bluuebunny/crossref_metadata_2025_split huggingface dataset:
Turning high-throughput structural biology into predictive inhibitor design
Authors: Saar Kadi L. , Fearon Daren ,   The COVID Moonshot Consortium, von Delft Frank , Chodera John D. , Lee Alpha A. 
Published: October 2021

AbstractA common challenge in drug design pertains to finding chemical modifications to a ligand that increases its affinity to the target protein. An underutilised advance is the increase in structural biology throughput, which has progressed from an artisanal endeavour to a monthly throughput of up to 100 different ligands against a protein in modern synchrotrons. However, the missing piece is a framework that turns high throughput crystallography data into predictive models for ligand design. Here we designed a simple machine learning approach that predicts protein-ligand affinity from experimental structures of diverse ligands against a single protein paired with biochemical measurements. Our key insight is using physics-based energy descriptors to represent protein-ligand complexes, and a learning-to-rank approach that infers the relevant differences between binding modes. We ran a high throughput crystallography campaign against the SARS-CoV-2 Main Protease (MPro), obtaining parallel measurements of over 200 protein-ligand complexes and the binding activity. This allows us to design a one-step library syntheses which improved the potency of two distinct micromolar hits by over 10-fold, arriving at a non-covalent and non-peptidomimetic inhibitor with 120 nM antiviral efficacy. Crucially, our approach successfully extends ligands to unexplored regions of the binding pocket, executing large and fruitful moves in chemical space with simple chemistry.
Diet-induced obese mice are resistant to improvements in cardiac function resulting from short-term adropin treatment
Authors: Thapa Dharendra , Xie Bingxian , Mushala Bellina A.S. , Zhang Manling , Manning Janet R. , Bugga Paramesha , Stoner Michael W. , Jurczak Michael J. , Scott Iain 
Published: October 2021

ABSTRACTPrevious studies have shown that treatment with recombinant adropin, a circulating peptide secreted by the liver and brain, restores glucose utilization in the hearts of diet-induced obese mice. This restoration of fuel substrate flexibility, which is lost in obese and diabetic animals, has the potential to improve contractile function in the diabetic heart. Using an ex vivo approach, we examined whether short-term adropin treatment could enhance cardiac function in a mouse model of diet-induced obesity. Our study showed that acute adropin treatment reduces inhibitory phosphorylation of pyruvate dehydrogenase in primary neonatal cardiomyocytes, and leads to moderate improvements in ex vivo cardiac function in mice fed a low fat diet. Conversely, short-term exposure to adropin led to a small decrease in cardiac function in mice fed a long-term high fat diet. Insulin treatment did not significantly alter cardiac function in adropin treated hearts from either low or high fat diet mice, however acute adropin treatment did moderately restore downstream insulin signaling in high fat diet fed mice. Overall, these data suggest that in an ex vivo setting, acute adropin treatment alone is not sufficient to promote improved cardiac function in obese animals.
Characterization of Cell-cell Communication in Autistic Brains with Single Cell Transcriptomes
Authors: Astorkia Maider , Lachman Herbert M. , Zheng Deyou 
Published: October 2021

