bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibodies to the SARS-CoV-2 receptor-binding domain that maximize breadth and resistance to viral escape
Authors: Starr Tyler N. , Czudnochowski Nadine , Zatta Fabrizia , Park Young-Jun , Liu Zhuoming , Addetia Amin , Pinto Dora , Beltramello Martina , Hernandez Patrick , Greaney Allison J. , Marzi Roberta , Glass William G. , Zhang Ivy , Dingens Adam S. , Bowen John E. , Wojcechowskyj Jason A. , De Marco Anna , Rosen Laura E. , Zhou Jiayi , Montiel-Ruiz Martin , Kaiser Hannah , Tucker Heather , Housley Michael P. , di Iulio Julia , Lombardo Gloria , Agostini Maria , Sprugasci Nicole , Culap Katja , Jaconi Stefano , Meury Marcel , Dellota Exequiel , Cameroni Elisabetta , Croll Tristan I. , Nix Jay C. , Havenar-Daughton Colin , Telenti Amalio , Lempp Florian A. , Pizzuto Matteo S. , Chodera John D. , Hebner Christy M. , Whelan Sean P.J. , Virgin Herbert W. , Veesler David , Corti Davide , Bloom Jesse D. , Snell Gyorgy
Published: April 2021

An ideal anti-SARS-CoV-2 antibody would resist viral escape1–3, have activity against diverse SARS-related coronaviruses4–7, and be highly protective through viral neutralization8–11 and effector functions12,13. Understanding how these properties relate to each other and vary across epitopes would aid development of antibody therapeutics and guide vaccine design. Here, we comprehensively characterize escape, breadth, and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD), including S3094, the parental antibody of the late-stage clinical antibody VIR-7831. We observe a tradeoff between SARS-CoV-2 in vitro neutralization potency and breadth of binding across SARS-related coronaviruses. Nevertheless, we identify several neutralizing antibodies with exceptional breadth and resistance to escape, including a new antibody (S2H97) that binds with high affinity to all SARS-related coronavirus clades via a unique RBD epitope centered on residue E516. S2H97 and other escape-resistant antibodies have high binding affinity and target functionally constrained RBD residues. We find that antibodies targeting the ACE2 receptor binding motif (RBM) typically have poor breadth and are readily escaped by mutations despite high neutralization potency, but we identify one potent RBM antibody (S2E12) with breadth across sarbecoviruses closely related to SARS-CoV-2 and with a high barrier to viral escape. These data highlight functional diversity among antibodies targeting the RBD and identify epitopes and features to prioritize for antibody and vaccine development against the current and potential future pandemics.
Caspase-dependent cleavage of DDX21 suppresses host innate immunity
Authors: Wu Wei , Qu Yang , Yu Shengqing , Wang Sa , Yin Yuncong , Liu Qinfang , Meng Chunchun , Liao Ying , Rehman Zaib Ur , Tan Lei , Song Cuiping , Qiu Xusheng , Liu Weiwei , Ding Chan , Sun Yingjie
Published: April 2021

DEAD (Glu-Asp-Ala-Glu)-box RNA helicases have been proven to contribute to antiviral innate immunity. DDX21 RNA helicase was identified as a nuclear protein involved in ribosomal RNA processing and RNA unwinding. DDX21 was also proved to be the scaffold protein in the complex of DDX1-DDX21-DHX36 which senses double strand RNA and initiates downstream innate immunity. Here, we identified that DDX21 undergoes caspase-dependent cleavage after virus infection and treatment with RNA/DNA ligands, especially for RNA virus and ligands. Caspase-3/6 cleave DDX21 at D126and promotes its translocation from the nucleus to the cytoplasm in response to virus infection. The cytoplasmic cleaved DDX21 negatively regulates the IFN-β signaling pathway by suppressing the formation of DDX1-DDX21-DHX36 complex. Thus, our data identify DDX21 as a regulator of immune balance and most importantly uncover a potential role of DDX21 cleavage in the innate immunity response towards virus.

Importance

Innate immunity serves as the first barrier against virus infection. DEAD (Glu-Asp-Ala-Glu)-box RNA helicases, originally considered to be involved RNA processing and RNA unwinding, have been shown to play an important role in anti-viral innate immunity. The precise regulation of innate immunity is critical for the host because the aberrant production of cytokines leads to unexpected pathological consequences. Here, we identified DDX21 was cleaved at D126by virus infection and treatment with RNA/DNA ligands via the caspase-3/6-dependent pathway. The cytoplasmic cleaved DDX21 negatively regulates the IFN-β signaling pathway by suppressing the formation of DDX1-DDX21-DHX36 complex. In sum, our data identify DDX21 as a regulator of immune balance and most importantly uncover a potential role of DDX21 cleavage in the innate immunity response towards virus.
Tracking of Anopheles stephensi in Ethiopia using mitochondrial DNA reveals pattern of spread
Authors: Carter Tamar E. , Yared Solomon , Getachew Dejene , Spear Joseph , Choi Sae Hee , Samake Jeanne N. , Mumba Peter , Dengela Dereje , Yohannes Gedeon , Chibsa Sheleme , Murphy Matthew , Dissanayake Gunawardena , Flately Cecilia , Lopez Karen , Janies Daniel , Zohdy Sarah , Irish Seth R. , Balkew Meshesha
Published: April 2021

