bluuebunny/crossref_metadata_2025 huggingface dataset:
An optimal growth law for RNA composition and its partial implementation through ribosomal and tRNA gene locations in bacterial genomes
Authors: Hu Xiao-Pan , Lercher Martin J.
Published: February 2021

The distribution of cellular resources across bacterial proteins has been quantified through phenomenological growth laws. Here, we describe a complementary bacterial growth law for RNA composition, emerging from optimal cellular resource allocation into ribosomes and ternary complexes. The predicted decline of the tRNA/rRNA ratio with growth rate agrees quantitatively with experimental data. Its regulation appears to be implemented in part through chromosomal localization, as rRNA genes are typically closer to the origin of replication than tRNA genes and thus have increasingly higher gene dosage at faster growth. At the highest growth rates inE. coli, the tRNA/rRNA ratio appears to be regulated entirely through this effect.
CD8+ T cell immunogenicity induced by endogenous EVs engineered by antigens fused to a truncated Nefmut EV-anchoring protein
Authors: Chiozzini Chiara , Manfredi Francesco , Ferrantelli Flavia , Leone Patrizia , Giovannelli Andrea , Olivetta Eleonora , Federico Maurizio
Published: February 2021

Intramuscular injection of DNA vectors expressing the extracellular vesicle (EV)-anchoring protein Nefmut fused at its C-terminus to viral and tumor antigens elicits a potent, effective, and anti-tolerogenic CD8+ T cell immunity against the heterologous antigen. The immune response is induced through the production of EVs incorporating Nefmut-derivatives released by muscle cells. In the perspective to a possible translation into the clinic of the Nefmut-based vaccine platform, we aimed at increasing its safety profile by identifying the minimal part of Nefmut retaining the EV-anchoring protein property. We found that a C-terminal deletion of 29-amino acids did not affect the ability of Nefmut to associate with EVs. Furthermore, the EV-anchoring function was preserved when antigens from both HPV16 (i.e., E6 and E7) and SARS-CoV-2 (i.e., S1 and S2) were fused to its C-terminus. By analyzing the immune responses induced after intramuscular injection of DNA vectors expressing fusion products based on the four viral antigens, we found that the Nefmut C-terminal deletion did not impact on the levels of antigen –specific CD8+ T lymphocytes as evaluated by IFN-γ EliSpot analysis and intracellular cytokine staining. In addition, immune responses at distal sites remained unaffected, as indicated by the similar percentages of SARS-CoV-2 S1- and S2-specific CD8+ T cells detected in spleens and lung airways of mice injected with DNA vectors expressing the viral antigens fused with either Nefmut or NefmutPL.

We concluded that the C-terminal Nefmut truncation does not affect stability, EV-anchoring, and CD8+ T cell immunogenicity of the fused antigen. Hence, NefmutPL represents a safer alternative to full-length Nefmut for the design of CD8+ T cell vaccines for humans.
The cryo-EM structure of vesivirus 2117 highlights functional variations in entry pathways for viruses in different clades of the Vesivirus genus
Authors: Sutherland Hazel , Conley Michaela J. , Emmott Edward , Streetley James , Goodfellow Ian G. , Bhella David
Published: February 2021

Vesivirus 2117 is an adventitious agent that has been responsible for lost productivity in biopharmaceutical production following contamination of Chinese hamster ovary cell cultures in commercial bioreactors. A member of theCaliciviridae, 2117 is classified within the Vesivirus genus in a clade that includes canine and mink caliciviruses but is distinct from the vesicular exanthema of swine clade, which includes the extensively studied feline calicivirus (FCV). We have used cryogenic electron microscopy (cryo-EM) to determine the structure of the capsid of this small, icosahedral, positive-sense RNA containing virus. We show that the outer face of the dimeric capsomeres, which contains the receptor binding site and major immunodominant epitopes in all caliciviruses studied thus far, is quite different from that of FCV. This is a consequence of a 22 amino-acid insertion in the sequence of the FCV major capsid protein that forms a ‘cantilevered arm’, which plays an important role in both receptor engagement and undergoes structural rearrangements thought to be important for genome delivery to the cytosol. Our data highlight a potentially important difference in the attachment and entry pathways employed by the different clades of the Vesivirus genus.
The glycosphingolipid inhibitor eliglustat inhibits autophagy in osteoclasts to increase bone mass and reduce myeloma bone disease
Authors: Leng Houfu , Zhang Hanlin , Li Linsen , Zhang Shuhao , Wang Yanping , Ersek Adel , Morris Emma , Sezgin Erdinc , Lee Yi-Hsuan , Li Yunsen , Mi Jianqing , Zhong Qing , Edwards Claire , Simon Anna Katharina , Horwood Nicole J.
Published: February 2021

