bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating electrocatalytic properties of β12-borophene as a cathode material for an efficient lithium-oxygen battery: a first-principles study
Authors: Fwalo C. , Kochaev A. , Mapasha R. E.
Published: August 2024

Responding to the pressing need to mitigate climate change effects due to fossil fuel consumption, there is a collective push to transition towards renewable and clean energy sources. However, the effectiveness of this move depends on an efficient energy storage system that surpasses current lithium-ion battery technology. The lithium-oxygen battery, having significantly high theoretical specific capacity compared to other systems, has emerged as a promising solution. However, the issues of poor cathode electrode conductivity and slow kinetics during discharge product formation have limited its practical applications. In this work, the first principles-based density functional theory was used to investigate the electrocatalytic properties of β12-borophene as a cathode electrode material for a high-performance lithium-oxygen battery. The adsorption energy, charge density distributions, Gibbs free energy changes, and diffusion energy barriers of lithium superoxide (LiO2) on β12-borophene were calculated. Our findings revealed several important insights: The adsorption energy was found to be − 3.70 eV, suggesting a strong tendency for the LiO2 to remain anchored to the material during the discharging process. The dynamics in the charge density distributions between LiO2 and the β12-borophene substrate exhibited complex behavior. The analysis of the Gibbs free energy changes of the reactions yielded an overpotential of − 1.87 V, this moderate value suggests spontaneous reactions during the formation of the discharge products. Most interestingly, the density of states and band structure analysis suggested the preservation of metallic properties and improved electrical conductivity of the material after the adsorption of LiO2. Additionally, β12-borophene has a relatively low diffusion energy barrier of 1.08 eV, implying effortless diffusion of the LiO2 and an increase in the rate of discharging process. Ultimately, the predicted electronic properties of β12-borophene, make it a strong candidate as a cathode electrode material for an efficient lithium-oxygen battery.
Dual Mach-Zehnder Interferometer Based on DCF and FCF for Temperature and Strain Measurement
Authors: Gao Ya , Jin Shu , Zuo Cheng , Yu Benli , Zhen Shenglai
Published: August 2024

In this paper, a dual Mach-Zehnder interferometer for measuring both temperature and strain is proposed and verified by experiments. The sensor configuration involves cascading a four-core fiber and a double-clad fiber between two single-mode fibers. By exploiting the different responses of the two Mach-Zehnder interferometers to temperature and strain, we construct a matrix using two selected resonance dips from the transmission spectra, so that both temperature and strain can be measured simultaneously. The experimental results show the sensor’s remarkable performance, with the maximum temperature sensitivity of −94.2 pm/°C and the maximum strain sensitivity of 2.68 pm/µε. The maximum temperature error and strain error are found to be ±0.35 °C and ±4.8 µε, respectively. Compared with other optical fiber sensors, the sensor has high sensitivity, a simple structure, and ease to manufacture and implement, making it a structure choice for applications in quality inspection of materials.
Assessing the Impact of Catastrophic Electricity Loss on the Food Supply Chain
Authors: Blouin Simon , Herwix Alexander , Rivers Morgan , Tieman Ross J. , Denkenberger David C.
Published: August 2024

The food supply chain’s heavy reliance on electricity poses significant vulnerabilities in the event of prolonged and widespread power disruptions. This study introduces a system-dynamics model that integrates five critical infrastructures—electric grid, liquid fossil fuels, Internet, transportation, and human workforce—to evaluate the resilience of food supply chains to major power outages. We validated the model using the 2019 Venezuelan blackouts as a case study, demonstrating its predictive validity. We then explored how more extreme electricity losses would disrupt the supply chain. More specifically, we modeled the impact of a large-scale cyberattack on the US electric grid and a high-altitude electromagnetic pulse (HEMP) event. A cyberattack severely damaging the US electric grid and allowing for recovery within a few weeks or months would lead to substantial drops in food consumption. However, it would likely still be possible to provide adequate calories to everyone, assuming that food is equitably distributed. In contrast, a year-long recovery from a HEMP event affecting most of the continental United States could precipitate a state of famine. Our analysis represents a first attempt at quantifying how food availability progressively worsens as power outages extend over time. Our open-source model is made publicly available, and we encourage its application to other catastrophic scenarios beyond those specifically considered in this work (for example, extreme solar storms, high-lethality pandemics).
Distractibility and Impulsivity in ADHD as an Evolutionary Mismatch of High Trait Curiosity
Authors: Le Cunff Anne-Laure
Published: August 2024

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition characterized by symptoms that include inattention, hyperactivity, and impulsivity. Recent research suggests that individuals with ADHD might exhibit higher levels of curiosity, which may be linked to their tendencies toward distractibility and impulsivity. This paper proposes an evolutionary mismatch hypothesis for high trait curiosity in ADHD, positing that ‘hypercuriosity’, which may have been adaptive in ancestral environments characterized by scarce resources and unpredictable risks, has become mismatched in industrialized societies where environments are more stable and information rich. The theory predicts that individuals with ADHD will demonstrate heightened levels of novelty-seeking and exploratory behaviors, manifesting as symptoms labeled as distractibility and impulsivity in modern environments. The paper explores the potential evolutionary benefits of high trait curiosity, the consequences of an evolutionary mismatch, and the implications for research and practice. The limitations of the theory are addressed, such as the need for more targeted research on curiosity in ADHD and potential differences among ADHD subtypes. Future research directions are proposed to refine and test the hypothesis, ultimately contributing to a more nuanced understanding of ADHD and informing the development of strength-based interventions. This theoretical framework offers a novel perspective on the adaptive value of ADHD traits and their manifestation in modern societies.
Inhibiting Voltage Decay in Li-Rich Layered Oxide Cathode: From O3-Type to O2-Type Structural Design
Authors: Zhang Guohua , Wen Xiaohui , Gao Yuheng , Zhang Renyuan , Huang Yunhui
Published: August 2024