The recent detection of the South Asian malaria vector Anopheles stephensi in the Horn of Africa (HOA) raises concerns about the impact of this mosquito on malaria transmission in the region. The mode and history of introduction is important for predicting the likelihood of continued introduction and future spread. Analysis of An. stephensi genetic diversity and population structure can provide insight into the history of the mosquito in the HOA. We investigated genetic diversity of An. stephensi in eastern Ethiopia where detection suggests a range expansion to this region to understand the history of this invasive population. We sequenced the cytochrome oxidase subunit I (COI) and cytochrome B gene (CytB) in 187 An. stephensi collected from 10 sites in Ethiopia in 2018. Phylogenetic analyses using a maximum-likelihood approach and minimum spanning network were conducted for Ethiopian sequences. Molecular identification of bloodmeal sources was also performed using universal vertebrate CytB sequencing. Six COI-CytB haplotypes were observed based on five segregating sites, with the highest number of haplotypes in the northeastern sites (Semera, Bati, and Gewana towns) relative to the southeastern sites (Kebridehar, Godey, and Degehabur) in eastern Ethiopia. In the phylogenetic and network analysis, we observed population differentiation based on the distribution of the haplotypes across the northeastern and central sites (Erer Gota, Dire Dawa, and Awash Sebat Kilo) compared to the southeastern sites and evidence of a South Asian origin of the HOA An. stephensi lineages. The presence of the putative South Asian haplotype of origin at sites closest to Ethiopia’s northeastern borders support route of introductions into Ethiopia from the northeast. Finally, molecular bloodmeal analysis revealed evidence of feeding on bovines, goats, dogs, and humans, as well as evidence of multiple (mixed) blood meals. In conclusion, we find support for the hypothesis for the recent expansion of An. stephensi into southeastern Ethiopia with multiple introductions. We also find evidence that supports the hypothesis that HOA An. stephensi populations originate from South Asia rather than the Arabian Peninsula. The evidence of both zoophagic and anthropophagic feeding support the potential for livestock movement to play a role in vector spread in this region.
Effective gene expression prediction from sequence by integrating long-range interactions
Authors: Avsec Žiga , Agarwal Vikram , Visentin Daniel , Ledsam Joseph R. , Grabska-Barwinska Agnieszka , Taylor Kyle R. , Assael Yannis , Jumper John , Kohli Pushmeet , Kelley David R.
Published: April 2021

The next phase of genome biology research requires understanding how DNA sequence encodes phenotypes, from the molecular to organismal levels. How noncoding DNA determines gene expression in different cell types is a major unsolved problem, and critical downstream applications in human genetics depend on improved solutions. Here, we report substantially improved gene expression prediction accuracy from DNA sequence through the use of a new deep learning architecture called Enformer that is able to integrate long-range interactions (up to 100 kb away) in the genome. This improvement yielded more accurate variant effect predictions on gene expression for both natural genetic variants and saturation mutagenesis measured by massively parallel reporter assays. Notably, Enformer outperformed the best team on the critical assessment of genome interpretation (CAGI5) challenge for noncoding variant interpretation with no additional training. Furthermore, Enformer learned to predict promoter-enhancer interactions directly from DNA sequence competitively with methods that take direct experimental data as input. We expect that these advances will enable more effective fine-mapping of growing human disease associations to cell-type-specific gene regulatory mechanisms and provide a framework to interpret cis-regulatory evolution. To foster these downstream applications, we have made the pre-trained Enformer model openly available, and provide pre-computed effect predictions for all common variants in the 1000 Genomes dataset.

One-sentence summary

Improved noncoding variant effect prediction and candidate enhancer prioritization from a more accurate sequence to expression model driven by extended long-range interaction modelling.
ULTRASTRUCTURAL STUDY OF THE ESOPHAGUS AND STOMACH OFArapaima gigas(Schinz 1822), JUVENILE PAICHE, CREATED EXCAVATED TANK
Authors: Pinto Keila Silva , de Melo Luana Félix , de Aquino Julia Bastos , Dantas Filho Jerônimo Vieira , Miglino Maria Angelica , de Vargas Schons Sandro , Rici Rose Eli Grassi
Published: April 2021

Paiche (Arapaima gigas)belongs to the KingdomAnimalia, PhylumChordata, ClassActinopterygii, OrderOsteoglossiformes,FamilyArapaimidae,GenusArapaima,and its origin may date to the Jurassic period. The species has natural habitat in the Amazonian rivers, found mainly in marginal lakes, being considered an important fishing resource, with high market value and high demand for meat and leather in both Brazilian and international trade. This study aims to describe the morphology of the esophagus and stomach by light microscopy and scanning electronics microscopy. The esophagus was presented as muscular, short, tubular and fan-shaped in the cranial portion, also presenting deep longitudinal folds, and the entire mucosa is covered by mucus secretory cells with distinct morphological characteristics. Pirarurcu’s stomach has a J-shape divided into three regions: cardiac with a lighter aspect, fundus portion with few folds in the mucosa, and pyloric with deeper folds, also presenting gastroliths in fundus and pyloric portions. Both microscopy studies highlighted three glandular regions, composed by mucoid columnar epithelial cells, gastric crypts with different shapes and sizes depending on each portion, in which the different shapes of the mucosal folds in each region of the stomach were evident, and digitiform microsaliences were found in the cardiac region, and micro-orifices and desmosome in the fundus region. Also, fundus and pyloric portions produce more mucus than the cardiac. Then morphology found was consistent with the eating habits and management of distinct characteristics of the digestive tract.
Precocious hippocampal structural and functional changes in gestational protein-restricted male elderly offspring: an Alzheimer-simile disease model?
Authors: Grigoletti-Lima Gabriel Boer , Lopes Marcelo Gustavo , Franco Ana Tereza Barufi , Damico Aparecida Marcela , Boer Patrícia Aline , Gontijo José Antonio Rocha
Published: April 2021

