bluuebunny/crossref_metadata_2025 huggingface dataset:
Centrifugal Compressor Performance and Flow Path Generation With Artificial Intelligence
Authors: Barannik Valentyn , Burlaka Maksym , Lysianskyi Bohdan , Moroz Leonid
Published: August 2024

Centrifugal compressors are widely used turbomachines employed across various fields as components of systems, such as being part of a turbocharger in an internal combustion engine or a refrigeration cycle. As a result of system analysis, the compressor parameters are determined with 0D or 1D solvers. Simultaneously, the compressor performance, as well as other components, influence the results of system analysis. The system analysis starts with compressor performance assumptions that could be taken from a prototype or based on the engineer’s experience and prior domain knowledge. If the new design deviates significantly from the prototype, its performance assumptions diverge from the actual compressor performance, necessitating numerous iterations to align system and component parameters with overall system requirements and constraints. Therefore, the design and development projects of modern centrifugal compressors are lengthy and very expensive.

The research described in this paper aims to develop highly accurate single-stage centrifugal compressor performance models coupled with flow path geometry generation models leveraging artificial intelligence (AI) technology. These models offer the potential to circumvent expensive design-build-test iterations, thereby substantially reducing the time and cost of developing modern centrifugal compressors.

In this paper, the various configurations of centrifugal compressors are considered, along with a description of the configurations of interest. The selection of input and output variables that provide sufficient information about compressor design with the respective ranges is justified. There is a detailed description of automated workflows for centrifugal compressor design and performance data generation for neural network training. The approaches for data preprocessing that enable high-accuracy predictions are provided, and the peculiarities of applying the AI technology developed by the authors for centrifugal compressors are discussed. An analysis of the trained model accuracy as well as the technique for quantitative assessment of prediction reliability is provided. The utilization of the centrifugal compressor AI model integrated into a gas turbine engine simulation environment is demonstrated.
Evaluation of Cold Flow Test Conditions and Test Fluid Selection for a 60-kW Radial Inflow Supercritical CO2 Turbine
Authors: Hoque Syed Jiaul , Gupta Shrey Sahai , Kumar Pramod
Published: August 2024

Indian Institute of Science, Bangalore, India, is developing a supercritical CO2 power block. The power block features a 60-kW single-stage, unshrouded, vaneless radial inflow turbine designed to operate at 55,000 rpm. A cold flow test rig is being built to test the turbine assembly under reduced operating conditions before integrating it into the power block. The cold flow test must mimic the performance of the actual design condition and should be able to operate at design speed. This paper uses similarity method to determine the operating conditions and appropriate test fluid for the cold flow test.

Four candidate test fluids are considered: air, subcritical CO2, Sulfur hexafluoride, and R134a. A lower turbine inlet pressure is recommended for the cold test to minimize capital costs and ensure safety. However, challenges are encountered to match all similarity parameters at lower turbine inlet pressures. The similarity parameters matching improves as inlet pressure increases. The maximum inlet pressure for R134a and SF6 is limited by their saturation pressures, and they require speeds below 20,000 rpm. Subcritical CO2 and air necessitate higher inlet pressures of ∼ 40–60 bar and operating speeds of 35,000 and 49,300 rpm, respectively, to ensure similarity.

Computational fluid dynamic (CFD) simulations are employed to compare the velocity distribution, flow structures, entropy generation, loss distribution, and efficiency between the design and test conditions. The findings highlight air as the best-suited test fluid, offering the best aerodynamic match. The turbine can be tested with air up to full speed without choking. Furthermore, air as test fluid eliminates the need for a discharge storage tank as it can be directly released into the atmosphere.
Utilizing a Multi-Degree of Freedom Reduced-Order Model for Identifying Non-Synchronous Vibrations in Turbomachinery
Authors: Hollenbach Richard
Published: August 2024

The interaction between an unsteady aerodynamic instability with a natural mode of vibration causes large, undesired vibration in turbomachinery. In a simple form, an unsteady instability might be von Karman vortex shedding; on the other hand, it might be as complex as tip gap flow, jet core flow, or even a rotating stall. If the aerodynamic event occurs at frequencies away from shaft rotational harmonics, it is described as non-synchronous. Thus, an unsteady aerodynamic instability occurring at a frequency which excites a natural bending or torsional blade mode can be described as Non-Synchronous Vibrations (NSV), or often referred to as Vortex-Induced Vibrations (VIV). Compared to other aeroelastic phenomena, NSV has no industry accepted design tool. That leaves NSV as the most important issue to tackle for the need of an industry design tool is great.

