bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure-guided design of aPlasmodium vivaxDuffy binding protein-based vaccine immunogen
Authors: Barber Natalie M. , Pholcharee Tossapol , Lias Amelia M , Quinkert Doris , Nugent James , King Lloyd D. W. , Draper Simon J. , Higgins Matthew K.
Published: June 2024

Plasmodium vivaxremains one of the major causative agents of human malaria and a vaccine is urgently required. It is an obligate intracellular parasites and replication within red blood cells is essential for development of disease and for transmission. The interaction between PvDBP on the parasite surface and the DARC receptor on human reticulocytes is essential for aPlasmodium vivaxblood stage infection. Human vaccination with the RII region of PvDBP slowed parasite replication, showing that PvDBP is a promising vaccine candidate. However, it did not induce sterile protection, and further development is required to generate a vaccine which protects from clinical malaria. In this study, we develop a vaccine immunogen containing a region of PvDBP-RII, known as subdomain 3, which contains the epitope for a broadly-reactive growth-inhibitory antibody, DB9. We used structure-guided approaches to resurface subdomain 3 such that it folds as an isolated molecule. We show that this engineered subdomain 3 is more stable and more easily produced than PvDBP-RII and induces a more effective growth-inhibitory antibody response. We therefore present an improved PvDBP-based immunogen for use in blood stage vaccines to prevent malaria due toPlasmodium vivax.

One sentence summary

Structure-guided design leads to a more effective Duffy-binding protein-based vaccine immunogen to preventPlasmodium vivax.
Reduced accrual of mineral-associated organic matter after two years of enhanced rock weathering in cropland soils, though no net losses of soil organic carbon
Authors: Sokol Noah W. , Sohng Jaeeun , Moreland Kimber , Slessarev Eric , Goertzen Heath , Schmidt Radomir , Samaddar Sandipan , Holzer Iris , Almaraz Maya , Geoghegan Emily , Houlton Benjamin , Montañez Isabel , Pett-Ridge Jennifer , Scow Kate
Published: June 2024

Enhanced rock weathering (ERW), the application of crushed silicate rock to soil, can remove atmospheric carbon dioxide by converting it to (bi)carbonate ions or solid carbonate minerals. However, few field studies have empirically evaluated ERW in field settings. A critical question remains as to whether additions of crushed rock might positively or negatively affect soil organic matter (SOM) – Earth’s largest terrestrial organic carbon (C) pool and a massive reservoir of organic nitrogen (N). Here, in three irrigated cropland sites in California, USA, we investigated the effect of crushed meta-basalt rock additions on different pools of soil organic carbon and nitrogen (i.e., mineral-associated organic matter and particulate organic matter), active microbial biomass, and microbial community composition. After two years of crushed rock additions, mineral-associated organic matter (MAOM) stocks were lower in the upper surface soil (0-10 cm) compared to unamended controls. At the two sites where baseline pre-treatment data were available, neither total SOC nor SON decreased over the two years of study in crushed rock or unamended control plots. However, the accrual rate of MAOM-C and MAOM-N at 0-10 cm was lower in plots with crushed rock vs. unamended controls. Before ERW is deployed at large scales, our results suggest that field trials should assess the effects of crushed rock on SOM pools, especially over multi-year time scales, to accurately assess changes in net C and understand the mechanisms driving interactions between ERW and SOM cycling.
Integrated single-cell RNA-seq analysis revealed PTN secreted by fibroblasts acting on itself and macrophages via SDC4 ligand in myocardial hypertrophy
Authors: Sheng Ke , Ran Yuqing , Guan Yuting , Tan Pingping , Zhang Rongrong , Qian Songwei , Lin Hongzhou , Wu Huilan , Peng Yongmiao , Huang Yuqing , Zhao Zhiguang , Zhu Guanghui , Ji Weiping , Guo Xiaoling
Published: June 2024

Background

Hypertrophic cardiomyopathy (HCM) is characterized by massive myocardial hypertrophy, which is the most frequent cause of sudden death and can lead to heart failure (HF) or stroke. The objective of this study was to explore the communication network among various cells in the heart of pathological HCM derived from transverse aortic constriction (TAC) mouse model, and investigate the potential mechanism through data mining, biological informatics analysis, and experimental validation.

Methods and Results

The integrated analyses including CellChat, Seurat, gene ontology (GO), pseudo-time trajectory analysis, and weighted gene co-expression network analysis (WGCNA) were performed based on the single-cell RNA-seq data (scRNA-seq). In vitrotests were conducted to verify bioinformatic analysis findings through enzyme-linked immunosorbent assay (ELISA), real-time quantitative PCR (RT-qPCR), Edu staining, and transwell assay.In vivotests were also performed to further verify bioinformatic analysis findings by western blot and immunofluorescence assays based on our established TAC mouse model with myocardial hypertrophy. Our results showed that in the heart of TAC mouse, the interaction between cardiac fibroblasts and macrophages was most common, and the increasing pleiotrophin (PTN) secreted by cardiac fibroblasts could promote themselves proliferation or invasion as well as stimulate macrophage activation to release inflammatory cytokines, such as TNF-α, IL-6, Cox-2, Cd83, Egr2, and IL-10 through acting on its ligand recombinant Syndecan 4 (SDC4), which may affect cardiomyocyte normal function and eventually cause HCM. This study first demonstrated that PTN derived from cardiac fibroblasts may act on SDC4 to play crucial role in myocardial hypertrophy, which may be a potential therapeutic targets for patients with pathological HCM.

