bluuebunny/crossref_metadata_2025_split huggingface dataset:
DIAHEMITONIC MODALITY: A QUARTER-TONAL COMPOSITION SYSTEM
Authors: Kaplan Simon 
Published: September 2023

AbstractThis article describes a design process for a composition system based upon the quarter-tone scale. As the semitone and quarter-tone scales share the same properties, a musical grammar based upon the former is used as a model to construct an analogous musical grammar based upon the latter. Within the scope of diatonic modal music, the organisation of pitches and durations is analysed from a scientific perspective. Several parameters are taken into consideration: scale, mode, chord, cadence, metre and rhythm. The one-to-one mapping of each facet of diatonic modality onto quarter-tonality results in diahemitonic modality.
Lapse risk modeling in insurance: a Bayesian mixture approach
Authors: Lobo Viviana G. R. , Fonseca Thaís C. O. , Alves Mariane B. 
Published: September 2023

AbstractThis paper focuses on modeling surrender time for policyholders in the context of life insurance. In this setup, a large lapse rate at the first months of a contract is often observed, with a decrease in this rate after some months. The modeling of the time to cancelation must account for this specific behavior. Another stylized fact is that policies which are not canceled in the study period are considered censored. To account for both censoring and heterogeneous lapse rates, this work assumes a Bayesian survival model with a mixture of regressions. The inference is based on data augmentation allowing for fast computations even for datasets of over millions of clients. Moreover, frequentist point estimation based on Expectation–Maximization algorithm is also presented. An illustrative example emulates a typical behavior for life insurance contracts, and a simulated study investigates the properties of the proposed model. A case study is considered and illustrates the flexibility of our proposed model allowing different specifications of mixture components. In particular, the observed censoring in the insurance context might be up to$50\%$of the data, which is very unusual for survival models in other fields such as epidemiology. This aspect is exploited in our simulated study.
Erhebungsmethoden zur Erfassung der Erzählfähigkeit von Kindern im Vor- und Grundschulalter
Authors: Meier Birte , Neitzel Isabel 
Published: September 2023

Zusammenfassung: Theoretischer Hintergrund: Die Erzählfähigkeit ist von hoher schulischer Relevanz. Die kindlichen Leistungen variieren je nach Erhebungsmethode, bisher fehlen jedoch konkrete Vergleichsdaten über Vor- und Schulalter hinweg. Fragestellung: Welche Erzählleistung zeigen deutschsprachige Kinder mit typischer Sprachentwicklung in den Altersklassen von drei bis neun Jahren in Abhängigkeit von der Erzählform (Nacherzählung vs. freie Erzählung)? Methode: Erzählungen anhand eines non-verbalen Bilderbuchs von 89 Kindern im Alter von 3 – 9 Jahren wurden in zwei Subgruppen (Nacherzählung: 3, 5, 9 Jahre; freie Erzählung: 4 – 8 Jahre) verglichen. Die Daten der Gruppe freie Erzählung stammten aus einem CHILDES-Korpus. Die Transkripte wurden anhand eines Punktbewertungssystems (NSS) in sieben Erzählkategorien (z. B. Referenzierung, Schluss) bewertet. Ergebnisse: Die Erzählleistung steigt signifikant über die gesamte Altersspanne ohne auftretende Deckeneffekte, ist aber bei Schuleintritt noch deutlich reduziert. Die freie Erzählung liegt bei Neunjährigen, gemessen am mittleren NSS-Score, 3 – 4 Jahre hinter der Nacherzählung zurück. Diskussion und Schlussfolgerung: Die fortschreitende Entwicklung der Erzählfähigkeit im Grundschulalter sowie das Schwierigkeitsniveau der Erzählformen sollten im Schulkontext beachtet werden.
How Do Rift‐Related Fault Network Distributions Evolve? Quantitative Comparisons Between Natural Fault Observations and 3D Numerical Models of Continental Extension
Authors: Pan Sophie , Naliboff John , Bell Rebecca , Jackson Chris 
Published: September 2023

