bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated design of hydrogen-fired turboprop and commuter aircraft
Authors:   Mälardalen University, Bermperis Dimitrios , Vouros Stavros ,   Mälardalen University, Kyprianidis Konstantinos ,   Mälardalen University
Published: October 2024

Hydrogen for propulsion could lead the industry to achieving the set environmental goals. This work performs a comparative cycle and engine design for a hydrogen-fired and conventional Jet-A burning configuration. Aircraft design and mission performance complete the conceptual design loop. A 19-passenger small commuter aircraft is investigated. A multi-disciplinary framework is developed for the study. A multipoint synthesis scheme is employed for conventional, and hydrogen powered engine assessment. Cryogenic hydrogen tanks and a thermal management system are integrated in the aircraft and their volumetric and gravimetric impact are assessed showing an expected 13% increase of aircraft mass. Direct combustion of hydrogen leads to more efficient and smaller turboprop engines due to the increased specific heat capacity of combustion products. Engine cycle design reveals that the optimum aircraft energy consumption lies at an overall pressure ratio at cruise of 15 and a combustor outlet temperature of 1400 K. However, the hydrogen tanks and fuel conditioning system increase aircraft mass sufficiently to offset the fuel consumption benefits resulting in increased block energy demand between the H2 and Jet-A configurations by 3-4%. This work reveals a lower bound of H2 fuel system gravimetric performance due to aircraft weight certification and highlights the design guidelines for the engine, aircraft, and storage system.
Model development of novel wastegate valve design of double scroll turbines utilised for engine-tailored assessment
Authors:   Imperial College London, Carola Freytag Carola , Pablo Ale Pablo ,   Imperial College London, Barrera-Medrano Maria E ,   Imperial College London, Martinez-Botas Ricardo F ,   Imperial College London, Jinnai Yasuaki ,   Mitsubishi Heavy Industries
Published: October 2024

Despite the shift towards electric vehicles, there is a pressing need to develop efficient solutions to enhance turbocharger performance. For this reason, a novel wastegate design methodology was developed for this research. The concept allows scroll connection to take place for double-entry turbines. The key challenge is to create a design that maintains scroll separation at low engine RPM to achieve high torque, allowing scroll connection at higher engine RPM and reducing the back pressure. A detailed analysis was conducted based on the results of both experimental and computational (CFD) evaluations, and the data was used to enable 1D system-level assessment and optimise the design. This paper develops a new 1D methodology to characterise wastegate and scroll connection interaction. The approach is calibrated against a large data set using a ”scroll–bypass” method and validated against full-stage steady and unsteady data for different degrees of scroll connection. The final stage relates to optimising the scroll connection of a double scroll turbine model in GT-Power for fuel consumption. This optimisation is carried out over key operating points across the engine map.
CFD Assessment of a Novel Dynamic Formulation of the Double Multiple Stream-Tube Model for Floating Vertical-Axis Wind Turbines
Authors:   Department of Energy, Politecnico di Milano, Sanvito Andrea G. , Tomassoni Claudio ,   Department of Energy, Politecnico di Milano, Persico Giacomo ,   Department of Energy, Politecnico di Milano, Dossena Vincenzo ,   Department of Energy, Politecnico di Milano
Published: October 2024

The objective of this study is to enhance the formulation of a validated 3D Blade Element Momentum model designed for VAWTs in floating offshore scenarios, considering surge platform motion. The aerodynamic modelling of the rotor relies on the traditional Double Multiple Stream Tube Model, bolstered by high-order corrections addressing flow curvature, dynamic stall, tip losses, and strut passive losses. The innovative model incorporates a time-resolved dynamic formulation of a three-dimensional Blade Element Momentum model, featuring a specific treatment of the induction perceived by the blades working in the downstream phase. The validation process for the Dynamic Double Multiple Stream Tube Model involves a comparison with Computational Fluid Dynamics simulations of a 2D section of the VAWT in both fixed-bottom and platform surge displacement. The cross-comparison between low and high fidelity codes shows several insights in the modelling of the platform surge: despite the challenge to resolve correctly the rotor-resolved torque with a low-fidelity model, both Double Multiple Steamtube and Computational Fluid Dynamics predict a very close aerodynamic behaviour of the power peaks under the effect of the apparent wind variation induced by the surge platform motion. The main difference in the overall power coefficient prediction resides into the inherent limit of Double Multiple Stream Tube model to resolve the flow around the blades, essential to correctly estimate the interaction of the shed vortices between the blades. A further finding of the paper demonstrates that Computational Fluid Dynamics tool is able to capture an increment of the average power coefficient by 4.5% with respect to fixed-bottom case.
A digital twin-oriented lightweight modeling approach for gas turbine performance degradation monitoring
Authors:   School of Mechanics and Aerospace Engineering Dalian University of Technology, Liu Yiyang , Jiang Xiaomo ,   School of Mechanics and Aerospace Engineering Dalian University of Technology, Wei Manman ,   School of Mechanics and Aerospace Engineering Dalian University of Technology, Ge Xin ,   School of Mechanics and Aerospace Engineering Dalian University of Technology
Published: October 2024