Conclusions

In this study, the complex interaction network between cardiac fibroblasts and macrophages of TAC mice based on the scRNA-seq data was investigated, and we found that the increasing PTN secreted by cardiac fibroblasts under cardiac pressure overload could promote themselves proliferation or invasion as well as stimulate macrophage activation to release inflammatory cytokines through acting on SDC4 ligand, which may affect cardiomyocyte normal function and eventually cause HCM. In addition, our study suggested that PTN derived from cardiac fibroblasts may act on SDC4 ligand to play crucial role in myocardial hypertrophy, which may be a potential therapeutic targets for patients with pathological HCM.
‘Vivaldi’: An amplicon-based whole genome sequencing method for the four seasonal human coronaviruses 229E, NL63, OC43 & HKU1, alongside SARS-CoV-2’
Authors: McClure C. Patrick , Tsoleridis Theocharis , Holmes Nadine , Chappell Joseph G. , Byaruhanga Timothy , Duncan Joshua , Tofan Miruna , Khater Abdul , Berry Louise , Clark Gemma , Irving William L. , Tarr Alexander W. , Ball Jonathan K. , Astbury Stuart , Loose Matt
Published: June 2024

Prior to the emergence of SARS-CoV-2 in 2019, Alphacoronaviruses 229E and NL63 and Betacoronaviruses OC43 and HKU1 were already established endemic ‘common cold’ viral infections. Despite their collective contribution towards global respiratory morbidity and mortality and potential to inform the future trajectory of SARS-CoV-2 endemicity, they are infrequently sequenced. We therefore developed a 1200bp amplicon-based whole genome sequencing scheme targeting all four seasonal coronaviruses and SARS-CoV-2.

The ‘Vivaldi’ method was applied retrospectively and prospectively using Oxford Nanopore Technology to approximately 400 seasonal coronavirus infections diagnosed in Nottingham, UK, from February 2016 to July 2023. We demonstrate that the amplicon multiplex strategy can be applied agnostically to determine complete genomes of five different species from two coronaviral genera. 304 unique seasonal coronavirus genomes of greater than 95% coverage were achieved: 64 for 229E, 85 for NL63, 128 for OC43 and 27 for HKU1. They collectively indicated a dynamic seasonal coronavirus genomic landscape, with co-circulation of multiple variants emerging and declining over the UK winter respiratory infection season, with further geographical distinction when compared to a global dataset. Prolonged infection with concomitant intra-host evolution was also observed for both Alpha-(NL63) and Betacoronaviruses (OC43).

This data represents the largest single cohort of seasonal coronavirus genomes to date and also a novel amplicon scheme for their future global surveillance suitable for widespread and easy adoption in the post-SARS-CoV-2 era of viral genomics.
Defining the disturbance in cortical glutamate and GABA function in psychosis and its origins and consequences
Authors: Deakin Bill , Liddle Elizabeth , Rathnaiah Mohanbabu , Gregory Cathy , Katshu Mohammad , Williams Gemma , Conen Silke , Smallman Richard , Koelewijn Loes C. , Anton Adriana , Kumar Jyothika , Gasgoyne Lauren E. , Chen Chen , Nikkheslat Naghmeh , Evans John , Lanz Bernard , Walters James , Talbot Peter , Palaniyappan Lena , Singh Krish D. , Morris Peter , Williams Steven R. , Liddle Peter F.
Published: June 2024

It is widely thought that the onset of psychotic symptoms in schizophrenia may arise from an early neurotoxic phase, possibly related to oxidative stress or inflammation, and a late residual damage phase associated with persistent negative symptoms. We tested this hypothesis in a 3-centre study using magnetic resonance spectroscopy (MRS) to determine whether abnormalities in glutamate, glutamine and GABA content in anterior cingulate cortex (ACC) differed between people with minimally treated ‘Recent’ onset schizophrenia and an ‘Established’ group with > 10 years of treatment. We tested whether neurochemical abnormalities were i) mediated by raised circulating inflammatory cytokine concentrations, c-reactive protein (CRP) and interleukin-6 (IL-6), or depletion of glutathione and ii) associated with ratings of positive and negative symptoms. Relative to age-matched controls, the Established group showed significantly greater reduction in ACC glutamate than the Recent group, which did not differ from controls. This effect was not attributable to antipsychotic drug exposure. Patient ACC glutathione was negatively correlated with age. IL-6 was increased in both clinical groups, while increases in CRP were greater in the Established than Recent group. Elevated CRP was entirely accounted for by greater antipsychotic drug exposure and BMI, while residual elevation in IL-6 in the Established group did not account for their lower ACC glutamate. GABA was reduced relative to controls across ACC and occipital voxels. This reduction was not associated with drug treatment, BMI or cytokine levels. Only ACC GABA content correlated significantly with symptoms, lower content with greater positive and negative symptoms across both groups.
The Lived Experience of Mothers of Children with Cancer
Authors: Seyoum Lidya K. , Berhane Adugnaw , Girma Eshetu
Published: June 2024

Background

Thus, the path of mothers with cancer children is intricate and severe. Several studies have addressed this topic. Most have considered the long-term effects of the children’s cancer diagnosis on the mother from a mental health perspective. The experience of living with cancer children as mothers reveals the urgent need to pay attention to the mother’s emotional, psychological, and social factors shaping caregiving.

