bluuebunny/crossref_metadata_2025 huggingface dataset:
CIP2A is a prime synthetic-lethal target for BRCA-mutated cancers
Authors: Adam Salomé , Rossi Silvia Emma , Moatti Nathalie , Zompit Mara De Marco , Ng Timothy F. , Álvarez-Quilón Alejandro , Desjardins Jessica , Bhaskaran Vivek , Martino Giovanni , Setiaputra Dheva , Noordermeer Sylvie M. , Ohsumi Toshiro K. , Hustedt Nicole , Szilard Rachel K. , Chaudhary Natasha , Munro Meagan , Veloso Artur , Melo Henrique , Yin Shou Yun , Papp Robert , Young Jordan T.F. , Zinda Michael , Stucki Manuel , Durocher Daniel
Published: February 2021

BRCA1/2-mutated cancer cells must adapt to the genome instability caused by their deficiency in homologous recombination. Identifying and targeting these adaptive mechanisms may provide new therapeutic strategies. Here we present the results of genome-scale CRISPR/Cas9-based synthetic lethality screens in isogenic pairs of BRCA1- and BRCA2-deficient cells that identified the gene encoding CIP2A as essential in a wide range ofBRCA1- andBRCA2-mutated cells. Unlike PARP inhibition, CIP2A-deficiency does not cause accumulation of replication-associated DNA lesions that require homologous recombination for their repair. CIP2A is cytoplasmic in interphase but, in mitosis, accumulates at DNA lesions as part of a complex with TOPBP1, a multifunctional genome stability factor. In BRCA-deficient cells, the CIP2A-TOPBP1 complex prevents lethal mis-segregation of acentric chromosomes that arises from impaired DNA synthesis. Finally, physical disruption of the CIP2A-TOPBP1 complex is highly deleterious in BRCA-deficient cells and tumors, indicating that targeting this mitotic chromosome stability process represents an attractive synthetic-lethal therapeutic strategy forBRCA1- andBRCA2-mutated cancers.
Infant brain regional cerebral blood flow dynamics supporting emergence of vital functional networks
Authors: Yu Qinlin , Ouyang Minhui , Detre John A. , Kang Huiying , Hu Di , Hong Bo , Fang Fang , Peng Yun , Huang Hao
Published: February 2021

Human infancy is characterized by most rapid cerebral blood flow (rCBF) increases across lifespan and emergence of a fundamental brain system default-mode network (DMN). However, how infant rCBF change spatiotemporally across the brain and how the rCBF dynamics support emergence of vital functional networks such as DMN remains unknown. Here, by acquiring cutting-edge multi-modal MRI including pseudo-continuous arterial-spin-labeled perfusion MRI and resting-state functional MRI of infants aged 0 to 24 months, we elucidated unprecedented 4D spatiotemporal infant rCBF framework and region-specific physiology-function coupling across infancy. We found faster rCBF increases in the DMN than other regions. We also found strongly coupled increases of rCBF and network strength specifically in the DMN, suggesting faster local blood flow increase to meet extra neuronal metabolic demands in the DMN maturation. These results offer insights into physiological mechanism of brain functional network emergence and have important implications in altered network maturation in brain disorders.
Efficacy of CDK4/6 inhibitors in preclinical models of malignant pleural mesothelioma
Authors: Aliagas Elisabet , Alay Ania , Martínez-Iniesta Maria , Hernández-Madrigal Miguel , Cordero David , Gausachs Mireia , Pros Eva , Saigí Maria , Busacca Sara , Sharkley Annabel J. , Dawson Alan , Palmero Ramón , Padrones Susana , Aso Samantha , Escobar Ignacio , Ramos Ricard , Llatjós Roger , Vidal August , Varela Mar , Sánchez-Céspedes Montse , Fennell Dean , Muñoz-Pinedo Cristina , Villanueva Alberto , Solé Xavi , Nadal Ernest
Published: February 2021

There is no effective therapy for patients with malignant pleural mesothelioma (MPM) who progressed to platinum-based chemotherapy and immunotherapy. Here, we investigate the antitumor activity of CDK4/6 inhibitors usingin vitroandin vivopreclinical models of MPM. Based on publicly available transcriptomic data of MPM, patients withCDK4orCDK6overexpression had shorter overall survival. Treatment with abemaciclib or palbociclib at 100 nM significantly decreased cell proliferation in all cell models. Both CDK4/6 inhibitors significantly induced G1 cell cycle arrest thereby increasing cell senescence and increased the expression of interferon signaling pathway and tumor antigen presentation process in culture models of MPM.In vivopreclinical studies showed that palbociclib significantly reduced tumor growth and prolonged overall survival in a platinum-naïve and platinum resistant MPM mouse model. Treatment of MPM with CDK4/6 inhibitors decreased cell proliferation, mainly by promoting cell cycle arrest at G1 and by induction of cell senescence. Our preclinical studies provide evidence for evaluating CDK4/6 inhibitors in the clinic for the treatment of MPM.
Mechanisms of GPCR hijacking byStaphylococcus aureus
Authors: Grison Claire M. , Leyrat Cédric , Lambey Paul , Jeannot Sylvain , Del Nero Elise , Fontanel Simon , Peysson Fanny , Heuninck Joyce , Sounier Rémy , Durroux Thierry , Granier Sébastien , Bechara Cherine
Published: February 2021