A gas turbine (GT) is usually operating under harsh environment such as high temperature, high pressure and high corrosion, resulting in the decreased efficiency and the increased failures. In the past decade predictive maintenance has become a promising tool to reduce maintenance cost, increase productivity and improve the efficiency and reliability of the GT system. However, this method usually requires the high-accuracy predictive analytics based on numerous multi-model data, which is quite challenging for a given machine. This paper presents a universal deep learning operator network as a lightweight modeling approach to integrate data-physics-AI for high-efficiency performance modeling of a heavy-duty gas turbine with limited data, towards the digital twin-oriented predictive maintenance. Data optimization is first conducted to produce the high-quality data for system modeling. The thermodynamic heat balance principle is then applied to model the performance of three subsystems and the entire system. A deep neural network operator model is developed as a lightweight approach to integrate the operating data and physics-based model for performance degradation simulation of the gas turbine in different scenarios. The model is integrated on a GT virtual reality platform to realize the DT-based performance degradation monitoring. The proposed methodology is illustrated with a real-world GT and event data.
Acceleration of High-Fidelity Simulation for Unsteady Flows with Low Reduced Frequency Using Harmonic Balance Method: Application for Airfoil Flows
Authors:   Department of Aeronautics and Astronautics, The University of Tokyo, Iwamoto Yuma , Teramoto Susumu ,   Department of Aeronautics and Astronautics, The University of Tokyo, Okamoto Koji ,   Department of Advanced Energy, The University of Tokyo
Published: October 2024

This paper presents an application of harmonic-balanced large-eddy simulation(HB-LES) to a transonic buffet flow around OAT15 airfoil. HB-LES is a novel numerical technique developed by the authors, which combines LES with the harmonic balance method using the difference in timescales between the periodic flow and the turbulent fluctuations to accelerates high-fidelity simulation of low reduced frequency unsteady flows. In HB-LES, both the periodic component and the turbulent fluctuations as well as their nonlinear mutual interaction are resolved by iterating short-time LES and harmonic balance method. Numerical results show that HB-LES predicted both the mean and fluctuation amplitude of pressure and velocity in the separated boundary layer quantitatively well. HB-LES successfully reproduced the unsteady behaviour of the shock-wave and the separated boundary layer reported in the conventional time-accurate Wall-Modeled LES. The computation time of HB-LES is reduced by a factor of 0.067 compared to the conventional time-accurate LES.
The role of corrugated impingement cooling geometries at high temperature ratios for future gas turbines
Authors:   Mitsubishi Heavy Industries, Ltd., Hatta Masayoshi , Merritt-Webster Thomas ,   University of Oxford, Rosic Budimir ,   University of Oxford
Published: October 2024

Gas turbines are likely to be crucial in decarbonisation through their role in the transition to sustainable fuels and for enabling flexible operation power stations. In designing for the new demands of future gas turbines, there is a drive to improve efficiency and reduce manufacturing cost. In order to improve efficiency, designers seek to reduce cooling air mass flow rate, resulting in high temperature ratios between the metal temperature and cooling air. Manufacturing cost can be lowered by reducing the dependence on film cooling, which also leads to higher temperature ratios. Impingement cooling is well-known as an effective heat transfer method, and it is commonly used to cool high temperature turbine components. A key problem for impingement cooling is that high temperature ratios negatively impacts jet performance. Literature shows that corrugated style impingement geometries are a reliable and effective way to manage crossflow in low temperature ratio conditions. This study numerically explores the application of corrugated geometries for a range of high temperature ratio and crossflow conditions. The study evaluates temperature ratios of 1.1 to 2.0 and uses a working fluid of air. Calculations are performed for a Reynolds number of 10,000 and an SST k- turbulence model is used. Impingement jet diameter, jet to jet pitch and distance from impingement plate to target plate are kept the same for each structure. Increasing temperature ratio is found to increase crossflow momentum and cause jet distortion, reducing performance of the flat plate geometry by up to 30%. By mitigating the detrimental effects of crossflow and restoring idealised impingement, corrugated geometries enhance the effectiveness of impingement cooling by up to 47% compared to the flat case at high temperature ratio and crossflow conditions.
PENGARUH BRAND IMAGE DAN KUALITAS PRODUK TERHADAP KEPUTUSAN PEMBELIAN MOBIL SUZUKI ALL NEW ERTIGA DI PT. SUZUKI AMM JOMBANG
Authors: Nahdliyah Ulfa , Irawati Winaika
Published: October 2024

Penelitian ini merupakan penelitian kuantitatif. Tujuan dari penelitian ini untuk mengetahui pengaruh brand image, dan kualitas produk terhadap keputusan pembelian. Populasi pada penelitian ini yaitu konsumen mobil Suzuki All New Ertiga di PT. Suzuki Abadi Megah Motor Jombang. Teknik pengambilan sampel menggunakan sampling jenuh dengan jumlah sampel sebanyak 50 konsumen. Teknik pengumpulan data menggunakan kuessioner yang telah diujikan validitas dan reliabilitas. Teknik analisis yang digunakan dalam penelitian ini yaitu analisis regresi linier berganda. Hasil penelitian uji t (parsial) menunjukkan bahwa variabel brand image (X1) memiliki pengaruh positif dan signifikan terhadap keputusan pembelian (Y) dengan tingkat signifikan 0,027 < 0,05, dan variabel kualitas produk (X2) memiliki pengaruh positif dan signifikan terhadap keputusan pembelian (Y) dengan nilai signifikansi sebesar 0,000 < 0,005. Hasil penelitian uji F menunjukkan hasil bahwa brand image/citra merek (X1) dan kualitas produk (X2) secara keseluruhan berpengaruh simultan dan signifikan terhadap keputusan pembelian. (Y) dibuktikan dengan nilai F sebesar 22,491 dan signifikansi 0,00  < 0,05.
PENGARUH DISPLAY PRODUK DAN HARGA TERHADAP KEPUTUSAN PEMBELIAN KONSUMEN PADA SAKINAH SUPERMARKET (STUDI KASUS PADA KONSUMEN SAKINAH SUPERMARKET SURABAYA)
Authors: Assyamsi Moch. Na’iem , Irawati Winaika
Published: October 2024