Objective

This study aimed to look further into the lived experiences of Ethiopian mothers with children suffering from childhood cancer.

Method

Interpretive phenomenological approach of qualitative study conducted at the pediatric oncology unit of Tikur Anbessa Specialized Hospital and Tesfa Addis Parents Childhood Organization. Study participants were selected using the snowball purposive sampling technique. Data were collected using semi-structured interviews. A total of 12 mothers were interviewed. Interpretative phenomenological analysis was employed and Open Code 4.3 software was used for data management and used thematic analysis.

Result

When raising a child with childhood cancer, mothers encounter a wide range of issues in the context of childhood cancer care, including fatigue, poor access to high-quality medical care, divorce, parenting withdrawal, excessive medical expenses, lack of sufficient and accurate information, anxiety, impatience, forgetfulness, regret, and spiritual struggles. To overcome such difficulties, mothers employ loans, financial aid, and the sale of their homes and other assets to reduce their financial burden. Mothers’ other coping method was to accept many sorts of support from family, friends, strangers, and organizations. The assistance received helped mothers gain resilience.

Conclusion

The study provides crucial insights into the experiences of mothers of children with childhood cancer. The diagnosis of childhood cancer has a profound impact on mothers, and it elicits various reactions from them. Investigate the emotional, mental, and social drivers of caregiving, emphasizing important factors such as financial pressure, insufficient quality medical treatment, emotional disturbances, and strategies of coping with their children by the mothers. Establish counseling and support schemes for mothers to cope with cancer therapy for their child. Organize community awareness campaigns to increase understanding, reduce stigma, and promote early treatment.
Mortality risk in survivors of acute COVID-19 and the urinary proteome: Follow-up results from a multinational study that prospectively evaluated a proteomic urine test for early and accurate prognosis of critical course complications in patients with SARS-CoV-2 infection (CRIT-COV-U)
Authors: Siwy Justyna , Wendt Ralph , Keller Felix , Banasik Miroslaw , Peters Björn , Dudoignon Emmanuel , Mebazaa Alexandre , Gülmez Dilara , Spasovski Goce , Lazo Mercedes Salgueira , Mischak Harald , Hecking Manfred , Beige Joachim ,   UriCoV working group
Published: June 2024

Survival prospects following SARS-CoV-2 infection extend beyond the acute phase, influenced by various factors including age, health conditions, and infection severity. We investigated mortality risk among 651 post-acute COVID-19 patients, assessing the association between urinary peptides and future death. Data spanning until December 2023 were collected from six countries, comparing mortality trends with age- and sex-matched non-infected controls. A death prediction classifier was developed and validated using pre-existing urinary peptidomics datasets. Notably, 13.98% of post-COVID-19 patients succumbed during the follow-up, with mortality rates significantly higher than non-infected controls, particularly evident in younger individuals (<65 years). Urinary peptide analysis identified 201 peptides linked to mortality, integrated into a predictive classifier (DP201). Higher DP201 scores, alongside age and BMI, significantly predicted death. These findings underscore the utility of urinary peptides in prognosticating post-acute COVID-19 mortality, offering insights for targeted interventions.
Visual Cortical Thickness Increases with Prolonged Artificial Vision Restoration
Authors: Stiles Noelle R. B. , Choupan Jeiran , Ameri Hossein , Patel Vivek R. , Shi Yonggang
Published: June 2024

The Argus II retinal prosthesis restores visual perception to late blind patients. It has been shown that structural changes occur in the brain due to late-onset blindness, including cortical thinning in visual regions of the brain. Following vision restoration, it is not yet known whether these visual regions are reinvigorated and regain a normal cortical thickness or retain the diminished thickness from blindness.

We evaluated the cortical thicknesses of ten Argus II Retinal Prostheses patients, ten blind patients, and thirteen sighted participants. The Argus II patients on average had a thicker left Cuneus Cortex and Lateral Occipital Cortex relative to the blind patients. The duration of the Argus II use (time since implant in active users) significantly partially correlated with thicker visual cortical regions in the left hemisphere. Furthermore, in the two case studies (scanned before and after implantation), the patient with longer device use (44.5 months) had an increase in the cortical thickness of visual regions, whereas the shorter-using patient did not (6.5 months). Finally, a third case, scanned at three time points post-implantation, showed an increase in cortical thickness in the Lateral Occipital Cortex between 43.5 and 57 months, which was maintained even after 3 years of disuse (106 months).