Atypical chemokine receptor 1 (ACKR1) is a G protein-coupled receptor (GPCR) targeted byStaphylococcus aureus(SA) bi-component pore-forming leukotoxins to promote bacterial growth and immune evasion. Here we have developed an integrative molecular pharmacology and structural biology approach in order to characterize the effect of leukotoxins HlgA and HlgB on ACKR1 structure and function. Interestingly, we found that both components HlgA and HlgB compete with endogenous chemokines through a direct binding to ACKR1 captured by native mass spectrometry (MS). Unexpectedly, HDX-MS analysis revealed that toxin binding allosterically modulates the intracellular G protein-binding domain of the receptor, resulting in dissociation of ACKR1–G protein complexes in living cells. Altogether, our study brings important molecular insights into the initial steps of leukotoxins targeting a host GPCR. Our findings may open the way to develop antibiotics inhibiting host receptors binding, a mechanism of action less prone to resistance.
Whole genome 6-methyladenosine sequencing (6-mA-Seq) enables bacterial epigenomics studies
Authors: Spurbeck Rachel R. , Minard-Smith Angela T. , Catlin Lindsay A. , Murdoch Robert W. , Chou Rich M. , Albrecht Kristy Montoya
Published: February 2021

Methylation sequencing using bisulfite treatment has revolutionized the field of molecular biology for eukaryotic systems, unveiling levels of intricacy in regulation of gene expression in response to different environmental conditions. While bacteria also utilize methylation to regulate gene expression, bisulfite sequencing does not work as well in bacteria as in eukaryotes, because bacteria methylate adenosine instead of cytosine. Therefore, global bacterial methylation patterns cannot be studied using common Illumina sequencers. In this work, we demonstrate 6mA-seq, a method that can be used to identify patterns in bacteria that methylate adenosines at GATC sites. Furthermore, this method was used onEscherichia colicultured on four different carbon sources to demonstrate different methylation patterns due to carbon utilization. 6mA-seq can increase the speed in which epigenetic research is conducted in bacteria.
Calculating likelihoods and likelihood ratios at SNPs-based mixtures. A reappraisal of the binomial inference, as applied to forensic identity tests
Authors: Pascali Vincenzo L.
Published: February 2021

Single nucleotide polymorphisms (SNPs) are useful forensic markers. When a SNPs-based forensic protocol targets a body fluid stain, it returns elementary evidence regardless of the number of individuals that might have contributed to the stain deposition. Therefore, drawing inference from a mixed stain with SNPs is different than drawing it while using multinomial polymorphisms. We here revisit this subject, with a view to contribute to a fresher insight into it. First, we manage to model conditional semi-continuous likelihoods in terms of matrices of genotype permutations vs number of contributors (NTZsc). Secondly, we redefine some algebraic formulas to approach the semi-continuous calculation. To address allelic dropouts, we introduce a peak height ratio index (‘h’, or: the minor read divided by the major read at any NGS-based typing result) into the semi-continuous formulas, for they to act as an acceptable proxy of the ‘split drop’ (Haned et al, 2012) model of calculation. Secondly, we introduce a new, empirical method to deduct theexpectedquantitative ratio at which the contributors of a mixture have originally mixed and theobservedratio generated by each genotype combination at each locus. Compliance between observed and expected quantity ratios is measured in terms of (1-χ2) values at each state of a locus deconvolution. These probability values are multiplied, along with the h index, to the relevant population probabilities to weigh the overall plausibility of each combination according to the quantitative perspective. We compare calculation performances of our empirical procedure (NITZq) with those of the EUROFORMIX software ver.3.0.3. NITZq generates LR values a few orders of magnitude lower than EUROFORMIX when true contributors are used as POIs, but much lower LR values when false contributors are used as POIs. NITZ calculation routines may be useful, especially in combination with mass genomics typing protocols.
Recognition and Differentiation of Dural Puncture Click Sensation: A Subjective and Objective Prospective Study of Dural Puncture Forces Using Fine-Gauge Spinal Needles
Authors: Utsumi Isao , Hascilowicz Tomasz , Omi Sachiko
Published: February 2021

Background

We hypothesized that the click perceived when puncturing the dura-arachnoid with fine-gauge spinal needles can be subjectively identified, and investigated whether it may be distinguishable among different needle types.

Methods

Subjective and objective evaluations were performed. First, physicians punctured the polyamide film or porcine dura mater (n=70 and n=20, respectively) with seven types of spinal needles and numerically evaluated the perceived click sensations. Using an 11-point numerical rating scale (from “0” for “no click sensation” to “10” for “the strongest click perceived”) data, subjective differentiation among needle types was assessed. Second, in the objective part of the study, total forces elicited by polyamide film or porcine dura mater punctures with each needle were measured using a biomechanical testing device, and load-displacement curves evaluated. Third, the results of subjective and objective evaluations were compared.