This paper is a conclusion of multiple papers on utilizing a reduced-order model for NSV. For a pitching airfoil model, the first degree-of-freedom is the structure, while the second is the oscillating vortex shedding, captured using a Van der Pol and Duffing oscillator equation. These coupled equations create a fluid-structure interaction model which is tuned to replicate the experimental results of a wind tunnel airfoil exhibiting NSV. For the three-degree-of-freedom model, the compressor blade is given the motions of plunge and pitch, which the third degree is again the fluid. The tuned model is compared to experimental turbomachinery data. For both models, phase shift and work done per cycle are calculated and analyzed; the former depicts times for constructive and deconstructive interference, the latter demonstrates the dominant contributors to work. Finally, a framework for a full NSV design tool for industry is described including next steps for the eventually implementation of it within the research stages of turbomachinery geometry. Immediate next steps as well as long term future work are also described for this tool.
Experimental Investigation on Combustion Instabilities in a Lean Premixed Bluff Body Combustor Producing Acoustically Long Flame
Authors: Ikwubuo Melvin , Lee Jong Guen
Published: August 2024

The global and local characteristics of thermoacoustic instability occurring in a bluff body combustor which produces an acoustically non-compact flame (the Helmholtz number, He = kLflame, between 0.29 to 0.60) are reported. Over the flow conditions employed (Mach number of 0.05–0.13 and equivalence ratio of 0.60–0.85), the unstable flames are observed for a short combustor (CL = 0.66 m) with partially-closed combustor exit and a long combustor (CL = 1.22 m) with open combustor exit. The dominant peaks of pressure oscillation are found over a frequency range of 150–230Hz for the former and a frequency range of 200–280Hz for the latter. The discrepancy between the estimated and measured frequency is far greater for the short combustor than for the long combustor, which is attributed to the relatively longer flame length for the short combustor with respect to the combustor length than that for the long combustor, suggesting the relative flame length with respect to the characteristic wavelength is an important factor in determining the instability frequency and hence the prediction of thermoacoustic instability. The phase-averaged chemiluminescence image sequence during one period of pressure oscillation shows that the flame length changes significantly, responding to the pressure fluctuation during unstable combustion. Further analysis shows that for unstable flames, a region of flame where the local heat release fluctuation is out of phase with respect to the local pressure fluctuation and a region of flame where the local heat release fluctuation is in phase with respect to the local pressure fluctuation coexist over the flame length. The peak values of both damping and growing acoustic energy source increase as the Mach number increases, but the total acoustic source term becomes positive and its total value increases as the instability becomes strong.
Large-Eddy Simulation of a Non-Premixed Ammonia-Hydrogen Flame: NOx Emission and Flame Characteristics Validation
Authors: Ansari Naseem , Orsino Stefano , Meloni Roberto , Pucci Egidio , Castellani Simone , Andreini Antonio , Valera-Medina A.
Published: August 2024

The interest in ammonia and ammonia-hydrogen combustion as fuel for Gas Turbine (GT) applications implies the resolution of many technical challenges. The prediction of their flame characteristics, like flame morphology and pollutant emissions, through numerical simulations and specifically through Computational Fluid Dynamics (CFD) is one of them. In terms of NOx and unburnt emissions, the main roadblock is often related to a wide discrepancy of the results changing the employed chemistry set.

In the present work a non-premixed ammonia-hydrogen flame is investigated numerically and compared with the experimental findings retrieved in a test condition of the atmospheric pressure test campaign presented by Pugh et al. [1]. The CFD simulation is based on the species transport model with a different closure of the chemical source term depending on the cell-based combustion regime. The numerical case is based on a skeletal mechanism retrieved ad hoc to optimize the computational effort and preserve the main species needed for the calculation of the NOx emission. A detailed assessment of the CFD calculated NOx is carried out comparing it with experimental data. Following that a Chemical Reactor Network (CRN) model is used for NOx evaluation leveraging the time-averaged numerical solution from CFD. Some of the most accurate detailed chemical mechanisms present in literature are tested using the CRN model. The results from CFD and CRN reveal that there is a need to improve the pollutant emission for ammonia-hydrogen flame operating under lean non-premixed conditions.
A Comparative Analysis of Various Machine Learning Approaches for Fault Diagnostics of Hydrogen Fueled Gas Turbines
Authors: Hashmi Muhammad Baqir , Fentaye Amare Desalegn , Mansouri Mohammad , Kyprianidis Konstantinos G.
Published: August 2024

Global energy transition efforts towards decarbonization requires significant advances within the energy sector. In this regard, hydrogen is envisioned as a long-term alternative fuel for gas turbines. Accordingly, the gas turbine industry has expedited their efforts in developing 100% hydrogen compliant burners and associated auxiliary components for retrofitting the existing gas turbines. The utilization of hydrogen in gas turbines has some underlying challenges such as corrosion mainly originating from increased steam content in the hot gas path. In addition to corrosion, the gas turbine compressor is vulnerable to fouling which is the most commonly occurring fault in gas turbine operating over certain time window. Both faults are susceptible to performance and health degradation. To avoid expensive asset loss caused by unexpected downtimes and shutdowns, timely maintenance decision making is required. Therefore, simple, accurate and computationally efficient fault detection and diagnostics models become crucial for timely assessment of health status of the gas turbines.