Li-rich layered oxide (LRLO) cathodes have been regarded as promising candidates for next-generation Li-ion batteries due to their exceptionally high energy density, which combines cationic and anionic redox activities. However, continuous voltage decay during cycling remains the primary obstacle for practical applications, which has yet to be fundamentally addressed. It is widely acknowledged that voltage decay originates from the irreversible migration of transition metal ions, which usually further exacerbates structural evolution and aggravates the irreversible oxygen redox reactions. Recently, constructing O2-type structure has been considered one of the most promising approaches for inhibiting voltage decay. In this review, the relationship between voltage decay and structural evolution is systematically elucidated. Strategies to suppress voltage decay are systematically summarized. Additionally, the design of O2-type structure and the corresponding mechanism of suppressing voltage decay are comprehensively discussed. Unfortunately, the reported O2-type LRLO cathodes still exhibit partially disordered structure with extended cycles. Herein, the factors that may cause the irreversible transition metal migrations in O2-type LRLO materials are also explored, while the perspectives and challenges for designing high-performance O2-type LRLO cathodes without voltage decay are proposed.
Process of SCR Catalyst Deactivation by Dimethylsiloxanes Present in Marine Fuels
Authors: Kolb Marit , Wesemann Lars , Eilts Peter , Fuhrländer Liliane , Wichmann Hubertus
Published: August 2024

In recent years, there have been reports of the deactivation of selective catalytic reduction (SCR) exhaust gas catalysts after a short period of operation in marine applications. The trigger and the processes of this catalyst damage have now been investigated experimentally using a fuel burner test bench and various analysis techniques. It was found that organic silicon compounds (OSCs), which are present in marine fuels after use in mineral oil extraction and processing, cause the catalyst deactivation. In practice, these are predominantly dimethylsiloxanes. By the burner experiments, it was found that the OSCs were completely converted into combustion products, in particular SiO2. Measurements of particle size distributions and particle number concentrations up- and downstream of the catalyst showed that SiO2 particles < 20 nm in particular were retained in the catalyst. This filtration effect decreased until no further reduction was observed for particles > 50 nm. Other inorganic, particulate, SiO2-containing fuel impurities (catalyst fines) had no poisoning effect here, as these particles are mostly > 50 nm. The small particles formed a closed SiO2 layer with a thickness of approx. 5 µm on the catalyst surface which grew from the catalyst inlet to the outlet and blocked the catalyst as a diffusion barrier. As the SiO2 layer increased, the NO conversion rate decreased. The poisoning effects were observed experimentally at OSC concentrations of 5 to 60 mg Si kg−1 fuel. A field-aged catalyst that had been operated on board of a merchant ship revealed the same findings.
Unlocking the potential of underground hydrogen storage for clean energy solutions
Authors: Dodangoda Chatura , Ranjith P. G. , Haque A.
Published: August 2024

This review paper provides a critical examination of underground hydrogen storage (UHS) as a viable solution for large-scale energy storage, surpassing 10 GWh capacities, and contrasts it with aboveground methods. It exploes into the challenges posed by hydrogen injection, such as the potential for hydrogen loss and alterations in the petrophysical and petrographic characteristics of rock structures, which could compromise the efficiency of UHS systems. Central to our analysis is a detailed overview of hydrogen solubility across various solvents, an extensive database of potential mineralogical reactions within underground storage environments, and their implications for hydrogen retention. We particularly focus on the effects of these reactions on the porosity of reservoir and cap rocks, the role of diffusion in hydrogen loss, and the consequences of multiphase flow induced by hydrogen injection. Our findings highlight the critical mineralogical reactions—specifically, goethite reduction and calcite dissolution—and their pronounced impact on increasing cap rock porosity. We underscore a notable discovery: hydrogen's solubility in non-aqueous phases is significantly higher than in aqueous phases, nearly an order of magnitude greater. The paper not only presents quantitative insights into the mechanisms of hydrogen loss but also pinpoints areas in need of further research to deepen our understanding of UHS dynamics. By identifying these research gaps, we aim to guide future studies towards enhancing the operational efficiency and safety of UHS facilities, thereby supporting the transition towards sustainable energy systems. This work is pivotal for industry stakeholders seeking to optimize UHS practices, ensuring both the effective utilization of hydrogen as a clean energy carrier and the advancement of global sustainable energy goals.
An improved three-dimensional extension of Hoek–Brown criterion for rocks
Authors: Xiao Junjie , Liu Jiacun , Xu Ying , Li Xing , Liu Ang , Xia Kaiwen
Published: August 2024

