bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolome profiling and transcriptome analysis filling the early crucial missing steps of piperine biosynthesis in Piper nigrum L.
Authors: Lv Yuanyuan , Zhu Jinjin , Huang Sihui , Xing Xiaoli , Zhou Shen , Yao Hui , Yang Zhuang , Liu Ling , Huang Sishu , Miao Yuanyuan , Liu Xianqing , Fernie Alisdair R. , Ding Yuanhao , Luo Jie 
Published: September 2023

SUMMARYBlack pepper (Piper nigrum L.), the world renown as the King of Spices, is not only a flavorsome spice but also a traditional herb. Piperine, a species‐specific piper amide, is responsible for the major bioactivity and pungent flavor of black pepper. However, several key steps for the biosynthesis of piperoyl‐CoA (acyl‐donor) and piperidine (acyl‐acceptor), two direct precursors for piperine, remain unknown. In this study, we used guilt‐by‐association analysis of the combined metabolome and transcriptome, to identify two feruloyldiketide‐CoA synthases responsible for the production of the C5 side chain scaffold feruloyldiketide‐CoA intermediate, which is considered the first and important step to branch metabolic fluxes from phenylpropanoid pathway to piperine biosynthesis. In addition, we also identified the first two key enzymes for piperidine biosynthesis derived from lysine in P. nigrum, namely a lysine decarboxylase and a copper amine oxidase. These enzymes catalyze the production of cadaverine and 1‐piperideine, the precursors of piperidine. In vivo and in vitro experiments verified the catalytic capability of them. In conclusion, our findings revealed enigmatic key steps of piperine biosynthetic pathway and thus provide a powerful reference for dissecting the biosynthetic logic of other piper amides.
The impact of acute and chronic stress on gastrointestinal physiology and function: a microbiota–gut–brain axis perspective
Authors: Leigh Sarah‐Jane , Uhlig Friederike , Wilmes Lars , Sanchez‐Diaz Paula , Gheorghe Cassandra E. , Goodson Michael S. , Kelley‐Loughnane Nancy , Hyland Niall P. , Cryan John F. , Clarke Gerard 
Published: September 2023

AbstractThe physiological consequences of stress often manifest in the gastrointestinal tract. Traumatic or chronic stress is associated with widespread maladaptive changes throughout the gut, although comparatively little is known about the effects of acute stress. Furthermore, these stress‐induced changes in the gut may increase susceptibility to gastrointestinal disorders and infection, and impact critical features of the neural and behavioural consequences of the stress response by impairing gut–brain axis communication. Understanding the mechanisms behind changes in enteric nervous system circuitry, visceral sensitivity, gut barrier function, permeability, and the gut microbiota following stress is an important research objective with pathophysiological implications in both neurogastroenterology and psychiatry. Moreover, the gut microbiota has emerged as a key aspect of physiology sensitive to the effects of stress. In this review, we focus on different aspects of the gastrointestinal tract including gut barrier function as well as the immune, humoral and neuronal elements involved in gut–brain communication. Furthermore, we discuss the evidence for a role of stress in gastrointestinal disorders. Existing gaps in the current literature are highlighted, and possible avenues for future research with an integrated physiological perspective have been suggested. A more complete understanding of the spatial and temporal dynamics of the integrated host and microbial response to different kinds of stressors in the gastrointestinal tract will enable full exploitation of the diagnostic and therapeutic potential in the fast‐evolving field of host–microbiome interactions.
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Conformal Geometric Algebra–Based Geometric Modeling Method for Forward Displacement Analysis of 6-4 Stewart Platforms
Authors: Zhu Ganmin , Wei Shimin , Li Duanling , Wang Yingli , Liao Qizheng 
Published: September 2023

Abstract
This paper presents a novel geometric modeling method for direct displacement analysis of 6-4 Stewart platforms based on conformal geometric algebra (CGA). First, a geometric constraint relationship of four lines and a plane intersecting at a point is published. Second, a new coordinate-invariant geometric constraint equation of 6-4 Stewart platforms is deduced by CGA operation. Third, five polynomial equations are established by CGA theory. Fourth, based on the above six equations, a 5 × 5 Sylvester’s matrix is formulated by using Sylvester’s Dialytic elimination method and Gröbner bases method under the graded reverse lexicographical order. Finally, the coordinates of four points on the moving platform are revealed. Besides, a numerical example is used to prove the validity of the proposed method. The novelty of this study is that a whole geometric modeling method by geometric constraint relationship of four lines and a plane intersecting at a point is put forward under the CGA framework, which has good intuition and offers a novel idea for solving the other complex mechanisms. At the same time, Sylvester’s matrix constructed by this method is the smallest one in the known literature for forward displacement analysis of 6-4 Stewart platforms.
Methodology and Validation of Surge Modeling in a Three-Shaft Compression System
Authors: Zhao Fanzhou , Moreno Jose , Dodds John , Vahdati Mehdi 
Published: September 2023

