bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Scalable Conjugate Heat Transfer Method Applied to Engine Transients
Authors: Paul Neil H. E. , Atkins Nicholas R. , Brandvik Tobias 
Published: August 2024

Abstract
This paper introduces a scalable implementation of a loosely coupled approach for solving unsteady conjugate heat transfer (CHT) problems. The framework uses segregated solvers; computational fluid dynamics (CFD) to solve the Reynolds-averaged Navier-Stokes (RANS) equations on the fluid side, and an iterative finite element analysis (FEA) method to solve the heat equation on the solid side. Thermal coupling is achieved through an iterative procedure that applies temperature (Dirichlet) boundary conditions on the fluid side, and convective (Robin) boundary conditions on the solid side. It is assumed that the disparity in characteristic timescales between fluid and solid is such that the fluid can be treated as quasi-steady, permitting the use of steady CFD. The loosely coupled approach allows simulations to time-march at time steps suitable for the solid side, offering at least an order of magnitude speed-up compared to a fully coupled approach, which is limited by the stability of the fluid side. For validation purposes, the framework is applied to two test cases: a flat plate and a rotating cavity with radial inflow. The convergence characteristics for a range of relaxation levels are compared. Under certain conditions, as has been reported in the literature, loosely coupled CHT methods can become unstable. We discuss these instability mechanisms, and offer practical guidelines for maintaining stability for complex cases. Computational scalability is demonstrated using a 100+ million cell full-annulus radial inflow cavity model, which is run through an engine representative transient in ∼ 24 hours.
Thermal Load Control in High-Temperature Heat Pumps: A Comparative Study
Authors: Pettinari Matteo , Frate Guido Francesco , Ferrari Lorenzo , Yücel Fatma Cansu , Tran A. Phong , Stathopoulos Panagiotis , Kyprianidis Konstantinos 
Published: August 2024

Abstract
High-temperature heat pumps (HTHPs) are becoming increasingly relevant in the industry as they represent a promising solution for decarbonising industrial heat. These technologies can enable the electrification of industrial processes by exploiting electricity from renewables to provide process heat at temperatures above 250 °C, as in the case of emerging Brayton-based HTHPs.
To succeed in this purpose, HTHPs must also ensure operational flexibility, which entails the ability to operate safely under varying loads and promptly respond to fluctuations in demand, while maintaining high efficiencies. Moreover, the ability to provide large flexible electric loads to transmission system operators, has the potential to unlock innovative business cases and further promote the use of these systems. Common control strategies for achieving this, include employing bypass mechanisms, fluid inventory control, and adjusting turbomachinery rotational speeds. Despite their variety, the simultaneous use of such control strategies is often limited as they may lead to significantly different system behaviours, both in terms of transient and steady performance.
In this paper, rotational speed and fluid inventory control are examined from a transient perspective to maintain the desired sink temperature while regulating the thermal load of the system. Results indicate that rotational speed control leads to negligible sink temperature residuals, while fluid inventory control better preserves the HTHP performances for varying temperature glides.
Development of a Dynamic Model of a Two-Shaft Turbine for Control Tuning and Testing
Authors: Ferrari Lorenzo , Bigazzi Tommaso , Di Gioia Gabriele , Bagni Gianni , Giovanardi Lorenzo 
Published: August 2024

Abstract
An accurate prediction of the dynamic performance of gas turbines is still of primary importance in industrial applications, both for control development and diagnostic purposes. In this study, a dynamic model of a two-shaft low-emission gas turbine based on a grey-box approach is proposed. As a first step, a grey-box static model of the turbine was developed in Matlab Simulink based a dataset of multiple simulations of a commercial tool. The results of the grey-box model turned out to be able to predict both machine performance and operating thermodynamic conditions of its components. Starting from these results, a dynamic model was developed of the machine operating in open loop conditions by using time series data from the field. Pattern search and genetic algorithms have been employed to optimize the matching between model and machine outputs. The accuracy and reliability of the dynamic model were tested by using historical data of engine performance. Finally, the model was used in a closed-loop configuration by linking the control software simulator with the system simulator in Simulink, creating a co-simulation between the two environments. This co-simulation allowed for the accurate simulation of the closed-loop system and has proven to be a solid foundation for future developments.
A New Experimental Facility for the Study of Blade Tip Rubs at Engine Relevant Temperatures
Authors: Broski Noah , Keener Christopher , Loizos Theodore , Mathison Randall , D’Souza Kiran , Kasprow Thomas , Wusatowska-Sarnek Agnieszka M. 
Published: August 2024