The present study encompassed development of a physics-based performance model of a 100-kWe micro gas turbine running on 100% hydrogen fuel. The model is validated with experimental data acquired from test campaigns at the University of Stavanger. Data synthesized from experimentally validated performance model are utilized further for training machine learning algorithms. To identify an accurate algorithm, various algorithms such as support vector machine, decision tree, random forest algorithm, k-nearest neighbors, and artificial neural network were tested. The findings from fault diagnostics process (classification) revealed that ANN outperformed its counterpart algorithm by giving accuracy of 94.55%. Similarly, ANN also showed higher accuracy in performance degradation estimation process (regression) by showing the MSE of training loss as low as ∼0.14. The comparative analysis of all the chosen algorithms in the present study revealed ANN as the most accurate algorithm for fault diagnostics of hydrogen fueled gas turbines. However, there is need to further implement the ensemble machine learning models or deep learning model to explore and expedite the real time fault diagnostic accuracy to avoid false alarms and missed detections in context of hydrogen fuel.
Adjoint Optimization of Non-Axisymmetric Endwall Contours to Reduce Losses in a High-Pressure Turbine
Authors: Hendrickson Austin , Sperling Spencer , Nguyen Bao , Celestina Richard , Liu Jong , Aksoy Hakan , Nickol Jeremy , Mathison Randall
Published: August 2024

As modern gas turbines continue to evolve, further efficiency gains become more difficult to realize. The parasitic loss from secondary flows become a larger component of the overall loss, making aerodynamic optimization of secondary effects ever more critical. Specifically, the secondary flow losses created by the passage vortex can become a dominant loss factor. There has been much research and development over the past 40 years into the mitigation of these secondary flow structures, but manufacturing advances are opening up the realm of what designs can be practically implemented.

This paper discusses the development of an adjoint optimization method for three-dimensional endwall contouring using an adjoint solver in commercially available software. The primary goals of the study are to establish best practices for a holistic process of endwall optimization and compare the optimized design to the baseline geometry. An array of CFD analyses has been conducted for a high-pressure turbine stage to investigate the impact of the sensitivity radius parameter with regard to isentropic efficiency convergence. The results of these simulations are discussed and the effectiveness of the use of the adjoint model with respect to endwall contouring is discussed. Comparisons between the baseline geometry and optimized endwall shape are used to highlight how small changes in the endwall geometry impact the development of secondary flow structures such as the passage vortex. It was found that the optimized endwall geometry drove secondary losses down through a pinching mechanism at vortex formation, with a critical sensitivity radius providing the highest gains.
Experimental Study of the Real Gas Effects of CO2 on the Aerodynamic Performance Characteristics of a 1.5-Stage Axial Compressor
Authors: Kang Jeongseek , Vorobiev Alex , Cameron Joshua D. , Morris Scott C. , Turner Mark G. , Sedlacko Kyle , Miller Jason D. , Held Timothy J.
Published: August 2024

The thermodynamic properties of CO2 do not obey the ideal gas law and the simplified equation of state. The enthalpy and sonic speed depend on both temperature and pressure whereas the enthalpy and the speed of sound of ideal gas, like atmospheric air, depend only on its temperature. These effects add additional complexity to the design and operation of CO2 compressors compared to compressors utilizing air as their working fluid. For example, if the compressor inlet pressure changes during operation, its flow Mach number changes due to the change of the sonic speed which is followed by the change of corrected speed and the performance.

This paper focused on the experimental investigation of the performance parameters of a 1.5 stage axial compressor with CO2 gas. The design speed and the design pressure ratio of the compressor are 19,800 rpm and 1.41 respectively. The testing was completed using a 10MW closed CO2 compressor test loop at the University of Notre Dame Turbomachinery Laboratory. The compressor performance was measured at various compressor inlet conditions to demonstrate the effectiveness of the generalized corrected speed and the corrected flow coefficient in the CO2 compressor performance. Additionally, it is shown that the Reynolds number is connected to other performance parameters through the sonic speed and a set of experimental data is presented with an attempt to separate the effect of the Reynolds number and the effect of the corrected speed on the compressor performance.
A temperature-responsive dual-hormone foam nanoengine improves rectal absorptivity of insulin-pramlintide for diabetes treatment
Authors: Feng Shujun , Zhang Yu , Hou Chunyuan , Liu Yuta , Gao Yanfeng , Song Yujun , Luo Jun
Published: August 2024

Despite the therapeutic benefits of insulin-pramlintide dual-hormone therapy in diabetes, its application potential has been limited due to a lack of efficient delivery routes. Here, we developed a temperature-responsive dual-hormone foam nanoengine (HormFoam) and combined it with a customized spraying device to further construct an in situ foam-generating system for improving the rectal bioavailability of dual-hormone therapy. To support rapid clinical translation, a continuous microfluidic preparation for HormFoam was proposed, including the power unit of perfluorocarbon nanodroplets and the pharmaceutical components Pluronic F127–functionalized liposomal insulin and pramlintide. We found that HormFoam could consistently generate foams to drive drugs forward after rectal administration, which enhanced intestinal distribution and mucosa absorption, leading to systemic codelivery of insulin-pramlintide. HormFoam reproduced the physiology of endocrine pancreas for glycemic control and induced body weight loss while reversing metabolic disorders in diabetic mice with good biosafety. Therefore, HormFoam represents a state-of-the-art dual-hormone regimen with the potential to address unmet needs in diabetes management.
Mountain building process of the Taiwan orogeny
Authors: Tan Eh , Lee Yuan-Hsi , Chang Jia-Bin , Zheng Ming-Jung , Shyu Chase J.
Published: August 2024