Multiple myeloma (MM) is a fatal hematological malignancy, where the majority of patients are diagnosed with, or develop, destructive and debilitating osteolytic bone lesions. Current treatments for MM bone disease such as the bisphosphonate zoledronic acid can result in deleterious side effects at high doses. In this study, eliglustat, an FDA approved glycosphingolipid inhibitor, was shown to reduce MM bone disease in preclinical models of MM. Mechanistically, eliglustat alters the lipid composition and plasma membrane fluidity and acts as an autophagy flux inhibitor in bone-resorbing osteoclasts (OC). Autophagic degradation of the signaling molecule TRAF3 is key step in OC differentiation; this was prevented by eliglustat in OC precursors. In addition, eliglustat works depend on TRAF3in vivo. Furthermore, the combination of eliglustat and zoledronic acid was found to have an additive effect to reduce MM bone disease, suggesting the potential for combination therapies that would allow for drug dose reductions. Taken together, this project identifies a novel mechanism in which glycosphingolipid inhibition reduces osteoclastogenesis via autophagy and highlights the translational potential of eliglustat for the treatment of bone loss disorders such as MM.

One Sentence Summary

Translational use of eliglustat as an autophagy inhibitor to limit bone lesions in multiple myeloma.
Strong transgenerational effects but no genetic adaptation in zooplankton 24 years after an abrupt +10°C climate change
Authors: Pais-Costa Antónia Juliana , Lievens Eva J. P. , Redón Stella , Sánchez Marta I. , Jabbour-Zahab Roula , Joncour Pauline , Van Hoa Nguyen , Van Stappen Gilbert , Lenormand Thomas
Published: February 2021

The climate is currently warming fast, threatening biodiversity all over the globe. Adaptation is often rapid when the environment changes quickly, but for climate warming very little evidence is available. Here, we investigate the pattern of adaptation to an extreme +10°C climate change in the wild, following the introduction of brine shrimpArtemia franciscanafrom San Francisco Bay, USA, to Vinh Chau saltern in Vietnam. We use a resurrection ecology approach, hatching diapause eggs from the ancestral population and the introduced population after 13 and 24 years (resp. ~54 and ~100 generations). In a series of coordinated experiments, we determined whether the introducedArtemiashow increased tolerance to higher temperatures, and the extent to which genetic adaptation, developmental plasticity, transgenerational effects, and local microbiome differences contributed to this tolerance. We find that introduced brine shrimp do show increased phenotypic tolerance to warming. Yet strikingly, these changes do not have an additive genetic component, are not caused by mitochondrial genetic variation, and are not caused by epigenetic marks set by adult parents exposed to warming. Further, we do not find any developmental plasticity in response to warming, nor any protective effect of heat-tolerant local microbiota. We conclude that the evolution of shrimp’s extreme thermal tolerance is only due to transgenerational (great)grandparental effects, possibly epigenetic marks set by parents who were exposed to high temperatures as juveniles. This finding challenges standard models of genetic and plastic adaptive responses, and our conception of how species may cope with climate warming.

Significance statement

Adaptation is often rapid when environments change quickly, but for climate warming little evidence is available. Many studies report no genetic responses due to pre-existing plasticity, while others point towards epigenetics and microbiota effects. In this study, we take advantage of a natural experiment to study all of these effects. We use a set of coordinated experiments and a ‘resurrection ecology’ approach, reviving resting eggs of brine shrimp up to100 generations after their introduction from a temperate to a tropical saltern. We find that heat adaptation occurs, but heritability is fully “missing”. Plasticity and microbiota play no role either, indicating that only transgenerational (great)grandmaternal effects are involved. This finding prompts us to reconsider the relative importance of the different possible mechanisms by which phenotypic change can occur, especially in response to temperature variation.
Activity pulses induce spontaneous flow reversals in viscoelastic environments
Authors: VI M. Plan Emmanuel L. C. , Yeomans Julia M. , Doostmohammadi Amin
Published: February 2021

Complex interactions between cellular systems and their surrounding extracellular matrices are emerging as important mechanical regulators of cell functions such as proliferation, motility, and cell death, and such cellular systems are often characterized by pulsating acto-myosin activities. Here, using an active gel model, we numerically explore the spontaneous flow generation by activity pulses in the presence of a viscoelastic medium. The results show that cross-talk between the activity-induced deformations of the viscoelastic surroundings with the time-dependent response of the active medium to these deformations can lead to the reversal of spontaneously generated active flows. We explain the mechanism behind this phenomenon based on the interaction between the active flow and the viscoelastic medium. We show the importance of relaxation timescales of both the polymers and the active particles and provide a phase-space over which such spontaneous flow reversals can be observed. Our results suggest new experiments investigating the role of controlled pulses of activity in living systems ensnared in complex mircoenvironments.
Predictive systems biomarkers of response to immune checkpoint inhibitors
Authors: Lapuente-Santana Óscar , van Genderen Maisa , Hilbers Peter , Finotello Francesca , Eduati Federica
Published: February 2021