Abstract
In this paper an efficient numerical strategy for computational fluid dynamics (CFD) simulation of surge events in a three-shaft engine compression system is presented. Numerical results are compared against measured data and the sources of discrepancies and uncertainties are addressed. It is discovered that the engine bleed system has a major impact in reducing the aerodynamic loading during surge in the core system. To the best knowledge of the authors, this is the first time that such a complex CFD computation is attempted and compared against real engine measured data and will provide valuable information to other CFD users as well as gas turbine manufacturers.
Thermo-Economic Assessment of Pumped Thermal Electricity Storage Systems Employing Reversible Turbomachinery
Authors: Parisi Simone , Desai Nishith Babubhai , Haglind Fredrik 
Published: September 2023

Abstract
The objective of this paper is to assess the thermo-economic performance of different cycle configurations for pumped thermal electricity storage (PTES), including the effects of charging electricity cost. Reversible turbomachinery is employed to reduce the capital cost. Brayton cycles with different working fluids and a subcritical Rankine cycle operating with ammonia are compared. Liquid thermal energy storage systems are used. For the Brayton cycle, also packed bed storage systems are considered as an alternative.
A new cost correlation for turbomachines, initially developed for organic Rankine cycles, is adapted for compressors and reversible machines. This correlation is based on the number of stages and physical size of the machine, which are estimated considering thermodynamic as well as mechanical limitations on the enthalpy difference that can be attained per stage.
The results indicate that for a plant size of 50 MW and a discharge duration of 8 hours, the Brayton system with liquid storage and helium as a working fluid has the lowest levelized cost of storage at 0.138 $/kWh, mainly due to the high thermal conductivity of the fluid. Packed bed systems were found to be more expensive than liquid storage systems due to the large cost of the pressure vessels, with cost parity reached at a discharge duration of 4 hours. However, at this duration lithium ion batteries are likely to be cheaper. The results suggest that the levelized cost of storage for the Rankine cycle is slightly higher, 0.151 $/kWh. In addition, the Rankine cycle has disadvantages related to the higher storage volume and less flexibility for part load operation.
Line Chilldown and Flow Boiling Heat Transfer Characteristics of Stainless Steel Tubes
Authors: Narayanan Jayachandran K. , Shingote Chinmay , Qiu Yue , Hartwig Jason W. , Mackey Jeffrey R. , Kassemi Mohammad , Kharangate Chirag R. 
Published: September 2023

Abstract
As part of the ongoing efforts to develop and test a two-phase flow chilldown experimental setup onboard the International Space Station (ISS), experiments are conducted to analyze the line chilldown and flow boiling heat transfer characteristics of SS-316 using a simulant fluid PF-5060 in this study. The cryogenic transfer line chilldown process is pre-dominated by the film boiling regime for most of the duration followed by transition and nucleate boiling regimes. The line chilldown tests performed in this study are designed to mimic the cryogenic transfer line chilldown by heating the tubes to around 250 °C and then allowing the PF-5060 liquid flow to cool down the tubes. The test module consists of the main heated section, and a bypass section to maintain the flow rate while the test section preheating is undergoing. The main heating section is 60 cm long with wall temperature measurements at top and bottom sides of the tubes placed at equal distances. A fibre-glass insulated Nichrome tape heater achieves the desired initial temperature conditions, and a three-way valve activates to divert flow from the bypass section to the main test section when all the wall thermocouples read 250 °C or above. The present experimental design captured the entire chilldown curve from film boiling to single phase liquid regions.
Experimental Study of Enhanced Heat Transfer in Phase Change Material Based Thermal Energy Storage in Compact Heat Exchangers
Authors: Kannan Sarath , Jog Milind A. , Manglik Raj M. 
Published: September 2023