Background

Maternal undernutrition has been associated with psychiatric and neurological disorders characterized by learning and memory impairment. Considering the lack of evidence for this, we aimed to analyze the effects of gestational protein restriction on learning and memory function later in life. This research associates behavioral findings with hippocampal cell numbers and protein content related to neurodegenerative brain disease.

Methods

Experiments were conducted in animals subjected to a low-protein (LP, 6% casein) or regular-protein (NP, 17% casein) diet throughout their pregnancy. Behavioral tests, isolated hippocampal isotropic fractionator cell studies, immunoblotting, and survival lifetime tests were performed. The results confirmed that the birthweight of LP male pups significantly reduced relative to NP male pups and that hippocampal mass increased in 88-week-old LP compared to age-matched NP offspring. We used the Morris water maze proximity measure, which is the sum of 10 distances each second between rat position and location of a hidden platform target, as a suitable test for assessing age-related learning or memory impairment in aged offspring.

Results

The results showed an increased proximity measure in 87-week-old LP rats (52.6 × 104± 10.3 × 104mm) as compared to NP rats (47.0 × 104± 10.6 × 103mm, p = 0.0007). In addition, LP rats exhibited anxiety-like behaviors compared to NP rats at 48 and 86 weeks of life.

Additionally, the estimated neuron number was unaltered in LP rats; however, glial and other cell numbers increased in LP compared to NP rats. Here, we showed unprecedented hippocampal deposition of brain-derived neurotrophic factor, β-amyloid peptide (Aβ), and tau protein in 88-week-old LP compared to age-matched NP offspring. To date, no predicted studies showed changes in hippocampal neuron and glial cell numbers in maternal protein-restricted elderly offspring. The current data suggest that maternal protein restriction has a high impact on lifespan and brain structure, and function.

Conclusion

the gestational protein restriction may accelerate hippocampal function loss, impacting learning/memory performance, and supposedly developing diseases similar to Alzheimer’s disease (AD) in elderly offspring. Thus, we propose that maternal protein restriction could be a probable, elegant, and novel method for constructing an AD-like model in adult male offspring.
Lignin accumulation in phloem and outer bark is not associated with resistance to mountain pine beetle in high elevation pines
Authors: Soderberg David N. , Kyre Bethany , Bonello Pierluigi , Bentz Barbara J.
Published: April 2021

A key component in understanding plant-insect interactions is the nature of host defenses. Research on defense traits amongPinusspecies has focused on specialized metabolites and axial resin ducts, but the role of lignin in defense within diverse systems is unclear. We investigated lignin levels in the outer bark and phloem ofP. longaeva,P. balfouriana, andP. flexilis; high elevation species in the western United States known to differ in susceptibility to mountain pine beetle (Dendroctonus ponderosae; MPB). Relative toP. flexilis,P. longaevaandP. balfourianaare attacked by MPB less frequently, and MPB brood production inP. longaevais limited. Because greater lignification of feeding tissues has been shown to provide defense against bark beetles in related genera, such asPicea, we hypothesized thatP. longaevaandP. balfourianawould have greater lignin concentrations thanP. flexilis. Contrary to expectations, we found that the more MPB-susceptibleP. flexilishad greater phloem lignin levels than the less susceptibleP. longaevaandP. balfouriana. No differences in outer bark lignin levels among the species were found. We conclude that lignification inPinusphloem and outer bark is likely not adaptive as a physical defense against MPB.
Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp15 Endoribonuclease
Authors: Canal Berta , Fujisawa Ryo , McClure Allison W. , Deegan Tom , Wu Mary , Ulferts Rachel , Weissmann Florian , Drury Lucy S. , Bertolin Agustina P. , Zeng Jingkun , Beale Rupert , Howell Michael , Labib Karim , Diffley John F.X
Published: April 2021