AbstractContinental extension is primarily accommodated by the evolution of normal fault networks. Rifts are shaped by complex tectonic processes and it has historically been difficult to determine the key rift controls using only observations from natural rifts. Here, we use 3D thermo‐mechanical, high‐resolution (<650 m) forward models of continental extension to investigate how fault network patterns vary as a function of key rift parameters, including extension rate, the magnitude of strain weakening, and the distribution and magnitude of initial crustal damage. We quantitatively compare modeled fault networks with observations of fault patterns in natural rifts, finding key similarities in their along‐strike variability and scaling distributions. We show that fault‐accommodated strain summed across the entire 180 × 180 km study area increases linearly with time. We find that large faults do not abide by power‐law scaling as they are limited by an upper finite characteristic, ω0. Fault weakening, and the spatial distribution of initial plastic strain blocks, exert a key control on fault characteristics. We show that off‐fault (i.e., non‐fault extracted) deformation accounts for 25%–45% of the total extensional strain, depending on the rift parameters. As fault population statistics produce distinct characteristics for our investigated rift parameters, further numerical and observational data may enable the future reconstruction of key rifting parameters through observational data alone.
The Impact of the Madden‐Julian Oscillation on the Formation of the Arabian Sea Monsoon Onset Vortex
Authors: Dhavale Shreyas , Aiyyer Anantha 
Published: September 2023

AbstractDuring certain years, a synoptic scale vortex called the monsoon onset vortex (MOV) forms within the northward advancing zone of precipitating convection over the Arabian Sea. The MOV does not form each year and the reason is unclear. Since the Madden‐Julian Oscillation (MJO) is known to modulate convection and tropical cyclones in the tropics, we examined its role in the formation of the MOV. While the convective and transition phases of the MJO do not always lead to MOV formation, the suppressed phase of the MJO hinders the formation of the MOV more consistently. This asymmetric relationship between the MJO and MOV can be partially explained by the modulation of the large‐scale environment, measured by a tropical cyclone genesis index. It also suggests that the Arabian Sea is generally near a critical state that is favorable for MOV formation during the monsoon onset period.
Crustal Block and Muted Ring Development During the Formation of Mercury's Caloris Megabasin
Authors: Gosselin G. J. , Freed A. M. , Johnson B. C. 
Published: September 2023

AbstractIn contrast to multiring basins, megabasins lack clear ring structures and display crustal profiles characterized by a thin layer of crust at their center that gradually increases in thickness to the surrounding region. The 1,550‐km‐diameter Caloris basin on Mercury is often speculated to be a multiring basin; however, its crustal structure is indicative of a megabasin, perhaps explaining the lack of discernible rings. Here, we model the formation of Caloris basin using iSALE‐2D under a range of preimpact thermal conditions to determine whether the processes responsible for its megabasin crustal structure could lead to the formation of basin rings. We find that thermal gradients between 22 and 30 K/km—hotter than previously inferred—facilitate the reproduction of Caloris basin's crustal structure through crustal flowback, though such preimpact thermal structures preclude its formation as a multiring basin. Instead, repeated thrusting and necking events during transient crater collapse induce instances of fault reactivation, which diminish initial fault offsets and produce a series of discrete crustal blocks. Models assuming cooler thermal gradients lead to overly thin or non‐existent crust at the basin center, in contrast to observations. Even if crustal deficits were made up via a differentiating melt pool, the crust elsewhere would be overly thick, supporting the idea that the crustal structure of megabasins is primarily associated with transient crater collapse. We conclude that the transition to a megabasin morphology on terrestrial planetary surfaces, like the multiring transition, is dependent upon the size of the basin compared to the lithospheric thickness.
Impact of Pressure Waves on Water Imbibition and Flow in Unsaturated Porous Media
Authors: Kalisman Doron , Yakirevich Alexander , Sorek Shaul , Kamai Tamir 
Published: September 2023

AbstractThe wetting front dynamics during water imbibition in dry porous media affect the ultimate water distribution pattern. In this study, we investigate the impact of pressure pulses that emit waves in the water phase on the water distribution and imbibition patterns in porous media. We present experimental results of water spatial distribution in sand columns following infiltration under abrupt pressured‐water pulses and compare them with those of continuous inflow. Applying pressure waves during infiltration increases pressure gradients behind the wetting front, which can overcome capillary and gravitational forces, leading to uniform imbibition. To simulate the process, we developed a pore‐network model incorporating an analytical solution of pressure wave attenuation to predict the imbibition pattern. Our results demonstrate that the amplitude of the pressure wave is associated with a sharp wetting front, resulting in higher water content compared to Darcy‐type continuous flow. The findings suggest that pressure waves have the potential to achieve high water content in unsaturated media and provide insights into the spatial extent of their impact on water distribution.
Elevated FBXL6 expression in hepatocytes activates VRK2-transketolase-ROS-mTOR-mediated immune evasion and liver cancer metastasis in mice
Authors: Zhang Jie , Lin Xiao-Tong , Yu Hong-Qiang , Fang Lei , Wu Di , Luo Yuan-Deng , Zhang Yu-Jun , Xie Chuan-Ming 
Published: September 2023

