaques received no therapeutic intervention. All five macaques that were vaccinated and subsequently treated with MIL77 showed no evidence of clinical illness and survived challenge. In contrast, all five animals that only received the rVSV-ZEBOV vaccine became ill and 2/5 survived; all five macaques that only received MIL77 only also became ill and 4/5 survived. Enhanced efficacy of vaccinated animals that were treated with MIL77 was associated with delayed EBOV viremia attributed to the vaccine. These results suggest that rVSV-ZEBOV augments immunotherapy.
SnoRNA signatures in cartilage ageing and osteoarthritis
Authors: Peffers Mandy J , Chabronova Alzbeta , Balaskas Panagiotis , Fang Yongxiang , Dyer Philip , Cremers Andy , Emans Pieter , Feczko Peter , Caron Marjolein , Welting Tim JM 
Published: April 2020

ABSTRACTObjectivesOsteoarthritis (OA) presents as a change in the chondrocyte phenotype and an imbalance between anabolic and catabolic processes. Age affects its onset and progression. Small nucleolar RNAs (SnoRNAs) direct chemical modification of RNA substrates to fine-tune spliceosomal and rRNA function, accommodating changing requirements for splicing and protein synthesis during health and disease. This study was undertaken to examine how changes in snoRNAs expression may have a role in OA.MethodsArticular cartilage from young, old and OA knees was used in a microarray study to identify alterations in snoRNA expression. Changes in expression of snoRNAs in OA-like conditions were studied in chondrocytes using interleukin-1 and OA synovial fluid. SNORD26 and SNORD96A knockdown and overexpression were undertaken using antisense oligonucleotides and overexpression plasmids.ResultsWe identified panels of snoRNAs differentially expressed due to ageing (including SNORD96A, SNORD44) and OA (including SNORD26 and SNORD116) and findings were validated in an independent cohort.In vitroexperiments using OA-like conditions affected snoRNA expression. Knockdown or overexpression of SNORD26 or SNORD96A resulted in changes in chondrogenic, hypertrophic, rRNA and osteoarthritis related gene expression.ConclusionWe demonstrate that snoRNA expression changes in cartilage ageing, and OA and in OA-like conditions, and when the expression of these snoRNAs is altered this affects chondrogenic and hypertrophic gene expression. Thus, we propose an additional dimension in the molecular mechanisms underlying cartilage ageing and OA through the dysregulation of snoRNAs.
Visualising G-quadruplex DNA dynamics in live cells by fluorescence lifetime imaging microscopy
Authors: Summers Peter A. , Lewis Benjamin W. , Gonzalez-Garcia Jorge , Porreca Rosa M. , Lim Aaron H.M. , Cadinu Paolo , Martin-Pintado Nerea , Mann David , Edel Joshua B. , Vannier Jean Baptiste , Kuimova Marina K. , Vilar Ramon 
Published: April 2020

ABSTRACTGuanine rich regions of oligonucleotides fold into quadruple-stranded structures called G-quadruplexes (G4). Increasing evidence suggests that these G4 structures formin vivoand play a crucial role in cellular processes. However, their direct observation in live cells remains a challenge. Here we demonstrate that a fluorescent probe (DAOTA-M2) in conjunction with Fluorescence Lifetime Imaging Microscopy (FLIM) can identify G4 within nuclei of live and fixed cells. We present a new FLIM-based cellular assay to study the interaction of non-fluorescent small molecules with G4 and apply it to a wide range of drug candidates. We also demonstrate thatDAOTA-M2can be used to study G4 stability in live cells. Reduction ofFancJandRTEL1expression in mammalian cells increases theDAOTA-M2lifetime and therefore suggests an increased number of G4 in these cells, implying thatFancJandRTEL1play a role in resolving G4 structuresin cellulo.
NOGEA: Network-Oriented Gene Entropy Approach for Dissecting Disease Comorbidity and Drug Repositioning
Authors: Guo Zihu , Fu Yingxue , Huang Chao , Zheng Chunli , Wu Ziyin , Chen Xuetong , Gao Shuo , Ma Yaohua , Shahen Mohamed , Li Yan , Tu Pengfei , Zhu Jingbo , Wang Zhenzhong , Xiao Wei , Wang Yonghua 
Published: April 2020