The Hoek–Brown (H–B) criterion has found widespread application in numerous rock engineering projects. However, its efficacy is compromised by an underestimation of rock strength due to its neglect of the influence of the intermediate principal stress ($$\sigma_{2}$$

σ
2

). Experimental evidence underscores the significant impact of $$\sigma_{2}$$

σ
2

. Consequently, there exists an imperative to formulate a three-dimensional (3D) criterion. In this study, a new deviatoric function with two additional parameters ($$k$$
k
and $$A$$
A
) is developed firstly, which ensure compliance with the prerequisites of smoothness and convexity. In addition, the parameters $$k$$
k
and $$A$$
A
are bonded with the weakening effect of the Lode angle ($$\theta_{\sigma }$$

θ
σ

) and the strengthening effect of the mean stress ($$\sigma_{m}$$

σ
m

), respectively. Then a new 3D strength criterion for rocks is proposed by combining this new deviatoric function and the triaxial compression meridian function of the original H–B criterion. Four distinct sets of test data encompassing various rock types are employed to validate the proposed criterion. The results demonstrate that the proposed criterion adeptly captures the strength characteristics of the four rock types, providing a good depiction of failure surfaces within the 3D principal stress space. Comparative analyses involve the utilization of several existing 3D H–B criteria for strength predictions. The proposed criterion exhibits superior fitting performance for all the selected rocks.
Predictive ability of Achilles tendon elastography for frailty in older adults
Authors: Ceker Eda , Fadiloglu Ayse , Cataltepe Esra , Sendur Halit Nahit , Allahverdiyeva Seriyye , Varan Hacer Dogan
Published: August 2024

Purpose

The Achilles tendon (AT) is the largest and strongest tendon in the human body, and its elasticity is known to be affected by the aging process. However, the relation between AT stiffness and frailty in older individuals remains uncertain. This study aims to explore the potential of Achilles tendon shear wave elastography (AT-SWE) as a tool for assessing physical frailty in older adults.

Methods

A total of 148 patients aged 65 years and over were included in this cross-sectional study. Patients with heart failure, AT injury, stroke history, active malignancy, and claudication were excluded. All patients underwent a comprehensive geriatric assessment. Physical frailty assessment was performed with the fried frailty phenotype. Achilles tendon elastography was measured by ultrasound.

Results

The mean age of the participants was 73.8 years and 62.2% were female. 30.4% of the participants were defined as frail. Achilles tendon shear wave elastography measurements were statistically lower in the frail group (p < 0.05). In the multivariate regression analysis, AT-SWE demonstrated a statistically significant association with frailty independent of confounding factors (OR 0.982, 95% CI 0.965–0.999, p value = 0.038). In the ROC curve analysis, the area under the curve for AT-SWE was 0.647 (95% CI, 0.564–0.724, p < 0.01) and the optimum cut-off point was 124.1 kilopascals.

Conclusion

These findings highlight the value of AT-SWE as a non-invasive and objective tool for predicting frailty in older adults.
Adaptive decomposition with guided filtering and Laplacian pyramid-based image fusion method for medical applications
Authors: Shukla Nirdesh , Sood Meenakshi , Kumar Amod , Choudhary Gaurav
Published: August 2024

Medical image fusion enhances diagnostic precision and facilitates clinical decision-making by integrating information from multiple medical imaging modalities. However, this field is still challenging as the output integrated image, whether from spatial or transform domain algorithms, may suffer from drawbacks such as low contrast, blurring effect, noise, over smoothness, etc. Also, some existing novel works are restricted to specific image datasets. So, to address such issues, a new multi-modal medical image fusion approach based on the advantageous effects of multiple transforms has been introduced in the present work. For this, we use an adaptive image decomposition tool known as Hilbert vibration decomposition (HVD). HVD decomposes an image into different energy components, and after a proper decomposition of the source images, the desirable features of the decomposed components are then passed through a guided filter (GF) for edge preservation. Then, the Laplacian pyramid integrates these filtered parts using the choose max rule. Since HVD offers better spatial resolution and is independent of fixed cut-off frequencies like other transforms, the subjective outputs from this method for different publicly available medical image datasets are clear and better than the previously 20 state-of-the-art published results. Moreover, the obtained values of different objective evaluation metrics such as information entropy (IE): 7.6943, 5.9737, mean: 110.6453, 54.6346, standard deviation (SD): 85.5376, 61.8129, average gradient (AG): 109.2818, 64.6451, spatial frequency (SF): 0.1475, 0.1100, and edge metric (QHK/S): 0.5400, 0.6511 demonstrate its comparability to others. The algorithm's running period of just 0.161244 s also indicates high computational efficiency.
Road damage detection and classification using deep neural networks
Authors: Jiang Yiwen
Published: August 2024

In addressing the challenges of enhancing road damage detection efficiency and accuracy, this paper introduces an optimized YOLOv8 model suitable for embedded systems. The model significantly enhances precision, recall, and mean Average Precision (mAP), achieving 65.7% mAP on the RDD2022 dataset, thereby surpassing models such as Faster R-CNN and SSD. This advancement is attributed to the integration of a Deformable Attention Transformer, a GSConv-powered slim-neck module, and the MPDIoU loss function. These innovations not only contribute to the model's high performance but also set a new benchmark in road damage detection technology, thereby paving the way for future enhancements in the field.
Sustainable environmental design: evaluating the integration of sustainable knowledge in Saudi Arabian architectural programs
Authors: Aloshan Mohammed
Published: August 2024