Cancer cells can leverage several cell-intrinsic and -extrinsic mechanisms to escape immune system recognition. The inherent complexity of the tumor microenvironment, with its multicellular and dynamic nature, poses great challenges for the extraction of biomarkers of immune response and immunotherapy efficacy. Here, we use RNA-seq data combined with different sources of prior-knowledge to derive system-based signatures of the tumor microenvironment, quantifying immune-cell composition and intra- and inter-cellular communications. We applied multi-task learning to these signatures to predict different hallmarks of immune responses and derive cancer-type-specific models based on interpretable systems biomarkers. By applying our models to independent RNA-seq data from cancer patients treated with PD-1 inhibitors, we demonstrated that our method to Estimate Systems Immune Response (EaSIeR) accurately predicts therapeutic outcome. We anticipate that EaSIeR will be a valuable tool to provide a holistic description of immune responses in complex and dynamic systems such as tumors using available RNA-seq data.
The differentiation of pluripotent stem cells towards transplantable endothelial progenitor cells
Authors: Qin Kezhou , Yang Jun
Published: February 2021

Endothelial progenitor cells (EPCs) and endothelial cells (ECs) have been applied in the clinic to treat pulmonary arterial hypertension (PAH), a disease characterized by disordered pulmonary vasculature. However, the lack of sufficient transplantable cells before the deterioration of disease condition is a current limitation to apply cell therapy in patients. It is necessary to differentiate pluripotent stem cells (PSCs) into EPCs and identify their characteristics. Comparing previously reported methods of human PSCs-derived ECs, we optimized a highly efficient differentiation protocol to obtain cells that match the phenotype of isolated EPCs from healthy donors. The protocol is compatible with chemically defined medium (CDM), it could produce a large number of clinically applicable cells with low cost. Moreover, we also found PSCs-derived EPCs express CD133, have some characteristics of mesenchymal stem cells and are capable of homing to repair blood vessels in zebrafish xenograft assays. In addition, we further revealed that IPAH PSCs-derived EPCs have higher expression of proliferation-related genes and lower expression of immune-related genes than normal EPCs and PSCs-derived EPCs through microarray analysis. In conclusion, we optimized a highly efficient differentiation protocol to obtain PSCs-derived EPCs with the phenotypic and molecular characteristics of EPCs from healthy donors which distinguished them from EPCs from PAH.
Structure of human Nav1.5 reveals the fast inactivation-related segments as a mutational hotspot for the Long QT Syndrome
Authors: Li Zhangqiang , Jin Xueqin , Wu Tong , Zhao Xin , Wang Weipeng , Lei Jianlin , Pan Xiaojing , Yan Nieng
Published: February 2021

Nav1.5 is the primary voltage-gated Na+(Nav) channel in the heart. Mutations of Nav1.5 are associated with various cardiac disorders exemplified by the type 3 long QT syndrome (LQT3) and Brugada syndrome (BrS). E1784K is a common mutation that has been found in both LQT3 and BrS patients. Here we present the cryo-EM structure of the human Nav1.5-E1784K variant at an overall resolution of 3.3 Å. Structural mapping of 91 and 178 point mutations that are respectively associated with LQT3 and BrS reveals a unique distribution pattern for LQT3 mutations. Whereas the BrS mutations spread evenly on the structure, LQT3 mutations are mainly clustered to the segments in repeats III and IV that are involved in gating, voltage-sensing, and particularly inactivation. A mutational hotspot involving the fast inactivation segments is identified and can be mechanistically interpreted by our “door wedge” model for fast inactivation. The structural analysis presented here, with a focus on the impact of disease mutations on inactivation and late sodium current, establishes a structure-function relationship for the mechanistic understanding of Nav1.5 channelopathies.
Subgenomic RNAs as molecular indicators of asymptomatic SARS-CoV-2 infection
Authors: Wong Chee Hong , Ngan Chew Yee , Goldfeder Rachel L. , Idol Jennifer , Kuhlberg Chris , Maurya Rahul , Kelly Kevin , Omerza Gregory , Renzette Nicholas , De Abreu Francine , Li Lei , Browne Frederick A. , Liu Edison T. , Wei Chia-Lin
Published: February 2021

In coronaviridae such as SARS-CoV-2, subgenomic RNAs (sgRNA) are replicative intermediates, therefore, their abundance and structures could infer viral replication activity and severity of host infection. Here, we systematically characterized the sgRNA expression and their structural variation in 81 clinical specimens collected from symptomatic and asymptomatic individuals with a goal of assessing viral genomic signatures of disease severity. We demonstrated the highly coordinated and consistent expression of sgRNAs from individuals with robust infections that results in symptoms, and found their expression is significantly repressed in the asymptomatic infections, indicating that the ratio of sgRNAs to genomic RNA (sgRNA/gRNA) is highly correlated with the severity of the disease. Using long read sequencing technologies to characterize full-length sgRNA structures, we also observed widespread deletions in viral RNAs, and identified unique sets of deletions preferentially found primarily in symptomatic individuals, with many likely to confer changes in SARS-CoV-2 virulence and host responses. Furthermore, based on the sgRNA structures, the frequently occurred structural variants in SARS-CoV-2 genomes serves as a mechanism to further induce SARS-CoV-2 proteome complexity. Taken together, our results show that differential sgRNA expression and structural mutational burden both appear to be correlated with the clinical severity of SARS-CoV-2 infection. Longitudinally monitoring sgRNA expression and structural diversity could further guide treatment responses, testing strategies, and vaccine development.
A behavioral syndrome linking boldness and flexibility facilitates invasion success in sticklebacks
Authors: Bensky Miles K. , Bell Alison M.
Published: February 2021