Results

All participants recognized the click and could discriminate among needles of different tip shape. The load-displacement curves for polyamide film and porcine dura mater were similar and needle-specific. The subjective numerical rating scale values corresponded well with the objectively measured changes in total forces (R2= 0.862 andR2= 0.881 for polyamide film and porcine dura mater, respectively), indicating that an increase in the largest drop in total force value of 0.30 N or 0.21 N would produce an increase of numerical rating scale value of 1 for polyamide film and porcine dura mater, respectively.

Conclusions

We provide an objective proof of the click sensation felt upon dural puncture using different fine-gauge spinal needles. Click recognition could be used as an additional indicator of successful spinal puncture.
Automatic Detection of Larval Zebrafish ECG: Computational Tool for High-throughput Cardiac Activity Analysis
Authors: Barrett Richard , Hurst Rhiannon , Tarte Edward , Müller Ferenc , Sik Attila
Published: February 2021

Automatic analysis of larval zebrafish electrocardiographs (ECG) is essential for high-throughput measurements in environmental toxicity assays, cardiotoxicity measurements and drug screening. We have developed a MATLAB based software is built on methods that have previously been used to analyze human ECG, such as the Pan-Tompkins algorithm and Wavelet. For the first time these sophisticated tools have been applied to larval zebrafish ECG to automatically characterize the heart-beat waveforms. The ability of the automated algorithm to detect the QT interval for both normal and pharmacologically altered larval ECG is found and compared to previously used software that is built into LabChart®(AD Instruments). Using wavelet transforms it is shown that the typical larval ECG features are within the frequency range of 1 to 31 Hz. It is also shown that the automated software is capable of detecting QTc (heartrate corrected heartbeat interval) changes within pharmacologically altered zebrafish larval ECG. The automated process is a significant improvement on the approaches that were previously applied to the zebrafish ECG. The automated process described here that is based on established techniques of analyzing ECG can sensitively measure pharmacologically induced changes in the ECG. The novel, automated software is faster, more sensitive at detecting ECG changes and less dependent on user involvement, thus minimizing user error and human bias. The automated process can also be applied to human ECG.
Protistan grazing impacts microbial communities and carbon cycling at deep-sea hydrothermal vents
Authors: Hu Sarah K. , Herrera Erica L. , Smith Amy R. , Pachiadaki Maria G. , Edgcomb Virginia P. , Sylva Sean P. , Chan Eric W. , Seewald Jeffrey S. , German Christopher R. , Huber Julie A.
Published: February 2021

Microbial eukaryotes (or protists) in marine ecosystems are a link between microbial primary producers and all higher trophic levels. The rate at which heterotrophic protistan grazers consume microbial prey and recycle organic matter is an important factor that influences marine microbial food webs and carbon cycling. At deep-sea hydrothermal vents, chemosynthetic bacteria and archaea form the base of a food web that functions in the absence of sunlight, but the role of protistan grazers in these highly productive ecosystems is largely unexplored. Here, we pair grazing experiments with a molecular survey to quantify protistan grazing and to characterize the composition of vent-associated protists in low-temperature venting fluids from Gorda Ridge in the North East (NE) Pacific Ocean. Results reveal protists exert higher predation pressure at vents compared to the surrounding deep seawater environment and may account for consuming 28-62% of the daily stock of prokaryotic biomass within the hydrothermal vent food web. The vent-associated protistan community was more species rich relative to the background deep sea, and patterns in the distribution and co-occurrence of vent microbes provide additional insights into potential predator-prey interactions. Ciliates, followed by dinoflagellates, Syndiniales, rhizaria, and stramenopiles dominated the vent protist community and included bacterivorous species, species known to host symbionts, and parasites. Our findings provide an estimate of protistan grazing pressure within hydrothermal vent food webs, highlighting the role that diverse deep-sea protistan communities have in carbon cycling.

Significance

Heterotrophic protists are ubiquitous in all aquatic ecosystems and represent an important ecological link because they transfer organic carbon from primary producers to higher trophic levels. Here, we quantify the predator-prey trophic interaction among protistan grazers and microbial prey at multiple sites of hydrothermal venting near the Gorda Ridge spreading center in the NE Pacific Ocean. Grazing pressure was higher at the site of active diffuse flow and was carried out by a highly diverse assemblage of protistan species; elevated grazing rates are attributed to higher concentrations of chemosynthetic microorganisms and biological diversity localized to hydrothermal vent environments.
Semi-continuous propagation of influenza A virus and its defective interfering particles: analyzing the dynamic competition to select candidates for antiviral therapy
Authors: Pelz Lars , Rüdiger Daniel , Dogra Tanya , Alnaji Fadi G. , Genzel Yvonne , Brooke Christopher B. , Kupke Sascha Y. , Reichl Udo
Published: February 2021