AbstractMetastatic hepatocellular carcinoma (HCC) is the most lethal malignancy and lacks effective treatment. FBXL6 is overexpressed in human hepatocellular carcinoma (HCC), but whether this change drives liver tumorigenesis and lung metastasis in vivo remains unknown. In this study, we aimed to identify FBXL6 (F-Box and Leucine Rich Repeat Protein 6) as a key driver of HCC metastasis and to provide a new paradigm for HCC therapy. We found that elevated FBXL6 expression in hepatocytes drove HCC lung metastasis and was a much stronger driver than Kras mutation (KrasG12D/+;Alb-Cre), p53 haploinsufficiency (p53+/-) or Tsc1 loss (Tsc1fl/fl;Alb-Cre). Mechanistically, VRK2 promoted Thr287 phosphorylation of TKT and then recruited FBXL6 to promote TKT ubiquitination and activation. Activated TKT further increased PD-L1 and VRK2 expression via the ROS-mTOR axis, leading to immune evasion and HCC metastasis. Targeting or knockdown of TKT significantly blocked FBXL6-driven immune evasion and HCC metastasis in vitro and in vivo. Notably, the level of active TKT (p-Thr287 TKT) was increased and was positively correlated with the FBXL6 and VRK2 expression levels in HCC patients. Our work provides novel mechanistic insights into FBXL6-driven HCC metastasis and suggests that targeting the TKT-ROS-mTOR-PD-L1/VRK2 axis is a new paradigm for treating patients with metastatic HCC with high FBXL6 expression.
Scalable production of tissue-like vascularized liver organoids from human PSCs
Authors: Harrison Sean P. , Siller Richard , Tanaka Yoshiaki , Chollet Maria Eugenia , de la Morena-Barrio María Eugenia , Xiang Yangfei , Patterson Benjamin , Andersen Elisabeth , Bravo-Pérez Carlos , Kempf Henning , Åsrud Kathrine S. , Lunov Oleg , Dejneka Alexandr , Mowinckel Marie-Christine , Stavik Benedicte , Sandset Per Morten , Melum Espen , Baumgarten Saphira , Bonanini Flavio , Kurek Dorota , Mathapati Santosh , Almaas Runar , Sharma Kulbhushan , Wilson Steven R. , Skottvoll Frøydis S. , Boger Ida C. , Bogen Inger Lise , Nyman Tuula A. , Wu Jun Jie , Bezrouk Ales , Cizkova Dana , Corral Javier , Mokry Jaroslav , Zweigerdt Robert , Park In-Hyun , Sullivan Gareth J. 
Published: September 2023

AbstractThe lack of physiological parity between 2D cell culture and in vivo culture has led to the development of more organotypic models, such as organoids. Organoid models have been developed for a number of tissues, including the liver. Current organoid protocols are characterized by a reliance on extracellular matrices (ECMs), patterning in 2D culture, costly growth factors and a lack of cellular diversity, structure, and organization. Current hepatic organoid models are generally simplistic and composed of hepatocytes or cholangiocytes, rendering them less physiologically relevant compared to native tissue. We have developed an approach that does not require 2D patterning, is ECM independent, and employs small molecules to mimic embryonic liver development that produces large quantities of liver-like organoids. Using single-cell RNA sequencing and immunofluorescence, we demonstrate a liver-like cellular repertoire, a higher order cellular complexity, presenting with vascular luminal structures, and a population of resident macrophages: Kupffer cells. The organoids exhibit key liver functions, including drug metabolism, serum protein production, urea synthesis and coagulation factor production, with preserved post-translational modifications such as N-glycosylation and functionality. The organoids can be transplanted and maintained long term in mice producing human albumin. The organoids exhibit a complex cellular repertoire reflective of the organ and have de novo vascularization and liver-like function. These characteristics are a prerequisite for many applications from cellular therapy, tissue engineering, drug toxicity assessment, and disease modeling to basic developmental biology.
Drug conjugates for targeting regulatory T cells in the tumor microenvironment: guided missiles for cancer treatment
Authors: Yang Juwon , Bae Hyunsu 
Published: September 2023

