bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep Multimodal Graph-Based Network for Survival Prediction from Highly Multiplexed Images and Patient Variables
Authors: Fu Xiaohang , Patrick Ellis , Yang Jean Y. H. , Feng David Dagan , Kim Jinman
Published: July 2022

The spatial architecture of the tumour microenvironment and phenotypic heterogeneity of tumour cells have been shown to be associated with cancer prognosis and clinical outcomes, including survival. Recent advances in highly multiplexed imaging, including imaging mass cytometry (IMC), capture spatially resolved, high-dimensional maps that quantify dozens of disease-relevant biomarkers at single-cell resolution, that contain potential to inform patient-specific prognosis. However, existing automated methods for predicting survival typically do not leverage spatial phenotype information captured at the single-cell level, and current methods tend to focus on a single modality, such as patient variables (PVs). There is no end-to-end method designed to leverage the rich information in whole IMC images and all marker channels, and aggregate this information with PVs in a complementary manner to predict survival with enhanced accuracy. We introduce a deep multimodal graph-based network (DMGN) that integrates entire IMC images and multiple PVs for end-to-end survival prediction of breast cancer. We propose a multimodal graph-based module that considers relationships between spatial phenotype information in all image regions and all PVs, and scales each region–PV pair based on its relevance to survival. We propose another module to automatically generate embeddings specialised for each PV to enhance multimodal aggregation. We show that our modules are consistently effective at improving survival prediction performance using two public datasets, and that DMGN can be applied to an independent validation dataset across the same antigens but different antibody clones. Our DMGN outperformed state-of-the-art methods at survival prediction.
Formulation of FMD vaccine in Naloxone/Alum mixture: A potency study
Authors: Alemalhoda Danasadat , Ajamian Farzam , Khorasani Akbar , Haghighat Setareh , Amreie Mona Mahdavi , Sarkeshikzadeh Moghadas Fatemeh Sadat , Asgarhalvaei Fatemeh , Kalantari Alireza , Mahdavi Mehdi
Published: July 2022

Background

Current Foot-and-Mouth disease (FMD) vaccines are commonly formulated in the alum adjuvant. Several studies showed that this form of vaccine, although able to control the infection, lacks the ability to eradicate the infection completely.

Objectives

In this study, the FMD vaccine was formulated in a naloxone/alum mixture as an adjuvant, and its potency was compared with the alum-formulated vaccine.

Methods

Experimental Balb/c mice were immunized with a commercial vaccine or naloxone/alum-based vaccine two times, subcutaneously at two-week intervals. Lymphocyte proliferation was assessed using BrdU, and IL-4, IFN-γ, and TNF-α cytokines, specific total IgG as well as IgG1/IgG2a were evaluated by ELISA. In addition, the gene expression profiles of IL-12, IL-17, and IFN-γ cytokines were determined by real-time PCR.

Results

Results showed that mice immunized with the FMD vaccine formulated with the naloxone/alum mixture exhibited a tiny increase in the production of IFN-γ and TNF-α cytokines compared to the routine vaccine. However, mice immunized with the FMD vaccine formulated with the naloxone/alum mixture revealed a significant increase in the expression of IL-12, IL-17, and IFN-γ cytokines compared to those immunized with the routine vaccine. In addition, the novel formulation led to increased production of specific total IgG in comparison with the routine vaccine.

Conclusions

Our findings suggest that naloxone formulated in the FMD vaccine could improve cellular and humoral immune responses. However, the effect of this formulation on the efficacy of vaccine is remained to be clarified in future studies.
Slow integrin-dependent migration organizes networks of tissue-resident mast cells
Authors: Bambach Sarah K. , Kaltenbach Lukas , Aizarani Nadim , Martzloff Paloma , Gavrilov Alina , Glaser Katharina M. , Thünauer Roland , Mihlan Michael , Stecher Manuel , Thiriot Aude , Wienert Stephan , von Andrian Ulrich , Schmidt-Supprian Marc , Nerlov Claus , Klauschen Frederick , Roers Axel , Bajénoff Marc , Grün Dominic , Lämmermann Tim
Published: July 2022

Many leukocytes use fast and flexible amoeboid migration strategies to move autonomously throughout tissues. Here, we show that the movement of mast cells (MCs), leukocytes with important roles during allergies and anaphylaxis, fundamentally differs from this rapid adhesion-free leukocyte migration. We identify a crucial role for integrin-dependent adhesion in controlling slow MC movement, which shapes the positioning and network-like tissue distribution of this long-lived immune cell type. In contrast to other immune and non-immune cells, MCs cannot compensate for the lack of integrin function by switching to another migration mode. Single-cell RNA-sequencing revealed a special role for integrins in defining a mature MC phenotype in the periarteriolar tissue space where several stromal cell types provide an anatomical niche rich in Kit ligand, the major MC growth and survival factor. Collectively, this study highlights substrate-dependent haptokinesis as an important mechanism for MC network formation and the tissue organization of resident immune cells.
Growth anisotropy of the extracellular matrix drives mechanics in a developing organ
Authors: Harmansa Stefan , Erlich Alexander , Eloy Christophe , Zurlo Giuseppe , Lecuit Thomas
Published: July 2022