The Taiwan orogeny, an example of arc-continental collision, exhibits complex geological structures and rapid exhumation. Many models have tried and failed to fully capture the dynamics of these processes. We developed a comprehensive thermomechanical model that considers the transition from brittle to ductile behavior with depth, lithology-dependent erosion and observed decollement and backstop geometries. This model successfully reproduces the intricate structures observed within the Taiwan orogeny, aligns with structural complexities, metamorphic temperature profiles, thermochronological records, strain distributions, and the rates of exhumation and cooling and elucidates the roles of ductile deformation and ramp structures in forming the Hsuehshan Range and the Western fold and thrust belt. The insights from this model offer potential applicability to other orogenic wedges worldwide.
Chemokine-mediated F-actin dynamics, polarity, and migration in B lymphocytes depend on WNK1 signaling
Authors: Hwang Il-Young , Kim Ji Sung , Harrison Kathleen A. , Park Chung , Shi Chong Shan , Kehrl John H.
Published: August 2024

Ligand-engaged chemokine receptors trigger nucleotide exchange in heterotrimeric Gα
i
proteins, which stimulates cytoskeletal reorganization and cell polarity changes. To better understand the signaling events responsible for these cellular changes, we focused on early changes in F-actin dynamics after engagement of the chemokine receptor CXCR5 in murine splenic B cells. Within 10 seconds of exposure to the CXCR5 ligand CXCL13, three-dimensional lamellar-like pseudopods and F-actin–rich ridges appeared. The transient F-actin increase depended on Gα
i2/3
signaling, the PI3K/AKT pathway, ERK activation, phospholipase C activity, and Rac1/2 activation mediated by Dock2 (dedicator of cytokinesis 2). Immunoblot analyses identified the kinase WNK1 (with no lysine kinase 1) as a potential early AKT effector. Treating B cells with specific WNK inhibitors disrupted F-actin dynamics and impaired B cell polarity, motility, and chemotaxis. These changes were mimicked in a murine B cell line by CRISPR-Cas9 gene editing of
Wnk1
, which also suggested that WNK1 contributed to B cell proliferation. Administration of a single dose of a WNK inhibitor transiently reduced B cell motility and polarity in the lymph nodes of live mice. These results indicate that WNK1 signaling maintains B cell responsiveness to CXCL13 and suggest that pharmacological inhibition of WNK1, which is involved in cancer progression and blood pressure regulation, may affect humoral immunity.
Onametostat, a PfPRMT5 inhibitor, exhibits antimalarial activity to
Plasmodium falciparum
Authors: Min Hui , Lucky Amuza Byaruhanga , Madsen Jesper J. , Chim-Ong Anongruk , Li Xiaolian , Cui Liwang , Miao Jun
Published: August 2024

Protein arginine methyltransferases (PRMTs) play critical roles in
Plasmodium falciparum
, a protozoan causing the deadliest form of malaria, making them potential targets for novel antimalarial drugs. Here, we screened 11 novel PRMT inhibitors against
P. falciparum
asexual growth and found that onametostat, an inhibitor for type II PRMTs, exhibited strong antimalarial activity with a half-maximal inhibitory concentration (IC
50
) value of 1.69 ± 0.04 µM.
In vitro
methyltransferase activities of purified PfPRMT5 were inhibited by onametostat, and a shift of IC
50
to onametostat was found in the
PfPRTM5
disruptant parasite line, indicating that PfPRTM5 is the primary target of onametostat. Consistent with the function of PfPRMT5 in mediating symmetric dimethylation of histone H3R2 (H3R2me2s) and in regulating invasion-related genes, onametostat treatment led to the reduction of H3R2me2s level in
P. falciparum
and caused the defects on the parasite’s invasion of red blood cells. This study provides a starting point for identifying specific PRMT inhibitors with the potential to serve as novel antimalarial drugs.
Loss of glycerol catabolism confers carbon-source-dependent artemisinin resistance in
Mycobacterium tuberculosis
Authors: Martini Maria Carla , Alonso Maria Natalia , Cafiero Juan Hilario , Xiao Junpei , Shell Scarlet S.
Published: August 2024

In view of the urgent need for new antibiotics to treat human infections caused by multidrug-resistant pathogens, drug repurposing is gaining strength due to the relatively low research costs and shorter clinical trials. Such is the case of artemisinin, an antimalarial drug that has recently been shown to display activity against
Mycobacterium tuberculosis
(Mtb), the causative agent of tuberculosis. To gain insight into how Mtb is affected by artemisinin, we used RNAseq to assess the impact of artemisinin on gene expression profiles, revealing the induction of several efflux pumps and the KstR2 regulon. To anticipate the artemisinin resistance-conferring mutations that could arise in clinical Mtb strains, we performed an
in vitro
evolution experiment in the presence of lethal concentrations of artemisinin. We obtained artemisinin-resistant isolates displaying different growth kinetics and drug phenotypes, suggesting that resistance evolved through different pathways. Whole-genome sequencing of nine isolates revealed alterations in the
glpK
and
glpQ1
genes, both involved in glycerol metabolism, in seven and one strains, respectively. We then constructed a
glpK
mutant and found that loss of
glpK
increases artemisinin resistance only when glycerol is present as a major carbon source. Our results suggest that mutations in glycerol catabolism genes could be selected during the evolution of resistance to artemisinin when glycerol is available as a carbon source. These results add to recent findings of mutations and phase variants that reduce drug efficacy in carbon-source-dependent ways.
Construction nanobiotechnology approach for performance enhancement of microbially induced biomineralization (MIB) using a biopolymer encapsulated spore-based system
Authors: Debnath Ankita , Sen Ramkrishna
Published: August 2024