For a species to expand its range, it needs to be good at dispersing and also capable of exploiting resources and adapting to different environments. Therefore, behavioral and cognitive traits could play key roles in facilitating invasion success. Here, we show that dispersing sticklebacks are bold, while sticklebacks that have recently established in a new region are flexible. Moreover, boldness and flexibility are negatively correlated with one another at the individual, family and population levels. Multiple lines of evidence suggest that the divergence in boldness and flexibility is likely to be evolutionary in origin. If boldness is favored in invaders during the initial dispersal stage, while flexibility is favored in recent immigrants during the establishment stage, then the link between boldness and flexibility could generate positive correlations between successes during both dispersal and establishment, and therefore play a key role in facilitating colonization success in sticklebacks and other organisms.
Discovery of fungal-specific targets and inhibitors using chemical phenotyping of pathogenic spore germination
Authors: Ortiz Sébastien C. , Huang Mingwei , Hull Christina M.
Published: February 2021

There is a critical need for new antifungal drugs; however, the lack of available fungal-specific targets is a major hurdle in the development of antifungal therapeutics. Spore germination is a differentiation process absent in humans that could harbor uncharacterized fungal-specific targets. To capitalize on this possibility, we developed novel phenotypic assays to identify and characterize inhibitors of spore germination of the human fungal pathogenCryptococcus. Using these assays, we carried out a high throughput screen of ~75,000 drug-like small molecules and identified and characterized 191 novel inhibitors of spore germination, many of which also inhibited yeast replication and demonstrated low cytotoxicity against mammalian cells. Using an automated, microscopy-based, quantitative germination assay (QGA), we discovered that germinating spore populations can exhibit unique phenotypes in response to chemical inhibitors. Through the characterization of these spore population dynamics in the presence of the newly identified inhibitors, we classified 6 distinct phenotypes based on differences in germination synchronicity, germination rates, and overall population behavior. Similar chemical phenotypes were induced by inhibitors that targeted the same cellular function or had shared substructures. Leveraging these features, we used QGAs to identify outliers among compounds that fell into similar structural groups and thus refined relevant structural moieties, facilitating target identification. This approach led to the identification of complex II of the electron transport chain as the putative target of a promising structural cluster of germination inhibitory compounds. These inhibitors showed high potency againstCryptococcusspore germination, while maintaining low cytotoxicity against mammalian cells, making them prime candidates for development into novel antifungal therapeutics.
Ex vivodelivery of regulatory T cells for control of alloimmune priming in the donor lung
Authors: Miyamoto Ei , Takahagi Akihiro , Ohsumi Akihiro , Martinu Tereza , Hwang David , Boonstra Kristen M. , Joe Betty , Umana Juan Mauricio , Bei Ke F. , Vosoughi Daniel , Liu Mingyao , Cypel Marcelo , Keshavjee Shaf , Juvet Stephen C.
Published: February 2021

Survival after lung transplantation (LTx) is hampered by uncontrolled inflammation and alloimmunity. Regulatory T cells (Tregs) are being studied for post-implantation cell therapy in solid organ transplantation. Whether these systemically administered Tregs can function at the appropriate location and time is an important concern. We hypothesized thatin vitroexpanded, recipient-derived Tregs can be delivered to donor lungs prior to LTx viaex vivolung perfusion (EVLP), maintaining their immunomodulatory ability.

In a rat model, Wistar Kyoto (WKy) CD4+CD25highTregs were expandedin vitroprior to EVLP. Expanded Tregs were administered to Fisher 344 (F344) donor lungs during EVLP; left lungs were transplanted into WKy recipients. Treg localization and function post-transplant were assessed. In a proof-of-concept experiment, cryopreserved expanded human CD4+CD25+CD127lowTregs were thawed and injected into discarded human lungs during EVLP. Rat Tregs entered the lung parenchyma and retained suppressive function. Expanded Tregs had no adverse effect on donor lung physiology during EVLP; lung water as measured by wet- to-dry weight ratio was reduced by Treg therapy. The administered cells remained in the graft at 3 days post-transplant where they reduced activation of intragraft effector CD4+T cells; these effects were diminished by day 7. Human Tregs entered the lung parenchyma during EVLP where they expressed key immunoregulatory molecules (CTLA4+, 4-1BB+, CD39+, and CD15s+). Pre-transplant Treg administration can inhibit alloimmunity within the lung allograft at early time points post- transplant. Our organ-directed approach has potential for clinical translation.
Likelihood-based estimation of substructure content from single-wavelength anomalous diffraction (SAD) intensity data
Authors: Hatti Kaushik S , McCoy Airlie J , Read Randy J
Published: February 2021