Defective interfering particles (DIPs) of influenza A virus (IAV) are naturally occurring mutants that comprise an internal deletion in one of their eight viral RNA (vRNA) segments, rendering them propagation-incompetent. Upon co-infection with infectious standard virus (STV), DIPs interfere with STV replication through competitive inhibition. Thus, DIPs are proposed as potent antivirals for treatment of the influenza disease. To select corresponding candidates, we studiedde novogeneration of DIPs and propagation competition between different defective interfering (DI) vRNAs in a STV co-infection scenario in cell culture. A small-scale two-stage cultivation system that allows long-term semi-continuous propagation of IAV and its DIPs was used. Strong periodic oscillations in virus titers were observed due to the dynamic interaction of DIPs and STVs. Using next-generation sequencing, we detected a predominant formation and accumulation of DI vRNAs on the polymerase-encoding segments. Short DI vRNAs accumulated to higher fractions than longer ones, indicating a replication advantage. Yet, a sweet spot of fragment length was observed. Some DI vRNAs showed breaking points in a specific part of their bundling signal (belonging to the packaging signal), suggesting its dispensability for DI vRNA propagation. Over a total cultivation time of 21 days, several individual DI vRNAs accumulated to high fractions, while others decreased. Using reverse genetics for IAV, purely clonal DIPs derived from highly replicating DI vRNAs were generated. We confirm that these DIPs exhibit a superiorin vitrointerfering efficacy than DIPs derived from lowly accumulated DI vRNAs and suggest promising candidates for efficacious antiviral treatment.

Importance

Defective interfering particles (DIPs) emerge naturally during viral infection and typically show an internal deletion in the viral genome. Thus, DIPs are propagation-incompetent. Previous research suggests DIPs as potent antiviral compounds for many different virus families due to their ability to interfere with virus replication by competitive inhibition. For instance, the administration of influenza A virus (IAV) DIPs resulted in a rescue of mice from an otherwise lethal IAV dose. Moreover, no apparent toxic effects were observed when only DIPs were administered to mice and ferrets. IAV DIPs show antiviral activity against many different IAV strains, including pandemic and highly pathogenic avian strains, and even against non-homologous viruses, like SARS-CoV-2, by stimulation of innate immunity. Here, we used a cultivation/infection system, which exerted selection pressure toward accumulation of highly competitive IAV DIPs. These DIPs showed a superior interfering efficacyin vitro, and we suggest them for effective antiviral therapy.
Neural epidermal growth factor-like 1 protein variant increases survival and modulates the inflammatory and immune responses in human ACE-2 transgenic mice infected with SARS-CoV-2
Authors: Biswas Roopa , Eaker Shannon , Soni Dharmendra Kumar , Kar Swagata , LoBato Denae , Culiat Cymbeline
Published: February 2021

Coronavirus disease 2019 (COVID-19) is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is a worsening global pandemic. COVID-19 has caused at least 1.7 million deaths worldwide and over 300,000 in the United States. Recently, two promising vaccines are being administered in several countries. However, there remains an urgent need for a therapeutic treatment for COVID-19 patients with severe respiratory damage that can lead to intensive care, prolonged hospitalization, or mortality. Moreover, an increasing population of patients manifest lingering disabling symptoms (called Long Haulers). Here, we tested the efficacy of a recombinant neural epidermal growth factor like 1 protein variant (NELL1-NV1) in a COVID-19 mouse model, transgenic mice expressing the human angiotensin I-converting enzyme 2 (ACE2) receptor (tg-mice hACE2) infected with SARS-CoV-2. The administration of NELL1-NV1 to SARS-CoV-2-infected tg-mice hACE2 significantly improved clinical health score and increased survival. Analyses of bronchoalveolar (BAL) fluid demonstrated decreased levels of several cytokines and chemokines (IFN-γ, IL-10, IL-12 p70, CXCL-10/IP-10, MIG and Rantes), in NV1-treated treated mice compared to controls. Cytokines including IL-1α, IL-9, IL-6, LIX/CXCL5, KC/CXCL1, MIP-2/CXCL2, MIP-1α/CCL3, and G-CSF, critical to immune responses such as neutrophil recruitment, viral clearance and vascularization, were increased compared to controls. Our data suggest the potential of NELL1-NV1-based therapy to mitigate the cytokine storm, modulate the abnormal immune response and repair respiratory tissue damage in COVID-19 patients.
Software Evaluation forde novoDetection of Transposons
Authors: Rodriguez Matias , Makałowski Wojciech
Published: February 2021

Transposable elements (TEs) are major genomic components in most eukaryotic genomes and play an important role in genome evolution. However, despite their relevance the identification of TEs is not an easy task and a number of tools were developed to tackle this problem. To better understand how they perform, we tested several widely used tools forde novoTE detection and compared their performance on both simulated data and well curated genomic sequences. As expected, tools that build TE-models performed better than k-mer counting ones, with RepeatModeler beating competitors in most datasets. However, there is a tendency for most tools to identify TE-regions in a fragmented manner and it is also frequent that small TEs or fragmented TEs are not detected. Consequently, the identification of TEs is still a challenging endeavor and it requires a significant manual curation by an experienced expert. The results will be helpful for identifying common issues associated with TE-annotation and for evaluating how comparable are the results obtained with different tools.
Neuroblastoma formation requires unconventional CD4 T cells and myeloid amino acid metabolism
Authors: Van de Velde Lee-Ann , Allen E. Kaitlynn , Crawford Jeremy Chase , Wilson Taylor L. , Guy Clifford S. , Russier Marion , Zeitler Leonie , Bahrami Armita , Finkelstein David , Pelletier Stephane , Schultz-Cherry Stacey , Thomas Paul G. , Murray Peter J.
Published: February 2021