SARS-CoV-2 is responsible for COVID-19, a human disease that has caused over 2 million deaths, stretched health systems to near-breaking point and endangered the economies of countries and families around the world. Antiviral treatments to combat COVID-19 are currently lacking. Remdesivir, the only antiviral drug approved for the treatment of COVID-19, can affect disease severity, but better treatments are needed. SARS-CoV-2 encodes 16 non-structural proteins (nsp) that possess different enzymatic activities with important roles in viral genome replication, transcription and host immune evasion. One key aspect of host immune evasion is performed by the uridine-directed endoribonuclease activity of nsp15. Here we describe the expression and purification of nsp15 recombinant protein. We have developed biochemical assays to follow its activity, and we have found evidence for allosteric behaviour. We screened a custom chemical library of over 5000 compounds to identify nsp15 endoribonuclease inhibitors, and we identified and validated NSC95397 as an inhibitor of nsp15 endoribonucleasein vitro. Although NSC95397 did not inhibit SARS-CoV-2 growth in VERO E6 cells, further studies will be required to determine the effect of nsp15 inhibition on host immune evasion.
Structural basis for broad sarbecovirus neutralization by a human monoclonal antibody
Authors: Tortorici M. Alejandra , Czudnochowski Nadine , Starr Tyler N. , Marzi Roberta , Walls Alexandra C. , Zatta Fabrizia , Bowen John E. , Jaconi Stefano , iulio Julia di , Wang Zhaoqian , De Marco Anna , Zepeda Samantha K. , Pinto Dora , Liu Zhuoming , Beltramello Martina , Bartha Istvan , Housley Michael P. , Lempp Florian A. , Rosen Laura E. , Dellota Exequiel , Kaiser Hannah , Montiel-Ruiz Martin , Zhou Jiayi , Addetia Amin , Guarino Barbara , Culap Katja , Sprugasci Nicole , Saliba Christian , Vetti Eneida , Giacchetto-Sasselli Isabella , Fregni Chiara Silacci , Abdelnabi Rana , Foo Shi-Yan Caroline , Havenar-Daughton Colin , Schmid Michael A. , Benigni Fabio , Cameroni Elisabetta , Neyts Johan , Telenti Amalio , Snell Gyorgy , Virgin Herbert W. , Whelan Sean P.J. , Bloom Jesse D. , Corti Davide , Veesler David , Pizzuto Matteo Samuele
Published: April 2021

The recent emergence of SARS-CoV-2 variants of concern (VOC) and the recurrent spillovers of coronaviruses in the human population highlight the need for broadly neutralizing antibodies that are not affected by the ongoing antigenic drift and that can prevent or treat future zoonotic infections. Here, we describe a human monoclonal antibody (mAb), designated S2×259, recognizing a highly conserved cryptic receptor-binding domain (RBD) epitope and cross-reacting with spikes from all sarbecovirus clades. S2×259 broadly neutralizes spike-mediated entry of SARS-CoV-2 including the B.1.1.7, B.1.351, P.1 and B.1.427/B.1.429 VOC, as well as a wide spectrum of human and zoonotic sarbecoviruses through inhibition of ACE2 binding to the RBD. Furthermore, deep-mutational scanning and in vitro escape selection experiments demonstrate that S2×259 possesses a remarkably high barrier to the emergence of resistance mutants. We show that prophylactic administration of S2×259 protects Syrian hamsters against challenges with the prototypic SARS-CoV-2 and the B.1.351 variant, suggesting this mAb is a promising candidate for the prevention and treatment of emergent VOC and zoonotic infections. Our data unveil a key antigenic site targeted by broadly-neutralizing antibodies and will guide the design of pan-sarbecovirus vaccines.
SARS-CoV-2 infection in the Syrian hamster model causes inflammation as well as type I interferon dysregulation in both respiratory and non-respiratory tissues including the heart and kidney
Authors: Francis Magen E. , Goncin Una , Kroeker Andrea , Swan Cynthia , Ralph Robyn , Lu Yao , Etzioni Athema L. , Falzarano Darryl , Gerdts Volker , Machtaler Steven , Kindrachuk Jason , Kelvin Alyson A.
Published: April 2021

COVID-19 (coronavirus disease 2019) caused SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is a disease affecting several organ systems. A model that captures all clinical symptoms of COVID-19 as well as long-haulers disease is needed. We investigated the host responses associated with infection in several major organ systems including the respiratory tract, the heart, and the kidneys after SARS-CoV-2 infection in Syrian hamsters. We found significant increases in inflammatory cytokines (IL-6, IL-1beta, and TNF) and type II interferons whereas type I interferons were inhibited. Examination of extrapulmonary tissue indicated inflammation in the kidney, liver, and heart which also lacked type I interferon upregulation. Histologically, the heart had evidence of mycarditis and microthrombi while the kidney had tubular inflammation. These results give insight into the multiorgan disease experienced by people with COVID-19 and possibly the prolonged disease in people with post-acute sequelae of SARS-CoV-2 (PASC).
Synthetic repertoires derived from convalescent COVID-19 patients enable discovery of SARS-CoV-2 neutralizing antibodies and a novel quaternary binding modality
Authors: Goike Jule , Hsieh Ching-Lin , Horton Andrew , Gardner Elizabeth C. , Bartzoka Foteini , Wang Nianshuang , Javanmardi Kamyab , Herbert Andrew , Abbassi Shawn , Renberg Rebecca , Johanson Michael J. , Cardona Jose A. , Segall-Shapiro Thomas , Zhou Ling , Nissly Ruth H. , Gontu Abhinay , Byrom Michelle , Maranhao Andre C. , Battenhouse Anna M. , Gejji Varun , Soto-Sierra Laura , Foster Emma R. , Woodard Susan L. , Nikolov Zivko L. , Lavinder Jason , Voss Will N. , Annapareddy Ankur , Ippolito Gregory C. , Ellington Andrew D. , Marcotte Edward M. , Finkelstein Ilya J. , Hughes Randall A. , Musser James M. , Kuchipudi Suresh V. , Kapur Vivek , Georgiou George , Dye John M. , Boutz Daniel R. , McLellan Jason S. , Gollihar Jimmy D.
Published: April 2021