Abstract
As aircraft engines become more and more efficient, minimizing blade tip clearance in all rotating components of the turbomachinery is critical. This has reduced the distance between the rotating blade tips and the stationary casing to the point that small deviations in manufacturing, uneven thermal expansion, or centrifugal growth can cause the blade to contact the engine’s abradable casing lining. This abradable lining is added to the casing with the foresight that blades are likely to rub against it. In some cases, the clearances are designed so that the blades will cut into this abradable on the first run of the engine. Understanding the interactions between this abradable casing lining and the blades at engine relevant conditions is imperative to the safe and efficient operation of engines. The Ohio State Gas Turbine Laboratory and Pratt & Whitney have developed an in-ground experimental facility for studying the material interactions occurring during blade tip rub events. This facility is designed to allow for variable abradable incursion rates, abradable incursion depths, and blade rotational speed. Additional capabilities of the facility include: the use of an optical temperature sensitive paint system for non-contact sub ambient blade temperature measurements, high speed infrared measurement of blade temperatures, temperature control capabilities for the blades and abradable liner, and blade force measurements on the abradable liner. In this work, a temperature control system for sub and hyper ambient temperatures is presented along with the philosophy and design process for the creation of this system. To aid in designing the temperature control system, a transient heat transfer model was developed and validated in non-rotating experiments. The results of these experiments are discussed and the applicability of these results to the rotating case are examined.
Factors Influencing Hard Running Distances in National Collegiate Athletics Association Division I Women’s Soccer Players
Authors: Sam Isaac A. , Anderson Amanda A. , Johnson Emma L. , Yang Hyung Suk 
Published: August 2024

As the total distances covered in soccer games have remained relatively constant, the hard running distances (HRDs) covered by players have shown variations due to the higher physical demands and dynamics of team running performances. Although factors affecting the total distances covered in a match are multifactorial, no study has specifically examined match performance indicators (MPIs) that impact HRD. Consequently, the purpose of this study was to better understand how MPIs (hard running efforts, turnovers, minutes played, duels won, duels lost, and pass completions) are associated with HRD and to investigate how each variable contributes to HRD using multiple regression analysis. The study included a sample of 21 female Division I soccer players aged between 18 and 22 years (mean ± SD = 20 ± 1.32 years), all of whom were outfield players: center backs (n = 5), defensive midfielders (n = 4), outside midfielders (n = 5), center-attacking midfielders (n = 4), and center forwards (n = 3). Overall, all MPIs were positively associated (.639 ≤ r ≤ .992) with HRD, yet hard running efforts showed the strongest relationship with HRDs (r = .992). The regression models indicated that all variables contributed to HRD. In particular, hard running effort had the most significant impact (p < .001), implying its dominant influence on HRD compared with other variables. These findings may play a pivotal role in supporting coaches and trainers to better understand the influence of MPIs on HRD. The models developed could help predict a player’s workload related to HRD.
Zidovudine in synergistic combination with nitrofurantoin or omadacycline:
in vitro
and in murine urinary tract or lung infection evaluation against multidrug-resistant
Klebsiella pneumoniae
Authors: Tian Ping , Li Qing-Qing , Guo Ming-Juan , Zhu Yun-Zhu , Zhu Rong-Qing , Guo Ya-Qin , Yang Yi , Liu Yan-Yan , Yu Liang , Li Ya-Sheng , Li Jia-Bin 
Published: August 2024