By mirroring their function as tissue repair organizers in normal tissues, immune cells regulate tumor growth. To understand the different facets of immune-tumor collaboration through genetics, spatial transcriptomics, and immunological manipulation with non-invasive, longitudinal imaging, we generated a penetrant double oncogene-driven autochthonous model of neuroblastoma. Using spatial transcriptomic analysis, we co-localized CD4+and myeloid populations within the tumor parenchyma, while CD8+T cells and B cells were peripherally dispersed. Depletion of CD4+T cells or CCR2+macrophages, but not B cells, CD8+, or NK cells, prevented tumor formation. Tumor CD4+T cells displayed unconventional phenotypes, were clonotypically diverse, and antigen-independent. Within the myeloid fraction, tumor growth required myeloid cells expressing Arginase-1. Overall, our results suggest that arginine-metabolizing myeloid cells conspire with pathogenic CD4+T cells to create permissive conditions for tumor formation, and therefore suggest that these pro-tumorigenic pathways can be disabled by targeting myeloid amino acid metabolism.
Simultaneous functional MRI of socially interacting marmosets
Authors: Gilbert Kyle M. , Cléry Justine C. , Gati Joseph S. , Hori Yuki , Mashkovtsev Alexander , Zeman Peter , Menon Ravi S. , Schaeffer David J. , Everling Stefan
Published: February 2021

Social cognition is a dynamic process that requires the perception and integration of a complex set of idiosyncratic features between interacting conspecifics. Here we present a method for simultaneously measuring the whole-brain activation of two socially interacting marmoset monkeys using functional magnetic resonance imaging. MRI hardware (a radiofrequency coil and peripheral devices) and image-processing pipelines were developed to assess brain responses to socialization, both on an intra-brain and inter-brain level. Notably, brain-activation maps acquired during constant interaction demonstrated neuronal synchrony between marmosets in regions of the brain responsible for processing social interaction. This method enables a wide range of possibilities for studying social function and dysfunction in a non-human primate model, including using transgenic models of neuropsychiatric disorders.
Mechanistic insight into substrate processing and allosteric inhibition of human p97
Authors: Pan Man , Yu Yuanyuan , Ai Huasong , Zheng Qingyun , Xie Yuan , Liu Lei , Zhao Minglei
Published: February 2021

p97 processes ubiquitinated substrates and plays a central role in cellular protein homeostasis. Previous studies have showed that it is a potential drug target for cancer, neurodegenerative disease, and viral infections. Here, we report a series of cryo-electron microscopy (cryo-EM) structures of substrate-engaged human p97 complex that captured “power stroke”-like motions of both the D1 and D2 ATPase rings of p97. A key feature of these structures is the critical conformational changes of the inter-subunit signaling (ISS) motifs, which tightens the binding of nucleotides and neighboring subunits, and contributes to the spiral staircase conformation of the D1 and D2 rings. We further determined the cryo-EM structure of human p97 in complex with NMS-873, the most potent p97 inhibitor. The structures showed that NMS-873 binds at a cryptic groove in the D2 domain and interacts with the ISS motif, preventing its conformational change, thus blocking substrate translocation allosterically.
Existing function in primary visual cortex is not perturbed by new skill acquisition of a non-matched sensory task
Authors: Jeon Brian B. , Fuchs Thomas , Chase Steven M. , Kuhlman Sandra J.
Published: February 2021

Acquisition of new skills has the potential to disturb existing network function. To directly assess whether previously acquired cortical function is altered during learning, mice were trained in an abstract task in which selected activity patterns were rewarded using an optical brain-computer interface device coupled to primary visual cortex (V1) neurons. Excitatory neurons were longitudinally recorded using 2-photon calcium imaging. Despite significant changes in local neural activity during task performance, tuning properties and stimulus encoding assessed outside of the trained context were not perturbed. Similarly, stimulus tuning was stable in neurons that remained responsive following a different, visual discrimination training task. However, visual discrimination training increased the rate of representational drift. Our results indicate that while some forms of perceptual learning may modify the contribution of individual neurons to stimulus encoding, new skill learning is not inherently disruptive to the quality of stimulus representation in adult V1.
Whole pair distribution function modeling: the bridging of Bragg and Debye scattering theories
Authors: Leonardi Alberto
Published: February 2021