The final size and shape of organs results from volume expansion by growth and shape changes by contractility. Complex morphologies arise from differences in growth rate between tissues. We address here how differential growth drives epithelial thickening and doming during the morphogenesis of the growing Drosophila wing imaginal disc. We report that 3D morphology results from elastic deformation due to differential growth between the epithelial cell layer and its enveloping extracellular matrix (ECM). Furthermore, the ECM envelope exhibits differential growth anisotropy (i.e. anisotropic expansion in 3D), growing in-plane on one side, but out of plane on the other side. The elasticity, anisotropy and morphogenesis is fully captured by a mechanical bilayer model. Moreover, differential expression of the Matrix metalloproteinase MMP2 controls growth anisotropy of the two ECM layers. This study shows that the ECM is a controllable mechanical constraint whose intrinsic growth anisotropy directs tissue morphogenesis in a developing organ.
Adipocyte-secreted IL-6 sensitizes macrophages to IL-4 signaling
Authors: Luan Danny , Dadpey Benyamin , Zaid Jessica , Bridge-Comer Pania E. , DeLuca Julia H. , Xia Wenmin , Castle Joshua , Reilly Shannon M.
Published: July 2022

Complex bidirectional crosstalk between adipocytes and adipose tissue immune cells plays an important role in regulating adipose function, inflammation, and insulin responsiveness. Adipocytes secrete the pleiotropic cytokine IL-6 in response to both inflammatory and catabolic stimuli. Previous studies suggest that IL-6 secretion from adipocytes in obesity may promote adipose tissue inflammation. Here we investigated catabolic stimulation of adipocyte IL-6 secretion and its impact on adipose tissue immune cells. In obesity, catecholamine resistance reduces cAMP-driven adipocyte IL-6 secretion in response to catabolic signals. By restoring adipocyte catecholamine sensitivity in obese adipocytes, amlexanox stimulates adipocyte-specific IL-6 secretion. Here we report that in this context, adipocyte secreted IL-6 activates local macrophage STAT3 to promoteIl4raexpression, thereby sensitizing them to IL-4 signaling, and promoting an anti-inflammatory gene expression pattern. Supporting a paracrine adipocyte to macrophage mechanism, these effects could be recapitulated using adipocyte conditioned media to pretreat bone marrow derived macrophages prior to polarization with IL-4. The effects of IL-6 signaling in the adipose tissue are complex and context specific. These results suggest that cAMP driven IL-6 secretion from adipocytes sensitizes adipose tissue macrophages to IL-4 signaling.
DEFECTIVELY ORGANIZED TRIBUTARIES 5is not required for leaf venation patterning inArabidopsis thaliana
Authors: Vlad Daniela , Langdale Jane A.
Published: July 2022

The search for genetic regulators of leaf venation patterning started over thirty years ago, primarily focussed on mutant screens in the eudicotyledonArabidopsis thaliana. Developmental perturbations in either cotyledons or true leaves led to the identification of transcription factors required to elaborate the characteristic reticulated vein network. An ortholog of one of these, the C2H2 Zn finger protein DEFECTIVELY ORGANIZED TRIBUTARIES 5 (AtDOT5), was recently identified through transcriptomics as a candidate regulator of parallel venation in maize leaves. To elucidate howAtDOT5orthologs regulate vein patterning, we generated three independent loss of function mutations by gene editing in Arabidopsis. Surprisingly, none of them exhibited any obvious phenotypic perturbations. To reconcile our findings with earlier reports, we re-evaluated the originalAtdot5-1andAtdot5-2alleles. By genome sequencing, we show that reported mutations at theAtdot5-1locus are actually polymorphisms between Landsbergerectaand Columbia ecotypes, and that other mutations present in the background most likely cause the pleiotropic mutant phenotype observed. We further show that a T-DNA insertion in theAtdot5-2locus has no impact on leaf venation patterns when segregated from other T-DNA insertions present in the original line. We thus conclude thatAtDOT5plays no role in leaf venation patterning in Arabidopsis.

Significance statement

An understanding of gene function is often derived on the basis of loss of function mutant phenotypes and thus correct identification of mutated loci is crucial. Through gene editing we reveal previous mis-identification of a causative mutation that led to inappropriate functional assignation for theDEFECTIVELY ORGANIZED TRIBUTARIES 5 geneinArabidopsis thaliana.
Multi-modal quantification of pathway activity with MAYA
Authors: Landais Yuna , Vallot Céline
Published: July 2022

Signaling pathways can be activated through various cascades of genes depending on cell identity and biological context. Single-cell atlases now provide the opportunity to inspect such complexity in health and disease. Yet, existing reference tools for pathway scoring resume activity of each pathway to one unique common metric across cell types. Here, we present MAYA a computational method that enables the automatic detection and scoring of the diverse modes of activation of biological pathways across cell populations. MAYA improves the granularity of pathway analysis by detecting subgroups of genes within reference pathways, each characteristic of a cell population and how it activates a pathway. Using multiple single-cell datasets, we demonstrate the biological relevance of identified modes of activation, the robustness of MAYA to noisy pathway lists and batch effect. MAYA can also predict cell types starting from lists of reference markers in a cluster-free manner. Finally, we show that MAYA reveals common modes of pathway activation in tumor cells across patients, opening the perspective to discover shared therapeutic vulnerabilities.
Imputation of ancient genomes
Authors: Sousa da Mota Bárbara , Rubinacci Simone , Cruz Dávalos Diana Ivette , Amorim Carlos Eduardo G. , Sikora Martin , Johannsen Niels N. , Szmyt Marzena , Włodarczak Piotr , Szczepanek Anita , Przybyła Marcin M. , Schroeder Hannes , Allentoft Morten E. , Willerslev Eske , Malaspinas Anna-Sapfo , Delaneau Olivier
Published: July 2022