The integration of green construction practices within the built environment has been significantly advanced by biotechnological innovations, among which microbially induced biomineralization (MIB), predominantly facilitated by various strains of spore-forming bacilli, emerges as a pivotal mechanism for the self-healing of concrete. However, the practical deployment of this technology faces challenges, notably the compromised viability of bacterial spores due to germination triggered by severe shear stress during concrete mixing. To address this limitation, a water-insoluble polymer (extracellular polymeric substance) produced by
Cellulomonas flavigena
was utilized to encapsulate and protect the spores. The encapsulation process was rigorously verified through physicochemical methodologies, including X-ray diffraction (XRD) analysis, which revealed alterations in the interlayer spacings of the extracellular polymeric substance (EPS) structure during the encapsulation process, indicating successful EPS coating of the spores. Furthermore, a proof of concept for the enhanced biomineralization capacity of EPS-coated spores was demonstrated. Standard analytical techniques confirmed the precipitation of calcite and vaterite among other minerals, underscoring the effectiveness of this novel approach. This breakthrough paves the way for the development of innovative, sustainable bioconcrete applications, aligning with broader environmental objectives and advancing the field of green construction technology.

IMPORTANCE

Development of bioconcrete with self-healing capability through MIB constitutes an important sustainable construction biotechnology approach for restoration and repair of built environment. Like every promising technology, MIB also suffers from certain shortcomings in terms of compromised viability of the microbial cells after premature germination of the spores on exposure to shear stress caused during concrete mixing. In this study, these challenges were adequately addressed by successfully providing a protective coating of indigenously extracted EPS to the bacterial spores and elucidating the interactive mechanisms between them. The results showed stable encapsulation of the spores while providing mechanistic insights of the encapsulation phenomenon. The data also showed enhanced rate of biomineralization by encapsulated microbes when subjected to stress conditions.
TolC and EmrA1 contribute to
Francisella novicida
multidrug resistance and modulation of host cell death
Authors: Kopping Erik J. , Benziger P. Todd , Thanassi David G.
Published: August 2024

Francisella
spp. are Gram-negative, facultative intracellular pathogens.
Francisella tularensis
causes the human disease tularemia and is considered a biological threat agent due to its high infectivity and virulence. A central aspect of
Francisella
virulence is its ability to dampen host immune responses. We previously identified the outer membrane channel (OMC) protein TolC as a critical
F. tularensis
virulence factor required for suppression of apoptotic and proinflammatory responses during macrophage infection. TolC functions as part of multidrug efflux systems and the type I secretion pathway that exports bacterial effector proteins. In these systems, TolC forms tripartite complexes together with an inner membrane transporter and periplasmic membrane fusion protein (MFP). To advance understanding of TolC function in
Francisella
, we analyzed OMC and MFP homologs in
Francisella novicida
, a widely used model species that causes a tularemia-like disease in mice. In agreement with the previous
F. tularensis
studies, all three OMCs present in
F. novicida
contributed to multidrug resistance, but only TolC was important for suppressing macrophage cell death. In addition, we identified the EmrA1 MFP as important for resisting antimicrobial compounds and dampening host cell death. In contrast to results obtained with
F. tularensis
, the cell death triggered during infection with the
F. novicida tolC
and
emrA1
mutants was dominated by pyroptosis rather than apoptosis. These data expand our understanding of TolC function in
Francisella
and underscore both conserved and differential aspects of
F. novicida
and
F. tularensis
.

IMPORTANCE

Francisella tularensis
is a Gram-negative intracellular bacterial pathogen and causative agent of tularemia. We previously identified the outer membrane channel protein TolC as contributing to antimicrobial resistance and subversion of host responses by
F. tularensis
. To advance understanding of TolC function in
Francisella
and to identify components that might work together with TolC, we took advantage of a transposon mutant library in
F. novicida
, a model species that causes a tularemia-like disease in mice. Our findings identify TolC and the membrane fusion protein EmrA1 as important for both antimicrobial resistance and suppression of macrophage cell death. This study also revealed differences in cell death pathways triggered by
F. novicida
versus
F. tularensis
infection that may relate to differences in virulence.
Subnanometer structure of medusavirus capsid during maturation using cryo-electron microscopy
Authors: Watanabe Ryoto , Song Chihong , Takemura Masaharu , Murata Kazuyoshi
Published: August 2024

Medusavirus is a giant virus classified into an independent family of
Mamonoviridae
. Amoebae infected with medusavirus release immature particles in addition to virions. These particles were suggested to exhibit the maturation process of this virus, but the structure of these capsids during maturation remains unknown. Here, we apply a block-based reconstruction method in cryo-electron microscopy (cryo-EM) single particle analysis to these viral capsids, extending the resolution to 7–10 Å. The maps reveal a novel network composed of minor capsid proteins (mCPs) supporting major capsid proteins (MCPs). A predicted molecular model of the MCP fitted into the cryo-EM maps clarified the boundaries between the MCP and the underlining mCPs, as well as between the MCP and the outer spikes, and identified molecular interactions between the MCP and these components. Several structural changes of the mCPs under the fivefold vertices of the immature particles were observed, depending on the presence or absence of the underlying internal membrane. In addition, the lower part of the penton proteins on the fivefold vertices was also missing in mature virions. These dynamic conformational changes of mCPs indicate an important function in the maturation process of medusavirus.

