bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying and Classifying Streamflow Ensembles Using a Broad Range of Metrics for an Evidence‐Based Analysis: Colorado River Case Study
Authors: Salehabadi Homa , Tarboton David G. , Wheeler Kevin G. , Smith Rebecca , Baker Sarah 
Published: July 2024

AbstractStochastic hydrology produces ensembles of time series that represent plausible future streamflow to simulate and test the operation of water resource systems. A premise of stochastic hydrology is that ensembles should be statistically representative of what may occur in the future. In the past, the application of this premise has involved producing ensembles that are statistically equivalent to the observed or historical streamflow sequence. This requires a number of metrics or statistics that can be used to test statistical similarity. However, with climate change, the past may no longer be representative of the future. Ensembles to test future systems operations should recognize non‐stationarity and include time series representing expected changes. This poses challenges for their testing and validation. In this paper, we suggest an evidence‐based analysis in which streamflow ensembles, whether statistically similar to and representative of the past or a changing future, should be characterized and assessed using an extensive set of statistical metrics. We have assembled a broad set of metrics and applied them to annual streamflow in the Colorado River at Lees Ferry to illustrate the approach. We have also developed a tree‐based classification approach to categorize both ensembles and metrics. This approach provides a way to visualize and interpret differences between streamflow ensembles. The metrics presented, along with the classification, provide an analytical framework for characterizing and assessing the suitability of future streamflow ensembles, recognizing the presence of non‐stationarity. This contributes to better planning in large river basins, such as the Colorado, facing water supply shortages.
YAP/TAZ interacts with RBM39 to confer resistance against indisulam
Authors: Ando Toshinori , Okamoto Kento , Ueda Yume , Kataoka Nanako , Shintani Tomoaki , Yanamoto Souichi , Miyauchi Mutsumi , Kajiya Mikihito 
Published: July 2024

AbstractThe Hippo pathway and its downstream effectors, Yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ), are essential for cell growth and organ development. Emerging evidence revealed that the Hippo pathway and YAP/TAZ are frequently dysregulated by multiple genetic alterations in solid cancers including head and neck squamous cell carcinoma (HNSCC); however, the YAP/TAZ-nuclear interactome remains unclear. RNA-binding motif protein 39 (RBM39) enhances transcriptional activity of several transcription factors and also regulates mRNA splicing. Indisulam degrading RBM39 induces alternative splicing, leading to cell death. However, clinical trials of indisulam have failed to show effectiveness. Therefore, clarifying the resistance mechanism against splicing inhibitors is urgently required. In this study, we identified RBM39 as a novel YAP/TAZ-interacting molecule by proteome analysis. RBM39 promoted YAP/TAZ transcriptional activity. We further elucidated that indisulam reduces RBM39/YAP/TAZ-mediated integrin or collagen expression, thereby inactivating focal adhesion kinase (FAK) important for cell survival. Moreover, indisulam also induced alternative splicing of cell cycle- or DNA metabolism-related genes. YAP/TAZ hyperactivation delayed indisulam-induced RBM39 degradation, which restored the integrin/collagen expression to activate FAK, and alternative splicing, thereby conferring resistance against indisulam in vitro and in vivo. Our findings may aid to develop a novel cancer therapy focusing on YAP/TAZ/RBM39 interaction.
SHR-A1811 (antibody-drug conjugate) in advanced HER2-mutant non-small cell lung cancer: a multicenter, open-label, phase 1/2 study
Authors: Li Ziming , Song Zhengbo , Hong Wei , Yang Nong , Wang Yongsheng , Jian Hong , Liang Zibin , Hu Sheng , Peng Min , Yu Yan , Wang Yan , Jiao Zicong , Zhao Kaijing , Song Ke , Li You , Shi Wei , Lu Shun 
Published: July 2024