SAD phasing can be challenging when the signal-to-noise ratio is low. In such cases, having an accurate estimate of substructure content can determine whether or not the substructure of anomalous scatterer positions can successfully be determined. We propose a likelihood-based target function to accurately estimate the strength of the anomalous scattering contribution directly from measured intensities, determining a complex correlation parameter relating the Bijvoet mates as a function of resolution. This gives a novel measure of intrinsic anomalous signal. The SAD likelihood target function also accounts for correlated errors in the measurement of intensities from Bijvoet mates, which can arise from the effects of radiation damage. When the anomalous signal is assumed to come primarily from a substructure comprised of one anomalous scatterer with a known value of f” and when the protein composition of the crystal is estimated correctly, the refined complex correlation parameters can be interpreted in terms of the atomic content of the primary anomalous scatterer, before the substructure is known. The maximum likelihood estimation of substructure content was tested on a curated database of 357 SAD cases with useful anomalous signal. The prior estimates of substructure content are highly correlated to the content determined by phasing calculations, with a correlation coefficient (on a log-log basis) of 0.72.

Synopsis

An intensity-based likelihood method is provided to estimate scattering from an anomalous substructure considering the effect of measurement errors in Bijvoet pairs and correlations between those errors.
Wave propagation and focusing of soft X-rays by spherical bent microchannel plates
Authors: Mazuritskiy M. I. , Lerer A. M. , Marcelli A. , Dabagov S. B. , Coreno M. , D'Elia A. , Rezvani S. J.
Published: February 2021

Synchrotron radiation sources have been used to study the focusing properties and angular distribution of X-ray radiation at the exit of spherically bent microchannel plates (MCPs). In this contribution it is shown how soft X-ray radiation at energies up to 1.5 keV can be focused by spherically bent MCPs with curvature radii R of 30 mm and 50 mm. For these devices, a focus spot is detectable at a distance between the detector and the MCP of less than R/2, with a maximum focusing efficiency up to 23% of the flux illuminating the MCP. The soft X-ray radiation collected at the exit of microchannels of spherically bent MCPs are analyzed in the framework of a wave approximation. A theoretical model for the wave propagation of radiation through MCPs has been successfully introduced to explain the experimental results. Experimental data and simulations of propagating radiation represent a clear confirmation of the wave channeling phenomenon for the radiation in spherically bent MCPs.
Upgrade of the SPECIES beamline at the MAX IV Laboratory
Authors: Kokkonen Esko , Lopes da Silva Felipe , Mikkelã Mikko-Heikki , Johansson Niclas , Huang Shih-Wen , Lee Jenn-Min , Andersson Margit , Bartalesi Antonio , Reinecke Benjamin N. , Handrup Karsten , Tarawneh Hamed , Sankari Rami , Knudsen Jan , Schnadt Joachim , Såthe Conny , Urpelainen Samuli
Published: February 2021

The SPECIES beamline has been transferred to the new 1.5 GeV storage ring at the MAX IV Laboratory. Several improvements have been made to the beamline and its endstations during the transfer. Together the Ambient Pressure X-ray Photoelectron Spectroscopy and Resonant Inelastic X-ray Scattering endstations are capable of conducting photoelectron spectroscopy in elevated pressure regimes with enhanced time-resolution and flux and X-ray scattering experiments with improved resolution and flux. Both endstations offer a unique capability for experiments at low photon energies in the vacuum ultraviolet and soft X-ray range. In this paper, the upgrades on the endstations and current performance of the beamline are reported.
Upgrade of BL-5C as a highly automated macromolecular crystallography beamline at Pohang Light Source II
Authors: Jeong Jae-Hee , Eo Cheolsoo , Kim Hyo-Yun , Kim Jin-Hong , Lee Chae-Soon , Choi Hyeong-Joo , Kim Yeon-Gil
Published: February 2021

BL-5C is an in-vacuum undulator beamline dedicated to macromolecular crystallography (MX) at the 3 GeV Pohang Light Source II in Korea. The beamline delivers X-ray beams with a focal spot size of 200 µm × 40 µm (FWHM, H × V) over the energy range 6.5–16.5 keV. The measured flux is 7 × 1011 photons s−1 at 12.659 keV through an aperture size of 50 µm. The experimental station is newly equipped with the photon-counting detector EIGER 9M, the multi-axis micro-diffractometer MD2, and a robotic sample changer with a high-capacity dewar. These instruments enable the operation of this beamline as an automated MX beamline specialized in X-ray fragment screening. This beamline can collect more than 400 data sets a day without human intervention, and a difference map can be automatically calculated by using the data processing pipeline for ligand or fragment identification.
Structure–functional relationship of cellular retinoic acid-binding proteins I and II interacting with natural and synthetic ligands
Authors: Tomlinson Charles W. E. , Cornish Katy A. S. , Whiting Andrew , Pohl Ehmke
Published: February 2021