AbstractAutism spectrum disorder is a neurodevelopmental disorder, affecting 1-2% of children. Studies have revealed genetic and cellular abnormalities in the brains of affected individuals, leading to both regional and distal cell communication deficits. Recent application of single cell technologies, especially single cell transcriptomics, has significantly expanded our understanding of brain cell heterogeneity and further demonstrated that multiple cell types and brain layers or regions are perturbed in autism. The underlying high-dimensional single cell data provides opportunities for multi-level computational analysis that collectively can better deconvolute the molecular and cellular events altered in autism. Here, we apply advanced computation and pattern recognition approaches on single cell RNA-seq data to infer and compare inter-cell-type signaling communications in autism brains and controls. Our results indicate that at a global level there are cell-cell communication differences in autism in comparison to controls, largely involving neurons as both signaling senders and receivers, but glia also contribute to the communication disruption. Although the magnitude of change is moderate, we find that excitatory and inhibitor neurons are involved in multiple intercellular signaling that exhibit increased strengths in autism, such as NRXN and CNTN signaling. Not all genes in the intercellular signaling pathways are differentially expressed, but genes in the pathways are enriched for axon guidance, synapse organization, neuron migration, and other critical cellular functions. Furthermore, those genes are highly connected to and enriched for genes previously associated with autism risks. Overall, our proof-of-principle computational study using single cell data uncovers key intercellular signaling pathways that are potentially disrupted in the autism brains, suggesting that more studies examining cross-cell type affects can be valuable for understanding autism pathogenesis.
Transcriptomic responses of Galápagos finches to avian pox virus infection
Authors: McNew Sabrina M. , Yepez Janaí , Loyola C. Diana , Andreadis Catherine , Fessl Birgit 
Published: October 2021

AbstractEmerging pathogens can have devastating effects on naïve hosts, but disease outcomes often vary among hosts. Comparing the cellular response of different host species to infection can provide insight into mechanisms of host defense and the basis of host susceptibility to disease. Here, we used RNA-seq to characterize the transcriptomic response of Darwin’s finches to avian poxvirus, which is introduced to the Galápagos Islands. We tested whether gene expression differs between infected and uninfected birds, and whether transcriptomic differences were related either to known antiviral mechanisms and/or the co-option of the host cellular environment by the virus. We compared two species, the medium ground finch (Geospiza fortis) and the vegetarian finch (Platyspiza crassirostris), to determine whether related species have similar responses to the same novel pathogen. We found that medium ground finches had a strong transcriptomic response to infection, upregulating genes involved in the innate immune response including interferon production, inflammation, and other immune signaling pathways. In contrast, vegetarian finches had a more limited response to infection. Our results also revealed evidence of viral manipulation of the host’s cellular function and metabolism, providing insight into the ways in which poxviruses affect their hosts. Many of the transcriptomic responses to infection mirrored known processes seen in model and in-vitro studies of poxviruses indicating that many pathways of host defense against poxviruses are conserved among vertebrates and present even in hosts without a long evolutionary history with the virus. At the same time, the variation we observed between closely related species indicates that some endemic species of Galápagos finch may be more susceptible to avian pox than others.
Tiam1-mediated synaptic plasticity drives comorbid depressive symptoms in chronic pain
Authors: Ru Qin , Lu Yungang , Saifullah Ali Bin , Blanco Francisco A , Yao Changqun , Cata Juan P , Li De-Pei , Tolias Kimberley F , Li Lingyong 
Published: October 2021

SummaryHyperactivity in the anterior cingulate cortex (ACC) drives comorbid depressive symptoms in chronic pain, but the cause of ACC hyperactivity is currently unclear. Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, induces rapid and sustained antidepressant-like effects in chronic pain-induced depression in both patients and animal models. However, the mechanisms underlying ketamine’s sustained antidepressant effects remain elusive. Here, we show that Tiam1, a Rac1-specific guanine nucleotide exchange factor (GEF) that was previously identified as a critical mediator of NMDAR-dependent dendritic spine development, is activated in the ACC in chronic pain mice displaying depressive-like behaviors. Conditional deletion of Tiam1 from postnatal forebrain excitatory neurons, specific deletion of Tiam1 from ACC neurons, or pharmacological inhibition of the Tiam1-Rac1 signaling pathway prevents chronic pain-induced depressive-like behaviors in mice. Biochemical, morphological, and electrophysiological assays reveal that Tiam1 orchestrates synaptic structural and functional remodeling in ACC neurons via actin cytoskeleton reorganization and synaptic NMDAR stabilization. This Tiam1-coordinated synaptic plasticity underpins ACC hyperactivity and drives chronic pain-induced depressive-like behaviors. Ketamine induces sustained antidepressant effects in chronic pain by blocking Tiam1-mediated synaptic structural and functional plasticity in ACC neurons. Our results reveal Tiam1 as a key factor in the pathophysiology of chronic pain-induced depression and in the sustained antidepressant effects of ketamine in ACC neurons. These findings highlight Tiam1 as a potential therapeutic target for the treatment of comorbid depressive symptoms in chronic pain.
CFD analysis of variable geometric angle winglets
Authors: Kazim Ali Hussain , Malik Abdullah Hamid , Ali Hammad , Raza Muhammad Usman , Khan Awais Ahmad , Aized Tauseef , Shabbir Aqsa 
Published: October 2021