AbstractWithin the tumor microenvironment (TME), regulatory T cells (Tregs) play a key role in suppressing anticancer immune responses; therefore, various strategies targeting Tregs are becoming important for tumor therapy. To prevent the side effects of nonspecific Treg depletion, such as immunotherapy-related adverse events (irAEs), therapeutic strategies that specifically target Tregs in the TME are being investigated. Tumor-targeting drug conjugates are efficient drugs in which a cytotoxic payload is assembled into a carrier that binds Tregs via a linker. By allowing the drug to act selectively on target cells, this approach has the advantage of increasing the therapeutic effect and minimizing the side effects of immunotherapy. Antibody–drug conjugates, immunotoxins, peptide–drug conjugates, and small interfering RNA conjugates are being developed as Treg-targeting drug conjugates. In this review, we discuss key themes and recent advances in drug conjugates targeting Tregs in the TME, as well as future design strategies for successful use of drug conjugates for Treg targeting in immunotherapy.
Structure-based drug discovery of a corticotropin-releasing hormone receptor 1 antagonist using an X-ray free-electron laser
Authors: Kim Hoyoung , Lim Taehyun , Ha Go Eun , Lee Jee-Young , Kim Jun-Woo , Chang Nienping , Kim Si Hyun , Kim Ki Hun , Lee Jaeick , Cho Yongju , Kim Byeong Wook , Abrahamsson Alva , Kim Sung Hwan , Kim Hyo-Ji , Park Sehan , Lee Sang Jae , Park Jaehyun , Cheong Eunji , Kim B. Moon , Cho Hyun-Soo 
Published: September 2023

AbstractThus far, attempts to develop drugs that target corticotropin-releasing hormone receptor 1 (CRF1R), a drug target in stress-related therapy, have been unsuccessful. Studies have focused on using high-resolution G protein-coupled receptor (GPCR) structures to develop drugs. X-ray free-electron lasers (XFELs), which prevent radiation damage and provide access to high-resolution compositions, have helped accelerate GPCR structural studies. We elucidated the crystal structure of CRF1R complexed with a BMK-I-152 antagonist at 2.75 Å using fixed-target serial femtosecond crystallography. The results revealed that two unique hydrogen bonds are present in the hydrogen bond network, the stalk region forms an alpha helix and the hydrophobic network contains an antagonist binding site. We then developed two antagonists—BMK-C203 and BMK-C205—and determined the CRF1R/BMK-C203 and CRF1R/BMK-C205 complex structures at 2.6 and 2.2 Å, respectively. BMK-C205 exerted significant antidepressant effects in mice and, thus, may be utilized to effectively identify structure-based drugs against CRF1R.
A novel mutation in intron 1 of Wnt1 causes developmental loss of dopaminergic neurons in midbrain and ASD-like behaviors in rats
Authors: Li Yongyi , Zhu Mingwei , Chen Wen-Xiong , Luo Jing , Li Xin , Cao Yangyang , Zheng Meng , Ma Shanshan , Xiao Zhilan , Zhang Yani , Jiang Linyan , Wang Xiumin , Tan Ting , Li Xia , Gong Qian , Xiong Xiaoli , Wang Jun , Tang Mingxi , Li Mingtao , Tang Ya-Ping 
Published: September 2023

AbstractAutism spectrum disorder (ASD) is a group of neurodevelopmental disorders with a strong genetic liability. Despite extensive studies, however, the underlying pathogenic mechanism still remains elusive. In the present study, we identified a homozygous mutation in the intron 1 of Wnt1 via large-scale screening of ASD risk/causative genes and verified that this mutation created a new splicing donor site in the intron 1, and consequently, a decrease of WNT1 expression. Interestingly, humanized rat models harboring this mutation exhibited robust ASD-like behaviors including impaired ultrasonic vocalization (USV), decreased social interactions, and restricted and repetitive behaviors. Moreover, in the substantia nigra compacta (SNpc) and the ventral tegmental area (VTA) of mutant rats, dopaminergic (DAergic) neurons were dramatically lost, together with a comparable decrease in striatal DAergic fibers. Furthermore, using single-cell RNA sequencing, we demonstrated that the decreased DAergic neurons in these midbrain areas might attribute to a shift of the boundary of the local pool of progenitor cells from the hypothalamic floor plate to the midbrain floor plate during the early embryonic stage. Moreover, treatments of mutant rats with levodopa could attenuate the impaired USV and social interactions almost completely, but not the restricted and repetitive behaviors. Our results for the first time documented that the developmental loss of DAergic neurons in the midbrain underlies the pathogenesis of ASD, and that the abnormal progenitor cell patterning is a cellular underpinning for this developmental DAergic neuronal loss. Importantly, the effective dopamine therapy suggests a translational significance in the treatment of ASD.
Microbial gene expression in Guaymas Basin subsurface sediments responds to hydrothermal stress and energy limitation
Authors: Mara Paraskevi , Zhou Ying-Li , Teske Andreas , Morono Yuki , Beaudoin David , Edgcomb Virginia 
Published: September 2023