Overall, the Argus II patients’ cortical thickness was on average significantly rejuvenated in two higher visual regions and, patients using the implant for a longer duration had thicker visual regions. This research raises the possibility of structural plasticity reversing visual cortical atrophy in late-blind patients with prolonged vision restoration.
Data release and baseline analysis of the largest collection of 6-minute walk tests: the My Heart Counts Cardiovascular Health Study, a fully digital smartphone platform
Authors: Kim Daniel Seung , Schuetz Narayan , Johnson Anders , Tolas Alexander , Mantena Sriya , O’Sullivan Jack W , Hershman Steven G , King Abby C , Christle Jeffrey W , Oppezzo Marily , Rodriguez Fatima , Mattsson C. Mikael , Wheeler Matthew T , Taylor Herman A , Murphy Susan , Ashley Euan A
Published: June 2024

The six-minute walk test (6MWT) is a sub-maximal exercise test used clinically as a measure of functional capacity. With the emergence of advanced sensors, 6MWTs were commonly performed remotely via smartphones and other devices. The My Heart Counts Cardiovascular Health Study is a smartphone application that serves as a digital platform for studies of human cardiovascular health. It has been used to perform 30,475 6MWTs on 25,539 unique participants. Here, we report on the associations of demographic and clinical variables with 6MWT distance at baseline (N=4,576), validating prior associations with male gender, height, and baseline physical activity with 6MWT distance in multivariable regression analysis. We also report associations of 6MWT baseline distance with working status (+26.8m +5.2m, P<0.001) and feeling depressed (−3.78m, +0.79m, P<0.001). In a subset of participants who conducted repeat 6MWTs separated by at least 1-week but no greater than 3-months (N=2,269), we found that use of theMy Heart Countsapp resulted in a statistically significant increase in 6MWT distance (+21.5m +5.72m,P<0.001). Finally, we present the public data release of our 30,475 6MWTs and the launch of a webpage-based data viewer of summary-level statistics, to compare the relative health of an individual by their age, gender, and chronic disease status. Given the importance of 6MWTs in assessment of functional capacity, our publicly-available data will serve an important purpose as a healthy and disease-specific reference for investigators worldwide.
Panacea: A foundation model for clinical trial search, summarization, design, and recruitment
Authors: Lin Jiacheng , Xu Hanwen , Wang Zifeng , Wang Sheng , Sun Jimeng
Published: June 2024

Clinical trials are fundamental in developing new drugs, medical devices, and treatments. However, they are often time-consuming and have low success rates. Although there have been initial attempts to create large language models (LLMs) for clinical trial design and patient-trial matching, these models remain task-specific and not adaptable to diverse clinical trial tasks. To address this challenge, we propose a clinical trial foundation model namedPanacea, designed to handle multiple tasks, including trial search, trial summarization, trial design, and patient-trial matching. We also assemble a large-scale dataset, namedTrialAlign, of 793,279 trial documents and 1,113,207 trial-related scientific papers, to infuse clinical knowledge into the model by pre-training. We further curateTrialInstruct, which has 200,866 of instruction data for fine-tuning. These resources enablePanaceato be widely applicable for a range of clinical trial tasks based on user requirements.

We evaluatedPanaceaon a new benchmark, namedTrialPanorama, which covers eight clinical trial tasks. Our method performed the best on seven of the eight tasks compared to six cutting-edge generic or medicine-specific LLMs. Specifically,Panaceashowed great potential to collaborate with human experts in crafting the design of eligibility criteria, study arms, and outcome measures, in multi-round conversations. In addition, Panacea achieved 14.42% improvement in patient-trial matching, 41.78% to 52.02% improvement in trial search, and consistently ranked at the top for five aspects of trial summarization. Our approach demonstrates the effectiveness ofPanaceain clinical trials and establishes a comprehensive resource, including training data, model, and benchmark, for developing clinical trial foundation models, paving the path for AI-based clinical trial development.
How to Detect the Early Cardiac Functional Change and Predict Heart Failure in Paroxysmal Atrial Fibrillation? A Prospective Cohort Study
Authors: Cheng Lei , Bao Lilian , Zhuang Xinyu , Yan Fangying , Gao Xiufang , Zhou Peng , Zhao Yikai , Yang Ke , Zhang Qi , Huang Guoqian , Bao Liwen
Published: June 2024

Backgrounds

20-30% atrial fibrillation (AF) may result in heart failure (HF). Noninvasive left ventricle myocardial work (LVMW) is a fairly new method for detecting LV function. We aimed to evaluate whether LVMW could detect the LV change function in paroxysmal atrial fibrillation (PAF) and predict HF incident.

Methods

In this prospective cohort study, 146 PAF subjects and 63 non-PAF subjects matched by age and gender set as the controls were enrolled. Noninvasive LVMW parameters, including global work index, global constructive work, global wasted work (GWW) and global work efficiency (GWE) were obtained from LV pressure-strain loop by 2D speckle tracking imaging. LA volume index (LAVI) was measured by 3D echocardiography. AF burden (AFB) was evaluated by questionnaire. The primary outcome was the incident HF.AFB deterioration was evaluated at the end of follow up. Stata15.0 and R4.1 were used for data analysis and description.

Results

The average age was 66.2±11.4 years and comprised 55% males in PAF. Compared with the controls, PAF had significantly elevated GWW (143.7±88.3mmHg% vs 115.5±59.6mmHg%, p<0.001) and impaired GWE (92.3±7.5% vs 93.8±2.8%, p=0.035) and they were correlated with increased LAVImax and LAVImin. Those with higher AFB showed significantly decreased LAEF and increased LAVImin. During the average 40.5 months follow-up, 9.9% PAF developed HF and ablation reduced the HF occurrence. In the non-ablation subgroup, baseline decreased LAEF rather than LVMW was a strong predictor for HF. As expected, AFB deterioration was strongly associated with HF incident.