Penelitian ini bertujuan untuk mengetahui pengaruh display produk dan harga terhadap keputusan pembelian pada sakinah supermarket surabaya. Metode yang digunakan pada penelitian ini adalah metode penelitian kuantitatif. Populasi dalam penelitian ini adalah 100 responden. Teknik pengambilan sampel adalah menggunakan teknik non-probability sampling karena penulis tidak mengetahui jumlah populasi secara pasti dimana jumlah konsumen yang tidak terhitung jumlahnya.Hasil penelitian menunjukan bahwa: (1) display produk secara parsial berpengaruh positif signifikan terhadap variabel keputusan pembelian pada Sakinah Supermarket Surabaya, (2) harga berpengaruh positif dan signifikan terhadap Keputusan pembelian Pada Sakinah Supermarket Surabaya, (3) display produk dan harga secara simultan Berpengaruh terhadap Keputusan pembelian Pada Sakinah Supermarket Surabaya.
ANALISIS REVIEW FOOD VLOGGER DAN PERAN MEDIA SOSIAL DALAM MENINGKATKAN PRODUKTIVITAS MIE PEDAS KEDAI HANAMIE JOMBANG PADA PANDEMI COVID19
Authors: Kurniawan Gali
Published: October 2024

Tujuan penelitian ini untuk menganalisis review food vlogger dan peran media sosial dalam meningkatkan produktivitas mie pedas kedai hanamie jombang pada pandemi covid-19. Penelitian ini menggunakan jenis penelitian kualitatif dengan pendekatan deskriptif, dan pengumpulan data dilakukan menggunakan observasi, wawancara, kuesioner, serta triangulasi data. Sebagai subjek penelitian adalah konsumen Kedai Hanamie dengan keseluruhan 10 orang responden dari penyebaran angket dan 5 orang informan dari wawancara. Berdasarkan hasi penelitian yang diperoleh dari penyebaran angket bahwa terjadi peningkatan produktivitas pada Kedai Hanamie dengan indikator dari review food vlogger dan peran media sosial yang mempengaruhi. Berdasarkan hasil penelitian melalui wawancara didapatkan bahwa yang mempengaruhi informan dalam melakukan pembelian dan meningkatkan produktivitas pada Kedai Hanamie adalah review food vlogger dan peran iklan di media sosial.
PENGARUH KOMPENSASI DAN LINGKUNGAN KERJA TERHADAP KEPUASAN KERJA KARYAWAN PADA SAKINAH SUPERMARKET SURABAYA
Authors: Kamilah Niswatul , Laili Choirun Nisful
Published: October 2024

Penelitian ini bertujuan untuk mengetahui pengaruh kompensasi dan lingkungan kerja terhadap kepuasan kerja karyawan pada sakinah supermarket surabaya. Metode yang digunakan pada penelitian ini adalah metode penelitian kuantitatif. Populasi dalam penelitian ini adalah 56 responden. Teknik pengambilan sampel adalah menggunakan teknik sampel jenuh yang menjadikan seluruh populasi sebagai sampel. Hasil penelitian menunjukan bahwa: (1) Kompensasi secara parsial tidak berpengaruh signifikan terhadap variabel kepuasan kerja pada Sakinah Supermarket Surabaya, (2) Lingkungan Kerja berpengaruh berpengaruh signifikan terhadap Kepuasan Kerja Karyawan Pada Sakinah Supermarket Surabaya, (3) Kompensasi dan Lingkungan Kerja secara simultan Berpengaruh terhadap Kepuasan Kerja Karyawan Pada Sakinah Supermarket Surabaya
PROFIL PENGOBATAN KEMOTERAPI PADA PASIEN KANKER PAYUDARA DI RUMAH SAKIT UMUM DAERAH KOTA BOGOR PADA TAHUN 2022
Authors: Anjani Dwi Cahya  , Halimatushadyah Ernie , Sari Dwi Puspita , Ekasari Dian
Published: October 2024

Breast cancer is cancer that starts in the breast tissue, which consists of milk-producing glands (lobules) and ducts that connect the lobules to the nipple. One of the efforts to reduce the morbidity rate of breast cancer is chemotherapy. Chemotherapy involves the use of cytostatic drugs aimed at stopping the growth and spread of cancer cells. The purpose of this study was to determine the pattern of drug use and evaluation of drug use in breast cancer patients. The study was conducted observational with retrospective data collection. The research was conducted from May to June 2023. The number of samples was 96 samples with the method of purposive sampling technique using the slovin formula, the data were analyzed qualitatively. The results of the chemotherapy treatment profile using single therapy 9 patients (9.38%), combination therapy 87 patients (90.63%) with a combination chemotherapy regimen of Epirubicin and Cyclophosphamide followed by Paclitaxel as many as 50 patients (57.47%). Evaluation of appropriate patient (98.96%), appropriate indication (100%), appropriate drug (100%), appropriate dose (19.79%), inappropriate dose (20.83%), under dose (34.48%), over dose (25%).
Empirical validation of the use of projective techniques in psychological testing using Galois fields
Authors: Suleimenov Ibragim , Kostsova Mariya , Grishina Anastasiya , Matrassulova Dinara , Vitulyova Yelizaveta
Published: October 2024

