bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microscopic Description of Basal Stress Generated by Granular Free‐Surface Flows
Authors: Du Junhan , Zhou Gordon G. D. , Cui Kahlil F. E. 
Published: May 2023

AbstractGeophysical flows grow in volume and impact potential by eroding and entraining bed material during movement, posing potential risks to human lives and facilities downstream. This granular process is controlled by the basal stress and its fluctuations at the flow‐bed interface. Therefore, it is essential to provide physical insights into the basal stresses generated by granular flows for hazard risk management. In this study, we conduct a series of DEM simulations of channelized granular free‐surface flows to gain a micromechanical understanding of particle‐bed interactions. Basal normal and shear stresses are recorded and analyzed quantitatively through three statistical metrics: time‐averaged mean value, maximum value, and standard deviation. The relationship of these quantities with the bulk and basal flow properties and the micromechanical quantities that control stress fluctuations are discussed. Results show that the basal stress exhibits a distinct transition from a dense to dilute flow regime at a critical Savage number of 0.1, coinciding with the transition of stress‐generating and transmission mechanisms from being friction‐dominated to collision‐dominated. Maximum basal normal and shear stresses scale with the particle‐bed impact velocities in the form of a power law relation. Stress fluctuations scale with the granular temperature, revealing its dependence on random particle motions. A unified scaling law is proposed to link the standard deviation of basal stresses with the free particle volume, covering a wide range of flow regimes from dense to dilute flow.
Dynamics of Air Flow in Partially Water‐Saturated Porous Media
Authors: Ben‐Noah Ilan , Friedman Shmulik P. , Berkowitz Brian 
Published: May 2023

AbstractDynamics of flowing air in partially water‐saturated, porous geological formations are governed by a wide range of forces and parameters. These dynamics are reviewed in the contexts of flow patterns that arise and the corresponding applicability of diverse modeling approaches. The importance of reliable gas‐liquid flow models draws from the key role gases play in earth systems, and the various engineering practices involving air injection into geological formations. Here, we focus on air flow in water‐wet porous media. We survey the factors that affect flow patterns and phase configurations, and the measures that quantify them. For single‐phase flow in saturated media (i.e., air flow in dry media or water flow in water‐saturated media), the continuum approach (Darcy's law) is generally applicable and offers a good interpretive tool. However, the coupled two‐phase flow continuum approach appears appropriate only for phase‐saturation degrees that allow both phases to be continuous in the flow domain. Furthermore, air flow in wet media is highly unstable. As a result, air commonly flows in preferential pathways or in the form of bubbles and ganglia, which are not amenable to continuum modeling. On the other hand, pore‐scale models that account for the complex geometries and interfaces between the fluids and the media require extreme computational efforts, and generally inaccessible details on medium characteristics. Other stochastically‐based representations, such as percolation theory, have value in the conceptualization of complex flow problems but demonstrate limited success in interpreting phase configurations, saturation degrees, and relative permeabilities.
Localization-enhanced moiré exciton in twisted transition metal dichalcogenide heterotrilayer superlattices
Authors: Zheng Haihong , Wu Biao , Li Shaofei , Ding Junnan , He Jun , Liu Zongwen , Wang Chang-Tian , Wang Jian-Tao , Pan Anlian , Liu Yanping 
Published: May 2023

AbstractThe stacking of twisted two-dimensional (2D) layered materials has led to the creation of moiré superlattices, which have become a new platform for the study of quantum optics. The strong coupling of moiré superlattices can result in flat minibands that boost electronic interactions and generate interesting strongly correlated states, including unconventional superconductivity, Mott insulating states, and moiré excitons. However, the impact of adjusting and localizing moiré excitons in Van der Waals heterostructures has yet to be explored experimentally. Here, we present experimental evidence of the localization-enhanced moiré excitons in the twisted WSe2/WS2/WSe2 heterotrilayer with type-II band alignments. At low temperatures, we observed multiple excitons splitting in the twisted WSe2/WS2/WSe2 heterotrilayer, which is manifested as multiple sharp emission lines, in stark contrast to the moiré excitonic behavior of the twisted WSe2/WS2 heterobilayer (which has a linewidth 4 times wider). This is due to the enhancement of the two moiré potentials in the twisted heterotrilayer, enabling highly localized moiré excitons at the interface. The confinement effect of moiré potential on moiré excitons is further demonstrated by changes in temperature, laser power, and valley polarization. Our findings offer a new approach for localizing moiré excitons in twist-angle heterostructures, which has the potential for the development of coherent quantum light emitters.
Phase 1 dose-escalation study evaluating the safety, pharmacokinetics, and clinical activity of OBI-3424 in patients with advanced or metastatic solid tumors
Authors: Tsimberidou Apostolia Maria , Verschraegen Claire F. , Wesolowski Robert , Shia Chi-Sheng , Hsu Pei , Pearce Tillman E. 
Published: May 2023

Abstract
Background
Report of a Phase 1 dose-escalation study of OBI-3424 monotherapy in patients with advanced solid tumors (NCT03592264).