Conclusions

Elevated GWW was detected by LVMW and it was strongly correlated with LA dilation in PAF. Higher AFB had adverse effect on LAVImin. Restoring sinus rhythm was significant for HF prevention, especially for PAF with lower LAEF.

Clinical Perspective

What is new?

Although GLS and LVEF remained normal, subtle LV dysfunction of elevated GWW and impaired GWE could be detected by LVMW in the early stage of PAF.

Increased LAVImin, rather than LAEF, was strongly associated with elevated GWW and higher AF burden in PAF.

Restoring sinus rhythm was important to early stage of PAF for HF prevention, especially in PAF with lower LAEF.

What are the clinical implications?

It is significant for PAF to protect LV function by maintaining sinus rhythm or keeping AFB at minimal-mild stage, even from the very early stage.

Increased LAVImin is an important indicator for detecting LV dysfunction in PAF and the underlying mechanism needs to be discovered.
Emerging Applications of NLP and Large Language Models in Gastroenterology and Hepatology: A Systematic Review
Authors: Omar Mahmud , SharIf Kassem , Glicksberg Benjamin , Nadkarni Girish N , Klang Eyal
Published: June 2024

Background and Aim

In the last two years, natural language processing (NLP) has transformed significantly with the introduction of large language models (LLM). This review updates on NLP and LLM applications and challenges in gastroenterology and hepatology.

Methods

Registered with PROSPERO (CRD42024542275) and adhering to PRISMA guidelines, we searched six databases for relevant studies published from 2003 to 2024, ultimately including 57 studies.

Results

Our review notes an increase in relevant publications in 2023-2024 compared to previous years, reflecting growing interest in newer models such as GPT-3 and GPT-4. The results demonstrate that NLP models have enhanced data extraction from electronic health records and other unstructured medical data sources. Key findings include high precision in identifying disease characteristics from unstructured reports and ongoing improvement in clinical decision-making. Risk of bias assessments using ROBINS-I, QUADAS-2, and PROBAST tools confirmed the methodological robustness of the included studies.

Conclusion

NLP and LLMs can enhance diagnosis and treatment in gastroenterology and hepatology. They enable extraction of data from unstructured medical records, such as endoscopy reports and patient notes, and for enhancing clinical decision-making. Despite these advancements, integrating these tools into routine practice is still challenging. Future work should prospectively demonstrate real-world value.
Tuning the performance of a TphR-based terephthalate biosensor with a design of experiments approach
Authors: Gonzalez Guadalupe Alvarez , Chacón Micaela , Butterfield Thomas , Dixon Neil
Published: June 2024

Transcription factor-based biosensors are genetic tools that aim to predictability link the presence of a specific input stimuli to a tailored gene expression output. The performance characteristics of a biosensor fundamentally determines its potential applications. However, current methods to engineer and optimise tailored biosensor responses are highly nonintuitive, and struggle to investigate multidimensional sequence/design space efficiently. In this study we employ a design of experiments (DoE) approach to build a framework for efficiently engineering activator-based biosensors with tailored performances, and we apply the framework for the development of biosensors for the polyethylene terephthalate (PET) plastic degradation monomer terephthalate (TPA). We simultaneously engineer the core promoter and operator regions of the responsive promoter, and by employing a dual refactoring approach, we were able to explore an enhanced biosensor design space and assign their causative performance effects. The approach employed here serves as a foundational framework for engineering transcriptional biosensors and enabled development of tailored biosensors with enhanced dynamic range and diverse signal output, sensitivity, and steepness. We further demonstrate its applicability on the development of tailored biosensors for primary screening of PET hydrolases and enzyme condition screening, demonstrating the potential of statistical modelling in optimizing biosensors for tailored industrial and environmental applications.

Abstract Figure

Graphical Abstract. Employment of a DoE framework for fine-tuning biosensor performance.

Highlights

Bioinformatic mining of allosteric transcription factors to produce TPA biosensors

Efficient sampling of complex sequence-function relationships of genetic circuits

Modelling to learn and optimise biosensor genetic circuits

Application of biosensors for primary and secondary enzyme screening applications
Ethylene Receptor Gain- and Loss-of-function Mutants Reveal an ETR1-dependent Transcriptional Network in Roots
Authors: Khoury Maleana G. , Harkey Alexandria F. , Mühlemann Joëlle K. , Olex Amy L. , Houben Maarten , Binder Brad M. , Muday Gloria K.
Published: June 2024