It is shown that the problem of the adequacy of psychological testing methods, which are varieties of “projective techniques”, is far from being universally recognized. To solve this problem, we used an empirical method based on collecting of statistics of respondents’ answers, as well as a method of analyzing this statistics by means of representing permutations through functions taking values in Galois fields. Based on experimental data, it is shown that the distribution of respondents’ answers to a test in which they are asked to rank pictures in accordance with their own preferences is not homogeneous. Experimental data show that there are answer options that are statistically most common. An interpretation of testing is proposed in which passing the test is considered as “connecting” an external additional layer to the neural network formed by the respondent’s brain. In accordance with this interpretation, the most frequently occurring answer options can be considered as the basis for the formation of classification characteristics. It is shown that during using tests of this type it is advisable to take into account the code distances between the answer of a particular respondent and the codes corresponding to the most frequently occurring sequences. The possibilities of generating psychological tests directly based on experimental data and images generated by neural networks are discussed.
A time-calibrated phylogeny of the diversification of Holoadeninae frogs
Authors: Chaves Júlio C. M. , Hepp Fábio , Schrago Carlos G. , Mello Beatriz
Published: October 2024

The phylogeny of the major lineages of Amphibia has received significant attention in recent years, although evolutionary relationships within families remain largely neglected. One such overlooked group is the subfamily Holoadeninae, comprising 73 species across nine genera and characterized by a disjunct geographical distribution. The lack of a fossil record for this subfamily hampers the formulation of a comprehensive evolutionary hypothesis for their diversification. Aiming to fill this gap, we inferred the phylogenetic relationships and divergence times for Holoadeninae using molecular data and calibration information derived from the fossil record of Neobatrachia. Our inferred phylogeny confirmed most genus-level associations, and molecular dating analysis placed the origin of Holoadeninae in the Eocene, with subsequent splits also occurring during this period. The climatic and geological events that occurred during the Oligocene-Miocene transition were crucial to the dynamic biogeographical history of the subfamily. However, the wide highest posterior density intervals in our divergence time estimates are primarily attributed to the absence of Holoadeninae fossil information and, secondarily, to the limited number of sampled nucleotide sites.
A millifluidic bioreactor allows the long term culture of primary lymphocytes or CD34+ hematopoietic cells while allowing the detection of tumorigenic expansion
Authors: Ritter Paolo , Oliveto Stefania , Cordiglieri Chiara , Fasciani Alessandra , Di Buduo Christian Andrea , della Volpe Lucrezia , Bocconi Alberto , Conci Claudio , Miguel Carolina Paula , Di Micco Raffaella , Balduini Alessandra , Raimondi Manuela Teresa , Biffo Stefano
Published: October 2024

Long-term culture of primary lymphocytes and hematopoietic stem and progenitor cells (HSPCs) is pivotal to their expansion and study. Furthermore, genetic engineering of the above-mentioned primary human cells has several safety needs, including the requirement of efficient in vitro assays for unwanted tumorigenic events. In this work, we tested and optimized the Miniaturized Optically Accessible Bioreactor (MOAB) platform. The MOAB consists of a millifluidic cell culture device with three optically-accessible culture chambers. Inside the MOAB, we inserted a silk-based framework that resembles some properties of the bone marrow environment and cultivated in this device either CD4+ T lymphocytes isolated from healthy donor buffy coat or cord blood-derived hematopoietic CD34+ cells. A fraction of these cells is viable for up to 3 months. Next, we tested the capability of the MOAB to detect tumorigenic events. Serial dilutions of engineered fluorescent tumor cells were mixed with either CD4+ or CD34+ primary cells, and their growth was followed. By this approach, we successfully detected as little as 100 tumorigenic cells mixed with 100,000 primary cells. We found that non-tumorigenic primary cells colonized the silk environment, whereas tumor cells, after an adaptation phase, expanded and entered the circulation. We conclude that the millifluidic platform allows the detection of rare tumorigenic events in the long-term culture of human cells.
Potential of a novel brine-struvite-based growth medium for sustainable biomass and phycocyanin production by Arthrospira platensis
Authors: Ende Stephan S. W. , Beyer Albert S. , Ebaid Reham , Elshobary Mostafa , Almeida Mafalda C. , Couto Cynthia , Chew Kit W. , Schwenkler Tamara , Henjes Joachim
Published: October 2024

Nutrient recovery is crucial for sustainability as it helps to recycle valuable resources, reduce environmental pollution, and promote the efficient use of natural materials in various agricultural and industrial processes. The present study investigated the impact of using brine and struvite as sustainable nutrient sources on the growth and c-phycocyanin (C-PC) production by the cyanobacterium Arthrospira platensis. Three modified growth media were compared to the standard SAG-spirul medium under yellow-white light [YLT], and blue-white light [BLT]. In the modified medium BSI, a struvite solution was utilized to replace dipotassium phosphate, while diluted brine was used to replace NaCl and de-ionized H2O. For BSII, struvite and brine were used as in BSI, with elimination of the micronutrient from the solution. In BSIII, no other nutrient sources than bicarbonate-buffer were used in addition to struvite and brine. For each medium, A. platensis was cultivated and incubated under YLT or BLT till the stationary phase. The results showed that the combinations of brine and struvite did not have any significant negative impact on the growth rates in BSIII. However, adding struvite as a phosphorus source boosted C-PC production just as effectively as YLT, with boosting biomass yield, unlike when only BLT was used. In conclusion, the brine/struvite-based media resulted in high biomass productivity with higher C-PC yields, making it an ideal growth medium for commercial sustainable C-PC production.
Australia at an educational crossroads: special schools and inclusive education
Authors: Cumming Therese M. , Jolly Jennifer L. , Saint-James Aaron
Published: October 2024