IMPORTANCE

The structural changes of giant virus capsids during maturation have not thus far been well clarified. Medusavirus is a unique giant virus in which infected amoebae release immature particles in addition to mature virus particles. In this study, we used cryo-electron microscopy to investigate immature and mature medusavirus particles and elucidate the structural changes of the viral capsid during the maturation process. In DNA-empty particles, the conformation of the minor capsid proteins changed dynamically depending on the presence or absence of the underlying internal membranes. In DNA-full particles, the lower part of the penton proteins was lost. This is the first report of structural changes of the viral capsid during the maturation process of giant viruses.
The 5′UTR of porcine reproductive and respiratory syndrome virus strain JXwn06 harbors a uORF that regulates cellular inflammation
Authors: Liu Teng , Shao Qi , Cui Zhiying , Qing Pengkai , Gao Peng , Zhang Yongning , Zhou Lei , Ge Xinna , Guo Xin , Han Jun , Yang Hanchun
Published: August 2024

The 5′ untranslated region (5′UTR) of many positive-stranded RNA viruses contain functional regulatory sequences. Here, we show that the porcine reproductive and respiratory syndrome virus (PRRSV), a member of arteriviruses, harbors small upstream open reading frames (uORFs) in its 5′UTR. Bioinformatics analysis shows that this feature is relatively well conserved among PRRSV strains and
Arteriviridae
. We also identified a uORF, namely uORF2, in the PRRSV strain JXwn06, that possesses translational activity and exerts a suppressive effect on the expression of the primary ORF evidenced by
in vitro
reporter assays. We tested its importance via reverse genetics by introducing a point mutation into the PRRSV infectious cDNA clone to inactivate the start codon of uORF2. The recovered mutant virus Mut2 surprisingly replicated to the same level as the wild-type virus (WT), but induced a higher level of inflammatory cytokines (e.g., TNF-
α
, IL-1
β
, and IL-6) both
in vitro
and in animal experiments, correlating well with more severe lung injury and higher death rate. In line with this, over-expression of uORF2 in transfected cells significantly inhibited poly(I:C)-induced expression of inflammatory cytokines. Together, our data support the idea that uORF2 encodes a novel, functional regulator of PRRSV virulence despite of its short size.

IMPORTANCE

PRRSV has remained a major challenge to the world swine industry, but we still do not know much about its biology and pathogenesis. Here, we provide evidence to show that the 5′UTR of PRRSV strain JXwn06 harbors a functional uORF that has the coding capacity and regulates induction of inflammation as demonstrated by
in vitro
assays and animal experiment. The findings reveal a novel viral factor that regulates cellular inflammation and provide insight into the understanding of PRRSV pathogenesis.
Protective role of cytosolic prion protein against virus infection in prion-infected cells
Authors: Hara Hideyuki , Chida Junji , Batchuluun Batzaya , Takahashi Etsuhisa , Kido Hiroshi , Sakaguchi Suehiro
Published: August 2024

Production of the amyloidogenic prion protein, PrP
Sc
, which forms infectious protein aggregates, or prions, is a key pathogenic event in prion diseases. Functional prion-like protein aggregations, such as the mitochondrial adaptor protein MAVS and the inflammasome component protein ASC, have been identified to play a protective role in viral infections in mammalian cells. In this study, to investigate if PrP
Sc
could play a functional role against external stimuli, we infected prion-infected cells with a neurotropic influenza A virus strain, IAV/WSN. We found that prion-infected cells were highly resistant to IAV/WSN infection. In these cells, NF-κB nuclear translocation was disturbed; therefore, mitochondrial superoxide dismutase (mtSOD) expression was suppressed, and mitochondrial reactive oxygen species (mtROS) was increased. The elevated mtROS subsequently activated NLRP3 inflammasomes, leading to the suppression of IAV/WSN-induced necroptosis. We also found that prion-infected cells accumulated a portion of PrP molecules in the cytosol, and that the N-terminal potential nuclear translocation signal of PrP impeded NF-κB nuclear translocation. These results suggest that PrP
Sc
might play a functional role in protection against viral infections by stimulating the NLRP3 inflammasome-dependent antivirus mechanism through the cytosolic PrP-mediated disturbance of NF-κB nuclear translocation, which leads to suppression of mtSOD expression and consequently upregulation of the NLRP3 inflammasome activator mtROS.

IMPORTANCE

Cytosolic PrP has been detected in prion-infected cells and suggested to be involved in the neurotoxicity of prions. Here, we also detected cytosolic PrP in prion-infected cells. We further found that the nuclear translocation of NF-κB was disturbed in prion-infected cells and that the N-terminal potential nuclear translocation signal of PrP expressed in the cytosol disturbed the nuclear translocation of NF-κB. Thus, the N-terminal nuclear translocation signal of cytosolic PrP might play a role in prion neurotoxicity. Prion-like protein aggregates in other protein misfolding disorders, including Alzheimer's disease were reported to play a protective role against various environmental stimuli. We here showed that prion-infected cells were partially resistant to IAV/WSN infection due to the cytosolic PrP-mediated disturbance of the nuclear translocation of NF-κB, which consequently activated NLRP3 inflammasomes after IAV/WSN infection. It is thus possible that prions could also play a protective role in viral infections.
Probing Open Charm Hadron Production with the ALICE-3 Detector at the High-Luminosity Large Hadron Collider
Authors: Malaev M. V. , Riabov V. G.
Published: August 2024