The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has sparked concern over the continued effectiveness of existing therapeutic antibodies and vaccines. Hence, together with increased genomic surveillance, methods to rapidly develop and assess effective interventions are critically needed. Here we report the discovery of SARS-CoV-2 neutralizing antibodies isolated from COVID-19 patients using a high-throughput platform. Antibodies were identified from unpaired donor B-cell and serum repertoires using yeast surface display, proteomics, and public light chain screening. Cryo-EM and functional characterization of the antibodies identified N3-1, an antibody that binds avidly (Kd,app= 68 pM) to the receptor binding domain (RBD) of the spike protein and robustly neutralizes the virusin vitro. This antibody likely binds all three RBDs of the trimeric spike protein with a single IgG. Importantly, N3-1 equivalently binds spike proteins from emerging SARS-CoV-2 variants of concern, neutralizes UK variant B.1.1.7, and binds SARS-CoV spike with nanomolar affinity. Taken together, the strategies described herein will prove broadly applicable in interrogating adaptive immunity and developing rapid response biological countermeasures to emerging pathogens.
Assessing acquired resistance to IDH1 inhibitor therapy by full-exon IDH1 sequencing and structural modeling
Authors: Oltvai Zoltán N. , Harley Susan E. , Koes David , Michel Stephen , Warlick Erica D. , Nelson Andrew C. , Yohe Sophia , Mroz Pawel
Published: April 2021

Somatic mutations in hotspot regions of the cytosolic or mitochondrial isoforms of the isocitrate dehydrogenase gene (IDH1 and IDH2, respectively) contribute to the pathogenesis of acute myeloid leukemia (AML) by producing the oncometabolite 2-hydroxyglutarate (2-HG). The allosteric IDH1 inhibitor, ivosidenib, suppresses 2-HG production and induces clinical responses in relapsed/refractory IDH1-mutant AML. Herein, we describe a clinical case of AML in which we detected the neomorphic IDH1 p.R132C mutation in consecutive patient samples with a mutational hotspot targeted next-generation sequencing (NGS) assay. The patient had a clinical response to ivosidenib, followed by relapse and disease progression. Subsequent sequencing of the relapsed sample using a newly developed all-exon, hybrid-capture-based NGS panel identified an additional IDH1 p.S280F mutation known to cause renewed 2-HG production and drug resistance. Structural modeling confirmed that serine-to-phenylalanine substitution at this codon sterically hinders ivosidenib from binding to the mutant IDH1 dimer interface and predicted a similar effect on the pan-IDH inhibitor AG-881. Joint full-exon NGS and structural modeling enables monitoring IDH1 inhibitor-treated AML patients for acquired drug resistance and choosing follow-up therapy.
Long-term survival of an ovarian cancer patient harboring a RAD51C missense mutation
Authors: Sullivan Meghan R. , Prakash Rohit , Rawal Yashpal , Wang Weibin , Sung Patrick , Radke Marc R. , Kaufmann Scott H. , Swisher Elizabeth M. , Bernstein Kara A. , Jasin Maria
Published: April 2021

Mutations in homologous recombination (HR) genes predispose to cancer but also sensitize to chemotherapeutics. Although therapy can initially be effective, cancers frequently cease responding, leading to recurrence and poor prognosis. Here we identify a germline mutation in RAD51C, a critical HR factor and known tumor suppressor, in an ovarian cancer patient with exceptionally long, progression-free survival. The RAD51C–T132P mutation is in a highly conserved residue within the nucleotide-binding site and interferes with single-strand DNA binding of the RAD51 paralog complex RAD51B–RAD51C–RAD51D–XRCC2 and association with another RAD51 paralog XRCC3. These biochemical defects lead to highly defective HR and drug sensitivity in tumor cells, ascribing RAD51C–T132P as a deleterious mutation that was likely causal for tumor formation. Conversely, its position within a critical site suggests that it is refractory to secondary mutations that would restore RAD51C gene function and lead to therapy resistance. A need for a greater understanding of the relationship between mutation position and reversion potential of HR genes is underscored, as it may help predict the effectiveness of therapies in patients with HR-deficient cancers.
Electrochemical corrosion resistance of thermal oxide formed on anodized stainless steel
Authors: Deng Hongda , Liu Yongliang , He Zhen , Gou Xiantao , Sheng Yefan , Chen Long , Ren Jianbing
Published: April 2021

Purpose

The purpose of this paper is to investigate and explain thermal oxide effect on electrochemical corrosion resistance anodized stainless steel (SS).

Design/methodology/approach

Electrochemical corrosion resistance of thermal oxides produced on anodized 304 SS in air at 350°C, 550°C, 750°C and 950°C in 3.5 wt.% NaCl solution have been investigated by dynamic potential polarization, EIS and double-loop dynamic polarization. Anodized 304 SS were obtained by anodization at the constant density of 1.4 mA.cm-2in the solution containing 28.0 g.L-1H3PO4, 20.0 g.L-1C6H8O7, 200.0 g.L-1H2O2at 70°C for 50 min. SEM and EDS had been also used to characterize the thermal oxides and passive oxide.