Purpose
Winglets play a major role in saving fuel costs because they reduce the lift-induced drag formed at the wingtips. The purpose of this paper is to obtain the best orientation of the winglet for the Office National d’Etudes et de Recherches Aérospatiales (ONERA) M6 wing at Mach number 0.84 in terms of lift to drag ratio.

Design/methodology/approach
A computational fluid dynamics analysis of the wing-winglet configuration based on the ONERA M6 airfoil on drag reduction for different attack angles at Mach 0.84 was performed using analysis of systems Fluent. First, the best values of cant and sweep angles in terms of aerodynamic performance were selected by performing simulations. The analysis included cant angle values of 30°, 40°, 45°, 55°, 60°, 70° and 75°, while for the sweep angles 35°, 45°, 55°, 65° and 75° angles were used. The aerodynamic performance was measured in terms of the obtained lift to drag ratios.

Findings
The results showed that slight alternations in the winglet configuration can improve aerodynamic performance for various attack angles. The best lift to drag ratio for the winglet was achieved at a cant angle of 30° and a sweep angle of 65°, which caused a 5.33% increase in the lift to drag ratio. The toe-out angle winglets as compared to the toe-in angles caused the lift to drag ratio to increase because of more attached flow at its surface. The maximum value of the lift to drag ratio was obtained with a toe-out angle (−5°) at an angle of attack 3° which was 2.53% greater than the zero-toed angle winglet.

Originality/value
This work is relatively unique because the cant, sweep and toe angles were analyzed altogether and led to a significant reduction in drag as compared to wing without winglet. The wing model was compared with the results provided by National Aeronautics and Space Administration so this validated the simulation for different wing-winglet configurations.
Assessing the financial condition and accounts receivable risk among US farmer cooperatives
Authors: Mashange Gerald , Briggeman Brian C. 
Published: October 2021

PurposeThe purpose of this paper is to examine the financial condition and ability of farmer cooperatives to withstand significant increases in bad debt expense.Design/methodology/approachA unique data set of farmer cooperative financial statements that spans from 1996 to 2019 is used to examine the changes in profitability, solvency, liquidity and accounts receivable risk. Also, a deterministic stress test model is designed to shock bad debt expense and the resulting write-off of accounts receivable for farmer cooperatives. The stress test provides insights to the resiliency of farmer cooperatives.FindingsResults find that farmer cooperatives are in a strong financial position, which has improved over time. The majority of farmer cooperatives are able to absorb a substantial increase in bad debt expense because of their sizable, retained earnings position. However, cooperatives that have significant profitability challenges do experience much larger losses, especially mixed farmer cooperatives (roughly equally amounts of grain and farm supply sales) and large cooperatives with more than $500 million in sales.Practical implicationsThe stress test results suggest farmer cooperative managers and boards of directors could re-examine their credit policies and consider extending additional credit. Also, cooperatives should consider monitoring and identifying an optimal accounts receivable to retained earnings ratio, which is similar to how banks examine their tier 1 capital ratios.Originality/valueThe value of this study is having data that allows for the examination of the financial condition of farmer cooperatives over time. Also, having current data means the accounts receivable stress test results are more relevant and timelier. This is important because these accounts receivable are primarily tied to crop input supplies, and farmer cooperatives are a significant market participant in the crop input supply market.
Predicting hybrid entrepreneurship among secondary school teachers in Nigeria
Authors: Adebusuyi Adeola Samuel , Adebusuyi Olubusayo Foluso 
Published: October 2021