The ongoing debate surrounding special schools and inclusive education in Australia has come to the forefront since the recommendations of the 2023 Royal Commission into Violence, Abuse, Neglect and Exploitation of People with Disability, where the Commissioners were split on the implementation of full educational inclusion and the elimination of special schools. The authors discuss the controversy surrounding segregated special education classes and schools, particularly considering the push for full inclusion. The concept of inclusion is examined through a brief review of national and international policies and academic and popular literature, including how the inclusion continuum is conceptualized by policymakers, academics, and families. Stakeholder perspectives on the complexities and challenges of implementing full inclusion in mainstream school settings offer differing experiences and opinions on what is possible. Lastly, by examining the nuances of the special school controversy, the authors provide recommendations on how best to meet the educational needs of all students, across the spectrum of abilities.
Transient voltage stability assessment and margin calculation based on disturbance signal energy feature learning
Authors: Chen Yan , Huang Zirui , Du Zhaobin , Zhong Guoduan , Gao Jiawei , Zhen Hongyue
Published: October 2024

With the increasing variation of the network topology and the high complexity of the processing measurement data, the transient voltage stability assessment of the new power system is facing significant challenges in low accuracy and high time costs. To address the shortcomings of the existing method and apply it to online assessment, this paper proposes an assessment method based on feature learning for disturbance signal energy (DSE) from bus voltages. Firstly, the relationship between DSE and system transient voltage stability is established, and the calculation of DSE from bus voltage time series is detailed. Subsequently, a transient voltage stability assessment method based on the ID3 Decision Tree algorithm and DSE is proposed. Finally, by employing the Support Vector Machine (SVM) to construct the optimal boundary in the feature space formed by the key buses, the transient voltage stability margin (TVSM) for specific scenarios is proposed. Simulation results on the IEEE 39-bus system demonstrate that the proposed method can rapidly and accurately assess the transient voltage stability of the system and calculate the stability margin, providing intuitive and interpretable results with high engineering application value.
TCRcost: a deep learning model utilizing TCR 3D structure for enhanced of TCR–peptide binding
Authors: Li Fan , Qian Xinyang , Zhu Xiaoyan , Lai Xin , Zhang Xuanping , Wang Jiayin
Published: October 2024

Introduction

Predicting TCR–peptide binding is a complex and significant computational problem in systems immunology. During the past decade, a series of computational methods have been developed for better predicting TCR–peptide binding from amino acid sequences. However, the performance of sequence-based methods appears to have hit a bottleneck. Considering the 3D structures of TCR–peptide complexes, which provide much more information, could potentially lead to better prediction outcomes.

Methods

In this study, we developed TCRcost, a deep learning method, to predict TCR–peptide binding by incorporating 3D structures. TCRcost overcomes two significant challenges: acquiring a sufficient number of high-quality TCR–peptide structures and effectively extracting information from these structures for binding prediction. TCRcost corrects TCR 3D structures generated by protein structure tools, significantly extending the available datasets. The main and side chains of a TCR structure are separately corrected using a long short-term memory (LSTM) model. This approach prevents interference between the chains and accurately extracts interactions among both adjacent and global atoms. A 3D convolutional neural network (CNN) is designed to extract the atomic features relevant to TCR–peptide binding. The spatial features extracted by the 3DCNN are then processed through a fully connected layer to estimate the probability of TCR–peptide binding.

Results

Test results demonstrated that predicting TCR–peptide binding from 3D TCR structures is both efficient and highly accurate with an average accuracy of 0.974 on precise structures. Furthermore, the average accuracy on corrected structures was 0.762, significantly higher than the average accuracy of 0.375 on uncorrected original structures. Additionally, the average root mean square distance (RMSD) to precise structures was significantly reduced from 12.753 Å for predicted structures to 8.785 Å for corrected structures.

Discussion

Thus, utilizing structural information of TCR–peptide complexes is a promising approach to improve the accuracy of binding predictions.
SARS-CoV-2 induced vitamin D deficiency and psychological stress: a manifestation of autoimmune disease onset
Authors: Alobaid Meshal A. , Alqabandi Bshaier S.
Published: October 2024

Introduction

The global SARS-CoV-2 pandemic significantly altered lifestyles, access to healthcare, and social interactions, introducing unprecedented physical and psychological stress all over the world. This study explores the relationship between psychological stress, vitamin D (Vit-D) levels, and autoimmune connective tissue diseases, including systemic lupus erythematosus, systemic sclerosis, polymyositis, dermatomyositis, and rheumatoid arthritis.

Methods

The analysis was based on over one million patient data points derived from anti-nuclear antibody (ANA) testing conducted both before and during the COVID-19 pandemic 2017-2021. In a subset of patients, longitudinal data were collected bi-yearly to yearly over 5-8 years using the same three-month criteria. The dataset was analyzed using GraphPad Prism9 using paired t-tests or ordinary one-way ANOVA with a significance threshold of p < 0.05 to ensure robust correlations between the variables.