Findings

Interestingly, anodized 304SS with thermal oxide produced at 350°C displayed more electrochemical corrosion and pitting resistance than anodized 304 SS only with passive oxide, as related to the formation of oxide film with higher chromium to iron ratio. Whereas, anodized 304SS with thermal oxide formed at 950°C shows the worse electrochemical corrosion and pitting resistance among those formed at the high temperatures due to thermal oxide with least compact.

Originality/value

When thermally oxidized in the range of 350°C–950°C, electrochemical corrosion and pitting corrosion resistance of anodized 304 SS decrease with the increase of temperature due to less compactness, more defects of thermal oxide.
Evaluation of the ACE employment programme: helping employers to make tailored adjustments for their autistic employees
Authors: López Beatriz , Kargas Niko , Udell Julie , Rubín Tomáš , Burgess Linda , Dew Dominic , McDonald Ian , O’Brien Ann , Templeton-Mepstead Karen
Published: April 2021

Purpose

The purpose of this study was to explore the views of autistic people, carers and practitioners regarding the barriers autistic employees face at work (Study 1) and to use these views to inform the design of an employment programme for autistic employees without learning disabilities (Study 2).

Design/methodology/approach

In Study 1, 16 (20%) carers, 17 (21%) practitioners and 47 (59%) autistic adults who had been or were currently employed, answered a survey regarding barriers at work. Study 2 evaluates the efficacy of a set of profiling assessment tools (PA) developed to help employers make individually-tailored adjustments for their autistic employees by delivering an employment programme consisting of 15, 8-week work placements.

Findings

In Study 1, only 25% of autistic adults reported having had adjustments in the workplace and all groups reported this as the main barrier – alongside employers’ lack of understanding. Two sets of results demonstrate the efficacy of the PA tools in addressing this barrier. First, a comparative cost simulation revealed a cost-saving in terms of on-job support of £6.67 per participant per hour worked relative to published data from another programme. Second, 83% of autistic employees reported having had the right adjustments at work.

Research limitations/implications

This is an exploratory study that did not include a comparison group. Hence, it was not possible to evaluate the efficacy of the PA tools relative to a standard employment programme intervention, nor to assess cost reduction, which currently is only estimated from already available published data.

Practical implications

Overall the findings from these studies demonstrate that the time invested in the high-quality assessment of the profile of autistic employees results in saving costs over time and better outcomes.

Originality/value

The originality of the Autism Centre for Employment programme resides in that, unlike other programmes, it shifts the focus from helping autistic employees to helping their employers.
Technological illiteracy in an increasingly technological world: methods to help employees create with rather than simply consume technology
Authors: Pfaltzgraf Daniel , Insch Gary S.
Published: April 2021

Purpose

This paper discusses the technology gap in today’s newer hires where younger employees are often believed to be more technologically astute than they really are. Younger employees are consumers of technology, but they have limited skills in using technology to solve business problems.

Design/methodology/approach

This paper reflects a review of theory and research on technology training and practice.

Findings

Three recommendations are presented that could aid employers in bridging the gap between technology literacy perceptions and actual practice: build proficiency of business software, be the convener of learning in digitally focused training programs, and applying design thinking in business settings.

Originality/value

Due to the Covid-19 pandemic, businesses have been forced to incorporate more technology applications in their operations. This has exposed a paradoxical gap between perceived technology knowledge in their younger employees and actual skill sets. This article describes practical suggestions for enhancing corporate training programs to address this challenge.
Aerodynamic preliminary design optimization of a centrifugal compressor turbocharger based on one-dimensional mean-line model
Authors: Bourabia Lakhdar , Abed Cheikh Brahim , Cerdoun Mahfoudh , Khalfallah Smail , Deligant Michaël , Khelladi Sofiane , Chettibi Taha
Published: April 2021

Purpose

The purpose of this paper is the development of a new turbocharger compressor is a challenging task particularly when both wider operating range and higher efficiency are required. However, the cumbersome design effort and the inherent calculus burden can be significantly reduced by using appropriate design optimization approaches as an alternative to conventional design techniques.

Design/methodology/approach

This paper presents an optimization-based preliminary-design (OPD) approach based on a judicious coupling between evolutionary optimization techniques and a modified one-dimensional mean-line model. Two optimization strategies are considered. The first one is mono-objective and is solved using genetic algorithms. The second one is multi-objective and it is handled using the non-dominated sorting genetic algorithm-II. The proposed approach constitutes an automatic search process to select the geometrical parameters of the compressor, ensuring the most common requirements of the preliminary-design phase, with a minimum involvement of the designer.

Findings

The obtained numerical results demonstrate that the proposed tool can rapidly produce nearly optimal designs as an excellent basis for further refinement in the phase by using more complex analysis methods such as computational fluid dynamics and meta-modeling.