Due to postmortem DNA degradation, most ancient genomes sequenced to date have low depth of coverage, preventing the true underlying genotypes from being recovered. Genotype imputation has been put forward to improve genotyping accuracy for low-coverage genomes. However, it is unknown to what extent imputation of ancient genomes produces accurate genotypes and whether imputation introduces bias to downstream analyses. To address these questions, we downsampled 43 ancient genomes, 42 of which are high-coverage (above 10x) and three constitute a trio (mother, father and son), from different times and continents to simulate data with coverage in the range of 0.1x-2.0x and imputed these using state-of-the-art methods and reference panels. We assessed imputation accuracy across ancestries and depths of coverage. We found that ancient and modern DNA imputation accuracies were comparable. We imputed most of the 42 high-coverage genomes downsampled to 1x with low error rates (below 5%) and estimated higher error rates for African genomes, which are underrepresented in the reference panel. We used the ancient trio data to validate imputation and phasing results using an orthogonal approach based on Mendel’s rules of inheritance. This resulted in imputation and switch error rates of 1.9% and 2.0%, respectively, for 1x genomes. We further compared the results of downstream analyses between imputed and high-coverage genomes, notably principal component analysis (PCA), genetic clustering, and runs of homozygosity (ROH). For these three approaches, we observed similar results between imputed and high-coverage genomes using depths of coverage of at least 0.5x, except for African genomes, for which the decreased imputation accuracy impacted ROH estimates. Altogether, these results suggest that, for most populations and depths of coverage as low as 0.5x, imputation is a reliable method with potential to expand and improve ancient DNA studies.
Vaccination shapes evolutionary trajectories of SARS-CoV-2
Authors: Meijers Matthijs , Ruchnewitz Denis , Łuksza Marta , Lässig Michael
Published: July 2022

The large-scale evolution of the SARS-CoV-2 virus has been marked by rapid turnover of genetic clades. New variants show intrinsic changes, notably increased transmissibility, as well as anti-genic changes that reduce the cross-immunity induced by previous infections or vaccinations1–4. How this functional variation shapes the global evolutionary dynamics has remained unclear. Here we show that selection induced by vaccination impacts on the recent antigenic evolution of SARS-CoV-2; other relevant forces include intrinsic selection and antigenic selection induced by previous infections. We obtain these results from a fitness model with intrinsic and antigenic fitness components. To infer model parameters, we combine time-resolved sequence data5, epidemiological records6,7, and cross-neutralisation assays8–10. This model accurately captures the large-scale evolutionary dynamics of SARS-CoV-2 in multiple geographical regions. In particular, it quantifies how recent vaccinations and infections affect the speed of frequency shifts between viral variants. Our results show that timely neutralisation data can be harvested to identify hotspots of antigenic selection and to predict the impact of vaccination on viral evolution.
Human Galectin-9 Promotes the Expansion of HIV Reservoirs in vivo in Humanized Mice
Authors: Yuan Zhe , Giron Leila B. , Hart Colin , Gyampoh Akwasi , Koshy Jane , Hong Kai Ying , Niki Toshiro , Premeaux Thomas A. , Ndhlovu Lishomwa C. , Montaner Luis J , Abdel-Mohsen Mohamed
Published: July 2022

Objective

The human endogenous β-galactoside-binding protein Galectin-9 (Gal-9) reactivates latently HIV-infected cells, which may allow for immune-mediated clearance of these cells. However, Gal-9 also activates T cell Receptor (TCR) signaling pathways, which could negatively affect HIV persistence by promoting T cell expansion and chronic activation/exhaustion. This potential “double-edged sword” effect of Gal-9 during HIV infection raises the question of the overall beneficial versus detrimental impact of Gal-9 on HIV persistence in vivo.

Design

We used the BLT (bone marrow, liver, thymus) humanized mouse model to evaluate the overall impact of Gal-9 on HIV persistence in vivo during antiretroviral therapy (ART).

Methods

Two independent cohorts of BLT mice with high human immune reconstitution were infected with HIV, placed on ART, and then treated with either recombinant human Gal-9 or PBS during ART suppression. Plasma viral loads and levels of tissue-associated HIV DNA and RNA were measured by qPCR. Markers of T cell activation/exhaustion were measured by flow cytometry, and plasma markers of inflammation were measured by multiplex cytokine arrays.

Results

Gal-9 treatment was tolerable in ART-suppressed humanized mice and did not significantly induce plasma markers of inflammation or T cell markers of activation/exhaustion. However, Gal-9 treatment during ART significantly increased levels of tissue-associated HIV DNA and RNA compared to controls (P=0.0007 and P=0.011, respectively, for cohort I and P=0.002 and P=0.005, respectively, for cohort II).