Abstract
Experimental data for the performance of a novel ultracompact thermal energy storage (TES) heat exchanger, designed as a micro-channel finned-tube exchanger are presented. A salt hydrate phase change material (PCM), Lithium Nitrate Trihydrate (LiNO3·3H2O; Tsf = 30°C, hsf = 274 kJ/kg), was encased on the fin side with water as the heat-cooling fluid. The TES performance was characterized experimentally to establish: (a) average heat transfer rates and power density with 10 and 24 fins/inch heat exchanger designs, and (b) TES reliability under thermal cycling field conditions. With high average heat transfer coefficients (Upcm = 100–500 W/m2K), a substantially high power density is obtained (∼ 367 kW/m3 during freezing) primarily due to the reduction in the PCM encasement length scale (L &lt; 3 mm). In the thermal cycling test, the TES was subjected to accelerated heating and cooling cycles under typical arid region conditions (diurnal variation between 42°C–25°C). Employing the self-seeding method to obviate subcooling, the TES was found to exhibit stable long-cycle operation with very high-power density. The results clearly establish that highly compact heat exchangers used as TES units are significantly superior and attractive alternatives to conventional ones.
Composite Phase Change Material With Metal Foam in Shell and Convergent Tube Thermal Energy Storage Systems
Authors: Buonomo Bernardo , Golia Maria Rita , Manca Oronzio , Nardini Sergio , Plomitallo Renato Elpidio 
Published: September 2023

Abstract
In order to decrease the negative effects on the environment and to handle the problem of a temporal and methodological mismatch between the energy required and the energy produced, energy storage systems have become highly relevant. In the proposed investigation, a simulation on a vertical shell and convergent tube geometry at different inclination angles composed of metal foam filled with a phase change material (PCM) is performed. The aluminum foam is used as porous media filled with pure paraffin wax as the PCM. The top, bottom, and external surfaces of the hollow cylinder are thought to be adiabatic, whereas the inner surface temperature is supposed to be constantly above the PCM melting point. Darcy-Forchheimer model is used to analyze the aluminum foam saturated with paraffin under the assumption of the local thermal non-equilibrium (LTNE), while the enthalpy-porosity theory is used to represent the phase change process in paraffin wax. Ansys-Fluent commercial code is used to perform the numerical solutions of the governing equations. The results of numerical simulations are shown as a function of time and are reported in terms of melting time, average temperature, and specific enthalpy. They show that the higher is the inclination angle, the faster is the system to reach the maximum energy stored. The converging system reaches the maximum energy storable faster than the diverging one.
A Bayesian Spatio-Temporal Modeling Approach to the Inverse Heat Conduction Problem
Authors: Olabiyi Ridwan , Pandey Hari , Hu Han , Iquebal Ashif 
Published: September 2023

Abstract
A wide range of science and engineering problems involve inferring the system behavior and the physical models from indirect observations. These are known as inverse problems. Unlike forward problems (predictive models), inverse problems are difficult to solve due to ill-posedness arising from one or more of non-existence, non-uniqueness (existence of many solutions), or instability (small perturbations in the measurements emerging from noise could lead to large changes in the solution). Therefore, direct inversion of the inverse problem in complex real-world systems is impractical. Several modeling approaches have been developed and adopted in the literature. However, the existing approaches do not consider spatio-temporal relationships. Meanwhile, various real systems and processes exist whose inverse problems can be comfortably modeled using spatio-temporal modeling techniques. We present a spatio-temporal inverse model considering interaction effects for modeling this type of inverse problem. We adopted a Bayesian inference framework for the subsequent parameter estimation problem and developed a Gibbs sampling algorithm to sample from the posterior distribution of the parameter of interest. Finally, we evaluate the proposed modeling technique and solution framework using several case studies of inverse problems in diverse heat conduction domains. Compared with conventional methods, the proposed framework performs better and can be adopted for solving inverse problems with spatio-temporal properties in various scientific and engineering domains.
Highly Trained Biathletes With a Fast-Start Pacing Pattern Improve Time-Trial Skiing Performance by Pacing More Evenly
Authors: Losnegard Thomas , Lund-Hansen Magne , Stubbe Erland Vedeler , Granrud Even Dahlen , Luchsinger Harri , Sandbakk Øyvind , Kocbach Jan 
Published: September 2023