Results

Data indicated that Vit-D levels peaked between 2017 and 2019 before declining, while ANA data demonstrated a rise in autoimmune connective tissue disease cases during the pandemic, reaching a peak in 2021. A clear correlation was observed, with autoimmune disease incidence increasing as Vit-D levels decreased. In-depth case analysis revealed that declining Vit-D levels preceded higher ANA titers and increased autoimmune disease severity, whereas improvements in Vit-D levels were associated with reduced ANA titers and less severe disease manifestations.

Conclusions

The findings suggest that maintaining mental health and ensuring adequate Vit-D supplementation could be essential strategies for mitigating autoimmune disease risks and maintaining immune stability, particularly in pandemic scenarios. Clinically, these results underscore the need for early interventions targeting both psychological well-being and Vit-D levels to reduce the burden of autoimmune diseases.
M protein ectodomain-specific immunity restrains SARS-CoV-2 variants replication
Authors: Tang Yibo , Tang Kaiming , Hu Yunqi , Ye Zi-Wei , Luo Wanyu , Luo Cuiting , Cao Hehe , Wang Ran , Yue Xinyu , Liu Dejian , Liu Cuicui , Ge Xingyi , Liu Tianlong , Chen Yaoqing , Yuan Shuofeng , Deng Lei
Published: October 2024

Introduction

The frequent occurrence of mutations in the SARS-CoV-2 Spike (S) protein, with up to dozens of mutations, poses a severe threat to the current efficacy of authorized COVID-19 vaccines. Membrane (M) protein, which is the most abundant viral structural protein, exhibits a high level of amino acid sequence conservation. M protein ectodomain could be recognized by specific antibodies; however, the extent to which it is immunogenic and provides protection remains unclear.

Methods

We designed and synthesized multiple peptides derived from coronavirus M protein ectodomains, and determined the secondary structure of specific peptides using circular dichroism (CD) spectroscopy. Enzyme-linked immunosorbent assay (ELISA) was utilized to detect IgG responses against the synthesized peptides in clinical samples. To evaluate the immunogenicity of peptide vaccines, BALB/c mice were intraperitoneally immunized with peptide-keyhole limpet hemocyanin (KLH) conjugates adjuvanted with incomplete Freund’s adjuvant (IFA). The humoral and T-cell immune responses induced by peptide-KLH conjugates were assessed using ELISA and ELISpot assays, respectively. The efficacy of the S2M2-30-KLH vaccine against SARS-CoV-2 variants was evaluated in vivo using the K18-hACE2 transgenic mouse model. The inhibitory effect of mouse immune serum on SARS-CoV-2 virus replication in vitro was evaluated using microneutralization assays. The subcellular localization of the M protein was evaluated using an immunofluorescent staining method, and the Fc-mediated antibody-dependent cellular cytotoxicity (ADCC) activity of the S2M2-30-specific monoclonal antibody (mAb) was measured using an ADCC reporter assay.

Results

Seroconversion rates for ectodomain-specific IgG were observed to be high in both SARS-CoV-2 convalescent patients and individuals immunized with inactivated vaccines. To assess the protective efficacy of the M protein ectodomain-based vaccine, we initially identified a highly immunogenic peptide derived from this ectodomain, named S2M2-30. The mouse serum specific to S2M2-30 showed inhibitory effects on the replication of SARS-CoV-2 variants in vitro. Immunizations of K18-hACE2-transgenic mice with the S2M2-30-keyhole limpet hemocyanin (KLH) vaccine significantly reduced the lung viral load caused by B.1.1.7/Alpha (UK) infection. Further mechanism investigations reveal that serum neutralizing activity, specific T-cell response and Fc-mediated antibody-dependent cellular cytotoxicity (ADCC) correlate with the specific immuno-protection conferred by S2M2-30.

Discussion

The findings of this study suggest that the antibody responses against M protein ectodomain in the population most likely exert a beneficial effect on preventing various SARS-CoV-2 infections.
Long-term efficacy of mepolizumab in patients with eosinophilic granulomatosis with polyangiitis: a propensity score matching analysis in the multicenter REVEAL cohort study
Authors: Shiomi Mayu , Watanabe Ryu , Matsuda Shogo , Kotani Takuya , Okazaki Ayana , Masuda Yuichi , Yoshida Tsuneyasu , Shoji Mikihito , Tsuge Ryosuke , Kadoba Keiichiro , Hiwa Ryosuke , Yamamoto Wataru , Takeda Akitoshi , Itoh Yoshiaki , Hashimoto Motomu
Published: October 2024

Background

Mepolizumab (MPZ) has demonstrated efficacy in clinical trials for eosinophilic granulomatosis with polyangiitis (EGPA); however, few studies compare the disease course between patients treated with MPZ (MPZ group) and those who were not treated with MPZ (non-MPZ group) in real-world settings.

Objectives

This study aimed to compare the disease course and outcomes between the two groups and assess the long-term efficacy of MPZ in a multicenter cohort in Japan. Methods: We enrolled 113 EGPA patients registered in the cohort until June 2023. Data on clinical characteristics, disease activity, organ damage, treatments, and outcomes were retrospectively collected. To minimize potential confounding factors, we conducted propensity score matching (PSM).