Abstract
Analyses of gene expression of subsurface bacteria and archaea provide insights into their physiological adaptations to in situ subsurface conditions. We examined patterns of expressed genes in hydrothermally heated subseafloor sediments with distinct geochemical and thermal regimes in Guaymas Basin, Gulf of California, Mexico. RNA recovery and cell counts declined with sediment depth, however, we obtained metatranscriptomes from eight sites at depths spanning between 0.8 and 101.9 m below seafloor. We describe the metabolic potential of sediment microorganisms, and discuss expressed genes involved in tRNA, mRNA, and rRNA modifications that enable physiological flexibility of bacteria and archaea in the hydrothermal subsurface. Microbial taxa in hydrothermally influenced settings like Guaymas Basin may particularly depend on these catalytic RNA functions since they modulate the activity of cells under elevated temperatures and steep geochemical gradients. Expressed genes for DNA repair, protein maintenance and circadian rhythm were also identified. The concerted interaction of many of these genes may be crucial for microorganisms to survive and to thrive in the Guaymas Basin subsurface biosphere.
Mapping epigenetic modifications by sequencing technologies
Authors: Chen Xiufei , Xu Haiqi , Shu Xiao , Song Chun-Xiao 
Published: September 2023

Abstract
The “epigenetics” concept was first described in 1942. Thus far, chemical modifications on histones, DNA, and RNA have emerged as three important building blocks of epigenetic modifications. Many epigenetic modifications have been intensively studied and found to be involved in most essential biological processes as well as human diseases, including cancer. Precisely and quantitatively mapping over 100 [1], 17 [2], and 160 [3] different known types of epigenetic modifications in histone, DNA, and RNA is the key to understanding the role of epigenetic modifications in gene regulation in diverse biological processes. With the rapid development of sequencing technologies, scientists are able to detect specific epigenetic modifications with various quantitative, high-resolution, whole-genome/transcriptome approaches. Here, we summarize recent advances in epigenetic modification sequencing technologies, focusing on major histone, DNA, and RNA modifications in mammalian cells.
Local symmetry distortion induced anomalous thermal conduction in thermoelectric layered oxyselenides
Authors: Wei Bin , Li Jiale , Yang Yueyang , Li Wang , Zhou Zhifang , Zheng Yunpeng , Zhang Wenyu , Chai Yifan , Chang Zheng , Nan Ce-Wen , Lin Yuan-Hua 
Published: September 2023

AbstractPolyhedral distortion, associated closely with the atomic arrangement and interatomic interactions, drives many unique behaviors in solids, such as phase transition and negative thermal expansion. In thermoelectric heteroanionic oxides, the anionic polyhedra are widely present, but their effect on thermal transport is rarely investigated. Here, we report an anomalous thermal conduction induced by local symmetry distortion in layered oxyselenides via solving the Boltzmann transport equation based on first-principles calculations. We found interestingly that lighter BiCuSeO exhibits lower thermal conductivity than heavier BiAgSeO. Due to the different distorted degrees of CuSe4 and AgSe4 tetrahedrons, Cu prefers the in-plane vibration, while Ag has more tendency of out-of-plane vibration. Thus, the heat-carrying phonons dominated by the rattling-like vibration of Cu are significantly suppressed, resulting in lower thermal conductivity of BiCuSeO. This study highlights the importance of polyhedral distortion in regulating thermal conduction in layered heteroanionic materials.
Complex Ga2O3 polymorphs explored by accurate and general-purpose machine-learning interatomic potentials
Authors: Zhao Junlei , Byggmästar Jesper , He Huan , Nordlund Kai , Djurabekova Flyura , Hua Mengyuan 
Published: September 2023

AbstractGa2O3 is a wide-band gap semiconductor of emergent importance for applications in electronics and optoelectronics. However, vital information of the properties of complex coexisting Ga2O3 polymorphs and low-symmetry disordered structures is missing. We develop two types of machine-learning Gaussian approximation potentials (ML-GAPs) for Ga2O3 with high accuracy for β/κ/α/δ/γ polymorphs and generality for disordered stoichiometric structures. We release two versions of interatomic potentials in parallel, namely soapGAP and tabGAP, for high accuracy and exceeding speedup, respectively. Both potentials can reproduce the structural properties of all the five polymorphs in an exceptional agreement with ab initio results, meanwhile boost the computational efficiency with 5 × 102 and 2 × 105 computing speed increases compared to density functional theory, respectively. Moreover, the Ga2O3 liquid-solid phase transition proceeds in three different stages. This experimentally unrevealed complex dynamics can be understood in terms of distinctly different mobilities of O and Ga sublattices in the interfacial layer.