AbstractRapid development of high-throughput technologies has permitted the identification of an increasing number of disease-associated genes (DAGs), which are important for understanding disease initiation and developing precision therapeutics. However, DAGs often contain large amounts of redundant or false positive information, leading to difficulties in quantifying and prioritizing potential relationships between these DAGs and human diseases. In this study, a network-oriented gene entropy approach (NOGEA) is proposed for accurately inferring master genes that contribute to specific diseases by quantitatively calculating their perturbation abilities on directed disease-specific gene networks. In addition, we confirmed that the master genes identified by NOGEA have a high reliability for predicting disease-specific initiation events and progression risk. Master genes may also be used to extract the underlying information of different diseases, thus revealing mechanisms of disease comorbidity. More importantly, approved therapeutic targets are topologically localized in a small neighborhood of master genes on the interactome network, which provides a new way for predicting new drug-disease associations. Through this method, 11 old drugs were newly identified and predicted to be effective for treating pancreatic cancer and then validated byin vitroexperiments. Collectively, the NOGEA was useful for identifying master genes that control disease initiation and co-occurrence, thus providing a valuable strategy for drug efficacy screening and repositioning. NOGEA codes are publicly available athttps://github.com/guozihuaa/NOGEA.
Noise propagation in gene expression in the presence of decoys
Authors: Dey Supravat , Singh Abhyudai 
Published: April 2020

AbstractGenetically-identical cells can show remarkable intercellular variability in the level of a given protein which is commonly known as the gene expression noise. Besides intrinsic fluctuations that arise from the inherent stochasticity of the biochemical processes, a significant source of expression noise is extrinsic. Such extrinsic noise in gene expression arises from cell-to-cell differences in expression machinery, transcription factors, cell size, and cell cycle stage. Here, we consider the synthesis of a transcription factor (TF) whose production is impacted by a dynamic extrinsic disturbance, and systematically investigate the regulation of expression noise by decoy sites that can sequester the protein. Our analysis shows that increasing decoy numbers reduce noise in the level of the free (unbound) TF with noise levels approaching the Poisson limit for large number of decoys. Interestingly, the suppression of expression noise compared to no-decoy levels is maximized at intermediate disturbance timescales. Finally, we quantify the noise propagation from the TF to a downstream target protein and find counterintuitive behaviors. More specifically, for nonlinear dose responses of target-protein activation, the noise in the target protein can increase with the inclusion of decoys, and this phenomenon is explained by smaller but more prolonged fluctuations in the TF level. In summary, our results illustrates the nontrivial effects of high-affinity decoys in shaping the stochastic dynamics of gene expression to alter cell fate and phenotype at the single-cell level.
Soft-wired long-term memory in a natural recurrent neuronal network
Authors: Casal Miguel A. , Galella Santiago , Vilarroya Oscar , Garcia-Ojalvo Jordi 
Published: April 2020

Neuronal networks provide living organisms with the ability to process information. They are also characterized by abundant recurrent connections, which give rise to strong feed-back that dictates their dynamics and endows them with fading (short-term) memory. The role of recurrence inlong-termmemory, on the other hand, is still unclear. Here we use the neuronal network of the roundwormC. elegansto show that recurrent architectures in living organisms can exhibit long-term memory without relying on specific hard-wired modules. A genetic algorithm reveals that the experimentally observed dynamics of the worm’s neuronal network exhibits maximal complexity (as measured by permutation entropy). In that complex regime, the response of the system to repeated presentations of a time-varying stimulus reveals a consistent behavior that can be interpreted as soft-wired long-term memory.A common manifestation of our ability to remember the past is the consistence of our responses to repeated presentations of stimuli across time. Complex chaotic dynamics is known to produce such reliable responses in spite of its characteristic sensitive dependence on initial conditions. In neuronal networks, complex behavior is known to result from a combination of (i) recurrent connections and (ii) a balance between excitation and inhibition. Here we show that those features concur in the neuronal network of a living organism, namelyC. elegans. This enables long-term memory to arise in an on-line manner, without having to be hard-wired in the brain.
Molecular free energy optimization on a computational graph
Authors: Cao Xiaoyong , Tian Pu 
Published: April 2020