Methods
A classic 3 + 3 design was used to determine the maximum tolerated dose and recommended Phase 2 dose (RP2D) of OBI-3424 administered intravenously, as a single agent, at doses of 1, 2, 4, 6, 8, or 12 mg/m2 (days 1 and 8 of a 21-day cycle, Schedule A) or 8, 10, 12, or 14 mg/m2 (day 1 of a 21-day cycle, Schedule B).

Results
Dose-limiting hematologic toxicities at 12 mg/m2 in Schedule A led to dose and schedule modifications (Schedule B). In Schedule B, maximum tolerated dose was not reached at the maximum dose tested (14 mg/m2). Grade ≥3 anemia was noted in 3/6 patients treated at 14 mg/m2; the RP2D was 12 mg/m2 (Schedule B). Grade ≥3 treatment-emergent adverse events were experienced by 19/39 (49%) and included anemia (41%) and thrombocytopenia (26%); three patients experienced serious treatment-emergent adverse events (grade ≥3 anemia and thrombocytopenia). One patient had a partial response and 21/33 (64%) had stable disease.

Conclusions
The RP2D is 12 mg/m2 once every 3 weeks. OBI-3424 was well tolerated; dose-dependent, noncumulative thrombocytopenia and anemia were dose-limiting.
Clinical-grade human umbilical cord-derived mesenchymal stem cells improved skeletal muscle dysfunction in age-associated sarcopenia mice
Authors: Wang Chao , Zhao Bichun , Zhai Jinglei , Wang Ailin , Cao Ning , Liao Tuling , Su Ruyu , He Lijuan , Li Yanhua , Pei Xuetao , Jia Yali , Yue Wen 
Published: May 2023

AbstractWith the expansion of the aging population, age-associated sarcopenia (AAS) has become a severe clinical disease of the elderly and a key challenge for healthy aging. Regrettably, no approved therapies currently exist for treating AAS. In this study, clinical-grade human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were administrated to two classic mouse models (SAMP8 mice and D-galactose-induced aging mice), and their effects on skeletal muscle mass and function were investigated by behavioral tests, immunostaining, and western blotting. Core data results showed that hUC-MSCs significantly restored skeletal muscle strength and performance in both mouse models via mechanisms including raising the expression of crucial extracellular matrix proteins, activating satellite cells, enhancing autophagy, and impeding cellular aging. For the first time, the study comprehensively evaluates and demonstrates the preclinical efficacy of clinical-grade hUC-MSCs for AAS in two mouse models, which not only provides a novel model for AAS, but also highlights a promising strategy to improve and treat AAS and other age-associated muscle diseases.
Revisiting the role of mesenchymal stem cells in tuberculosis and other infectious diseases
Authors: Devi Annu , Pahuja Isha , Singh Shashi Prakash , Verma Akanksha , Bhattacharya Debapriya , Bhaskar Ashima , Dwivedi Ved Prakash , Das Gobardhan 
Published: May 2023

AbstractMesenchymal stem cells (MSCs) play diverse roles ranging from regeneration and wound healing to immune signaling. Recent investigations have indicated the crucial role of these multipotent stem cells in regulating various aspects of the immune system. MSCs express unique signaling molecules and secrete various soluble factors that play critical roles in modulating and shaping immune responses, and in some other cases, MSCs can also exert direct antimicrobial effects, thereby helping with the eradication of invading organisms. Recently, it has been demonstrated that MSCs are recruited at the periphery of the granuloma containing Mycobacterium tuberculosis and exert “Janus”-like functions by harboring pathogens and mediating host protective immune responses. This leads to the establishment of a dynamic balance between the host and the pathogen. MSCs function through various immunomodulatory factors such as nitric oxide (NO), IDO, and immunosuppressive cytokines. Recently, our group has shown that M.tb uses MSCs as a niche to evade host protective immune surveillance mechanisms and establish dormancy. MSCs also express a large number of ABC efflux pumps; therefore, dormant M.tb residing in MSCs are exposed to a suboptimal dose of drugs. Therefore, it is highly likely that drug resistance is coupled with dormancy and originates within MSCs. In this review, we discussed various immunomodulatory properties of MSCs, their interactions with important immune cells, and soluble factors. We also discussed the possible roles of MSCs in the outcome of multiple infections and in shaping the immune system, which may provide insight into therapeutic approaches using these cells in different infection models.
Molecular basis for recognition and deubiquitination of 40S ribosomes by Otu2
Authors: Ikeuchi Ken , Ivic Nives , Buschauer Robert , Cheng Jingdong , Fröhlich Thomas , Matsuo Yoshitaka , Berninghausen Otto , Inada Toshifumi , Becker Thomas , Beckmann Roland 
Published: May 2023