ALICE-3 is a future upgrade of the current ALICE experiment to be operated at the high-luminosity Large Hadron Collider at CERN after 2030. One of the physics objectives of the experiment is to probe the hot and dense QCD matter produced in heavy-ion collisions by measuring the production of open charm hadrons. The ALICE-3 detector is equipped to measure the production of ground and excited states of D‑mesons in decay channels with charged particles in the final state. Results are presented from feasibility studies of recording of open charm hadrons in decay channels with neutral photons or mesons in the final state using the large acceptance electromagnetic calorimeter.
Trajectories of choriocapillaris perfusion in healthy individuals and patients with diabetes mellitus: a prospective cohort study
Authors: Zhong Xiaoying , Yang Shaopeng , Zhu Ziyu , Li Huangdong , Cheng Weijing , Wang Wei
Published: August 2024

Purpose

To evaluate the longitudinal rate of choriocapillaris flow deficits (CFD) in healthy participants and patients with diabetes mellitus.

Methods

This prospective cohort study included healthy individuals and diabetic patients without diabetic retinopathy (non-DR) or with mild-to-moderate non-proliferative DR (NPDR). The swept-source optical coherence tomography angiography (OCTA) was adopted for quantifying CFD annually, and linear mixed models were used to analyse the CFD change and its 95% CI overtime.

Results

A total of 1025 individuals were included, including 465 healthy controls, 454 in the non-DR group and 106 in the NPDR group. Significant increase in CFDs was observed in NPDR group (0.423%, 95% CI 0.230% to 0.616%) and non-DR group (0.319%, 95% CI 0.225% to 0.412%), which were higher than the CFD in healthy controls (0.173%, 95% CI 0.079% to 0.266%). After adjusting for other factors, the non-DR and NPDR group had a greater annual elevation of CFD by 0.171% (95% CI 0.060% to 0.283%; p=0.003) and 0.258% (95% CI 0.068% to 0.449%; p=0.008) in comparisons with controls. Furthermore, higher serum creatinine and glycated haemoglobin levels, poorer best-corrected visual acuity, lower OCTA image quality scores and smaller CFD at baseline were independently related to accelerated CFD worsening (all p<0.05).

Conclusions

The CFD among healthy individuals and patients with diabetes increased consistently overtime, regardless of the presence or absence of DR, suggesting that CFD alterations could be an early indicator of microvascular complications, potentially aiding in the earlier DR detection.
Effects of reducing sedentary behaviour by increasing physical activity, on cognitive function, brain function and structure across the lifespan: a systematic review and meta-analysis
Authors: Feter Natan , Ligeza Tomasz S , Bashir Neha , Shanmugam Ramiya J , Montero Herrera Bryan , Aldabbagh Tamara , Usman Anne-Farah , Yonezawa Ayumi , McCarthy Shane , Herrera Danielle , Vargas Denise , Mir Emaad M , Syed Talha , Desai Sanam , Shi Hector , Kim William , Puhar Natalie , Gowda Kushi , Nowak Olivia , Kuang Jin , Quiroz Flor , Caputo Eduardo L , Yu Qian , Pionke JJ , Zou Liye , Raine Lauren B , Gratton Gabriele , Fabiani Monica , Lubans David R , Hallal Pedro C , Pindus Dominika M
Published: August 2024

Objective

To examine the acute and chronic effects of reducing prolonged sedentary time (ST) with physical activity (PA) on cognitive and brain health.

Design

Systematic review and meta-analysis.

Data sources

PubMed, Scopus, CINAHL, PsycINFO, SPORTDiscus, Web of Science, and ProQuest Dissertation and Theses.

Eligibility criteria

Randomised controlled trials (RCTs) published from inception to 17 June 2024, with healthy participants without cognitive impairment or neurological conditions that affect cognitive functioning, aged ≥4 years, testing acute and chronic effects of reducing ST and/or prolonged ST by reallocating ST to PA on cognitive function, brain function, and structure.

Results

We included 25 RCTs (n=1289) investigating acute (21 studies) and chronic (4 studies) effects on cognitive function (acute: n=20, chronic: n=4) and brain function (acute: n=7, chronic: n=1); there were no studies on brain structure. Acutely interrupting continuous ST with either multiple or a single PA bout improved cognitive function measured from 3 hours to three consecutive days based on 91 effect sizes (
g
=0.17, 95% CI: 0.05 to 0.29, p=0.005,
I
2
=45.5%). When comparing single versus multiple PA bouts, only multiple PA bouts yielded a positive effect on cognitive function based on 72 effect sizes (
g
=0.20, 95% CI: 0.06 to 0.35, p=0.006;
I
2
=48.8%). Chronic studies reported null findings on cognitive function (n=4), with some evidence of improved neural efficiency of the hippocampus (n=1).

Conclusion

Interrupting ST with PA acutely improves cognitive function. The evidence from chronic studies remains inconclusive.