By aligning Saudi Vision 2030 with the UN's SDGs, this study highlights the significant role of integrating sustainable environmental design knowledge into architectural education in Saudi Arabia. Viewing this integration as a moral obligation, it emphasizes equipping future architects with the skills to create environmentally responsible and resource-efficient buildings, fostering a sustainable and resilient built environment. This paper aims to examine the degree of integration of sustainability knowledge and assess the structural models incorporated into the architectural programs of six Saudi Arabian universities. Adopting a quantitative approach with qualitative insights, this research focuses on universities certified by the National Architectural Accrediting Board (NAAB) or accredited by recognized national and international bodies. This study is limited to the meso-level (curricular management) and includes structural models, course descriptions, learning outcomes, course sequences, and alignment with program visions and missions. A comprehensive review was conducted on all courses related to sustainability, collecting data from program websites. The main variables analyzed included sustainable environmental knowledge, total contact hours dedicated to sustainability courses, distribution across various course types, and patterns over a 5-year period. The units of analysis encompass program plans, vision and mission statements, learning outcomes, course syllabi, and descriptions. The findings reveal significant disparities in sustainability emphasis among programs, with Imam Abdul Rahman Al-Faisal University dedicating 42% of contact hours to sustainability, compared to 25 to 11% at other universities. This study highlights the need for integrating sustainability across design studio levels to provide students with practical skills across disciplines. Most programs use a “linear/parallel” or “partially integrated” model, requiring sustainability principles in graduation projects. However, elective sustainability courses are unpopular and do not adequately address curriculum gaps. This study highlights the necessity of further investigating the effectiveness of incorporating sustainability knowledge in architectural programs. Exploring specific areas for future research to enhance the integration of sustainability in architectural education is also recommended.
Reasonable Bail or Bail at All Costs? Defence Counsel Perspectives on a Coercive Environment
Authors: Nixon Jenaya , Yule Carolyn , Baker Dennis
Published: August 2024

Bail decisions are largely shaped by private, out-of-court negotiations between Crown attorneys and defence lawyers. While accused persons rely on the professional expertise of defence lawyers to navigate bail negotiations and secure them the best possible outcome, much remains unknown about how lawyers prepare for and negotiate bail. This study examines the process of bail preparations and negotiations from the defence’s perspective based on data from 18 semi-structured interviews with defence lawyers. The findings show that, while defence lawyers argue for reasonable bail terms, their ultimate goal is to obtain a release for their client. Defence lawyers also prioritize collecting and strategically using information about the case and the Crowns and justices with whom they work. They often adopt a risk-averse and cooperative approach with Crowns to avoid delaying or preventing their client’s release, even if that means agreeing to additional conditions. Our findings inform efforts to reform bail processes.
Let’s Get Geophysical: Tracking the Evolution of AGU Journal Article Titles
Authors: Owen Rebecca
Published: August 2024

A new study catalogs the most frequently used words in the archive of AGU journal article titles and considers the story these words tell about the evolving fields of Earth and space sciences.
Lower Bound on Preserved Flood Duration in Fluvial Bedform Stratigraphy
Authors: Mahon Robert C. , Ganti Vamsi , Kelley Madeline M. , Das Debsmita , Sanchez Victoria , Portocarrero Giancarlo
Published: August 2024

River bedforms and their deposits—fluvial cross strata— respond to floods. However, it is unclear if all floods are equally represented in cross strata. Here, using a series of physical experiments in which bedforms were subjected to equivalent flood magnitudes over varying durations, we demonstrate the existence of a lower bound on flood durations that are represented in cross strata. We show that the scour depths and preserved set thickness are indistinguishable from baseflow conditions when the rising‐limb duration of floods is shorter than the baseflow‐equilibrated bedform turnover timescale—time required to displace the volume of a single bedform at baseflow conditions. In contrast, scour depth and preserved set thickness distributions deviate from baseflow conditions when flood rising‐limb duration exceeds the baseflow‐equilibrated bedform turnover timescale, causing preferential preservation of falling‐limb bedform dynamics. Our work provides a previously unrecognized quantitative bound on flood durations that are represented in fluvial cross strata.
Three‐Stage India‐Asia Collision Proposed by the Thrice Remagnetizations of the Tethyan Himalaya Terrane
Authors: Tong Yabo , Pei Junling , Qian Tao , Sun Shengsi , Hou Lifu , Sun Xinxin , Zhang Zijian , Yang Bin
Published: August 2024

Crustal deformation and hydrothermal percolation related to the India‐Asia collision have caused extensive remagnetization of the Tethyan Himalaya Terrane (THT). The present work identified three phases of regional remagnetization during 62.3–50.0 Ma for the east‐central THT. Consequently, a model of three‐stage India‐Asia collision was proposed. The east‐central THT first collided with the southward migrated southern margin of the Lhasa Terrane (LT) at 5.4 ± 0.9°N during 62.3–60.9 Ma. Subsequently, the THT continuously moved northward and pushed the southern margin of the LT back to its original position prior to the initiation of fore‐arc and back‐arc extension on both sides of the Gangdese magmatic arc. Since the final suturing of the THT with Asia at ∼10°N during 59.8–58.0 Ma, the east‐central THT remained stationary until India collided with it at 10.9 ± 5.1°N at ∼50.0 Ma.
Cholesterol imbalance and neurotransmission defects in neurodegeneration
Authors: Shin Kyung Chul , Ali Moussa Houda Yasmine , Park Yongsoo
Published: August 2024