ABSTRACT

Limited treatment options and multidrug-resistant (MDR)
Klebsiella pneumoniae
present a significant therapeutic challenge, underscoring the need for novel approaches. Drug repurposing is a promising tool for augmenting the activity of many antibiotics. This study aimed to identify novel synergistic drug combinations against
K. pneumoniae
based on drug repurposing. We used the clinically isolated GN 172867 MDR strain of
K. pneumoniae
to determine the reversal resistance activity of zidovudine (AZT). The combined effects of AZT and various antibiotics, including nitrofurantoin (NIT) and omadacycline (OMC), were examined using the checkerboard method, growth curves, and crystal violet assays to assess biofilms. An
in vitro
combination activity testing was carried out in 12 isolates of
K. pneumoniae. In vivo
murine urinary tract and lung infection models were used to evaluate the therapeutic effects of AZT + NIT and AZT + OMC, respectively. The fractional inhibitory concentration index and growth curve demonstrated that AZT synergized with NIT or OMC against
K. pneumoniae
strains. In addition, AZT + NIT inhibited biofilm formation and cleared mature biofilms.
In vivo
, compared with untreated GN 172867-infected mice, AZT + NIT and AZT + OMC treatment decreased colony counts in multiple tissues (
P
< 0.05) and pathological scores in the bladder and kidneys (
P
< 0.05) and increased the survival rate by 60% (
P
< 0.05). This study evaluated the combination of AZT and antibiotics to treat drug-resistant
K. pneumoniae
infections and found novel drug combinations for the treatment of acute urinary tract infections. These findings suggest that AZT may exert significant anti-resistance activity.
Pharmacokinetics and safety of TBAJ-876, a novel antimycobacterial diarylquinoline, in healthy subjects
Authors: Lombardi Antonio , Pappas Fran , Nedelman Jerry , Hickman Dean , Jaw-Tsai Sarah , Olugbosi Morounfolu , Bruinenberg Paul , Beumont Maria , Sun Eugene 
Published: August 2024

ABSTRACT

TBAJ-876, a second-generation diarylquinoline with greater antimycobacterial activity and a potentially better safety profile compared with bedaquiline, is under development for the treatment of drug-susceptible and drug-resistant tuberculosis (TB). A phase 1, first-in-human study of TBAJ-876, comprising a single-ascending dose (SAD) part including a food effect cohort, a multiple-ascending dose (MAD) part, and a relative bioavailability part of tablets versus oral suspension, was conducted on 137 healthy adults. A drug–drug interaction study was conducted on 28 healthy adults to evaluate the effects of TBAJ-876 on a cytochrome P450 3A4 substrate (midazolam) and a P-glycoprotein substrate (digoxin). TBAJ-876 was well-tolerated at single doses up to 800 mg and multiple doses up to 200 mg for 14 days. No deaths or serious adverse events occurred. No episodes of clinically significant prolongation of the QTc interval were observed. TBAJ-876 exposures were dose proportional in the SAD and MAD studies. TBAJ-876 exhibited multicompartmental pharmacokinetics (PK) with a long terminal half-life yielding quantifiable concentrations up to the longest follow-up of 10 weeks after a single dose and resulting in accumulation with multiple dosing. In the fed state, TBAJ-876 exposures approximately doubled with the tablet formulation, whereas M3 metabolite exposures decreased by approximately 20%. The relative bioavailability of TBAJ-876 was similar between tablets and the oral suspension at 100-mg doses. With co-administration of TBAJ-876, the AUC
0-inf
of midazolam was unchanged and the C
max
was reduced by 14%; the AUC
0-last
of digoxin was increased by 51%, and the C
max
was increased by 18%. These results support further investigation of TBAJ-876 for the treatment of tuberculosis.
Dose-fractionation studies of a
Plasmodium
phosphatidylinositol 4-kinase inhibitor in a humanized mouse model of malaria
Authors: Gibhard Liezl , Njoroge Mathew , Mulubwa Mwila , Lawrence Nina , Smith Dennis , Duffy James , Le Manach Claire , Brunschwig Christel , Taylor Dale , van der Westhuyzen Renier , Street Leslie J. , Basarab Gregory S. , Chibale Kelly 
Published: August 2024