PurposeThe purpose of this study is to investigate how degree-holding secondary school teachers cope in a recessive economy by embracing hybrid entrepreneurship (HE). Specifically, we investigated how comparison with referent others, underemployment and relative deprivation led to HE.Design/methodology/approachThe study adopted a cross-sectional research design. We used snowball and purposive sampling techniques to recruit 303 bachelor’s degree holders teaching in Nigerian public secondary schools in two states of the federation (Ondo and Ekiti states). We analyzed the data with regression path analysis and controlled for age and gender.FindingsThe results of this study showed the following. First, teachers were high in the feeling of pay underemployment and relative deprivation. Second, pay underemployment and relative deprivation directly led to HE. Third, teachers were indirectly high in HE through either pay underemployment or relative deprivation. Finally, underemployment and relative deprivation serially mediate the relationship between referent others and HE.Research limitations/implicationsOverall, the results suggest that teachers’ involvement in HE is necessity-driven to cope with the recessive Nigerian economy. However, future research should focus on a more experimental approach to determine the cause-effect relationship.Originality/valueThis is the first study to investigate how workers embrace HE to cope with the consequences of a recessive economy.
The rough road towards accounting harmonization of a developing country with a French accounting culture
Authors: Ben Slama Fatma , Oussii Ahmed Atef , Klibi Mohamed Faker 
Published: October 2021

Purpose
The purpose of this paper is to investigate in-depth and explain the issues related to the experience of Tunisia, a developing country, in its attempt to move from Euro-Continental rule-based generally accepted accounting principles (GAAPs) to an accounting system adapted to international financial reporting standards (IFRS).

Design/methodology/approach
The study is conducted via a qualitative methodology based on a content analysis of primary data from interviews with key actors involved in financial reporting in Tunisia.

Findings
Findings reveal that local Tunisian GAAPs, adapted to IFRS in their 1996 version, failed to establish a financial reporting accounting culture and meet public-interest firms’ informational needs. This is mainly related to factors, such as the simplified methods adopted (generally adequate to the identified needs of users of small and medium-sized entity financial statements) and the hybrid aspect of the Tunisian accounting standards due to the co-existence of Euro-Continental and Anglo-Saxon parties. Moreover, the findings show that the lack of political willpower and the absence of updates to changes in IFRS have compromised the proper functioning of standardization and control structures.

Practical implications
The study’s results may interest regulators and policymakers of many developing countries that have not pursued the harmonization of their local GAAPs with IFRS. In addition, findings from the research provide insights into the rough road towards harmonization, the dysfunctions of the latter and delays in developing countries.

Originality/value
The research highlights the complexity for an emerging country with Euro-Continental accounting traditions to move to IFRS.
Do young consumers care about ethical consumption? Modelling Gen Z's purchase intention towards fair trade coffee
Authors: Robichaud Zachary , Yu Hong 
Published: October 2021

PurposeA global shift in ethical/sustainable purchase drivers highlights Generation Z (persons aged 15–24) as an important market for producers and marketers. Although much research has touched on fair trade consumption, very little has focused on Gen Z's consumption patterns. This study provides insights into and implications of younger consumers' motivations in ethical/sustainable consumption.Design/methodology/approachThis research examines Gen Z's purchase intention towards fair trade coffee with the theory of reasoned action framework. Data were collected with a convenience sample, and analyses were conducted using structural equation modelling.FindingsThe research found a significant influence of knowledge of fair trade towards product interest. Furthermore, general attitudes towards fair trade had a significant influence on product interest, product likeability and convenience. Lastly, product interest and subjective norms significantly influenced Gen Z's purchase intentions towards fair trade coffee.Originality/valueFindings suggest that Gen Z's shift in ethical/sustainable consumption revolves around their subjective norms or peer influence circles and contributes to the notions of self-branding, identify claims and social currency. Younger generations are digital natives, and social media has created a looking glass into their actions. This digital expansion has created more opportunities for individuals to monitor the actions of others and release information in real-time. Therefore, ethical/sustainable consumption by Gen Z can be used as a communication tool among their peers to project personal values and ideological shifts and to influence others close to them.
Assessment of systemic and carcinogenic health risks of persistent organochlorine pesticide residues in four fruit vegetables in south-western Nigeria
Authors: Odewale Gideon Oluwasogo , Sosan Mosudi Babatunde , Oyekunle John Adekunle Oyedele , Adeleye Adeoluwa Oluwaseyi 
Published: October 2021