AbstractFree energy is arguably the most important property of molecular systems. Despite great progress in both its efficient estimation by scoring functions/potentials and more rigorous computation based on extensive sampling, we remain far from accurately predicting and manipulating biomolecular structures and their interactions. There are fundamental limitations, including accuracy of interaction description and difficulty of sampling in high dimensional space, to be tackled. Computational graph underlies major artificial intelligence platforms and is proven to facilitate training, optimization and learning. Combining autodifferentiation, coordinates transformation and generalized solvation free energy theory, we construct a computational graph infrastructure to realize seamless integration of fully trainable local free energy landscape with end to end differentiable iterative free energy optimization. This new framework greatly improves efficiency by replacing local sampling with differentiation. Its specific implementation in protein structure refinement achieves superb efficiency and competitive accuracy when compared with state of the art all-atom mainstream methods.
3D Hyaluronic Acid Hydrogels for Modeling Oligodendrocyte Progenitor Cell Behavior as a Function of Matrix Stiffness
Authors: Unal Deniz B. , Caliari Steven R. , Lampe Kyle J. 
Published: April 2020

AbstractThe lack of regenerative solutions for demyelination within the central nervous system (CNS) motivates the need for better understanding of the oligodendrocytes that give rise to myelination. In this work, we introduce a 3D hyaluronic acid (HA) hydrogel system to study the effects of mechanical properties on the behavior of oligodendrocyte progenitor cells (OPCs), the cells that differentiate into myelin-producing oligodendrocytes in the CNS. We tuned the stiffness of the hydrogels to match brain tissue (storage modulus 200 – 2000 Pa) and studied the effects of stiffness on metabolic activity, proliferation, and cell morphology of OPCs over a 7 day period. Although hydrogel mesh size decreased with increasing stiffness, all hydrogel groups facilitated OPC proliferation and mitochondrial metabolic activity to similar degrees. However, OPCs in the two lower stiffness hydrogel groups (169.8 ± 42.1 Pa and 793.9 ± 203.3 Pa) supported greater adenosine triphosphate (ATP) levels per cell than the highest stiffness hydrogels (2178.7 ± 127.2 Pa). Lower stiffness hydrogels also supported higher levels of cell viability and larger cell spheroid formation compared to the highest stiffness hydrogels. Together, these data suggest that 3D HA hydrogels are a useful platform for studying OPC behavior and that OPC growth/metabolic health may be favored in lower stiffness microenvironments mimicking brain tissue mechanics.
Caenorhabditis elegansdauers vary recovery in response to bacteria from natural habitat
Authors: Bubrig Louis T. , Sutton John M. , Fierst Janna L. 
Published: April 2020

AbstractMany species use dormant stages for habitat selection by tying recovery from the stage to informative external cues. Other species have an undiscerning strategy in which they recover randomly despite having advanced sensory systems. We investigated whether elements of a species’ habitat structure and life history can bar it from developing a discerning recovery strategy. The nematodeCaenorhabditis eleganshas a dormant stage called the dauer larva that disperses between habitat patches. On one hand,C. eleganscolonization success is profoundly influenced by the bacteria found in its habitat patches, so we might expect this to select for a discerning strategy. On the other hand,C. elegans’ habitat structure and life history suggest that there is no fitness benefit to varying recovery, which might select for an undiscerning strategy. We exposed dauers of three genotypes to a range of bacteria acquired from the worms’ natural habitat. We found thatC. elegansdauers recover in all conditions but increase recovery on certain bacteria depending on the worm’s genotype, suggesting a combination of undiscerning and discerning strategies. Additionally, the worms’ responses did not match the bacteria’s objective quality, suggesting that their decision is based on other characteristics.
Understanding the use of YouTube as a learning resource: a social cognitive perspective
Authors: Zhou Quan , Lee Chei Sian , Sin Sei-Ching Joanna , Lin Sijie , Hu Huijie , Fahmi Firdaus Bin Ismail Muhammad 
Published: April 2020