In Arabidopsis, a family of five receptors mediates ethylene responses in roots, with Ethylene Response 1 (ETR1) controlling increases in root hair proliferation and decreases in lateral root formation. To define the ETR1-dependent gene regulatory network (GRN) controlling root development, we profiled the root transcriptome from Col-0 and theetr1-3gain-of-function andetr1-7loss-of-function mutants in the presence and absence of ethylene or the ethylene precursor aminocyclopropane-1-carboxylic acid (ACC). We identified 4,522 differentially expressed (DE) transcripts in Col-0 roots with altered abundance in response to ethylene and/or ACC treatment, most with larger magnitude changes induced by ethylene. These included 553 DE transcripts that were ETR1-dependent, defined by a lack of response to treatment with ethylene and/or ACC in ethylene-insensitiveetr1-3and constitutively altered inetr1-7in the presence and absence of treatment relative to untreated Col-0. Within these ETR1 dependent transcripts were ethylene biosynthesis genes and transcription factors.ACC OXIDASE 2(ACO2)andACO3convert ACC to ethylene and were ETR1-dependent, andACOpromoter fusions were ACC regulated in root tissues in appropriate locations to control root development, withACO5localized to root hairs. Abundance of ETR1-dependent transcripts that were predicted to encode transcription factors and ACOs were examined in Col-0 and anein3eil1mutant with and without ACC treatment, revealing that the ETR1 and EIN3/EIL1 canonical ethylene signaling pathway regulated some, but not all, of these transcriptional responses. Together, these findings reveal features of an ETR1-dependent GRN that controls both ethylene synthesis and root growth and development.
Elucidating the kinetic and thermodynamic insight into regulation of glycolysis by lactate dehydrogenase and its impact on tricarboxylic acid cycle and oxidative phosphorylation in cancer cells
Authors: Zeng Siying , Wang Yuqi , Ying Minfeng , Jin Chengmeng , Ying Chang , Wang Di , Wu Hao , Hu Xun
Published: June 2024

Lactate dehydrogenase (LDH) stands at the intersection of pyruvate metabolism. While it is believed that inhibition of LDH redirects pyruvate to mitochondrial metabolism, suppressing glycolysis and boosting oxidative phosphorylation, the mechanism remains largely unexplored. We found that individual LDH A or B knockouts had minimal impact on glycolysis, tricarboxylic acid cycle (TCAC), or oxidative phosphorylation (OXPHOS). However, combining LDH knockout with LDH inhibitor GNE-140 significantly suppressed these processes. Inhibition of LDH led to an increase in free NADH concentration and a decrease in free NAD+concentration, the reduced free NAD+concentration inhibited GAPDH, disrupting the balance of glycolytic intermediates, which were linked with thermodynamic shift of the Gibbs free energy of reactions between phosphofructokinase 1 (PFK1) and phosphoglycerate mutase (PGAM) in the glycolytic pathway, favoring their reverse direction. This disrupted glycolysis led to impaired TCAC and mitochondrial respiration due to reduced pyruvate and glutamine carbon influx into TCAC. Under hypoxia, LDH inhibition had a stronger effect, inducing energy crisis, redox imbalance, and cancer cell death. Our study reveals LDH’s intricate control over glycolysis, TCAC, and mitochondrial respiration, highlighting the interplay of enzyme kinetics and thermodynamics in metabolic pathways—a crucial aspect for understanding metabolic regulation.

Impact statement

The biochemical mechanism underlying the flux regulation of glycolytic flux by lactate dehydrogenase in cancer cells, which have remained largely unexplored, is deciphered.

Funding information

This work has been supported in part by China Natural Science Foundation projects (82073038, 81772947), a key project (2018C03009) funded by Zhejiang Provincial Department of Sciences and Technologies, the Fundamental Research Funds for the Central Universities (226-2024-00062), to X.H.
Spiral to stripe transition in the two-dimensional Hubbard model
Authors: Scholle Robin , Metzner Walter , Vilardi Demetrio , Bonetti Pietro M.
Published: June 2024

We obtain an almost complete understanding of the mean-field phase diagram of the two-dimensional Hubbard model on a square lattice with a sizable next-nearest-neighbor hopping and a moderate interaction strength. In particular, we clarify the nature of the transition region between the spiral and the stripe phase. Complementing previous [] real-space Hartree-Fock calculations on large finite lattices, we solve the mean-field equations for coplanar unidirectional magnetic order directly in the thermodynamic limit, and we determine the nature of the magnetic states right below the mean-field critical temperature T* by a Landau free-energy analysis. While the magnetic order for filling factors n≥1 is always of Néel type, for n≤1 the following sequence of magnetic states is found as a function of increasing hole-doping: Néel, planar circular spiral, multispiral, and collinear spin-charge stripe states. Multispiral states are superpositions of several spirals with distinct wave vectors, and lead to concomitant charge order. We finally point out that nematic and charge orders inherited from the magnetic order can survive even in the presence of fluctuations, and we present a corresponding qualitative phase diagram.

Published by the American Physical Society
2024
Global constraint on the jet transport coefficient from single-hadron, dihadron, and
γ
-hadron spectra in high-energy heavy-ion collisions
Authors: Xie Man , Ke Weiyao , Zhang Hanzhong , Wang Xin-Nian
Published: June 2024

Modifications of large transverse momentum single-hadron, dihadron, and γ-hadron spectra in relativistic heavy-ion collisions are direct consequences of parton-medium interactions in the quark-gluon plasma (QGP). The interaction strength and underlying dynamics can be quantified by the jet transport coefficient q̂. We carry out the first global constraint on q̂ using a next-to-leading order pQCD parton model with higher-twist parton energy loss and combining world experimental data on single-hadron, dihadron, and γ-hadron suppression at both RHIC and LHC energies with a wide range of centralities. The global Bayesian analysis using the information field (IF) priors provides the most stringent constraint on q̂(T). We demonstrate in particular the progressive constraining power of the IF Bayesian analysis on the strong temperature dependence of q̂ using data from different centralities and colliding energies. We also discuss the advantage of using both inclusive and correlation observables with different geometric biases. As a verification, the obtained q̂(T) is shown to describe data on single-hadron anisotropy at high transverse momentum well. Predictions for future jet quenching measurements in oxygen-oxygen collisions are also provided.