ABSTRACT

UCT594 is a 2-aminopyrazine carboxylic acid
Plasmodium
phosphatidylinositol 4-kinase inhibitor with potent asexual blood-stage activity, the potential for interrupting transmission, as well as liver-stage activities. Herein, we investigated pharmacokinetic/pharmacodynamic (PK/PD) relationships relative to blood-stage activity toward predicting the human dose. Dose-fractionation studies were conducted in the
Plasmodium falciparum
NSG mouse model to determine the PK/PD indices of UCT594, using the
in vivo
minimum parasiticidal concentration as a threshold. UCT594 demonstrated concentration-dependent killing in the
P. falciparum
-infected NSG mouse model. Using this data and the preclinical pharmacokinetic data led to a low predicted human dose of <50 mg. This makes UCT594 an attractive potential antimalarial drug.
Host cell-specific metabolism of linoleic acid controls
Toxoplasma gondii
growth in cell culture
Authors: Hryckowian Nicole D. , Ramírez-Flores Carlos J. , Zinda Caitlin , Park Sung Chul , Kelty Martin T. , Knoll Laura J. 
Published: August 2024

ABSTRACT

The obligate intracellular parasite
Toxoplasma gondii
can infect and replicate in any warm-blooded cell tested to date, but much of our knowledge about
T. gondii
cell biology comes from just one host cell type: human foreskin fibroblasts (HFFs). To expand our knowledge of host–parasite lipid interactions, we studied
T. gondii
in intestinal epithelial cells, the first site of host–parasite contact following oral infection and the exclusive site of parasite sexual development in feline hosts. We found that highly metabolic Caco-2 cells are permissive to
T. gondii
growth even when treated with high levels of linoleic acid (LA), a polyunsaturated fatty acid (PUFA) that kills parasites in HFFs. Caco-2 cells appear to sequester LA away from the parasite, preventing membrane disruptions and lipotoxicity that characterize LA-induced parasite death in HFFs. Our work is an important step toward understanding host–parasite interactions in feline intestinal epithelial cells, an understudied but important cell type in the
T. gondii
life cycle.
Influenza virus antibodies inhibit antigen-specific
de novo
B cell responses in mice
Authors: Goodwin Eileen , Gibbs James S. , Yewdell Jonathan W. , Eisenlohr Laurence C. , Hensley Scott E. 
Published: August 2024

ABSTRACT

Antibody responses to influenza vaccines tend to be focused on epitopes encountered during prior influenza exposures, with little production of
de novo
responses to novel epitopes. To examine the contribution of circulating antibodies to this phenomenon, we passively transferred a hemagglutinin (HA)-specific monoclonal antibody (mAb) into mice before immunizing with whole inactivated virions. The HA mAb inhibited
de novo
HA-specific antibodies, plasmablasts, germinal center B cells, and memory B cells, while responses to a second antigen in the vaccine, neuraminidase (NA), were uninhibited. The HA mAb potently inhibited
de novo
antibody responses against epitopes near the HA mAb binding site. The HA mAb also promoted IgG1 class switching, an effect that, unlike the inhibition of HA responses, relied on signaling through Fc-gamma receptors. These studies suggest that circulating antibodies inhibit
de novo
B cell responses in an antigen-specific manner, which likely contributes to differences in antibody specificities elicited during primary and secondary influenza virus exposures.

IMPORTANCE

Most humans are exposed to influenza viruses in childhood and then subsequently exposed to antigenically drifted influenza variants later in life. It is unclear if antibodies elicited by earlier influenza virus exposures impact immunity against new influenza virus strains. Here, we used a mouse model to investigate how an anti-hemagglutinin (HA) monoclonal antibody (mAb) affects
de novo
B cell and antibody responses to the protein targeted by the monoclonal antibody (HA) and a second protein not targeted by the monoclonal antibody [neuraminidase (NA)]. Collectively, our studies suggest that circulating anti-influenza virus antibodies can potently modulate the magnitude and specificity of antibody responses elicited by secondary influenza virus exposures.
A reporter Oropouche virus expressing ZsGreen from the M segment enables pathogenesis studies in mice
Authors: Gunter Krista , Omoga Dorcus , Bowen James M. , Gonzalez Lorimar Robledo , Severt Sydney , Davis Mackenzie , Szymanski Megan , Sandusky George , Duprex W. Paul , Tilston-Lunel Natasha L. 
Published: August 2024