A detailed understanding of the interactions between small-molecule ligands and their proposed binding targets is of the utmost importance for modern drug-development programs. Cellular retinoic acid-binding proteins I and II (CRABPI and CRABPII) facilitate a number of vital retinoid signalling pathways in mammalian cells and offer a gateway to manipulation of signalling that could potentially reduce phenotypes in serious diseases, including cancer and neurodegeneration. Although structurally very similar, the two proteins possess distinctly different biological functions, with their signalling influence being exerted through both genomic and nongenomic pathways. In this article, crystal structures are presented of the L29C mutant of Homo sapiens CRABPI in complex with naturally occurring fatty acids (1.64 Å resolution) and with the synthetic retinoid DC645 (2.41 Å resolution), and of CRABPII in complex with the ligands DC479 (1.80 Å resolution) and DC645 (1.71 Å resolution). DC645 and DC479 are two potential drug compounds identified in a recent synthetic retinoid development program. In particular, DC645 has recently been shown to have disease-modifying capabilities in neurodegenerative disease models by activating both genomic and nongenomic signalling pathways. These co-crystal structures demonstrate a canonical binding behaviour akin to that exhibited with all-trans-retinoic acid and help to explain how the compounds are able to exert an influence on part of the retinoid signalling cascade.
Experimental and numerical simulation of the piston engine fueled with alternative fuel blends: CFD approach
Authors: Gaikwad Pradeep Uttam , Gnanamani Senthil , Subramani Nithya
Published: February 2021

Purpose

The purpose of this paper is to find the pressure and the knocking phenomena. To get the pressure values, the butterworth bandpass filter was used and the potential of knocking was found by using peak-to-peak pressure values and also the species concentration. Cooled exhaust gas recirculation was the method used to minimize the knocking occurrence in the engine. Moreover, the effect of premixed methanol and start of engine (SOI) on knocking were also determined.

Design/methodology/approach

This paper deals with the compression ignition engine to investigate the unfavorable knocking behavior. The tests were carried out with the 3D model of engine fueled with waste cooking oil blended with TiO2. A number of tests were taken to find the pressure variation and the species concentration at eight different locations in the computational model.

Findings

In doing the tests, the positive intended outcome was achieved. From results, it is clear that the SOI and premixed methanol mitigated the knocking process.

Originality/value

The species concentration and pressure in the form of filtered signal were proved to be the ideal methods for evaluating the knocking event in the engine.
Effect of storage temperature on the crispness, colour and bioactive compounds of an orange snack obtained by freeze-drying
Authors: Silva-Espinoza Marilú Andrea , Camacho María del Mar , Martínez-Navarrete Nuria
Published: February 2021

Purpose

A healthy and easy-to-use orange snack obtained from the freeze-dried orange pulp puree is proposed. Once the commercial packaging of the snack has been opened, the effect of conventional home storage temperature on its physicochemical properties and on the content of bioactive compounds has been studied. This research aims to recommend the consumer, and therefore the manufacturer, the best conditions for home storage of this product, keeping its nutritional quality and antioxidant capacity, as well as maintaining its colour and crispness.

Design/methodology/approach

The water content, water activity, hygroscopicity, crispness, colour, vitamin C, β-carotene, total phenolic compounds and antioxidant activity were characterised both when the orange snack was newly obtained and after one, two and six months of storage inside zipper bags, at 4 and 20 ºC.

Findings

The results indicated that, in these conditions, the orange snack increased its water content, causing a loss in both its porosity and its characteristic crispness. Nevertheless, the bioactive compounds remained stable throughout the storage period, with the exception of β-carotene, the content of which decreased markedly when the orange snack was stored at 20 ºC.

Originality/value

Few studies have evaluated the stability of food products during home storage. The findings showed that the maximum storage time to ensure a proper texture of the orange snack studied is between two and six months, both at 4 and 20 ºC. However, from the point of view of the conservation of both vitamin C and, especially, of β-carotene, it is recommended that this product be stored in refrigeration.
Identification of cause and effect relationships among barriers of Industry 4.0 using decision-making trial and evaluation laboratory method
Authors: Nimawat Dheeraj , Gidwani B.D.
Published: February 2021

Purpose

Industry 4.0 is regarded as a modern industrial phase wherein convergence between horizontal and vertical production systems, along with their interactions, would enable industries to obtain excellent industrial efficiency. This research thus explores the barriers relevant to Industry 4.0 and their cause and effect relations using the decision-making trial and evaluation laboratory (DEMATEL) technique, and this will assist in the implementation of Industry 4.0 in manufacturing industries.

Design/methodology/approach

A comprehensive literature review is carried out to outline the barriers for the Industry 4.0 implementation. The investigative techniques used in this research were conducted utilizing a questionnaire as an instrument for collecting data. The data collected were analysed using the method DEMATEL.

Findings

The findings indicate that key barriers to implementing Industry 4.0 include their cause and effect relationships. Reported “implementation costs” have been a critical barrier for Industry 4.0 implementation. Prioritization of barriers and their cause and effect relationships was achieved so that decision-makers could concentrate on overcoming such barriers for Industry 4.0 implementation.

Practical implications

The research is intended to assist executives in recognizing the barriers to Industry 4.0 implementation in their manufacturing industries. Furthermore, the strong functional and empirical importance of emerging and digital manufacturing technologies ensures that understanding the necessary barriers to implementation is important.