The brain contains the highest concentration of cholesterol in the human body, which emphasizes the importance of cholesterol in brain physiology. Cholesterol is involved in neurogenesis and synaptogenesis, and age-related reductions in cholesterol levels can lead to synaptic loss and impaired synaptic plasticity, which potentially contribute to neurodegeneration. The maintenance of cholesterol homeostasis in the neuronal plasma membrane is essential for normal brain function, and imbalances in cholesterol distribution are associated with various neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. This review aims to explore the molecular and pathological mechanisms by which cholesterol imbalance can lead to neurotransmission defects and neurodegeneration, focusing on four key mechanisms: (1) synaptic dysfunction, (2) alterations in membrane structure and protein clustering, (3) oligomers of amyloid beta (Aβ) protein, and (4) α-synuclein aggregation.
The potential role of gut microbiota-derived metabolites as regulators of metabolic syndrome-associated mitochondrial and endolysosomal dysfunction in Alzheimer’s disease
Authors: Jung Young Hyun , Chae Chang Woo , Han Ho Jae
Published: August 2024

Although the role of gut microbiota (GMB)-derived metabolites in mitochondrial and endolysosomal dysfunction in Alzheimer’s disease (AD) under metabolic syndrome remains unclear, deciphering these host–metabolite interactions represents a major public health challenge. Dysfunction of mitochondria and endolysosomal networks (ELNs) plays a crucial role in metabolic syndrome and can exacerbate AD progression, highlighting the need to study their reciprocal regulation for a better understanding of how AD is linked to metabolic syndrome. Concurrently, metabolic disorders are associated with alterations in the composition of the GMB. Recent evidence suggests that changes in the composition of the GMB and its metabolites may be involved in AD pathology. This review highlights the mechanisms of metabolic syndrome-mediated AD development, focusing on the interconnected roles of mitochondrial dysfunction, ELN abnormalities, and changes in the GMB and its metabolites. We also discuss the pathophysiological role of GMB-derived metabolites, including amino acids, fatty acids, other metabolites, and extracellular vesicles, in mediating their effects on mitochondrial and ELN dysfunction. Finally, this review proposes therapeutic strategies for AD by directly modulating mitochondrial and ELN functions through targeting GMB metabolites under metabolic syndrome.
Low-level brain somatic mutations in exonic regions are collectively implicated in autism with germline mutations in autism risk genes
Authors: Kim Il Bin , Kim Myeong-Heui , Jung Saehoon , Kim Woo Kyeong , Lee Junehawk , Ju Young Seok , Webster Maree J. , Kim Sanghyeon , Kim Ja Hye , Kim Hyun Jung , Kim Junho , Kim Sangwoo , Lee Jeong Ho
Published: August 2024

Low-level somatic mutations in the human brain are implicated in various neurological disorders. The contribution of low-level brain somatic mutations to autism spectrum disorder (ASD), however, remains poorly understood. Here, we performed high-depth exome sequencing with an average read depth of 559.3x in 181 cortical, cerebellar, and peripheral tissue samples to identify brain somatic single nucleotide variants (SNVs) in 24 ASD subjects and 31 controls. We detected ~2.4 brain somatic SNVs per exome per single brain region, with a variant allele frequency (VAF) as low as 0.3%. The mutational profiles, including the number, signature, and type, were not significantly different between the ASD patients and controls. Intriguingly, when considering genes with low-level brain somatic SNVs and ASD risk genes with damaging germline SNVs together, the merged set of genes carrying either somatic or germline SNVs in ASD patients was significantly involved in ASD-associated pathophysiology, including dendrite spine morphogenesis (p = 0.025), mental retardation (p = 0.012), and intrauterine growth retardation (p = 0.012). Additionally, the merged gene set showed ASD-associated spatiotemporal expression in the early and mid-fetal cortex, striatum, and thalamus (all p < 0.05). Patients with damaging mutations in the merged gene set had a greater ASD risk than did controls (odds ratio = 3.92, p = 0.025, 95% confidence interval = 1.12–14.79). The findings of this study suggest that brain somatic SNVs and germline SNVs may collectively contribute to ASD-associated pathophysiology.
Inhibition of BCAT1-mediated cytosolic leucine metabolism regulates Th17 responses via the mTORC1-HIF1α pathway
Authors: Kang Yeon Jun , Song Woorim , Lee Su Jeong , Choi Seung Ah , Chae Sihyun , Yoon Bo Ruem , Kim Hee Young , Lee Jung Ho , Kim Chulwoo , Cho Joo-Youn , Kim Hyun Je , Lee Won-Woo
Published: August 2024