Conclusions

Our study highlights the overall adverse effects of Gal-9 on HIV persistence and the potential need to block Gal-9 interactions during ART-suppressed HIV infection.
Mechanism of strand displacement DNA synthesis by the coordinated activities of human mitochondrial DNA polymerase and SSB
Authors: Ismael Plaza-G.A. , Lemishko Kateryna M. , Crespo Rodrigo , Truong Thinh Q. , Kaguni Laurie S. , Cao-García Francisco J. , Ciesielski Grzegorz L. , Ibarra Borja
Published: July 2022

Many replicative DNA polymerases couple DNA replication and unwinding activities to perform strand displacement DNA synthesis, a critical ability for DNA metabolism. Strand displacement is tightly regulated by partner proteins, such as single-stranded DNA (ssDNA) binding proteins (SSBs) by a poorly understood mechanism. Here, we use single-molecule optical tweezers and biochemical assays to elucidate the molecular mechanism of strand displacement DNA synthesis by the human mitochondrial DNA polymerase, Polγ, and its modulation by cognate and noncognate SSBs. We show that Polγ exhibits a robust DNA unwinding mechanism, which entails lowering the energy barrier for unwinding of the first base pair of the DNA fork junction, by ∼55%. However, the polymerase cannot prevent the reannealing of the parental strands efficiently, which limits by ∼30-fold its strand displacement activity. We demonstrate that SSBs stimulate the Polγ strand displacement activity through several mechanisms. SSB binding energy to ssDNA additionally increases the destabilization energy at the DNA junction, by ∼25%. Furthermore, SSB interactions with the displaced ssDNA reduce the DNA fork reannealing pressure on Polγ, in turn promoting the productive polymerization state by ∼3-fold. These stimulatory effects are enhanced by species-specific functional interactions and have significant implications in the replication of the human mitochondrial DNA.
Comprehensive analysis of platelet glycoprotein Ibα glycosylation
Authors: Hollenhorst Marie A , Tiemeyer Katherine H , Mahoney Keira E , Aoki Kazuhiro , Ishihara Mayumi , Lowery Sarah C. , Rangel-Angarita Valentina , Bertozzi Carolyn R , Malaker Stacy A
Published: July 2022

Background

Platelet glycoprotein (GP) Ibα is the major ligand-binding subunit of the GPIb-IX-V complex that binds von Willebrand Factor (VWF). GPIbα is heavily glycosylated, and its glycans have been proposed to play key roles in platelet clearance, VWF binding, and as target antigens in immune thrombocytopenia syndromes. Despite its importance in platelet biology, the glycosylation profile of GPIbα is not well characterized.

Objectives

The aim of this study was to comprehensively analyze GPIbα amino acid sites of glycosylation (glycosites) and glycan structures.

Methods

GPIbα ectodomain that was recombinantly expressed or that was purified from human platelets was analyzed by Western blot, mass spectrometry (MS) glycomics, and MS glycoproteomics to define glycosites and the structures of the attached glycans.

Results

We identified a diverse repertoire of N- and O-glycans, including sialoglycans, Tn antigen, T antigen, and ABH blood group antigens. In the analysis of the recombinant protein, we identified 62 unique O-glycosites. In the analysis of the endogenous protein purified from platelets, we identified at least 48 unique O-glycosites and 1 N-glycosite. The GPIbα mucin domain is densely O-glycosylated. Glycosites are also located within the macroglycopeptide domain and mechanosensory domain (MSD).

Conclusions

This comprehensive analysis of GPIbα glycosylation lays the foundation for further studies to determine the functional and structural roles of GPIbα glycans.

Essentials

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Glycosylation of glycoprotein Ibα (GPIbα) is important for platelet function.

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We report a comprehensive and site-specific analysis of human GPIbα glycosylation.

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GPIbα carries sialoglycans, Tn antigen, T antigen, and ABO blood group (ABH) antigens.

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We experimentally determined 48 O-glycosites and 1 N-glycosite by mass spectrometry.
Persistence of SARS-CoV-2 neutralizing antibodies longer than 13 months in naturally-infected, captive white-tailed deer (Odocoileus virginianus), Texas
Authors: Hamer Sarah A. , Nunez Chase , Roundy Christopher M. , Tang Wendy , Thomas Logan , Richison Jack , Benn Jamie S. , Auckland Lisa D. , Hensley Terry , Cook Walter E. , Pauvolid-Corrêa Alex , Hamer Gabriel L.
Published: July 2022

After identifying a captive herd of white-tailed deer (WTD) in central Texas with >94% seroprevalence with SARS-CoV-2 neutralizing antibodies in September 2021, we worked retrospectively through archived serum samples of 21 deer and detected seroconversion of all animals between December 2020 and January 2021. We then collected prospective samples to conclude that the duration of persistence of neutralizing antibodies is at least 13 months for 19 (90.5%) of the animals, with two animals converting to seronegative after six and eight months. Antibody titers generally waned over this time frame, but three deer had a temporary 4 to 8-fold increases in PRNT titers over a month after seroconversion; anamnestic response cannot be ruled out.
Two point mutations in protocadherin-1 disrupt Andes hantavirus recognition and afford protection against lethal infection
Authors: Slough Megan M. , Li Rong , Herbert Andrew S. , Lasso Gorka , Kuehne Ana I. , Bakken Russell R. , Monticelli Stephanie R. , Liu Yanan , Ghosh Agnidipta , Moreau Alicia M. , Zeng Xiankun , Almo Steven C. , Dye John M. , Jangra Rohit K. , Wang Zhongde , Chandran Kartik
Published: July 2022