ABSTRACT

Oropouche fever caused by Oropouche virus (OROV) is a significant zoonosis in Central and South America. Despite its public health significance, we lack high-throughput diagnostics, therapeutics, and a comprehensive knowledge of OROV biology. Reporter viruses are valuable tools to rapidly study virus dynamics and develop neutralization and antiviral screening assays. OROV is a tri-segmented bunyavirus, which makes generating a reporter virus challenging, as introducing foreign elements into the viral genome typically affects fitness. We previously demonstrated that the non-structural gene NSm on the OROV medium (M) segment is non-essential for replication
in vitro
. Taking advantage of this, we have now generated a recombinant OROV expressing fluorescent protein ZsGreen in place of NSm. This reporter OROV is both stable and pathogenic in IFNAR
-/-
mice and provides a powerful tool for OROV pathogenesis studies and assay development.

IMPORTANCE
Emerging and reemerging infectious agents such as zoonotic bunyaviruses are of global health concern. Oropouche virus (OROV) causes recurring outbreaks of acute febrile illness in the Central and South American human populations. Biting midges are the primary transmission vectors, whereas sloths and non-human primates are their reservoir hosts. As global temperatures increase, we will likely see an expansion in arthropod-borne pathogens such as OROV. Therefore, developing reagents to study pathogen biology to aid in identifying druggable targets is essential. Here, we demonstrate the feasibility and use of a fluorescent OROV reporter in mice to study viral dynamics and pathogenesis. We show that this reporter OROV maintains characteristics such as growth and pathogenicity similar to the wild-type virus. Using this reporter virus, we can now develop methods to assist OROV studies and establish various high-throughput assays.
The cellular protein phosphatase 2A is a crucial host factor for Marburg virus transcription
Authors: von Creytz Isabel , Rohde Cornelius , Biedenkopf Nadine 
Published: August 2024

ABSTRACT

Little is known regarding the molecular mechanisms that highly pathogenic Marburg virus (MARV) utilizes to transcribe and replicate its genome. Previous studies assumed that dephosphorylation of the filoviral transcription factor VP30 supports transcription, while phosphorylated VP30 reduces transcription. Here, we focused on the role of the host protein phosphatase 2A (PP2A) for VP30 dephosphorylation and promotion of viral transcription. We could show that MARV NP interacts with the subunit B56 of PP2A, as previously shown for the Ebola virus, and that this interaction is important for MARV transcription activity. Inhibition of the interaction between PP2A and NP either by mutating the B56 binding motif encoded on NP, or the use of a PP2A inhibitor, induced VP30 hyperphosphorylation, and as a consequence a decrease of MARV transcription as well as viral growth. These results suggest that NP plays a key role in the dephosphorylation of VP30 by recruiting PP2A. Generation of recombinant (rec) MARV lacking the PP2A-B56 interaction motif on NP was not possible suggesting an essential role of PP2A-mediated VP30 dephosphorylation for the MARV replication cycle. Likewise, we were not able to generate recMARV containing VP30 phosphomimetic mutants indicating that dynamic cycles of VP30 de- and rephosphorylation are a prerequisite for an efficient viral life cycle. As the specific binding motifs of PP2A-B56 and VP30 within NP are highly conserved among the filoviral family, our data suggest a conserved mechanism for filovirus VP30 dephosphorylation by PP2A, revealing the host factor PP2A as a promising target for pan-filoviral therapies.

IMPORTANCE
Our study elucidates the crucial role of host protein phosphatase 2A (PP2A) in Marburg virus (MARV) transcription. The regulatory subunit B56 of PP2A facilitates VP30 dephosphorylation, and hence transcription activation, via binding to NP. Our results, together with previous data, reveal a conserved mechanism of filovirus VP30 dephosphorylation by host factor PP2A at the NP interface and provide novel insights into potential pan-filovirus therapies.