Originality/value

This is one of the first few empirical studies in the field of Indian manufacturing industries that uses the DEMATEL method framework as a foundation for recognizing cause-effect interactions among the barriers that affect Industry 4.0.
Impact of earnings management on agency costs: evidence from MILA markets
Authors: Muñoz Mendoza Jorge Andrés , Veloso Ramos Carmen Lissette , Sepúlveda Yelpo Sandra María , Delgado Fuentealba Carlos Leandro , Fuentes-Solís Rodrigo Alberto
Published: February 2021

Purpose

The purpose of this article is to analyze the effects of accruals-based earnings management (AEM), International Financial Reporting Standard (IFRS) adoption and stock market integration for firms that belong to Latin-American Integrated Market (MILA).

Design/methodology/approach

The GMM estimator was used according to Arellano and Bover (1995) for panel data on a sample of 478 non-financial companies between 2000 and 2016. Multilevel mixed models was used for the robustness analysis.

Findings

AEM practices significantly and dynamically reduce agency costs. This result suggests companies use positive discretionary accruals to hide true agency costs and avoid shareholders monitoring, while negative discretionary accruals are ways to expropriate wealth and increase agency costs. This result implies that firms use AEM as a predetermined strategy to weaken corporate governance. The IFRS adoption and MILA implementation reduced agency costs. However, only IFRS adoption had the capability to mitigate the effects of AEM on agency costs.

Originality/value

These results reveal AEM constitutes a practice that managers use to weaken firms’ corporate governance and expropriate wealth from shareholders. These practices have effects at short-run and long-run. However, the IFRS adoption and market integration represented by MILA are mitigating factors for agency costs. These results have relevant implications for firms’ corporate governance because they guide investors and shareholders to strengthen corporate control and monitoring on business decision-making. These results also are relevant to policymakers because they orient the financial policies design to strengthen the benefits of IFRS and MILA.
The impact of board composition on the dividend policy of US firms
Authors: Thompson Ephraim Kwashie , Adasi Manu Sylvester
Published: February 2021

Purpose

This paper aims to examine whether the characteristics of boards are more important in determining dividend policy than management characteristics. The authors show that as the final declarers of dividend policy is a firm’s board, the composition of a firm’s board significantly subsumes the effect of management characteristics that may also influence dividend policy.

Design/methodology/approach

Using the dividend declaration dummy variable, the authors run a fixed effect logistic regression of the dividend indicator on board characteristics, and managerial characteristics with firm level controls, year effects and industry effects while clustering standard errors at the firm level. For dividend yield variable which is censored at zero, they use a fixed effect Tobit regression.

Findings

The results of the study show that board characteristics such as average age, female presence and size have a strong positive significant effect, whereas board independent chair and voting right of directors have a negative significant effect on the likelihood of dividend declaration. For dividend yields, the results suggest that the presence of directors with financial expertise and the board size are the main influencers of dividend policy. Managerial characteristics are subsumed by director characteristics for determining dividend policy. The results overall support the evidence on the monitoring role of boards on management.

Originality/value

The originality and value of this study lies in the approach of including a comprehensive number of board characteristics unlike previous studies which makes the study of the influence of board composition on dividends more encompassing.
Performance analysis of boost converter with cascaded inner loop fuzzy SMC
Authors: Yoganathan Rekha , Venkatesan Jamuna , I. William Christopher
Published: February 2021

Purpose

This paper intent to design, develop, and fabricate a robust cascaded controller based on the dual loop concept i.e. Fuzzy Sliding Mode concept in the inner loop and traditional Proportional Integral controller in the outer loop to reduce the unknown dynamics and disturbances that occur in the DC-DC Converter.

Design/methodology/approach

The proposed Fuzzy sliding mode approach combines the merits of both SMC and Fuzzy logic control. FSMC approach reduces the chattering phenomena that commonly occurs in the sliding mode control and speed up the response of the controller.

Findings

In most of the research work, the inner current loop of cascaded controller was designed by sliding mode control. In this paper FSMC is proposed and its efficacy is confirmed with SMC -PI. In most uncertainties, FSMC-PI produces null maximum peak overshoot and a very less settling time of 0.0005 sec.

Originality/value

The presence of Fuzzy SMC in the inner loop ensure satisfactory response against all uncertainties such as steady state, circuit parameter variations and sudden line and load disturbances.
Contribution of procurement capacity of public agencies to attainment of procurement objectives in infrastructure procurement
Authors: Manu Patrick , Asiedu Richard Ohene , Mahamadu Abdul-Majeed , Olomolaiye Paul Olaniyi , Booth Colin , Manu Emmanuel , Ajayi Saheed , Agyekum Kofi
Published: February 2021

Purpose

Effective procurement of infrastructure is linked to the attainment of the sustainable development goals set by the United Nations. While the capacity of organisations is generally thought to be related to organisational performance, there is a lack of empirical insights concerning the contribution of procurement capacity of public organisations towards the attainment of procurement objectives in infrastructure procurement. Thus, it is unclear which aspects of the capacity of public procurement organisations contribute the most to the attainment of procurement objectives in the procurement of infrastructure. This research sought to address this gap.

Design/methodology/approach

The research used a survey of public procurement professionals which yielded 590 responses.