Branched-chain amino acids (BCAAs), particularly leucine, are indispensable AAs for immune regulation through metabolic rewiring. However, the molecular mechanism underlying this phenomenon remains unclear. Our investigation revealed that T-cell receptor (TCR)-activated human CD4+ T cells increase the expression of BCAT1, a cytosolic enzyme responsible for BCAA catabolism, and SLC7A5, a major BCAA transporter. This upregulation facilitates increased leucine influx and catabolism, which are particularly crucial for Th17 responses. Activated CD4+ T cells induce an alternative pathway of cytosolic leucine catabolism, generating a pivotal metabolite, β-hydroxy β-methylbutyric acid (HMB), by acting on BCAT1 and 4-hydroxyphenylpyruvate dioxygenase (HPD)/HPD-like protein (HPDL). Inhibition of BCAT1-mediated cytosolic leucine metabolism, either with BCAT1 inhibitor 2 (Bi2) or through BCAT1, HPD, or HPDL silencing using shRNA, attenuates IL-17 production, whereas HMB supplementation abrogates this effect. Mechanistically, HMB contributes to the regulation of the mTORC1-HIF1α pathway, a major signaling pathway for IL-17 production, by increasing the mRNA expression of HIF1α. This finding was corroborated by the observation that treatment with L-β-homoleucine (LβhL), a leucine analog and competitive inhibitor of BCAT1, decreased IL-17 production by TCR-activated CD4+ T cells. In an in vivo experimental autoimmune encephalomyelitis (EAE) model, blockade of BCAT1-mediated leucine catabolism, either through a BCAT1 inhibitor or LβhL treatment, mitigated EAE severity by decreasing HIF1α expression and IL-17 production in spinal cord mononuclear cells. Our findings elucidate the role of BCAT1-mediated cytoplasmic leucine catabolism in modulating IL-17 production via HMB-mediated regulation of mTORC1-HIF1α, providing insights into its relevance to inflammatory conditions.
Ubiquitous short-range order in multi-principal element alloys
Authors: Han Ying , Chen Hangman , Sun Yongwen , Liu Jian , Wei Shaolou , Xie Bijun , Zhang Zhiyu , Zhu Yingxin , Li Meng , Yang Judith , Chen Wen , Cao Penghui , Yang Yang
Published: August 2024

Recent research in multi-principal element alloys (MPEAs) has increasingly focused on the role of short-range order (SRO) on material performance. However, the mechanisms of SRO formation and its precise control remain elusive, limiting the progress of SRO engineering. Here, leveraging advanced additive manufacturing techniques that produce samples with a wide range of cooling rates (up to 107 K s−1) and an enhanced semi-quantitative electron microscopy method, we characterize SRO in three CoCrNi-based face-centered-cubic (FCC) MPEAs. Surprisingly, irrespective of the processing and thermal treatment history, all samples exhibit similar levels of SRO. Atomistic simulations reveal that during solidification, prevalent local chemical order arises in the liquid-solid interface (solidification front) even under the extreme cooling rate of 1011 K s−1. This phenomenon stems from the swift atomic diffusion in the supercooled liquid, which matches or even surpasses the rate of solidification. Therefore, SRO is an inherent characteristic of most FCC MPEAs, insensitive to variations in cooling rates and even annealing treatments typically available in experiments.
Structural insights into strigolactone catabolism by carboxylesterases reveal a conserved conformational regulation
Authors: Palayam Malathy , Yan Linyi , Nagalakshmi Ugrappa , Gilio Amelia K. , Cornu David , Boyer François-Didier , Dinesh-Kumar Savithramma P. , Shabek Nitzan
Published: August 2024

Phytohormone levels are regulated through specialized enzymes, participating not only in their biosynthesis but also in post-signaling processes for signal inactivation and cue depletion. Arabidopsis thaliana (At) carboxylesterase 15 (CXE15) and carboxylesterase 20 (CXE20) have been shown to deplete strigolactones (SLs) that coordinate various growth and developmental processes and function as signaling molecules in the rhizosphere. Here, we elucidate the X-ray crystal structures of AtCXE15 (both apo and SL intermediate bound) and AtCXE20, revealing insights into the mechanisms of SL binding and catabolism. The N-terminal regions of CXE15 and CXE20 exhibit distinct secondary structures, with CXE15 characterized by an alpha helix and CXE20 by an alpha/beta fold. These structural differences play pivotal roles in regulating variable SL hydrolysis rates. Our findings, both in vitro and in planta, indicate that a transition of the N-terminal helix domain of CXE15 between open and closed forms facilitates robust SL hydrolysis. The results not only illuminate the distinctive process of phytohormone breakdown but also uncover a molecular architecture and mode of plasticity within a specific class of carboxylesterases.
Seismic response of mountain tunnel induced by fault slip
Authors: Xia Chen , Wang Zian , He Yongsheng , Chen Yeqing , Li Chunhai , Shi Lei , Zhao Chuan
Published: August 2024