Originality/value

This paper outlines a new fast OBPD approach for centrifugal compressor turbochargers. The proposal adopts an inverse design method and consists of two main phases: a formulation phase and a solution phase. The complexity of the formulated problem is reduced by using a sensitivity analysis. The solution phase requires to link, in an automatic way, three processes, namely, optimization, design and analysis.
Determinants of banks’ risk-taking behavior, stability and profitability: evidence from GCC countries
Authors: Saif-Alyousfi Abdulazeez Y.H. , Saha Asish
Published: April 2021

Purpose

This paper aims to examine the effect of bank-specific, financial structure and macroeconomic factors on the risk-taking behavior, stability and profitability of banks in Gulf Cooperation Council (GCC) economies during 1998–2017.

Design/methodology/approach

The authors use a two-step system generalized method of moments dynamic model to analyze the data.

Findings

The results show that non-traditional activities increase the risk and decrease the stability and profitability of banks that are highly capitalized, highly liquid and large. Banks in this group are less engaged in securities investments and their higher degree of loan exposure leads to a decrease in risk and an increase in their stability and profitability. Higher concentration increases the risk and decreases the stability and profitability of banks that are less capitalized, less liquid and small. Banks with a higher share of non-traditional activities are riskier and less stable and less profitable before the financial crisis. The study finds that banks with relatively higher capitalization and high lending growth rates are riskier, profitable and less stable during the crisis. Larger commercial banks are less risky and more stable and profitable than smaller banks before the global financial crisis. Islamic banks performed better in terms of fee income, capitalization, liquidity, asset quality and have higher market concentration than conventional banks.

Originality/value

The study provides the first comprehensive empirical evidence on the drivers of risk-taking behavior, stability and profitability of the GCC banks. It also investigates the differences across these variables based on the characteristics of financial strength such as capitalization, liquidity and size; before, during and after the financial crisis; and differences between Islamic and conventional banks.
Development and integrated assessment of the circular economy in the European Union: the outranking approach
Authors: Ūsas Jonas , Balezentis Tomas , Streimikiene Dalia
Published: April 2021

Purpose

The Green Deal strategy of the European Union (EU) as well as the increasing concerns over resource scarcity worldwide has put forward such concepts as the circular economy. This paper seeks to compare the progress of the development of the circular economy across the EU Member States. Such analysis is helpful in guiding the circular economy support policies.

Design/methodology/approach

This paper develops a quantitative framework for analysis of the implementation of the circular economy objectives in the EU Member States. The framework proposed includes three multi-criteria decision making methods representing reference point and outranking approaches. The use of multiple methods allows exploiting the differences in the underlying aggregation principles.

Findings

Germany, Sweden and the Netherlands appear as the most advanced in the sense of circular economy development. The results indicate that the water-locked small countries and the new EU Member States are among the lowest performing ones. The flows of the waste need to be monitored more tightly in order to increase the circularity. The development of recycling facilities can also increase circularity irrespectively of the economic development level (e.g. the case of Bulgaria).

Originality/value

The paper contributes to the discussion regarding the circular economy by proposing an indicator system and the multi-criteria analysis framework. The proposed indicator system covers input use (circularity), trade flows and recycling processes. The proposed framework can be applied to track the progress of different countries in implementing the targets of the circular economy.
Innovative response initiatives in the European Union to mitigate the effects of COVID-19
Authors: Almeida Fernando
Published: April 2021

Purpose

The COVID-19 pandemic has significantly impacted the European Union (EU) through heavy pressure on health services, business activity and people's life. To mitigate these effects, government agencies, civil society and the private sector are working together in proposing innovative initiatives. In this sense, this study aims to characterize and explore the relevance of these projects to mitigate the effects of COVID-19.

Design/methodology/approach

The Observatory of Public Sector Innovation provided by the Organization for Economic Co-operation and Development was considered to enable the identification and exploration of innovative projects to combat COVID-19. A methodology based on mixed methods is adopted to initially identify quantitatively the distribution of these projects, followed by a qualitative approach based on thematic analysis that allows exploring their relevance.

Findings

A total of 206 initiatives in the EU have been identified. The distribution of these projects is quite asymmetric, with Portugal and Austria totaling 33.52% of these projects. Most of these projects focus on the areas of public health, infection detection and control, virtual education, local commerce, digital services literacy, volunteering and solidarity and hackathons.

Originality/value

This work is relevant to identifying and understanding the various areas in which COVID-19 initiatives have been developed. This information is of great relevance for the actors involved in this process to be able to replicate these initiatives in their national, regional and local contexts.
A disaster relief commodity supply chain network considering emergency relief volunteers: a case study
Authors: Kebriyaii Omid , Hamzehei Marzieh , Khalilzadeh Mohammad
Published: April 2021

Purpose

The number of natural and man-made disasters is remarkable and threatened human lives at the time of occurrence and also after that. Therefore, an efficient response following a disaster can eliminate or mitigate the adverse effects. This paper aims to help address those challenges related to humanitarian logistics by considering disaster network design under uncertainty and the management of emergency relief volunteers simultaneously.

Design/methodology/approach

In this paper, a robust fuzzy stochastic programming model is proposed for designing a relief commodity supply chain network in a disaster by considering emergency relief volunteers. To demonstrate the practicality of the proposed model, a case study is presented for the 22 districts of Tehran and solved by an exact method.