Results

After PSM, 37 pairs of matched patients were identified. Clinical characteristics, including age at disease onset, sex, disease duration at last observation, antineutrophil cytoplasmic antibody positivity at disease onset, Birmingham Vasculitis Activity Score (BVAS) at disease onset, and Five-factor score at disease onset, were comparable between the groups. The median BVAS at the last observation was 0 in both groups; however, more cases in the non-MPZ group exhibited elevated BVAS, resulting in a significantly higher BVAS in the non-MPZ group at the last observation (median; MPZ group: 0, non-MPZ group: 0, p=0.028). The MPZ group had significantly lower glucocorticoid (GC) doses at the last observation (median; MPZ group: 4 mg/day, non-MPZ group: 5 mg/day, p=0.011), with a higher proportion achieving a GC dose ≤ 4 mg/day at the last observation (MPZ group: 51.4%, non-MPZ group: 24.2%, p=0.027). Three models of multivariable logistic regression analyses were performed to identify factors associated with GC doses ≤ 4 mg/day at the last observation. In all models, achieving a GC dose ≤ 4 mg/day was positively associated with MPZ administration and inversely associated with asthma at disease onset. Finally, we evaluated the survival rates between the groups, and the 5-year survival rates were significantly higher in the MPZ group compared to the non-MPZ group (MPZ group: 100%, non-MPZ group: 81.3%, p=0.012).

Conclusion

Mepolizumab not only contributes to disease activity control but also reduces the GC dose, which may lead to improved survival in EGPA patients.
Identification of PPREs and PPRE associated genes in the human genome: insights into related kinases and disease implications
Authors: Saha Pritha , Talwar Priti
Published: October 2024

Introduction

“Peroxisome Proliferator-Activated Receptors” (PPARs) belong to the class of transcription factors (TF) identified as Nuclear Receptors (NR). Upon activation by peroxisome proliferators (PPs), PPARs modulate a diverse range of genes, consequently regulating intra-cellular lipid metabolism, glucose uptake, apoptosis, and cell proliferation. Subsequent to the heterodimerization of Retinoid X Receptors (RXR) with PPARs induced by the binding of activators to PPARs, facilitates the binding of the resulting complex to Peroxisome Proliferator-Activated Receptors Response Elements (PPRE), with a consensus sequence 5’AGGTCANAGGTCA-3’, and regulate the transcription of the targeted genes.

Methods

A comprehensive screening of PPRE within the whole human genome was performed using the Genome Workbench and UCSC Genome Browser to find the associated genes. Subsequently, the kinase subset was isolated from the extracted list of PPRE-related genes. Functional enrichment of the kinases was performed using FunRich, ToppGene, and ShinyGO. Network analysis and enrichment studies were then further performed using NDEx to elucidate these identified kinases' connections and significance. Additionally, the disease association of the PPRE kinases was analyzed using DisGeNET data in R studio and the COSMIC dataset.

Results

A comprehensive analysis of 1002 PPRE sequences within the human genome (T2T), yielded the identification of 660 associated genes, including 29 kinases. The engagement of these kinases in various biological pathways, such as apoptosis, platelet activation, and cytokine pathways, revealed from the functional enrichment analysis, illuminates the multifaceted role of PPAR in the regulation of cellular homeostasis and biological processes. Network analysis reveals the kinases interact with approximately 5.56% of the Human Integrated Protein-Protein Interaction rEference (HIPPIE) network. Disease association analysis using DisGeNET and COSMIC datasets revealed the significant roles of these kinases in cellular processes and disease modulation.

Discussion

This study elucidates the regulatory role of PPAR-associated genes and their association with numerous biological pathways. The involvement of the kinases with disease-related pathways highlights new potential for the development of therapeutic strategies designed for disease management and intervention.
Dietary supplementation of Astragalus flavonoids regulates intestinal immunology and the gut microbiota to improve growth performance and intestinal health in weaned piglets
Authors: Che Yuyan , Li Lu , Kong Mengjie , Geng Yiwen , Wang Dong , Li Bin , Deng Lufang , Chen Guoshun , Wang Jing
Published: October 2024

Astragali Radix (AS) is a widely used herb in traditional Chinese medicine, with calycosin as its main isoflavonoid. Our previous study discovered that calycosin triggers host defense peptide (HDP) production in IPEC-J2 cells. The aim of this study is to investigate the alleviation effects of AS total flavone and AS calycosin on growth performance, intestinal immunity, and microflora in weaned piglets. Sixty-four piglets were assigned randomly to 4 treatment groups, (1) CON: the basal diet, (2) P-CON: the basal diet plus antibiotics (1 g/kg), (3) AS-TF: the basal diet plus AS total flavone at 60 mg/day per piglet, (4) AS-CA: the basal diet plus AS calycosin at 30 mg/day per piglet. Each treatment consists of 4 replicates with 4 piglets per replicate. Results showed that treatment with AS-TF and AS-CA enhanced average daily growth and average daily feed intake compared to the CON group (P < 0.01), while AS-CA significantly reduced the diarrhea rate (P < 0.05). Both AS-TF and AS-CA significantly increased serum immunoglobulin (Ig) A and IgG levels, with AS-CA further boosting intestinal mucosal secretory IgA levels (P < 0.05). Histological analysis revealed improvements in the morphology of the jejunum and ileum and goblet cell count by AS-TF and AS-CA (P < 0.05). Supplementation of AS-TF and AS-CA promoted the expression of several intestinal HDPs (P < 0.05), and the effect of AS-CA was better than that of AS-TF. In addition, the AS-TF and AS-CA regulated jejunal microbial diversity and composition, with certain differential bacteria genera were showing high correlation with serum cytokines and immunoglobulin levels, suggesting that the intestinal flora affected by AS-TF and AS-CA may contribute to host immunity. Overall, AS CA and AS TF all improved growth performance and health, likely by enhancing nutrition digestibility, serum and intestinal immunity, and intestinal microbial composition. They showed the similar beneficial effect, indicating AS CA appears to be a major compound contributing to the effects of AS TF. This study demonstrated the positive effect of AS flavonoids on weaned piglets and provided a scientific reference for the efficient use of AS products.
Mitophagy-associated programmed neuronal death and neuroinflammation
Authors: Zhu Yanlin , Zhang Jianning , Deng Quanjun , Chen Xin
Published: October 2024