With the rapid development of Chinese transportation networks, such as the Sichuan-Tibet railway, numerous tunnels are under construction or planned in mountainous regions. Some of these tunnels must traverse or be situated near active fault zones, which could suffer damage from fault slip. In this study, the seismic response of a mountain tunnel subjected to coseismic faulting was analyzed using a fault-structure system in a two-step process. Firstly, a nonuniform slip model was proposed to calculate the ground deformations and internal displacements induced by a specific active fault on a geological scale, considering nonuniform slips on the fault plane. The 1989 Loma Prieta and 2022 Menyuan earthquakes were chosen as case studies to validate the proposed slip model. Secondly, the calculated displacement of the Menyuan earthquake was used as the input load for the discrete–continuous coupling analysis of the Daliang tunnel on an engineering scale. The simulated deformation of the Daliang tunnel aligned with the on-site damage observations following the Menyuan earthquake. Lastly, the effects of different fault conditions on the tunnel seismic response were investigated. The results indicate that the distribution of the peak longitudinal strain of the lining is governed by fault mechanisms, and the degree of fault slip significantly influences the response of the tunnel. A tunnel passing through an active fault with a wider fault fracture zone and smaller dip angle experience less damage.
Feasibility of gamified visual desensitisation for visually-induced dizziness
Authors: Goodwin Nathan , Powell Georgina , Loizides Fernando , Derry-Sumner Hannah , Rajenderkumar Deepak , Sumner Petroc
Published: August 2024

Visually-induced dizziness (visual vertigo) is a core symptom of Persistent Perceptual Postural Dizziness (PPPD) and occurs in other conditions and general populations. It is difficult to treat and lacks new treatments and research. We incorporated the existing rehabilitation approach of visual desensitisation into an online game environment to enhance control over visual motion and complexity. We report a mixed-methods feasibility trial assessing: Usage and adherence; rehabilitation potential; system usability and enjoyment; relationship with daily dizziness. Participants played online with (intervention, N = 37) or without (control, N = 39) the visual desensitisation component for up to 5–10 min, twice daily for 6 weeks. Dropout was 45%. In the intervention group, N = 17 played for the recommended time while N = 20 played less. Decreases in visual vertigo symptoms, anxiety and depression correlated with playtime for the intervention but not control. System usability was high. Daily symptoms predicted playtime. Qualitative responses broadly supported the gamified approach. The data suggest gamified visual desensitisation is accessible, acceptable and, if adherence challenges can be overcome, could become a useful addition to rehabilitation schedules for visually-induced dizziness and associated anxiety. Further trials are needed.
Optimizing sustainable control of Meloidogyne javanica in tomato plants through gamma radiation-induced mutants of Trichoderma harzianum and Bacillus velezensis
Authors: Rostami Mahsa , Shahbazi Samira , Soleimani Reihaneh , Ghorbani Abozar
Published: August 2024

This study investigates the efficacy of Trichoderma spp. and Bacillus spp., as well as their gamma radiation-induced mutants, as potential biological control agents against Meloidogyne javanica (Mj) in tomato plants. The research encompasses in vitro assays, greenhouse trials, and molecular identification methodologies to comprehensively evaluate the biocontrol potential of these agents. In vitro assessments reveal significant nematicidal activity, with Bacillus spp. demonstrating notable effectiveness in inhibiting nematode egg hatching (16–45%) and inducing second-stage juvenile (J2) mortality (30–46%). Greenhouse trials further confirm the efficacy of mutant isolates, particularly when combined with chitosan, in reducing nematode-induced damage to tomato plants. The combination of mutant isolates with chitosan reduces the reproduction factor (RF) of root-knot nematodes by 94%. By optimizing soil infection conditions with nematodes and modifying the application of the effective compound, the RF of nematodes decreases by 65–76%. Molecular identification identifies B. velezensis and T. harzianum as promising candidates, exhibiting significant nematicidal activity. Overall, the study underscores the potential of combined biocontrol approaches for nematode management in agricultural settings. However, further research is essential to evaluate practical applications and long-term efficacy. These findings contribute to the development of sustainable alternatives to chemical nematicides, with potential implications for agricultural practices and crop protection strategies.
Population diversity control based differential evolution algorithm using fuzzy system for noisy multi-objective optimization problems
Authors: Subburaj Brindha , Maheswari J. Uma , Ibrahim S. P. Syed , Kavitha Muthu Subash
Published: August 2024

The objective measurements of the real-world optimization problems are mostly subject to noise which occurs due to several reasons like human measurement or environmental factors. The performance of the optimization algorithm gets affected if the effect of noise is higher than the negligible limit. The previous noise handling optimization algorithms use a large population size or multiple sampling at same region which increases the total count of function evaluations, and few methods work for a particular problem type. To address the above challenges, a Differential Evolution based Noise handling Optimization algorithm (NDE) to solve and optimize noisy bi-objective optimization problems is proposed. NDE is a Differential Evolution (DE) based optimization algorithm where the strategies for trial vector generation and the control parameters of DE algorithm are self-adapted using fuzzy inference system to improve the population diversity along the evolution process. In NDE, explicit averaging based method for denoising is used when the noise level is higher than negligible limit. Extending noise handling method enhances the performance of the optimization algorithm in solving real world optimization problems. To improve the convergence characteristics of the proposed algorithm, a restricted local search procedure is proposed. The performance of NDE algorithm is experimented using DTLZ and WFG problems, which are benchmark bi-objective optimization problems. The obtained results are compared with other SOTA algorithm using modified Inverted Generational Distance and Hypervolume performance metrics, from which it is confirmed that the proposed NDE algorithm is better in solving noisy bi-objective problems when compared to the other methods. To further strengthen the claim, statistical tests are conducted using the Wilcoxon and Friedman rank tests, and the proposed NDE algorithm shows significance over the other algorithms rejecting the null hypothesis.
GDNF improves the cognitive ability of PD mice by promoting glycosylation and membrane distribution of DAT
Authors: Chengcheng Ma , Panpan An , Yalong Yan , Mingyu Su , Wei Xu , Jing Chen , Chuanxi Tang
Published: August 2024