Microstructure-based design of materials requires an atomic level understanding of the mechanisms underlying structure-dependent properties. Methods for analyzing either the traditional diffraction profile or the pair distribution function (PDF) differ in how the information is accessed and in the approximations usually applied. Any variation of structural and microstructural features over the whole sample affects the Bragg peaks as well as any diffuse scattering. Accuracy of characterization relies, therefore, on the reliability of the analysis methods. Methods based on Bragg's law investigate the diffraction peaks in the intensity plot as distinct pieces of information. This approach reaches a limitation when dealing with disorder scenarios that do not conform to such a peak-by-peak basis. Methods based on the Debye scattering equation (DSE) are, otherwise, well suited to evaluate the scattering from a disordered phase but the structure information is averaged over short-range distances usually accessed by experiments. Moreover, statistical reliability is usually sacrificed to recover some of the computing-efficiency loss compared with traditional line-profile-analysis methods. Here, models based on Bragg's law are used to facilitate the computation of a whole PDF and then model powder-scattering data via the DSE. Models based on Bragg's law allow the efficient solution of the dispersion of a crystal's properties in a powder sample with statistical reliability, and the PDF provides the flexibility of the DSE. The whole PDF is decomposed into the independent directional components, and the number of atom pairs separated by a given distance is statistically estimated using the common-volume functions. This approach overcomes the need for an atomistic model of the material sample and the computation of billions of pair distances. The results of this combined method are in agreement with the explicit solution of the DSE although the computing efficiency is comparable with that of methods based on Bragg's law. Most importantly, the method exploits the strengths and different sensitivities of the Bragg and Debye theories.
Crystallographic models of SARS-CoV-2 3CLpro: in-depth assessment of structure quality and validation
Authors: Jaskolski Mariusz , Dauter Zbigniew , Shabalin Ivan G. , Gilski Miroslaw , Brzezinski Dariusz , Kowiel Marcin , Rupp Bernhard , Wlodawer Alexander
Published: February 2021

The appearance at the end of 2019 of the new SARS-CoV-2 coronavirus led to an unprecedented response by the structural biology community, resulting in the rapid determination of many hundreds of structures of proteins encoded by the virus. As part of an effort to analyze and, if necessary, remediate these structures as deposited in the Protein Data Bank (PDB), this work presents a detailed analysis of 81 crystal structures of the main protease 3CLpro, an important target for the design of drugs against COVID-19. The structures of the unliganded enzyme and its complexes with a number of inhibitors were determined by multiple research groups using different experimental approaches and conditions; the resulting structures span 13 different polymorphs representing seven space groups. The structures of the enzyme itself, all determined by molecular replacement, are highly similar, with the exception of one polymorph with a different inter-domain orientation. However, a number of complexes with bound inhibitors were found to pose significant problems. Some of these could be traced to faulty definitions of geometrical restraints for ligands and to the general problem of a lack of such information in the PDB depositions. Several problems with ligand definition in the PDB itself were also noted. In several cases extensive corrections to the models were necessary to adhere to the evidence of the electron-density maps. Taken together, this analysis of a large number of structures of a single, medically important protein, all determined within less than a year using modern experimental tools, should be useful in future studies of other systems of high interest to the biomedical community.
Assessing the impacts of global economic policy uncertainty and the long-term bond yields on oil prices
Authors: Ozcelebi Oguzhan
Published: February 2021

Purpose

Might the impact of the global economic policy uncertainty (GEPU) and the long-term bond yields on oil prices be asymmetric? This paper aims to consider the effects of the GEPU and the US long-term government bond yields on oil prices using quantile-based analysis and nonlinear vector autoregression (VAR) model. The author hypothesized whether the negative and positive changes in the GEPU and the long-term bond yields of the USA have different effects on oil prices.

Design/methodology/approach

To address this question, the author uses quantile cointegration model and the impulse response functions (IRFs) of the censored variable approach of Kilian and Vigfusson (2011).

Findings

The quantile cointegration test showed the existence of non-linear cointegration relationship, whereas Granger-causality analysis revealed that positive/negative variations in GEPU will have opposite effects on oil prices. This result was supported by the quantile regression model’s coefficients and nonlinear VAR model’s IRFs; more specifically, it was stressed that increasing/decreasing GEPU will deaccelerate/accelerate global economic activity and thus lead to a fall/rise in oil prices. On the other hand, the empirical models indicated that the impact of US 10-year government bond yields on oil prices is asymmetrical, while it was found that deterioration in the borrowing conditions in the USA may have an impact on oil prices by slowing down the global economic activity.

Originality/value

As a robustness check of the quantile-based analysis results, the slope-based Mork test is used.
Comparative study by DTM for unsteady viscous flow between the jet engines combustion unit subjected to inclined magnetic field
Authors: Anand V.W.J. , Ganesh S. , Kechil Seripah Awang
Published: February 2021

Purpose

The purpose of this study to analyze the unsteady magneto hydrodynamic incompressible viscous fluid flow along the porous parallel plates in which constant periodic suction/injection takes place at lower and upper plate, respectively. By the proper choice of stream function, they obtained exact solution analytically. Velocity components are obtained from exact solution.

Design/methodology/approach

Emissions of the pollutants from the aviation sectors are doubled compared to 2000. There are many recent developments that are actively developed to combat the emission by increasing the performance of the Jet engines. The role of the computational fluid dynamics and the numerical approaches are crucial in terms of research and development.

Findings

Velocity profiles like axial and radial have been drawn for various values of M, D, α and θ. The exact solutions have been solved by differential transformation method. The closed form analytical solutions are obtained for the stream function, axial and radial velocities and flow velocity.