AbstractIn actively translating 80S ribosomes the ribosomal protein eS7 of the 40S subunit is monoubiquitinated by the E3 ligase Not4 and deubiquitinated by Otu2 upon ribosomal subunit recycling. Despite its importance for translation efficiency the exact role and structural basis for this translational reset is poorly understood. Here, structural analysis by cryo-electron microscopy of native and reconstituted Otu2-bound ribosomal complexes reveals that Otu2 engages 40S subunits mainly between ribosome recycling and initiation stages. Otu2 binds to several sites on the intersubunit surface of the 40S that are not occupied by any other 40S-binding factors. This binding mode explains the discrimination against 80S ribosomes via the largely helical N-terminal domain of Otu2 as well as the specificity for mono-ubiquitinated eS7 on 40S. Collectively, this study reveals mechanistic insights into the Otu2-driven deubiquitination steps for translational reset during ribosome recycling/(re)initiation.
Germline modifiers of the tumor immune microenvironment implicate drivers of cancer risk and immunotherapy response
Authors: Pagadala Meghana , Sears Timothy J. , Wu Victoria H. , Pérez-Guijarro Eva , Kim Hyo , Castro Andrea , Talwar James V. , Gonzalez-Colin Cristian , Cao Steven , Schmiedel Benjamin J. , Goudarzi Shervin , Kirani Divya , Au Jessica , Zhang Tongwu , Landi Teresa , Salem Rany M. , Morris Gerald P. , Harismendy Olivier , Patel Sandip Pravin , Alexandrov Ludmil B. , Mesirov Jill P. , Zanetti Maurizio , Day Chi-Ping , Fan Chun Chieh , Thompson Wesley K. , Merlino Glenn , Gutkind J. Silvio , Vijayanand Pandurangan , Carter Hannah 
Published: May 2023

AbstractWith the continued promise of immunotherapy for treating cancer, understanding how host genetics contributes to the tumor immune microenvironment (TIME) is essential to tailoring cancer screening and treatment strategies. Here, we study 1084 eQTLs affecting the TIME found through analysis of The Cancer Genome Atlas and literature curation. These TIME eQTLs are enriched in areas of active transcription, and associate with gene expression in specific immune cell subsets, such as macrophages and dendritic cells. Polygenic score models built with TIME eQTLs reproducibly stratify cancer risk, survival and immune checkpoint blockade (ICB) response across independent cohorts. To assess whether an eQTL-informed approach could reveal potential cancer immunotherapy targets, we inhibitCTSS, a gene implicated by cancer risk and ICB response-associated polygenic models;CTSSinhibition results in slowed tumor growth and extended survival in vivo. These results validate the potential of integrating germline variation and TIME characteristics for uncovering potential targets for immunotherapy.
Magnetic excitations beyond the single- and double-magnons
Authors: Elnaggar Hebatalla , Nag Abhishek , Haverkort Maurits W. , Garcia-Fernandez Mirian , Walters Andrew , Wang Ru-Pan , Zhou Ke-Jin , de Groot Frank 
Published: May 2023

AbstractA photon carrying one unit of angular momentum can change the spin angular momentum of a magnetic system with one unit (ΔMs = ±1) at most. This implies that a two-photon scattering process can manipulate the spin angular momentum of the magnetic system with a maximum of two units. Herein we describe a triple-magnon excitation in α-Fe2O3, which contradicts this conventional wisdom that only 1- and 2-magnon excitations are possible in a resonant inelastic X-ray scattering experiment. We observe an excitation at exactly three times the magnon energy, along with additional excitations at four and five times the magnon energy, suggesting quadruple and quintuple-magnons as well. Guided by theoretical calculations, we reveal how a two-photon scattering process can create exotic higher-rank magnons and the relevance of these quasiparticles for magnon-based applications.
Upscaled production of an ultramicroporous anion-exchange membrane enables long-term operation in electrochemical energy devices
Authors: Song Wanjie , Peng Kang , Xu Wei , Liu Xiang , Zhang Huaqing , Liang Xian , Ye Bangjiao , Zhang Hongjun , Yang Zhengjin , Wu Liang , Ge Xiaolin , Xu Tongwen 
Published: May 2023