The core of clinic treatment of Parkinson's disease (PD) is to enhance dopamine (DA) signaling within the brain. The regulation of dopamine transporter (DAT) is integral to this process. This study aims to explore the regulatory mechanism of glial cell line-derived neurotrophic factor (GDNF) on DAT, thereby gaining a profound understanding its potential value in treating PD. In this study, we investigated the effects of GDNF on both cellular and mouse models of PD, including the glycosylation and membrane transport of DAT detected by immunofluorescence and immunoblotting, DA signal measured by neurotransmitter fiber imaging technology, Golgi morphology observed by electron microscopic, as well as cognitive ability assessed by behavior tests. This study revealed that in animal trials, MPTP-induced Parkinson's Disease (PD) mice exhibited a marked decline in cognitive function. Utilizing ELISA and neurotransmitter fiber imaging techniques, we observed a decrease in dopamine levels and a significant reduction in the intensity of dopamine signal release in the Prefrontal Cortex (PFC) of PD mice induced by MPTP. Intriguingly, these alterations were reversed by Glial Cell Line-Derived Neurotrophic Factor (GDNF). In cellular experiments, following MPP + intervention, there was a decrease in Gly-DAT modification in both the cell membrane and cytoplasm, coupled with an increase in Nongly-DAT expression and aggregation of DAT within the cytoplasm. Conversely, GDNF augmented DAT glycosylation and facilitated its membrane transport in damaged dopaminergic neurons, concurrently reversing the effects of GRASP65 depletion and Golgi fragmentation, thereby reducing the accumulation of DAT in the Golgi apparatus. Furthermore, overexpression of GRASP65 enhanced DAT transport in PD cells and mice, while suppression of GRASP65 attenuated the efficacy of GDNF on DAT. Additionally, GDNF potentiated the reutilization of neurotransmitters by the PFC presynaptic membrane, boosting the effective release of dopamine following a single electrical stimulation, ultimately ameliorating the cognitive impairments in PD mice.Therefore, we propose that GDNF enhances the glycosylation and membrane trafficking of DAT by facilitating the re-aggregation of the Golgi apparatus, thereby amplifying the utilization of DA signals. This ultimately leads to the improvement of cognitive abilities in PD mouse models. Our study illuminates, from a novel angle, the beneficial role of GDNF in augmenting DA utilization and cognitive function in PD, providing fresh insights into its therapeutic potential.
Integrated drug resistance and leukemic stemness gene-expression scores predict outcomes in large cohort of over 3500 AML patients from 10 trials
Authors: H. Elsayed Abdelrahman , Cao Xueyuan , Marrero Richard J. , Nguyen Nam H. K. , Wu Huiyun , Ni Yonhui , Ribeiro Raul C. , Tobias Herold , Valk Peter J. , Béliveau François , Richard-Carpentier Guillaume , Hébert Josée , Zwaan C. Michel , Gamis Alan , Kolb Edward Anders , Aplenc Richard , Alonzo Todd A. , Meshinchi Soheil , Rubnitz Jeffrey , Pounds Stanley , Lamba Jatinder K.
Published: August 2024

In this study, we leveraged machine-learning tools by evaluating expression of genes of pharmacological relevance to standard-AML chemotherapy (ara-C/daunorubicin/etoposide) in a discovery-cohort of pediatric AML patients (N = 163; NCT00136084) and defined a 5-gene-drug resistance score (ADE-RS5) that was predictive of outcome (high MRD1 positivity p = 0.013; lower EFS p < 0.0001 and OS p < 0.0001). ADE-RS5 was integrated with a previously defined leukemic-stemness signature (pLSC6) to classify patients into four groups. ADE-RS5, pLSC6 and integrated-score was evaluated for association with outcome in one of the largest assembly of ~3600 AML patients from 10 independent cohorts (1861 pediatric and 1773 adult AML). Patients with high ADE-RS5 had poor outcome in validation cohorts and the previously reported pLSC6 maintained strong significant association in all validation cohorts. For pLSC6/ADE-RS5-integrated-score analysis, using Group-1 (low-scores for ADE-RS5 and pLSC6) as reference, Group-4 (high-scores for ADE-RS5 and pLSC6) showed worst outcome (EFS: p < 0.0001 and OS: p < 0.0001). Groups-2/3 (one high and one low-score) showed intermediate outcome (p < 0.001). Integrated score groups remained an independent predictor of outcome in multivariable-analysis after adjusting for established prognostic factors (EFS: Group 2 vs. 1, HR = 4.68, p < 0.001, Group 3 vs. 1, HR = 3.22, p = 0.01, and Group 4 vs. 1, HR = 7.26, p < 0.001). These results highlight the significant prognostic value of transcriptomics-based scores capturing disease aggressiveness through pLSC6 and drug resistance via ADE-RS5. The pLSC6 stemness score is a significant predictor of outcome and associates with high-risk group features, the ADE-RS5 drug resistance score adds further value, reflecting the clinical utility of simultaneous testing of both for optimizing treatment strategies.