Originality/value

The effects of Darcy parameter, magnetic parameter, Suction Reynolds number and frequency parameter on lower and upper plates are discussed through graphs.
Strategic adaptation: leadership lessons for small business survival and success
Authors: Quansah Emmanuel , Hartz Dale E.
Published: February 2021

Purpose

Approximately half of all new businesses fail within the first five years of operation. This study was undertaken to understand the behavior of small business (SB) leaders, including their decision-making processes and adaptive leadership practices that enable their organizations to survive during periods of general crisis and intense competition.

Design/methodology/approach

In order to understand the lived experiences of our research participants, a constructivist grounded theory approach was used. Thirty-two CEOs and leaders from fifteen organizations were interviewed.

Findings

It was determined that successful SB leaders avoid organizational complacency by being continuous learners, who are agile and flexible in determining appropriate management strategies. Additionally, they leverage time management processes, build strong and productive relationship networks and create positive family-oriented workplace cultures to increase their odds of survival.

Research limitations/implications

This qualitative study was limited to interviews, observations and analysis of organizational archetypes; therefore, the authors can establish a pattern in behavior but cannot make a causality claim.

Practical implications

The findings provide SB leaders with effective concepts, practices and strategies from members of their peer group, which they can test, refine and implement.

Social implications

The impact of business failures is often devastating financially and emotionally for the families and employees involved. Learning methods for strategic adaptation that may help avoid business closures could provide a positive societal contribution.

Originality/value

There is little empirical research about how SBs strategically adapt during challenging periods. This study helps fill that gap and provides an understanding of how SB leaders adapt to continuous challenges, create value and remain competitive in difficult business environments.
Modified atmosphere packaging for milk cake: assessment of ideal gas composition for extending shelf life
Authors: Chawla Rekha , Sivakumar S. , Mishra Santosh Kumar , Kaur Harsimran , Anurag Rahul Kumar
Published: February 2021

Purpose

Milk cake is a well-renowned khoa-based dairy product in India, produced either from the buffalo milk or using a specific danedar variety of khoa. Under ambient conditions, shelf-life of milk cake is generally up to 3–4 days, whereas under refrigeration conditions, it can last up to 12–14 days. Therefore, the present study aims to evaluate the effect of modified atmosphere packaging (MAP) to enhance the shelf-life and keeping intact freshness of milk cake under refrigerated conditions (4 ± 2 °C).

Design/methodology/approach

Different gas concentrations of N2 and CO2 (70:30, 50:50 and 90:10) were used as a treatment, whereas control samples were kept under atmospheric air composition. The product was examined for sensory, physicochemical and microbiological parameters at weekly intervals.

Findings

The physicochemical and microbiological attributes displayed gradual elevation with progressive storage period in all the samples. However, the overall sensory profile of the product remained acceptable for a longer duration. Most of the quality parameters in control declined more rapidly with a shelf life of 14 days, in comparison to MAP packed samples, where gas flushing with the ratio 70:30 was found to be best suited for extending the shelf life of milk cake up to 28 days at refrigeration temperature.

Originality/value

To extend the shelf life of milk cake, modified atmosphere was provided with different gas ratios to reach a best-suited environment for sensory, storage life and proximate parameters.
Slope stability analysis considering the rotated anisotropy in soil properties
Authors: Wang Zhen , Wang Huanling , Xu Weiya , Xie W.C.
Published: February 2021

Purpose

This paper aims to analyze the influence of rotated anisotropy on the stability of slope, the random finite element method is used in this study.

Design/methodology/approach

The random field is generated by the discrete cosine transform (DCT) method, which can generate random field with different rotated angles conveniently.

Findings

Two idealized slopes are analyzed; it is observed that the rotated angle significantly affects the slope failure risk. The two examples support the conclusion that when the orientation of the layers is nearly perpendicular to the slip surface, the slope is in a relative stable condition. The results of heterogeneous slope with two clay layers demonstrate that the rotated angle of lower layer mainly controls the failure mechanism of the slope, and the rotated angle of upper layer exhibits a significant influence on the probability of slope failure.

Originality/value

The method for rotated anisotropy random field generation based on the DCT has a simple expression with few parameters and is convenient for implementation and practical application. The proposed method and the results obtained are useful for analyzing the stability of the heterogeneous slopes in engineering projects.
Deep learning or interpolation for inverse modelling of heat and fluid flow problems?
Authors: Löhner Rainald , Antil Harbir , Tamaddon-Jahromi Hamid , Chakshu Neeraj Kavan , Nithiarasu Perumal
Published: February 2021

Purpose

The purpose of this study is to compare interpolation algorithms and deep neural networks for inverse transfer problems with linear and nonlinear behaviour.

Design/methodology/approach

A series of runs were conducted for a canonical test problem. These were used as databases or “learning sets” for both interpolation algorithms and deep neural networks. A second set of runs was conducted to test the prediction accuracy of both approaches.

Findings

The results indicate that interpolation algorithms outperform deep neural networks in accuracy for linear heat conduction, while the reverse is true for nonlinear heat conduction problems. For heat convection problems, both methods offer similar levels of accuracy.