Mitochondria are crucial organelles that play a central role in cellular metabolism and programmed cell death in eukaryotic cells. Mitochondrial autophagy (mitophagy) is a selective process where damaged mitochondria are encapsulated and degraded through autophagic mechanisms, ensuring the maintenance of both mitochondrial and cellular homeostasis. Excessive programmed cell death in neurons can result in functional impairments following cerebral ischemia and trauma, as well as in chronic neurodegenerative diseases, leading to irreversible declines in motor and cognitive functions. Neuroinflammation, an inflammatory response of the central nervous system to factors disrupting homeostasis, is a common feature across various neurological events, including ischemic, infectious, traumatic, and neurodegenerative conditions. Emerging research suggests that regulating autophagy may offer a promising therapeutic avenue for treating certain neurological diseases. Furthermore, existing literature indicates that various small molecule autophagy regulators have been tested in animal models and are linked to neurological disease outcomes. This review explores the role of mitophagy in programmed neuronal death and its connection to neuroinflammation.
IgG reactivity to different desmoglein-3 ectodomains in pemphigus vulgaris: novel panels for assessing disease severity
Authors: Tavakolpour Soheil , Noormohammadi Zahra , Daneshpazhooh Maryam , Gholami Alireza , Mahmoudi Hamidreza
Published: October 2024

Introduction

Pemphigus vulgaris (PV) is an autoimmune disease characterized by IgG autoantibodies targeting desmoglein-3 (Dsg3), leading to blistering of mucous membranes and skin. Although commercial ELISA kits effectively diagnose PV, correlation with clinical phenotype remains unclear. This study assesses multiple panels for monitoring disease severity and activity by profiling IgG autoantibodies against Dsg3’s various extracellular ectodomains.

Method

We designed and expressed different extracellular domains of Dsg3 in HEK293T cell line and developed 15 different ELISA panels, each using a single or multi ectodomains encompassing the entire extracellular region of Dsg3 to detect specific autoantibodies against the particular part of Dsg3.

Results

To validate our approach, we compared our ELISA panel for the full Dsg3 (EC1-5) against a commercial kit using 154 random serum samples from PV patients, demonstrating a strong correlation. For evaluation of IgG autoantibody profiles in our panels, 59 PV patients were included, along with 11 bullous pemphigoid patients, and 49 healthy controls. For all the included subjects, 15 predefined ELISA panels were tested. The IgG autoantibodies against EC1 were detected in 86% of patients with a positive full Dsg3 ectodomain (EC1-5) ELISA, with 26% against EC2, 14% for EC3, 29% for EC4, and 23% for EC5. Among the panels with multiple Dsg3 ectodomains, EC1-3 and EC1-4 were representative of the entire Dsg3 ectodomain in terms of ELISA positivity across all included patients. A significant correlation (P<0.05) was observed between ELISA optical density (OD) and Pemphigus Disease Area Index (PDAI) scores in five panels, EC1, EC2-3, EC2-5, and EC3-4 in addition to the full ectodomain. It suggests an association with disease severity. Interestingly, while the ELISA panel for the entire Dsg3 extracellular ectodomains did not differentiate disease phases, in three of our panels, including EC1, EC3-5, and EC2-5, ANOVA analysis showed a statistically significant difference between the groups of patients in remission, partial remission or persistent lesions, and those with active disease (new cases or relapse). Among these three panels, EC1 was the only one that showed a significant difference in the multiple comparisons analysis; patients in the active phase had higher levels of autoantibodies than those in ‘partial remission or persistent lesions’ and ‘complete remission’ groups.

Conclusion

The level of autoantibodies against EC1 was not only correlated with the full ectodomain but also associated with higher disease severity and active disease phase. This study indicates that a detailed autoantibody profile against Dsg3 ectodomains could serve as a marker for PV severity and activity which may potentially enhance early treatment initiation.
IL-33-primed human mast cells drive IL-9 production by CD4+ effector T cells in an OX40L-dependent manner
Authors: Battut Louise , Leveque Edouard , Valitutti Salvatore , Cenac Nicolas , Dietrich Gilles , Espinosa Eric
Published: October 2024

Interleukin-33 (IL-33) is an alarmin released by epithelial cells in response to tissue damage. It activates resident immune sentinel cells, which then produce signals commonly associated with type 2 immune responses, particularly affecting infiltrating antigen-specific T cells. Given that mast cells (MCs) are a primary target of IL-33 and can shape T helper (Th) cell responses, we investigated the effect of IL-33 priming on the ability of MCs to influence Th cell cytokine production. To examine the Th cell/MC interaction, we developed human primary MC/memory CD4+ T-cell coculture systems involving both cognate and non-cognate interactions. Our results demonstrated that IL-33-primed MCs, whether as bystander cells cocultured with activated effector T cells or functioning as antigen-presenting cells, promoted IL-9 and increased IL-13 production in Th cells via an OX40L-dependent mechanism. This indicates that MCs sense IL-33-associated danger, prompting them to direct Th cells to produce the key type 2 effector cytokines IL-9 and IL-13.