AbstractThe lack of high-performance and substantial supply of anion-exchange membranes is a major obstacle to future deployment of relevant electrochemical energy devices. Here, we select two isomers (m-terphenyl and p-terphenyl) and balance their ratio to prepare anion-exchange membranes with well-connected and uniformly-distributed ultramicropores based on robust chemical structures. The anion-exchange membranes display high ion-conducting, excellent barrier properties, and stability exceeding 8000 h at 80 °C in alkali. The assembled anion-exchange membranes present a desirable combination of performance and durability in several electrochemical energy storage devices: neutral aqueous organic redox flow batteries (energy efficiency of 77.2% at 100 mA cm−2, with negligible permeation of redox-active molecules over 1100 h), water electrolysis (current density of 5.4 A cm−2at 1.8 V, 90 °C, with durability over 3000 h), and fuel cells (power density of 1.61 W cm−2under a catalyst loading of 0.2 mg cm−2, with open-circuit voltage durability test over 1000 h). As a demonstration of upscaled production, the anion-exchange membranes achieve roll-to-roll manufacturing with a width greater than 1000 mm.
Brain proteomic analysis implicates actin filament processes and injury response in resilience to Alzheimer’s disease
Authors: Huang Zhi , Merrihew Gennifer E. , Larson Eric B. , Park Jea , Plubell Deanna , Fox Edward J. , Montine Kathleen S. , Latimer Caitlin S. , Dirk Keene C. , Zou James Y. , MacCoss Michael J. , Montine Thomas J. 
Published: May 2023

AbstractResilience to Alzheimer’s disease is an uncommon combination of high disease burden without dementia that offers valuable insights into limiting clinical impact. Here we assessed 43 research participants meeting stringent criteria, 11 healthy controls, 12 resilience to Alzheimer’s disease and 20 Alzheimer’s disease with dementia and analyzed matched isocortical regions, hippocampus, and caudate nucleus by mass spectrometry-based proteomics. Of 7115 differentially expressed soluble proteins, lower isocortical and hippocampal soluble Aβ levels is a significant feature of resilience when compared to healthy control and Alzheimer’s disease dementia groups. Protein co-expression analysis reveals 181 densely-interacting proteins significantly associated with resilience that were enriched for actin filament-based processes, cellular detoxification, and wound healing in isocortex and hippocampus, further supported by four validation cohorts. Our results suggest that lowering soluble Aβ concentration may suppress severe cognitive impairment along the Alzheimer’s disease continuum. The molecular basis of resilience likely holds important therapeutic insights.
High-throughput single nucleus total RNA sequencing of formalin-fixed paraffin-embedded tissues by snRandom-seq
Authors: Xu Ziye , Zhang Tianyu , Chen Hongyu , Zhu Yuyi , Lv Yuexiao , Zhang Shunji , Chen Jiaye , Chen Haide , Yang Lili , Jiang Weiqin , Ni Shengyu , Lu Fangru , Wang Zhaolun , Yang Hao , Dong Ling , Chen Feng , Zhang Hong , Chen Yu , Liu Jiong , Zhang Dandan , Fan Longjiang , Guo Guoji , Wang Yongcheng 
Published: May 2023