PurposeThe study assessed the levels of organochlorine pesticides (OCPs) and their potential non-carcinogenic and carcinogenic health risks in four regularly consumed fruit vegetables.Design/methodology/approachThe OCPs’ residues were quantified using a gas chromatograph coupled with an electron capture detector (GC-ECD) and the dietary exposure of children, and adult consumers to the detected OCPs was evaluated using carcinogenic and systemic health risk estimations.FindingsAldrin, endrin, endrin aldehyde, a-endosulfan, β-endosulfan, endosulfan sulphate, heptachlor, heptachlor epoxide and dieldrin were detected in the four fruit vegetables. The predominant OCP residue in carrot, cucumber, tomatoes and watermelon was endosulfan sulphate with mean concentrations of 2.532 mg kg−1, 1.729 mg kg−1, 2.363 mg kg−1 and 1.154 mg kg−1, respectively. The residues levels in some of the fruit vegetables were higher than their respective maximum residue levels (MRLs) of 0.01–0.05 mg kg−1 set by the European Commission with concentrations above MRLs ranging between 25.5% and 100%. The systemic health risk estimations showed that the hazard index (HI) values for carrot (3.20), cucumber (9.25), tomatoes (50.21) and watermelon (16.76) were >1 for children consumers and the respective HI values of 2.87, 15.57 and 5.20 for adult consumers of cucumber, tomatoes and watermelon were >1 which implies potential systemic health risks. Four carcinogens (aldrin, dieldrin, heptachlor and heptachlor epoxide) had cancer risk index values greater than the acceptable risk of 1 in 1 million for both adult and children consumers.Originality/valueThe paper shows that despite the ban on the use of OCPs in Nigeria, they are still being used for agricultural production especially on some locally produced and regularly consumed fruit vegetables as reported in the present study. The non-existence of surveillance programmes on pesticide usage and the lack of proper monitoring of pesticide residues in food products including fruit and vegetables must have contributed to the levels of the detected OCP in the samples analysed. The current daily intake of OCP via contaminated vegetables may pose potential health risks to both the children and adult consumers of the fruit vegetables.
Exploring the benefits of service productisation: support for business processes
Authors: Harkonen Janne 
Published: October 2021

PurposeThe study aims to explore the benefits of service productisation to provide further understanding on the productisation concept as support for business processes and service management. The concept has been deficiently discussed regardless of the potential significance to the whole formed by service products, business processes, information technology (IT), people and data.Design/methodology/approachIn the study, the exploratory empirical evidence is presented from 16 cases, 4 of which are from companies that are globally well-known.FindingsThe key findings of the paper include an overview of the benefits of service productisation and the relation to service offering, service processes and related resources. The concept links to the management of the whole formed by service products, business processes, IT, people and data. The noted benefits seem to be applicable to productisation of different service types, whilst some service characteristics may affect the specific emphasis.Research limitations/implicationsThe limitations involve using secondary data, which, however, makes the cases less biased regarding the aims. Primary data are required to gain further insights into the phenomena and the identified benefits.Practical implicationsThe findings provide support for issues that are commonly discussed by practitioners on a concept that is less studied by the scientific literature. Practitioners can work towards organisational efficiency and effectiveness by understanding the benefits of productisation. Understanding service productisation can support the effective management of business processes and work towards prosperity in the service business.Originality/valueThe study is the first one to analyse the benefits of service productisation by exploring the issue through multiple cases and attempting to identify aspects for further attention by the academic community.