Andes virus and Sin Nombre virus are the etiologic agents of severe hantavirus cardiopulmonary syndrome (HCPS) in the Americas for which no FDA-approved countermeasures are available. Protocadherin-1 (PCDH1), a cadherin-superfamily protein recently identified as a critical host factor for ANDV and SNV, represents a new antiviral target; however, its precise role remains to be elucidated. Here, we used computational and experimental approaches to delineate the binding surface of the ANDV glycoprotein complex on PCDH1’s first extracellular cadherin repeat domain. Strikingly, a single amino acid residue in this PCDH1 surface influenced the host species-specificity of SNV glycoprotein-PCDH1 interaction and cell entry. Mutation of this, and a neighboring residue, substantially protected Syrian hamsters from pulmonary disease and death caused by ANDV. We conclude that PCDH1 is a bona fide entry receptor for ANDV and SNV whose direct interaction with hantavirus glycoproteins could be targeted to develop new interventions against HCPS.
Confined keratocytes mimic in vivo migration and reveal volume-speed relationship
Authors: Labuz Ellen C. , Footer Matthew J. , Theriot Julie A.
Published: July 2022

Fish basal epidermal cells, known as keratocytes, are well-suited for cell migration studies. In vitro, isolated keratocytes adopt a stereotyped shape with a large fan-shaped lamellipodium and a nearly spherical cell body. However, in their native in vivo environment, these cells adopt a significantly different shape during their rapid migration towards wounds. Within the epidermis, keratocytes experience 2D confinement between the outer epidermal cell layer and the basement membrane; these two deformable surfaces constrain keratocyte cell bodies to be flatter in vivo than in isolation. In vivo keratocytes also exhibit a relative elongation of the front-to-back axis and substantially more lamellipodial ruffling, as compared to isolated cells. We have explored the effects of 2D confinement, separated from other in vivo environmental cues, by overlaying isolated cells with an agarose hydrogel with occasional spacers, or with a ceiling made of PDMS elastomer. Under these conditions, isolated keratocytes more closely resemble the in vivo migratory shape phenotype, displaying a flatter apical-basal axis and a longer front-to-back axis than unconfined keratocytes. We propose that 2D confinement contributes to multiple dimensions of in vivo keratocyte shape determination. Further analysis demonstrates that confinement causes a synchronous 20% decrease in both cell speed and volume. Interestingly, we were able to replicate the 20% decrease in speed using a sorbitol hypertonic shock to shrink the cell volume, which did not affect other aspects of cell shape. Collectively, our results suggest that environmentally imposed changes in cell volume may influence cell migration speed, potentially by perturbing physical properties of the cytoplasm.
CDPK2A and CDPK1 form a signaling module upstream ofToxoplasmamotility
Authors: Shortt Emily , Hackett Caroline G. , Stadler Rachel V. , Ward Gary E. , Lourido Sebastian
Published: July 2022

The transition between parasite replication and dissemination is regulated in apicomplexan parasites by fluctuations in cytosolic calcium concentrations, effectuated by calcium-dependent protein kinases (CDPKs). We examined the role of CDPK2A in the lytic cycle ofToxoplasma, analyzing its role in the regulation of cellular processes associated with parasite motility. We used chemical-genetic approaches and conditional depletion to determine that CDPK2A contributes to the initiation of parasite motility through microneme discharge. We demonstrate that the N-terminal extension of CDPK2A is necessary for the protein’s function. Conditional depletion revealed an epistatic interaction between CDPK2A and CDPK1, suggesting that the two kinases work together to mediate motility in response to certain stimuli. This signaling module appears distinct from that of CDPK3 and PKG, which also controls egress. CDPK2A is revealed as an important regulator of theToxoplasmakinetic phase, linked to other kinases that govern this critical transition. Our work uncovers extensive interconnectedness between the signaling pathways that govern parasite motility.

IMPORTANCE

This work uncovers interactions between various signaling pathways that governToxoplasma gondiiegress. Specifically, we compare the function of three canonical calcium dependent protein kinases (CDPKs) using chemical-genetic and conditional-depletion approaches. We describe the function of a previously uncharacterized CDPK, CDPK2A, in theToxoplasmalytic cycle, demonstrating it contributes to parasite fitness through regulation of microneme discharge, gliding motility, and egress from infected host cells. Comparison of analog-sensitive (AS) kinase alleles and conditionally-depleted alleles uncovered epistasis between CDPK2A and CDPK1 implying a partial functional redundancy. Understanding the topology of signaling pathways underlying key events in the parasite life cycle can aid in efforts targeting parasite kinases for anti-parasitic therapies.
TransMeta simultaneously assembles multisample RNA-seq reads
Authors: Yu Ting , Zhao Xiaoyu , Li Guojun
Published: July 2022