Purpose: In sprint biathlon, a J-shaped pacing pattern is commonly used. We investigated whether biathletes with a fast-start pacing pattern increase time-trial skiing and shooting performance by pacing more evenly. Methods: Thirty-eight highly trained biathletes (∼21 y, 27 men) performed an individual 7.5 (3 × 2.5 km for women) or 10-km (3 × 3.3 km for men) time trial on roller skis with a self-selected pacing strategy (day 1). Prone (after lap 1) and standing shooting (after lap 2) stages were performed using paper targets. Based on their pacing strategy in the first time trial (ratio between the initial ∼800-m segment pace on lap 1 and average ∼800-m segment pace on laps 1–3), participants were divided into an intervention group with the fastest starting pace (INT, n = 20) or a control group with a more conservative starting pace (CON, n = 18). On day 2, INT was instructed to reduce their starting pace, while CON was instructed to maintain their day 1 strategy. Results: INT increased their overall time-trial performance more than CON from day 1 to day 2 (mean ± 95% CI; 1.5% ± 0.7% vs 0.0% ± 0.9%, P = .02). From day 1 to day 2, INT reduced their starting pace (5.0% ± 1.5%, P < .01), with reduced ratings of perceived exertion during lap 1 (P < .05). For CON, no change was found for starting pace (−0.8% ± 1.2%) or ratings of perceived exertion between days. No differences were found for shooting performance for either group. Conclusion: Highly trained biathletes with a pronounced fast-start pattern improve skiing performance without any change in shooting performance by pacing more evenly.
Developing Coaches’ Knowledge of the Athlete–Coach Relationship Through Formal Coach Education: The Perceptions of Football Association Coach Developers
Authors: Newland Andrew , Cronin Colum , Cook Gillian , Whitehead Amy 
Published: September 2023

Developing high-quality athlete–coach (A–C) relationships improves both athlete performance and well-being. However, content relating to the A–C relationship has been underrepresented within coach education. The study evaluates how coaches completing the English Football Association’s Union of European Football Associations A and B licenses develop knowledge of the A–C relationship. It does so by drawing on the perspectives of those who design and deliver the courses. Semistructured interviews were completed with nine experienced Football Association coach developers alongside a document analysis of seven key course documents. Data were analysed through an inductive thematic analysis and five themes were generated: (a) coach developers understand that the A–C relationship is built on trust, care, and hard and soft interpersonal approaches; (b) the triad of knowledge impacts on the A–C relationship, not just interpersonal knowledge; (c) the A–C relationship is not meaningfully addressed in the formalised course content; (d) in situ visits provide an effective medium to develop knowledge of the A–C relationship; and (e) the assessment framework does not align with the formalised course content. Findings demonstrate, despite a diversification in content, the A–C relationship is introduced in a superficial manner. Future research should clarify the knowledge coaches require to develop high-quality A–C relationships within a high-performance footballing context.
Novel non-HAP class A HBV capsid assembly modulators have distinct
in vitro
and
in vivo
profiles
Authors: Vanrusselt Hannah , Kum Dieudonné Buh , Taverniti Valerio , Liu Cheng , Acosta Sanchez Abel , Corthout Nikky , Munck Sebastian , Baumert Thomas F. , Beigelman Leonid , Blatt Lawrence M. , Symons Julian A. , Deval Jerome , Raboisson Pierre , Verrier Eloi R. , Jekle Andreas , Vendeville Sandrine , Debing Yannick 
Published: September 2023

ABSTRACT

Capsid assembly modulators (CAMs) are a novel class of therapeutic small molecules with the potential to address the continued global challenge posed by chronic hepatitis B (CHB). Class A CAMs (CAM-As) are particularly attractive because they induce loss of hepatitis B virus (HBV)-infected hepatocytes in animal models. All CAM-As described to date are heteroaryldihydropyrimidines (HAPs) which come with several drawbacks. Here, we report on the first non-HAP CAM-As ALG-005398 and ALG-005863 and provide a detailed
in vitro
intracellular characterization. These non-HAP CAM-As are potent inhibitors of HBV DNA production and also block the establishment of cccDNA. Non-HAP CAM-As can be classified into two distinct profiles: CAM-A
i
and CAM-A
t
, which are in turn differentiated from the HAP CAM-A
h
profile. CAM-A
i
molecules induce larger and more irregular capsids in electron microscopy and cellular HBV core protein (HBc) staining, whereas CAM-A
t
-induced capsids and aggregates are smaller but more numerous. CAM-A
i
and CAM-A
t
also induce a different subnuclear localization (no co-localization with promyelocytic leukemia bodies) and show a lower propensity to CAM-A-induced HBc-dependent cell death compared to CAM-A
h
. CAM-A
t
s ALG-005398 and ALG-006162 showed steady reductions of circulating HBsAg and HBeAg with minimal alanine aminotransferase (ALT) elevation in the adeno-associated virus (AAV)-HBV mouse model, accompanied by loss of the AAV-HBV episome and infected hepatocytes. Moreover, these effects were sustained for at least 13 weeks after end of treatment. The differentiated mechanism of action and sustained
in vivo
response make non-HAP CAM-As a promising potential component of future functional cure regimens for CHB patients.