Findings

The results indicate that there are many parameters affecting the design of a relief commodity supply chain network in a disaster, and also many parameters should be controlled so that, the catastrophe is largely prevented and the lives of many people can be saved by sending the relief commodity on time.

Practical implications

This model helps decision-makers and authorities to explore optimal location and allocation decisions without using complex optimization algorithms.

Originality/value

To the best of the authors’ knowledge, employee workforce management models have not received adequate attention despite their role in relief and recovery efforts. Hence, the proposed model focuses on the problem of managing employees and designing a disaster logistics network simultaneously. The robust fuzzy stochastic programming method is applied for the first time for controlling the uncertainties in the design of humanitarian relief supply chains.
Quality factors and performance outcome of cloud-based marketing system
Authors: Liu Ying , Wang Tang
Published: April 2021

Purpose

This study aims to propose an integrated model based on the DeLone and McLean Information System Success Model (DMISS) to examine whether quality factors (system, service and information) can affect user satisfaction and performance of cloud-based marketing systems.

Design/methodology/approach

Recently, technologies change quickly, innovation becomes a vital base of productivity and sustainable growth of businesses is widely accepted. Cyber-physical system technologies help industries change production and marketing cycles according to customers’ needs in real-time. In addition, processing information through cloud service helps companies meet customer needs. The advantages of cloud technology also make it easier for companies to quickly collect the latest data from various sources, making it more effective in decision-making. This research recommends cloud-based marketing to help companies maximize their revenue by providing useful information and better quality for business development. The data were gathered from China automotive companies’ customers. A total of 220 questionnaires were distributed, and 165 (82.5%) usable questionnaires were analyzed using structural equation modeling.

Findings

This study verified that costumers’ perceived information quality, system quality and service quality positively caused the user satisfaction in the cloud-based marketing system.

Practical implications

This paper presents beneficial advice for improving cloud-based marketing systems. Besides, the topic is relevant to cloud-based marketing systems’ success. A better understanding of the impact of intention to use and user satisfaction on cloud-based marketing systems could significantly enhance companies’ success. This paper’s theoretical and practical contributions are expressed to guide organizations and policymakers in increasing cloud-based marketing systems acceptance.

Originality/value

This study empirically tests the relationship of quality factors and performance outcome of cloud-based marketing system through a model based on DeLone and McLean theory. This study bridges the research gap by identifying the factors that drive the adoption of cloud-based services in marketing and the impact of user satisfaction and intention to use on the cloud-based marketing system performance in the case of china companies.
Controllability of performance measures and managerial performance: the mediating role of fairness
Authors: Su Sophia Xia , Baird Kevin , Nuhu Nuraddeen
Published: April 2021

Purpose

This study aims to examine the mediating role of the fairness of the performance evaluation system on the association between the controllability of financial and non-financial measures and managerial performance.

Design/methodology/approach

Data was collected using an online survey questionnaire, with 220 responses received from middle and lower-level managers in Australian manufacturing organisations. Covariance-based structural equation modelling using software AMOS 25 was applied to analyse the data. Specifically, Anderson and Gerbing’s (1988) two-step approach was followed with confirmatory factor analyses first conducted to ensure that the measurement model was valid and reliable before running the structural model.

Findings

The findings reveal that the influence of managers’ controllability of performance measures on managerial performance is enacted through their perceptions of fairness. Specifically, the impact of controllability of financial (non-financial) measures on managerial performance is enacted through managers’ perceptions of distributive (interpersonal) fairness.

Originality/value

The empirical findings contribute to the literature investigating the empirical consequences of managers’ controllability of performance measures on performance evaluation processes, with the results revealing that the controllability of both financial and non-financial performance measures is positively associated with managerial performance via managers’ perceptions of different dimensions of fairness. Such results suggest that organisations, most of which do not prioritise the use of controllable performance measures in the design of their performance evaluation systems, need to reconsider the importance of the controllability of both financial and non-financial measures in the performance evaluation processes.
Veterans’ experiences of successfully managing post-traumatic stress disorder
Authors: Parry Gemma , Hodge Suzanne Margaret , Barrett Alan
Published: April 2021

Purpose

Prevalence of post-traumatic stress disorder (PTSD) among UK veterans is higher than in the general population. However, prevalence figures do not reflect the complexity of this phenomenon and ways in which it may be bound up with veterans’ experiences of adjusting to civilian life. The purpose of this study is to explore veterans’ experiences of successfully managing PTSD.

Design/methodology/approach

Semi-structured interviews were conducted with six veterans who had served in the UK armed forces and analysed using interpretative phenomenological analysis.

Findings

Three themes were developed: accepting the problem, taking responsibility and gaining control; talking to the right people; and strategies, antidotes and circling back around. Managing PTSD appeared to be bound up with veterans’ experience of renegotiating their identity, where positive aspects of identity lost on leaving the military were rebuilt and problematic aspects were challenged. Participants sought to speak about their difficulties with others who understood the military context. They felt that their experiences made them a valuable resource to others, and they connected this with a positive sense of identity and value.

Practical implications

The findings suggest the importance of wider provision of peer support and education for civilian health services on veterans’ needs.

Originality/value

This study adds to the understanding of what meaningful recovery from PTSD may involve for veterans, in particular its potential interconnectedness with the process of adjusting to civilian life.