Assembling RNA-seq reads into full-length transcripts is crucial in transcriptomic studies and poses computational challenges. Here we present TransMeta, a simple and robust algorithm that simultaneously assembles RNA-seq reads from multiple samples. TransMeta is designed based on the newly introduced vector-weighted splicing graph model, which enables accurate reconstruction of the consensus transcriptome via incorporating a cosine similarity–based combing strategy and a newly designed label-setting path-searching strategy. Tests on both simulated and real data sets show that TransMeta consistently outperforms PsiCLASS, StringTie2 plus its merge mode, and Scallop plus TACO, the most popular tools, in terms of precision and recall under a wide range of coverage thresholds at the meta-assembly level. Additionally, TransMeta consistently shows superior performance at the individual sample level.
Diversifying the genomic data science research community
Authors:   The Genomic Data Science Community Network
Published: July 2022

Over the past 20 years, the explosion of genomic data collection and the cloud computing revolution have made computational and data science research accessible to anyone with a web browser and an internet connection. However, students at institutions with limited resources have received relatively little exposure to curricula or professional development opportunities that lead to careers in genomic data science. To broaden participation in genomics research, the scientific community needs to support these programs in local education and research at underserved institutions (UIs). These include community colleges, historically Black colleges and universities, Hispanic-serving institutions, and tribal colleges and universities that support ethnically, racially, and socioeconomically underrepresented students in the United States. We have formed the Genomic Data Science Community Network to support students, faculty, and their networks to identify opportunities and broaden access to genomic data science. These opportunities include expanding access to infrastructure and data, providing UI faculty development opportunities, strengthening collaborations among faculty, recognizing UI teaching and research excellence, fostering student awareness, developing modular and open-source resources, expanding course-based undergraduate research experiences (CUREs), building curriculum, supporting student professional development and research, and removing financial barriers through funding programs and collaborator support.
ATAC-STARR-seq reveals transcription factor–bound activators and silencers within chromatin-accessible regions of the human genome
Authors: Hansen Tyler J. , Hodges Emily
Published: July 2022

Massively parallel reporter assays (MPRAs) test the capacity of putative gene regulatory elements to drive transcription on a genome-wide scale. Most gene regulatory activity occurs within accessible chromatin, and recently described methods have combined assays that capture these regions—such as assay for transposase-accessible chromatin using sequencing (ATAC-seq)—with self-transcribing active regulatory region sequencing (STARR-seq) to selectively assay the regulatory potential of accessible DNA (ATAC-STARR-seq). Here, we report an integrated approach that quantifies activating and silencing regulatory activity, chromatin accessibility, and transcription factor (TF) occupancy with one assay using ATAC-STARR-seq. Our strategy, including important updates to the ATAC-STARR-seq assay and workflow, enabled high-resolution testing of ∼50 million unique DNA fragments tiling ∼101,000 accessible chromatin regions in human lymphoblastoid cells. We discovered that 30% of all accessible regions contain an activator, a silencer, or both. Although few MPRA studies have explored silencing activity, we demonstrate that silencers occur at similar frequencies to activators, and they represent a distinct functional group enriched for unique TF motifs and repressive histone modifications. We further show that Tn5 cut-site frequencies are retained in the ATAC-STARR plasmid library compared to standard ATAC-seq, enabling TF occupancy to be ascertained from ATAC-STARR data. With this approach, we found that activators and silencers cluster by distinct TF footprint combinations, and these groups of activity represent different gene regulatory networks of immune cell function. Altogether, these data highlight the multilayered capabilities of ATAC-STARR-seq to comprehensively investigate the regulatory landscape of the human genome all from a single DNA fragment source.
Sustainability learning for improved safe work environments for construction semi-skilled workers in Zimbabwe
Authors: Moyo Tirivavi , Crafford Gerrit , Emuze Fidelis
Published: July 2022

Purpose

Despite “decent work” being pertinent, as situated in the International Labour Organisation's “Decent Work Agenda”, one of its substantive elements on the need for safe work environments remains a concern for semi-skilled construction workers. Evidently, sustainability learning objectives within this element must be identified and implemented as a remedy. Therefore, the aim of the reported study was to reveal sustainability learning objectives that are significant towards attaining safe work environments, through also assessing statistically significant differences due to demographic variables.

Design/methodology/approach

The design of this research followed a quantitative questionnaire survey strategy to obtain insights from semi-skilled workers and site/project managers in Zimbabwe.

Findings

Knowledge of relevant prevention strategies to foster positive physical and mental well-being in the workplace was considered the most critical sustainability learning objective. Semi-skilled workers revealed the most interest in objectives that affected their socio-economic beings while site/project managers preferred those that had more economic value to the organisations they work for. Educational levels are also critical when instituting any training interventions.

Research limitations/implications

The absence of a database for semi-skilled workers was a limitation towards achieving the practical significance of the findings. Due to semi-skilled workers significantly contributing to unsafe work environments, structured on-the-job training schemes that are sufficiently planned, monitored and controlled are recommended.