Published by the American Physical Society
2024
Learning Quantum Processes Without Input Control
Authors: Fanizza Marco , Quek Yihui , Rosati Matteo
Published: June 2024

We introduce a general statistical learning theory for processes that take as input a classical random variable and output a quantum state. Our setting is motivated by the practical situation in which one desires to learn a quantum process governed by classical parameters that are out of one’s control. This framework is applicable, for example, to the study of astronomical phenomena, disordered systems and biological processes not controlled by the observer. We provide an algorithm for learning with high probability in this setting with a finite amount of samples, even if the concept class is infinite. To do this, we review and adapt existing algorithms for shadow tomography and hypothesis selection, and combine their guarantees with the uniform convergence on the data of the loss functions of interest. As a byproduct, we obtain sufficient conditions for performing shadow tomography of classical-quantum states with a number of copies, which depends on the dimension of the quantum register, but not on the dimension of the classical one. We give concrete examples of processes that can be learned in this manner, based on quantum circuits or physically motivated classes, such as systems governed by Hamiltonians with random perturbations or data-dependent phase shifts.

Published by the American Physical Society
2024
TAAM refinement on high-resolution experimental and simulated 3D ED/MicroED data for organic molecules
Authors: Kumar Anil , Jha Kunal Kumar , Olech Barbara , Goral Tomasz , Malinska Maura , Woźniak Krzysztof , Dominiak Paulina Maria
Published: June 2024

3D electron diffraction (3D ED), or microcrystal electron diffraction (MicroED), has become an alternative technique for determining the high-resolution crystal structures of compounds from sub-micron-sized crystals. Here, we considered L-alanine, α-glycine and urea, which are known to form good-quality crystals, and collected high-resolution 3D ED data on our in-house TEM instrument. In this study, we present a comparison of independent atom model (IAM) and transferable aspherical atom model (TAAM) kinematical refinement against experimental and simulated data. TAAM refinement on both experimental and simulated data clearly improves the model fitting statistics (R factors and residual electrostatic potential) compared to IAM refinement. This shows that TAAM better represents the experimental electrostatic potential of organic crystals than IAM. Furthermore, we compared the geometrical parameters and atomic displacement parameters (ADPs) resulting from the experimental refinements with the simulated refinements, with the periodic density functional theory (DFT) calculations and with published X-ray and neutron crystal structures. The TAAM refinements on the 3D ED data did not improve the accuracy of the bond lengths between the non-H atoms. The experimental 3D ED data provided more accurate H-atom positions than the IAM refinements on the X-ray diffraction data. The IAM refinements against 3D ED data had a tendency to lead to slightly longer X—H bond lengths than TAAM, but the difference was statistically insignificant. Atomic displacement parameters were too large by tens of percent for L-alanine and α-glycine. Most probably, other unmodelled effects were causing this behaviour, such as radiation damage or dynamical scattering.
Synthesis and structural characterizations of three carbonyl(α-diimine)hydrido(triphenylphosphine)ruthenium(II) complexes with derivatives of 1,10-phenanthroline
Authors: Wysocki Waldemar , Kamecka Anna , Karczmarzyk Zbigniew
Published: June 2024

Three new ruthenium(II) polypyridyl complexes containing α-diimine ligands, namely, carbonylhydrido(1,10-phenanthroline-κ2
N,N)bis(triphenylphosphine-κP)ruthenium(II) hexafluorophosphate, [RuH(C12H8N2)(C18H15P)2(CO)]PF6, carbonylhydrido(2,9-dimethyl-1,10-phenanthroline-κ2
N,N)bis(triphenylphosphine-κP)ruthenium(II) hexafluorophosphate, and carbonylhydrido(4,7-dimethyl-1,10-phenanthroline-κ2
N,N)bis(triphenylphosphine-κP)ruthenium(II) hexafluorophosphate, both [RuH(C14H12N2)(C18H15P)2(CO)]PF6, were synthesized and characterized by spectroscopic and X-ray diffraction methods. In these complexes, the ruthenium(II) ion adopts a distorted octahedral geometry. There are no intermolecular hydrogen bonds in the crystal structures of the analysed complexes and Hirshfeld surface analysis showed that the H...H contacts constitute a high percentage, close to 50%, of the intermolecular interactions.
Factors affecting macromolecule orientations in thin films formed in cryo-EM
Authors: Yadav Swati , Vinothkumar Kutti R.
Published: June 2024