Findings

Exploratory factor analysis of 23 organisational capacity items revealed three components of organisational procurement capacity: “management of the procurement process”; “human and physical resources”; and “financial resources and management”. Multiple regression modelling of the relationship between the components and the attainment of 12 procurement objectives further reveals that there is a significant positive relationship between the three components and all the objectives. However, “management of the procurement process” emerged as the greatest contributor to the attainment of seven objectives, whereas “human and physical resources”, and “financial resources and management” were the greatest contributor to the attainment of one objective and four objectives, respectively.

Originality/value

The study provides strong empirical justification for investment in the development of procurement capacity of public agencies involved in procurement of infrastructure. Furthermore, procurement capacity development of specific capacity components can be prioritised based on the relative contribution of capacity components to the attainment of desired procurement objectives. This should be useful to government policymakers as well as multilateral organisations that fund infrastructure and procurement reforms in various countries.
The effect of online academic coaches on supporting graduate students’ performance in intensive online learning environments: a three-course comparison
Authors: Park Sunyoung , Robinson Petra A.
Published: February 2021

Purpose

The purpose of this study is to examine how academic coaches, through academic student support, impact graduate student performance in a time-intensive online learning program for pursuing a master’s degree in leadership and human resource development in a research-intensive public university in the Southern USA.

Design/methodology/approach

The participants in this study were 435 graduate students enrolled in their online master’s degree program. Framed by the theory of transactional distance and by adopting a pre-experimental design and the analysis of variance (ANOVA) technique, the student performance in three courses was compared (principles of adult education, research methods and performance analysis) with academic coaches.

Findings

The findings indicate that the average score of students was higher when students received more feedback and comments from an academic coach than less feedback and comments in the performance analysis course. Students who had an academic coach in the adult education class performed better than those who did not have a coach. However, there was not a significant difference in academic performance based on the number of academic coaches (one versus three) in the research methods course.

Originality/value

This preliminary work may lead to a better understanding of how academic coaches can best support adult learners in their pursuits of online postsecondary education. This study would suggest implications for online instructors and institutions to enhance student success and retention in online learning activities by using academic coaching.
A novel approach to the creation of a labelling lexicon for improving emotion analysis in text
Authors: Segura Navarrete Alejandra , Martinez-Araneda Claudia , Vidal-Castro Christian , Rubio-Manzano Clemente
Published: February 2021

Purpose

This paper aims to describe the process used to create an emotion lexicon enriched with the emotional intensity of words and focuses on improving the emotion analysis process in texts.

Design/methodology/approach

The process includes setting, preparation and labelling stages. In the first stage, a lexicon is selected. It must include a translation to the target language and labelling according to Plutchik’s eight emotions. The second stage starts with the validation of the translations. Then, it is expanded with the synonyms of the emotion synsets of each word. In the labelling stage, the similarity of words is calculated and displayed using WordNet similarity.

Findings

The authors’ approach shows better performance to identification of the predominant emotion for the selected corpus. The most relevant is the improvement obtained in the results of the emotion analysis in a hybrid approach compared to the results obtained in a purist approach.

Research limitations/implications

The proposed lexicon can still be enriched by incorporating elements such as emojis, idioms and colloquial expressions.

Practical implications

This work is part of a research project that aids in solving problems in a digital society, such as detecting cyberbullying, abusive language and gender violence in texts or exercising parental control. Detection of depressive states in young people and children is added.

Originality/value

This semi-automatic process can be applied to any language to generate an emotion lexicon. This resource will be available in a software tool that implements a crowdsourcing strategy allowing the intensity to be re-labelled and new words to be automatically incorporated into the lexicon.
Use analysis of the digital library of PhD dissertations defended at the University of Novi Sad
Authors: Paskali Ljubomir , Ivanovic Lidija , Ivanović Dragan
Published: February 2021

Purpose

The purpose of this paper is to determine the digital library usage patterns as a means of improving the system, as well as the user experience, to give appropriate recognition to the most popular dissertations’ authors and to measure the interest of non-academic users for dissertations defended at the University of Novi Sad (UNS).

Design/methodology/approach

A logging module of the digital library of theses and dissertations of University of Novi Sad (PHD UNS) application has been implemented. The module recorded the messages relating to the search queries and downloads over a three-year period from 2017–2019. These logs are analysed using the Elasticsearch, Logstash and Kibana (ELK) technology stack and the results are shown using graphs and tables.

Findings

The analysis determined the perfect time for weekly maintenance of the system, defined a recommendation for improving the system and revealed the most popular dissertations. A significant number of downloads and queries originated from citizens, i.e. users outside the academic community.

Practical implications

The conducted analysis defined recommendations for the system improvement which can be used by PHD UNS research and development (R&D) team and revealed the most popular dissertations which are used for the promotion of its authors through faculties’ websites.

Originality/value

To the best of the authors’ knowledge, this is the first study of ELK based log analysis of a Serbian language documents’ repository. Besides, the value of results for the PHD UNS R&D team and UNS rector team, the study proves that PhD digital library presents an important Open Science communication channel for presenting scientific results to the citizens.