Originality/value

The determination of sustainability learning objectives for construction semi-skilled workers, through on-the-job training schemes, will contribute to the improvement of safe work environments.
Benchmarking strategic core competencies of performance across Chinese and South Korean manufacturing companies
Authors: Pati Niranjan , Lee Jooh
Published: July 2022

Purpose

This study empirically investigates the significance of the core competencies on various economic performance indices by utilizing accounting and market-based performance in Chinese and South Korean leading manufacturing companies.

Design/methodology/approach

This research employs a series of hierarchical regression models to test the hypotheses concerning the significance of R&D and export strategy on firms' performance.

Findings

This study finds that R&D intensity and foreign trade activities through export are most likely to be significantly associated with firm performance, particularly market-based performance, across the Chinese and South Korea manufacturing companies. The significance of other core strategic factors such as capital intensity, leverage, inventory turnover, labor productivity, administrative cost efficiency, and collection policy on performance was also contemplated.

Originality/value

The relationship between R&D and firm performance has been an interesting issue concerning the performance measures employed across different country settings. Research issues addressed in this paper relate to how R&D, and foreign trade by export influence firm performance across two diverse economic environments inherent of Chinese and South Korean leading manufacturing firms. Particularly, this study explores the directions and magnitudes of the operational and strategic relationships between key strategic factors, such as R&D intensity, export by foreign trade, and the firm's economic and market-based performance.
Designing AI implications in the venture creation process
Authors: Schiavone Francesco , Pietronudo Maria Cristina , Sabetta Annamaria , Bernhard Fabian
Published: July 2022

Purpose

The paper faces artificial intelligence issues in the venture creation process, exploring how artificial intelligence solutions intervene and forge the venture creation process. Drawing on the most recent literature on artificial intelligence and entrepreneurship, the authors propose a set of theoretical propositions.

Design/methodology/approach

The authors adopt a multiple case approach to assess propositions and analyse 4 case studies from which the authors provide (1) more detailed observation about entrepreneurial process phases influenced by artificial intelligence solutions and (2) more details about mechanics enabled by artificial intelligence.

Findings

The analysis demonstrates artificial intelligence contributes alongside the entrepreneurial process, enabling mechanisms that reduce costs or resources, generate new organizational processes but simultaneously expand the network needed for venture creation.

Originality/value

The paper adopts a deductive approach analyzing the contribution of AI-based startup offerings in changing the entrepreneurial process. Thus, the paper provides a practical view of the potentiality of artificial intelligence in enabling entrepreneurial processes through the analysis of compelling propositions and the technological ability of artificial intelligence solutions.
Development of cloud selection supporting model for green information and communication technology services
Authors: Godla Sanjiv Rao , Haro Jara Muda , Ch S.V.V.S.N. Murty , Krishna R.V.V.
Published: July 2022

Purpose

The purpose of the study is to develop a cloud supporting model for green computing. In today's contemporary world, information technology (IT) plays a significant role. Because of the rapid growth of the IT business and the high level of greenhouse gas emissions, salient data centers are increasingly considering green IT techniques to reduce their environmental impacts. Both developing and underdeveloped countries are widely adopting green infrastructure and services over the cloud because of its cost-effectiveness, scalability and guaranteed high uptime. Several studies have investigated the fact that cloud computing provides beyond green information and communication technology (ICT) services and solutions. Therefore, anything offered over clouds also needs to be green to reduce the adverse influence on the environment.

Design/methodology/approach

This paper examines the rationale for the use of green ICT in higher education and finds crucial success variables for the implementation of green ICT on the basis of an analysis of chosen educational organizations and interviews with key academic experts from the Universities of Ethiopia, in general, and BuleHora University, in particular.

Findings

Finally, this paper described the design and development of a green cloud selection supporting model for green ICTs in higher educational institutions that helps cloud service customers choose the most green cloud-based ICT products as well as services.

Originality/value

This study may be a significant source of new information for green ICT design and implementation in higher education institutions to preserve the environment and its impact on human life.
Augmented reality's perceived immersion effect on the customer shopping process: decision-making quality and privacy concerns
Authors: Sengupta Aniket , Cao Lanlan
Published: July 2022

Purpose

This study investigates the role of an augmented reality (AR)-based tool in customers' shopping processes.

Design/methodology/approach

Using the stimulus-organism-response (SOR) and consumer decision-making models, this study builds a comprehensive theoretical model that investigates the mechanism sequentially connected AR-enabled shopping tool and customer responses. Décor Matters was chosen as the AR-enabled mobile application for this study. Qualtrics, which conducted the survey, collected 150 responses in the USA. The authors used structural equation model to test the hypotheses.

Findings

This study enriches the retail-related AR theory by offering a holistic and structural view of the factors that connect customers' cognitive and affective internal processes with customers' shopping task. However, having used only one type of AR-enabled app in the study, the findings remain limited.

Research limitations/implications

This research advances the understanding of AR's role in the customer shopping process by validating the positive effect of immersion on purchase intention, as well as revealing the mediating effect of decision-making quality and the moderating effect of privacy concerns. However, as only one type of AR-enabled app was used in the study, the findings are still limited.

Practical implications

The findings can help retailers to understand why and how firms can benefit from investing in AR-enabled apps (i.e. by focussing on customer perceived immersion and decision-making quality with AR).