AbstractFormalin-fixed paraffin-embedded (FFPE) tissues constitute a vast and valuable patient material bank for clinical history and follow-up data. It is still challenging to achieve single cell/nucleus RNA (sc/snRNA) profile in FFPE tissues. Here, we develop a droplet-based snRNA sequencing technology (snRandom-seq) for FFPE tissues by capturing full-length total RNAs with random primers. snRandom-seq shows a minor doublet rate (0.3%), a much higher RNA coverage, and detects more non-coding RNAs and nascent RNAs, compared with state-of-art high-throughput scRNA-seq technologies. snRandom-seq detects a median of >3000 genes per nucleus and identifies 25 typical cell types. Moreover, we apply snRandom-seq on a clinical FFPE human liver cancer specimen and reveal an interesting subpopulation of nuclei with high proliferative activity. Our method provides a powerful snRNA-seq platform for clinical FFPE specimens and promises enormous applications in biomedical research.
PREDICT validity for prognosis of breast cancer patients with pathogenic BRCA1/2 variants
Authors: Muranen Taru A. , Morra Anna , Khan Sofia , Barnes Daniel R. , Bolla Manjeet K. , Dennis Joe , Keeman Renske , Leslie Goska , Parsons Michael T. , Wang Qin , Ahearn Thomas U. , Aittomäki Kristiina , Andrulis Irene L. , Arun Banu K. , Behrens Sabine , Bialkowska Katarzyna , Bojesen Stig E. , Camp Nicola J. , Chang-Claude Jenny , Czene Kamila , Devilee Peter ,   HEBON investigators, Domchek Susan M. , Dunning Alison M. , Engel Christoph , Evans D. Gareth , Gago-Dominguez Manuela , García-Closas Montserrat , Gerdes Anne-Marie , Glendon Gord , Guénel Pascal , Hahnen Eric , Hamann Ute , Hanson Helen , Hooning Maartje J. , Hoppe Reiner , Izatt Louise , Jakubowska Anna , James Paul A. , Kristensen Vessela N. , Lalloo Fiona , Lindeman Geoffrey J. , Mannermaa Arto , Margolin Sara , Neuhausen Susan L. , Newman William G. , Peterlongo Paolo , Phillips Kelly-Anne , Pujana Miquel Angel , Rantala Johanna , Rønlund Karina , Saloustros Emmanouil , Schmutzler Rita K. , Schneeweiss Andreas , Singer Christian F. , Suvanto Maija , Tan Yen Yen , Teixeira Manuel R. , Thomassen Mads , Tischkowitz Marc , Tripathi Vishakha , Wappenschmidt Barbara , Zhao Emily , Easton Douglas F. , Antoniou Antonis C. , Chenevix-Trench Georgia , Pharoah Paul D. P. , Schmidt Marjanka K. , Blomqvist Carl , Nevanlinna Heli 
Published: May 2023

AbstractWe assessed the PREDICT v 2.2 for prognosis of breast cancer patients with pathogenic germline BRCA1 and BRCA2 variants, using follow-up data from 5453 BRCA1/2 carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC). PREDICT for estrogen receptor (ER)-negative breast cancer had modest discrimination for BRCA1 carrier patients overall (Gönen & Heller unbiased concordance 0.65 in CIMBA, 0.64 in BCAC), but it distinguished clearly the high-mortality group from lower risk categories. In an analysis of low to high risk categories by PREDICT score percentiles, the observed mortality was consistently lower than the expected mortality, but the confidence intervals always included the calibration slope. Altogether, our results encourage the use of the PREDICT ER-negative model in management of breast cancer patients with germline BRCA1 variants. For the PREDICT ER-positive model, the discrimination was slightly lower in BRCA2 variant carriers (concordance 0.60 in CIMBA, 0.65 in BCAC). Especially, inclusion of the tumor grade distorted the prognostic estimates. The breast cancer mortality of BRCA2 carriers was underestimated at the low end of the PREDICT score distribution, whereas at the high end, the mortality was overestimated. These data suggest that BRCA2 status should also be taken into consideration with tumor characteristics, when estimating the prognosis of ER-positive breast cancer patients.
Vertex dominated superconductivity in intercalated FeSe
Authors: Acharya Swagata , Katsnelson Mikhail I. , van Schilfgaarde Mark 
Published: May 2023

AbstractBulk FeSe becomes superconducting below 9 K, but the critical temperature (Tc) is enhanced almost universally by a factor of ~4–5 when it is intercalated with alkali elements. How intercalation modifies the structure is known from in-situ X-ray and neutron scattering techniques, but why Tc changes so dramatically is not known. Here we show that there is one-to-one correspondence between the enhancement in magnetic instabilities at certain q vectors and superconducting pairing vertex, even while the nuclear spin relaxation rate 1/(T1T) may not reflect this enhancement. Intercalation modifies electronic screening both in the plane and also between layers. We disentangle quantitatively how superconducting pairing vertex gains from each such changes in electronic screening. Intercalated FeSe provides an archetypal example of superconductivity where information derived from the single-particle electronic structure appears to be insufficient to account for the origins of superconductivity, even when they are computed including correlation effects. We show that the five-fold enhancement in Tc on intercalation is not sensitive to the exact position of the dxy at Γ point, as long as it stays close to EF. Finally, we show that intercalation also significantly softens the collective charge excitations, suggesting the electron-phonon interaction could play some role in intercalated FeSe.