IMPORTANCE
Chronic hepatitis B is the most important cause of liver cancer worldwide and affects more than 290 million people. Current treatments are mostly suppressive and rarely lead to a cure. Therefore, there is a need for novel and curative drugs that target the host or the causative agent, hepatitis B virus itself. Capsid assembly modulators are an interesting class of antiviral molecules that may one day become part of curative treatment regimens for chronic hepatitis B. Here we explore the characteristics of a particularly interesting subclass of capsid assembly modulators. These so-called non-HAP CAM-As have intriguing properties in cell culture but also clear virus-infected cells from the mouse liver in a gradual and sustained way. We believe they represent a considerable improvement over previously reported molecules and may one day be part of curative treatment combinations for chronic hepatitis B.
Conditional replication and secretion of hepatitis B virus genome uncover the truncated 3′ terminus of encapsidated viral pregenomic RNA
Authors: Shen Sheng , Liu Wendong , Zeng Ge , Liang Hongyan , Yu Xiaoyang , Zhang Hu , Sun Jian , Guo Haitao 
Published: September 2023

ABSTRACT
Hepatitis B virus (HBV) pregenomic RNA (pgRNA) is packaged into capsid where reverse transcription takes place to synthesize viral DNA genome, and the encapsidated pgRNA is the predominant species of serum HBV RNA in patients as a serological biomarker. In this study, by utilizing various conditional HBV replication and secretion systems, we analyzed the intracellular and extracellular capsid pgRNA and revealed that the 3′ terminus of capsid pgRNA is scatteredly distributed between DR2 and poly(A) tail, except that the viral polymerase priming-defective mutant Y63D retained the sequence upstream of 3′ DR1. Mechanistically, the heterogeneity of capsid RNA 3′ terminus is due to the endogenous viral RNaseH activity during reverse transcription and exogenous MNase digestion during capsid RNA isolation; cellular ribonucleases may also participate in this process as the Y63D pgRNA 3′ terminus in the immunoprecipitated capsid without prior MNase treatment remains truncated into 3′ DR1. The major pgRNA splicing variant 1 of 2.1 kb and the artificial 3′ DR1 and ε deletion mutants also possess a truncated 3′ end of capsid RNA, indicating that the underrepresentation of the 3′ end of encapsidated pgRNA is independent of pgRNA length or 3′ terminal sequences. Altogether, our study suggests that the 3′ region of HBV capsid pgRNA downstream of 3′ DR1 is likely positioned outside of the capsid or loosely encapsulated, and thus is ribonuclease accessible. Furthermore, the detailed features of capsid pgRNA 3′ terminus will shed light on HBV pgRNA encapsidation and reverse transcription and aid the development of better diagnostics of serum HBV RNA.

IMPORTANCE
The biogenesis and clinical application of serum HBV pgRNA have been a research hotspot in recent years. This study further characterized the heterogeneity of the 3′ terminus of capsid RNA by utilizing a variety of experimental systems conditionally supporting HBV genome replication and secretion, and reveal that the 3′ truncation of capsid pgRNA is catalyzed by cellular ribonuclease(s) and viral RNaseH at positions after and before 3′ DR1, respectively, indicating the 3′ DR1 as a boundary between the encapsidated portion of pgRNA for reverse transcription and the 3′ unprotected terminus, which is independent of pgRNA length and the 3′ terminal sequence. Thus, our study provides new insights into the mechanism of pgRNA encapsidation and reverse transcription, as well as the optimization of serum HBV RNA diagnostics.