Originality/value

This study's originality lies in the SOR model's extension, which integrates the customer decision-making model, allowing for connecting customers' cognitive and affective internal experiences with their shopping task. The findings can help retail managers to understand more clearly and in-depth why and how AR works in customers' shopping process.
Incremental and parallel proximal SVM algorithm tailored on the Jetson Nano for the ImageNet challenge
Authors: Do Thanh-Nghi
Published: July 2022

Purpose

This paper aims to propose the new incremental and parallel training algorithm of proximal support vector machines (Inc-Par-PSVM) tailored on the edge device (i.e. the Jetson Nano) to handle the large-scale ImageNet challenging problem.

Design/methodology/approach

The Inc-Par-PSVM trains in the incremental and parallel manner ensemble binary PSVM classifiers used for the One-Versus-All multiclass strategy on the Jetson Nano. The binary PSVM model is the average in bagged binary PSVM models built in undersampling training data block.

Findings

The empirical test results on the ImageNet data set show that the Inc-Par-PSVM algorithm with the Jetson Nano (Quad-core ARM A57 @ 1.43 GHz, 128-core NVIDIA Maxwell architecture-based graphics processing unit, 4 GB RAM) is faster and more accurate than the state-of-the-art linear SVM algorithm run on a PC [Intel(R) Core i7-4790 CPU, 3.6 GHz, 4 cores, 32 GB RAM].

Originality/value

The new incremental and parallel PSVM algorithm tailored on the Jetson Nano is able to efficiently handle the large-scale ImageNet challenge with 1.2 million images and 1,000 classes.
A comparative performance assessment of hydrostatic thrust bearings operating with electrorheological lubricant
Authors: Singh Atul Kumar , Kumar Vivek , Singh Simran Jeet , Sharma Naveen , Choudhary Divya
Published: July 2022

Purpose

An electrorheological (ER) fluid comprises dielectric particles suspended in an insulating viscous medium. ER lubricants are considered smart lubricants. They have been applied in hydraulic valves, power transmission devices and damping systems. The purpose of this study is to investigate the performance of hydrostatic thrust bearing operating with ER lubricant.

Design/methodology/approach

Reynold’s equation was used to model the flow of the ER lubricant in the bearing. The continuous Bingham model was used to express the viscosity of the ER lubricant as a function of yielding stress, applied electric field and shear strain rate. The Reynolds equation is solved using the finite element method (weighted residual approach) to compute the film pressure as a primary variable and the lubricant flow rate, load-carrying capacity, stiffness and damping parameters as associated performance indices.

Findings

The effects of the pocket shape, compensating elements and ER lubricant on the bearing performance were investigated. The application of ER lubricant significantly enhanced the load-carrying capacity (48.2%), stiffness (49.8%) and damping (4.95%) of the bearings. Circular and triangular pocket bearings with constant-flow valves have been reported to provide better steady-state and rotor-dynamic performances, respectively.

Originality/value

This study presents the effect of an ER lubricant on the rotor-dynamic performance of hydrostatic thrust bearings with different pocket shapes.
The intention of small and medium enterprises' owners to participate in waqf: the case of Malaysia and Indonesia
Authors: Laila Nisful , Ratnasari Ririn Tri , Ismail Shafinar , Mohd Hidzir Putri Aliah , Mahphoth Mohd Halim
Published: July 2022

Purpose

The purpose of this study is to assess small and medium-sized enterprises (SMEs) owners’ intentions to participate in waqf, involving two countries, which are Malaysia and Indonesia, using the theory of planned behavior. SMEs are the backbone of many economies, representing 95% of all companies worldwide and accounting for 60% of employment. Based on this fact, this paper analyzes the influence of religiosity, knowledge and attitude to predict the intentions of SMEs’ owners in waqf participation in Malaysia and Indonesia.

Design/methodology/approach

Data were randomly obtained from 175 SMEs owners from Malaysia and Indonesia with the Statistical Package for the Social Sciences (SPSS) used for analysis.

Findings

The empirical analysis data suggest that knowledge and attitude show a significant impact on the intentions of SMEs’ owners to participate in waqf, while religiosity does not have a significant impact on the intentions of Malaysian and Indonesian SMEs’ owners to participate in waqf.

Practical implications

This study aims to assist SMEs in Malaysia and Indonesia to formulate appropriate strategies and marketing using waqf for the sustainability of SMEs which represent more than 90% of business establishments in both countries. The strategy is a necessity, especially because the government is targeting to promote a sustainable Islamic financial system, improve governance policy and halal industry for SMEs, strengthen the development of Malay Reserve land, providing as financial independence to higher learning institutions and invest in digitalization and advanced technology through waqf funds. Therefore, both countries should take the initiative to provide training to equip SMEs with extensive knowledge through multiple platforms to further encourage their participation in waqf.

Originality/value

Because of the increasing interest in waqf participation both in Malaysia and Indonesia, this study claims three essential contributions. First, it aims to examine the intention of SMEs in waqf participation among the business owners in Malaysia and Indonesia. Second, the study findings are expected to benefit the development of literature in accordance with Islamic social finance, particularly waqf. Third, this study provides an insight into the inclusive knowledge and attitude of SME owners and their intention to participate in waqf.