The formation of a vitrified thin film embedded with randomly oriented macromolecules is an essential prerequisite for cryogenic sample electron microscopy. Most commonly, this is achieved using the plunge-freeze method first described nearly 40 years ago. Although this is a robust method, the behaviour of different macromolecules shows great variation upon freezing and often needs to be optimized to obtain an isotropic, high-resolution reconstruction. For a macromolecule in such a film, the probability of encountering the air–water interface in the time between blotting and freezing and adopting preferred orientations is very high. 3D reconstruction using preferentially oriented particles often leads to anisotropic and uninterpretable maps. Currently, there are no general solutions to this prevalent issue, but several approaches largely focusing on sample preparation with the use of additives and novel grid modifications have been attempted. In this study, the effect of physical and chemical factors on the orientations of macromolecules was investigated through an analysis of selected well studied macromolecules, and important parameters that determine the behaviour of proteins on cryo-EM grids were revealed. These insights highlight the nature of the interactions that cause preferred orientations and can be utilized to systematically address orientation bias for any given macromolecule and to provide a framework to design small-molecule additives to enhance sample stability and behaviour.
Barriers to the implementation of enterprise risk management in Indian construction firms
Authors: Prakash Anand , Ambekar Sudhir
Published: June 2024

Purpose

Implementing enterprise risk management (ERM) systems in construction firms of developing countries like India is critical for targeting strong risk management strategies that support their growth. It requires such firms to holistically understand the major barriers in terms of their definitions, relationships with one another and interdependencies. Thus, this study aims to identify, model and analyze the barriers to implementing ERM in construction firms using interpretive structural modeling (ISM).

Design/methodology/approach

This study used a Delphi process to identify barriers to the implementation of ERM in Indian construction firms, ISM to model them and Matrice d’Impacts Croisés Multiplication Appliquée à un Classement (MICMAC) to analyze their interrelationships.

Findings

The study’s results revealed that individual-level factors are the most important among the barriers present at the lowest level in the hierarchical model, whereas organizational commitment with the highest dependence power is present at the highest level in the hierarchical model.

Research limitations/implications

Since the usage of ERM in the construction industry is highly culture-dependent and may have regional nuances, the data on ERM usage might accurately reflect the Indian construction industry but may not apply to other regions.

Practical implications

This study can be used to develop effective strategies to improve the implementation of ERM in construction firms in developing countries like India.

Social implications

ERM is crucial for managing risks in Indian construction firms due to the high degree of complexity and uncertainty associated with construction projects coming from changes due to technological advancement, regulatory changes, changes in consumer preferences, global competition and other socioeconomic and political factors.

Originality/value

The study’s results will help researchers and practitioners working in the construction industry of developing countries like India to identify the challenges in adopting ERM systems. It will guide construction firms to appropriately develop risk management strategies for managing the inevitable risks in their complex project environments. This will help improve their contribution to the country’s economic development.
Topology and parameter optimization of IPM motor considering mechanical strength by stress and connection constraints
Authors: Takenouchi Kou , Hiruma Shingo , Mifune Takeshi , Matsuo Tetsuji
Published: June 2024

Purpose

The purpose of this study is to apply the topology and parameter optimization (TPO) to interior permanent magnet (IPM) motors to obtain the optimized shape with higher torque, lower ripple and sufficient mechanical strength.

Design/methodology/approach

The constraints regarding the maximum stress, connectivity and mesh quality were considered to achieve not only high electrical performance but also high mechanical strength. To enhance the accuracy of the finite element analysis of the elastic analysis, this paper used body-fitted mesh adaptation technique to avoid the stress concentration.

Findings

The proposed method in this study resulted in feasible shapes with sufficiently high strength compared to previous studies. It is also shown that TPO yielded IPM motors with higher torque compared to topology optimization (TO) with fixed parameters.

Practical implications

Different from the existing studies on topology optimization of IPM motors, the mechanical strength is even considered by evaluating the stress values. Therefore, in the practical phase, geometries can be designed that are less likely to be damaged due to deformation, even in the high-speed rotation range.

Originality/value

This paper performed TO and parameter optimization (PO) simultaneously, considering not only the electrical performance but also the mechanical strength. Furthermore, the mechanical strength was evaluated more precisely by devising the elastic analysis conditions and mesh generation.
Effect of catalyst distribution in the combustion catalytic layer on heat and mass transport characteristics of the microchannel reactor
Authors: Kong Weiqiang , Shen Qiuwan , Huang Naibao , Yan Min , Li Shian
Published: June 2024

Purpose

The purpose of this study is to investigate the effect of catalyst distribution in the combustion catalytic layer on heat and mass transport characteristics of the auto-thermal methanol steam reforming microchannel reactor.

Design/methodology/approach

Computational fluid dynamics (CFD) method is used to study four different gradient designs. The corresponding distributions of temperature, species and chemical reaction rate are provided and compared.

Findings

The distributions of species, temperature and chemical reaction rate are significantly affected by the catalyst distribution in the combustion catalytic layer. A more uniform temperature distribution can be observed when the gradient design is used. Meanwhile, the methanol conversion rate is also improved.

Practical implications

This work reveals the effect of catalyst distribution in the combustion catalytic layer on heat and mass transport characteristics of the auto-thermal methanol steam reforming microchannel reactor and provides guidance for the design of reactors.

Originality/value

The temperature uniformity and hydrogen production performance can be improved by the gradient design in the combustion catalytic layer.