PurposeDrawing from social cognitive theory, the purpose of this study is to examine how personal, environmental and behavioral factors can interplay to influence people's use of YouTube as a learning resource.Design/methodology/approachThis study proposed a conceptual model, which was then tested with data collected from a survey with 150 participants who had the experience of using YouTube for learning. The bootstrap method was employed to test the direct and mediation hypotheses in the model.FindingsThe results revealed that personal factors, i.e. learning outcome expectations and attitude, had direct effects on using YouTube as a learning resource (person → behavior). The environmental factor, i.e. the sociability of YouTube, influenced the attitude (environment → person), while the behavioral factor, i.e. prior experience of learning on YouTube, affected learning outcome expectations (behavior → person). Moreover, the two personal factors fully mediated the influences of sociability and prior experience on YouTube usage for learning.Practical implicationsThe factors and their relationships identified in this study provide important implications for individual learners, platform designers, educators and other stakeholders who encourage the use of YouTube as a learning resource.Originality/valueThis study draws on a comprehensive theoretical perspective (i.e. social cognitive theory) to investigate the interplay of critical components (i.e. individual, environment and behavior) in YouTube's learning ecosystem. Personal factors not only directly influenced the extent to which people use YouTube as a learning resource but also mediated the effects of environmental and behavioral factors on the usage behavior.
Scattering by cracks in a conducting surface
Authors: Jacobs Ralf T. , Kost Arnulf 
Published: April 2020

Purpose
The purpose of this study is the formulation of an efficient method to compute and analyse the scattering characteristics of cracks or grooves in a conducting object, where the size of the crack is significantly larger than the wavelength of an incident plane wave.

Design/methodology/approach
A hybrid finite element-boundary element procedure is formulated for the computation of the scattering properties of the object, where the fast multipole method is used in the boundary integral formulation. The basic fast multipole procedure is enhanced by utilising a fast Fourier transform-based convolution algorithm for the computation of the interactions between groups of source and field elements.

Findings
The algorithm accelerates the evaluation of the group interactions and enables the reduction of the memory requirements without introducing an additional approximation into the procedure.

Originality/value
The fast multipole method with convolution algorithm shows to be more efficient for the computation of scattering problems with a large number of unknowns than the conventional procedure.
Factors influencing the intention to buy over-the-counter medicines: empirical study
Authors: Habash Raeda , Al-Dmour Hani 
Published: April 2020

Purpose
This study aims to examine the antecedent factors (internal and external) that influence intentions to buy over-the-counter (OTC) medicines in Jordan.

Design/methodology/approach
A conceptual framework was developed based on consumer buying behavior theoretical background and a review of the relevant literature. A quantitative approach and a convenience sampling method were used to obtain data from self-administered questionnaires, which were completed by 351 academic staff from selected Jordanian universities.

Findings
The results indicate that all antecedent factors (internal, external and combined) have significant positive influences on the intentions to buy OTC medicines. Internal factors are more influential than external factors; however, the combination of internal and external factors resulted in the greatest influence on buying OTC medicines compared to each category separately.

Originality/value
This paper has integrated and examined empirically the antecedent factors that influence intentions to buy OTC medicines (internal, external and combined) in Jordan’s business environment context as a developing country for the first time.
Factors affecting spectators’ adoption of digital ticketing: the case of interscholastic sports
Authors: Marquez Armin , Cianfrone Beth A. , Kellison Timothy 
Published: April 2020

PurposeThe paper investigates the factors influencing spectators’ adoption of digital (mobile) ticketing by expanding the Technology Acceptance Model (TAM; Davis, 1989) to include two variables overlooked in previous ticketing research: (1) trust of digital ticketing and (2) willingness to pay convenience fees. The study provides information on consumer behavior that may aid sports managers’ decision-making.Design/methodology/approachThrough a paper-and-pencil survey of high school American football spectators (N = 523) over 12 games, the study examined perceived ease of use, perceived usefulness, the trust of digital ticketing, willingness to pay convenience fees and their effects on spectators’ intention to use digital ticketing.FindingsTrust of digital ticketing, willingness to pay a convenience fee and the perceived ease of use were found to influence the perceived usefulness of the technology, which, in turn, had a significant effect on the intention to use. Willingness to pay fees also had a direct effect on intention.Research limitations/implicationsAlthough every intention was made to ascertain a diverse sampling of schools (urban vs. suburban, large vs. small), it is worth noting that the sample location may be a limitation for the overall applicability.Practical implicationsThe manuscript includes practical applications for marketers and ticket sales staff. Digital (mobile) ticketing is on the rise. As segments like high school athletics adopt the technology, spectators’ evaluation of digital ticketing must be considered, given its impact on intentions to use.Originality/valueThe findings support the use of willingness to pay convenience fees and trust of digital ticketing as considerations in the TAM for understanding digital ticketing.