Systematic review registration

PROSPERO CRD42020200998.
Effect of henagliflozin on left ventricular mass index in dialysis patients with HFpEF (HELD-HF): protocol for a multicentre, randomised, double-blind, placebo-controlled trial
Authors: Yan Hao , Wang Wei , Li Ying , Qi Yinghui , Lu Renhua , Zhou Yijun , Zhang Weiming , Liu Shang , Pang Huihua , Fang Yan , Li Zhenyuan , Wang Jieying , Jiang Meng , Pu Jun , Gu Leyi , Fang Wei
Published: August 2024

Introduction

Heart failure with preserved ejection fraction (HFpEF) is a prevalent comorbidity among patients with end-stage kidney disease. Although sodium-glucose cotransporter 2 inhibitors are validated in treating heart failure and ameliorating left ventricular hypertrophy among non-dialysis patients, the effects on dialysis patients are unknown. We previously investigated the pharmacokinetics of henagliflozin in patients undergoing haemodialysis (HD) or peritoneal dialysis (PD) and clarified its safety.

Methods and analysis

This multicentre, randomised, double-blind, placebo-controlled trial is being conducted at three hospitals in Shanghai, China. A target of 108 HD or PD patients with HFpEF are randomly allocated to treatment group (henagliflozin 5 mg/day in addition to standard therapy) or control group (placebo with standard therapy) at a ratio of 1:1. All subjects will be followed up for 24 weeks. The primary outcome is change in echocardiography-measured left ventricular mass index. The secondary interests include changes in left atrial volume index, E/e’, e’ and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Intergroup comparisons of change in echocardiography-related outcomes from baseline to 24 weeks are based on a linear regression model adjusted for baseline values (analysis of covariance), and repeated measure analysis of variance with Bonferroni adjustment is employed for comparison of change in NT-proBNP. Subgroup analyses of the primary and secondary outcomes are conducted to determine whether the effect of henagliflozin varies according to dialysis modality. The χ
2
method is used to compare the occurrence of adverse events and severe adverse events.

Ethics and dissemination

This trial has been approved by the Ethics Committee of Renji Hospital, School of Medicine, Shanghai Jiao Tong University (LY2023-127-B). All participants provide written informed consent before screening. The results of the trial will be disclosed completely in international peer-reviewed journals. Both positive and negative results will be reported.

Trial registration number

ChiCTR2300073169.
Fiscal Policy Determinants of Health Spending in India: State Versus Center
Authors: BEHERA DEEPAK KUMAR , RAHUT DIL BAHADUR , DASH UMAKANT
Published: August 2024

This study uses data from 1986 to 2021 and the auto-regressive distributed lag model to explore India’s fiscal policy determinants of government health spending. The results find two structural breaks in time: (i) 2002 for state government health spending (SGHS) and (ii) 2014 for central government health spending. The results also show that central revenue transfers to states have a positive and statistically significant effect on SGHS in the long run. The results imply that a 1% rise in central revenue transfers to states leads to a 0.399% increase in SGHS. Further, state government public debt exhibits a negative and statistically significant relationship with SGHS, implying that a 1% rise in public debt leads to a 0.119% fall in SGHS in the long run. Fiscal management (i.e., revenue mobilization and debt sustainability) is essential to prepare a long-term strategy for health-care financing.
Analysis of hysteresis loops and dielectric performance in the ovalene-like system: Monte Carlo study
Authors: Sabbah Hussein , Fadil Z. , El Fdil R. , Ifseisi Ahmad A. , Rosaiah P. , Raorane Chaitany Jayprakash
Published: August 2024

This Monte Carlo study offers a comprehensive analysis of the ovalene-like system, emphasizing its dielectric behavior, thermal performance and hysteresis loops. The investigation reveals intricate dynamics influenced by diverse parameters, contributing to a nuanced understanding of the system’s response. Additionally, the study scrutinizes the impact of various physical parameters on the thermal behavior of polarizations and susceptibilities. The examination thoroughly explores the influence of these parameters on loop characteristics, coercive field, and saturation behavior, unveiling the formation of multiple loops and polarization plateaus on the electric hysteresis. In summary, this study advances our understanding of the ovalene-like system’s dielectric response, thermal characteristics and hysteresis dynamics, providing valuable insights for future research and applications, particularly in advanced electronic devices.
Revealing Hidden Features of Chaotic Systems Using High-Performance Bifurcation Analysis Tools Based on CUDA Technology
Authors: Rybin Vyacheslav , Butusov Denis , Shirnin Kirill , Ostrovskii Valerii
Published: August 2024

Bifurcation analysis is an essential tool in nonlinear dynamics. Bifurcation diagrams help to discover subtle features of investigated dynamics such as chaotic and periodic regimes, hidden attractors and fixed points. However, plotting high-resolution bifurcation diagrams can be a computationally challenging task, especially in multiparametric evaluation. It should be noted that the bifurcation analysis is a task with natural parallelism and thus can be efficiently solved using hybrid central-graphics processing architectures. In this paper, we propose an advanced algorithm and special software for plotting bifurcation diagrams using calculations accelerated by graphics processing unit in combination with a highly efficient semi-implicit ordinary differential equation solver. Time series processing is based on the extraction of amplitude and phase features for the density-based spatial clustering of applications with noise to determine oscillation periodicity. We showcase the features of the application of proposed solutions on a set of test chaotic systems. The performance of the analysis algorithms is investigated in comparison with conventional solutions based on central processing unit and several approaches known from the literature. We explicitly show that the proposed algorithm outperforms known solutions in both calculation speed and precision.