Originality/value

This is the first time such a comparison has been made.
Influence of sublimation process on air permeability and water absorption dynamics
Authors: Kalendraite Brigita , Krisciunaite Jolita , Mikucioniene Daiva
Published: February 2021

Purpose

The purpose of this research was to find the influence of sublimation process on air permeability and water absorption dynamics of knitted and woven polyester-based fabrics.

Design/methodology/approach

Three different sublimation designs were prepared and applied (keeping the same sublimation parameters) for eight variants of knitted and four variants of woven polyester-based fabrics. Air permeability and water absorption dynamics during 180s period was measured and compared before and after the sublimation process.

Findings

According to the obtained results, high temperature and pressure applied in sublimation process have influence on the porosity and air permeability of knitted fabrics; however, the influence on water absorption dynamics is minimal. Sublimation design dos not have any influence on the mentioned properties.

Originality/value

The obtained results of the sublimation process influence on air permeability and water absorption dynamics of knitted and woven polyester-based fabrics will help to understand how sublimation process can affect comfort properties of textile fabrics.
Crisis leadership and coaching: a tool for building school leaders' self-efficacy through self-awareness and reflection
Authors: Brinkmann Jodie Lynn , Cash Carol , Price Ted
Published: February 2021

Purpose

This paper introduces a cognitive coaching and reflection tool to help school leaders build self-efficacy at a time when schools are facing a crisis in leadership. Key themes emerged from the data generated as part of a larger study of PK-12 administrators' leadership during the coronavirus pandemic.

Design/methodology/approach

This qualitative study is based on phenomenological research methods and uses naturalistic inquiry design.

Findings

The findings consider the building of school leaders' efficacy in crisis management during a pandemic. A total of seven data-driven reflection themes are identified: self-care, professional development (PD), communication, school climate, instruction, parent resources and advocacy.

Research limitations/implications

Investigated using a purposeful, nonrepresentative sample were the perceptions and experiences of PK-12 administrators as they served in their leadership role during the pandemic. Therefore, the results are not generalizable beyond the scope and context for which the research was conducted. An implication of this study is that this tool can be used by coaches working with school leaders and by leaders themselves to increase self-efficacy.

Originality/value

The cognitive coaching and reflection tool could be beneficial in developing leaders' self-awareness and reflection skills, in turn building self-efficacy. Although there are other tools to support leaders' self-awareness and reflection, the effects of the pandemic represent a unique opportunity for examining leader practices to adjust to, prepare for and deal with the impacts of a crisis.
Reliability analysis of gas pipeline with corrosion defect based on finite element method
Authors: Yang Yuan-Jian , Wang Guihua , Zhong Qiuyang , Zhang Huan , He Junjie , Chen Haijun
Published: February 2021

Purpose

Gas pipelines are facing serious risk because of the factors such as long service life, complex working condition and most importantly, corrosion. As one of the main failure reasons of gas pipeline, corrosion poses a great threat to its stable operation. Therefore, it is necessary to analyze the reliability of gas pipelines with corrosion defect. This paper uses the corresponding methods to predict the residual strength and residual life of pipelines.

Design/methodology/approach

In this paper, ASME-B31G revised criteria and finite element numerical analysis software are used to analyze the reliability of a special dangerous section of a gas gathering pipeline, and the failure pressure and stress concentration of the pipeline under three failure criteria are obtained. Furthermore, combined with the predicted corrosion rate of the pipeline, the residual service life of the pipeline is calculated.

Findings

This paper verifies the feasibility of ASME-B31G revised criteria and finite element numerical analysis methods for reliability analysis of gas pipelines with corrosion defect. According to the calculation results, the maximum safe internal pressure of the pipeline is 9.53 Mpa, and the residual life of the pipeline under the current operating pressure is 38.41 years, meeting the requirements of safe and reliable operation.

Originality/value

The analysis methods and analysis results provide reference basis for the reliability analysis of corroded pipelines, which is of great practical engineering value for the safe and stable operation of natural gas pipelines.
How Bayesian Are Farmers When Making Climate Adaptation Decisions? A Computer Laboratory Experiment for Parameterising Models of Expectation Formation
Authors: Eisele Marius , Troost Christian , Berger Thomas
Published: February 2021

As the consequences of climate change for agricultural production slowly unfold at the local level (sometimes with contradicting signals), farmers’ information processing and decision making become more relevant for policy analysis and modelling. The major challenge is to reveal patterns in the way farmers form expectations about future production outcomes and to encode these findings into models of heterogeneous expectation formation. We developed and tested a payout‐motivated field experiment to observe farmer decision‐making under climate change and to examine how they form their expectations in a recursive‐dynamic context. Participants were exposed to ambiguity and acquired incremental evidence about the true distribution of possible climate outcomes through repeated random draws. Simulation models used in agricultural and environmental research usually implement simple forms of adaptive agent expectation or completely neglect this issue by assuming perfect foresight or constant expectations. Our computer laboratory experiments with blue‐ and white‐collar farmers from Southwest Germany (n = 97) suggest that expectation behaviour of a large share of farmers can be well replicated with Bayesian types of expectation models.