AbstractA dose-escalation and expansion, phase 1/2 study (ClinicalTrials.gov, NCT04818333) was conducted to assess the novel antibody-drug conjugate SHR-A1811 in pretreated HER2-altered advanced non-small cell lung cancer (NSCLC). Here, we report results from the phase 1 portion. Patients who had previously failed or were intolerant to platinum-based chemotherapy were enrolled and received SHR-A1811 intravenously at doses of 3.2 to 8.0 mg/kg every 3 weeks. Dose escalation followed a Bayesian logistic regression model that included overdose control, with subsequent selection of tolerable levels for dose expansion. Overall, 63 patients were enrolled, including 43 receiving a recommended dose for expansion of 4.8 mg/kg. All patients had HER2-mutant disease. Dose-limiting toxicity occurred in one patient in the 8.0 mg/kg dose cohort. Grade ≥ 3 treatment-related adverse events occurred in 29 (46.0%) patients. One patient in the 6.4 mg/kg cohort died due to interstitial lung disease. As of April 11, 2023, the 4.8 mg/kg cohort showed an objective response rate of 41.9% (95% CI 27.0–57.9), and a disease control rate of 95.3% (95% CI 84.2–99.4). The median duration of response was 13.7 months, with 13 of 18 responses ongoing. The median progression-free survival was 8.4 months (95% CI 7.1–15.0). SHR-A1811 demonstrated favourable safety and clinically meaningful efficacy in pretreated advanced HER2-mutant NSCLC.
A combination treatment based on drug repurposing demonstrates mutation-agnostic efficacy in pre-clinical retinopathy models
Authors: Leinonen Henri , Zhang Jianye , Occelli Laurence M. , Seemab Umair , Choi Elliot H. , L.P. Marinho Luis Felipe , Querubin Janice , Kolesnikov Alexander V. , Galinska Anna , Kordecka Katarzyna , Hoang Thanh , Lewandowski Dominik , Lee Timothy T. , Einstein Elliott E. , Einstein David E. , Dong Zhiqian , Kiser Philip D. , Blackshaw Seth , Kefalov Vladimir J. , Tabaka Marcin , Foik Andrzej , Petersen-Jones Simon M. , Palczewski Krzysztof 
Published: July 2024

AbstractInherited retinopathies are devastating diseases that in most cases lack treatment options. Disease-modifying therapies that mitigate pathophysiology regardless of the underlying genetic lesion are desirable due to the diversity of mutations found in such diseases. We tested a systems pharmacology-based strategy that suppresses intracellular cAMP and Ca2+ activity via G protein-coupled receptor (GPCR) modulation using tamsulosin, metoprolol, and bromocriptine coadministration. The treatment improves cone photoreceptor function and slows degeneration in Pde6βrd10 and RhoP23H/WT retinitis pigmentosa mice. Cone degeneration is modestly mitigated after a 7-month-long drug infusion in PDE6A-/- dogs. The treatment also improves rod pathway function in an Rpe65-/- mouse model of Leber congenital amaurosis but does not protect from cone degeneration. RNA-sequencing analyses indicate improved metabolic function in drug-treated Rpe65-/- and rd10 mice. Our data show that catecholaminergic GPCR drug combinations that modify second messenger levels via multiple receptor actions provide a potential disease-modifying therapy against retinal degeneration.
Sustained North Atlantic warming drove anomalously intense MIS 11c interglacial
Authors: Hu Hsun-Ming , Marino Gianluca , Pérez-Mejías Carlos , Spötl Christoph , Yokoyama Yusuke , Yu Jimin , Rohling Eelco , Kano Akihiro , Ludwig Patrick , Pinto Joaquim G. , Michel Véronique , Valensi Patricia , Zhang Xin , Jiang Xiuyang , Mii Horng-Sheng , Chien Wei-Yi , Tsai Hsien-Chen , Sung Wen-Hui , Hsu Chia-Hao , Starnini Elisabetta , Zunino Marta , Shen Chuan-Chou 
Published: July 2024

AbstractThe Marine Isotope Stage (MIS) 11c interglacial and its preceding glacial termination represent an enigmatically intense climate response to relatively weak insolation forcing. So far, a lack of radiometric age control has confounded a detailed assessment of the insolation-climate relationship during this period. Here, we present 230Th-dated speleothem proxy data from northern Italy and compare them with palaeoclimate records from the North Atlantic region. We find that interglacial conditions started in subtropical to middle latitudes at 423.1 ± 1.3 thousand years (kyr) before present, during a first weak insolation maximum, whereas northern high latitudes remained glaciated (sea level ~ 40 m below present). Some 14.5 ± 2.8 kyr after this early subtropical onset, peak interglacial conditions were reached globally, with sea level 6–13 m above present, despite weak insolation forcing. We attribute this remarkably intense climate response to an exceptionally long (~15 kyr) episode of intense poleward heat flux transport prior to the MIS 11c optimum.
Discovery of a terpene synthase synthesizing a nearly non-flexible eunicellane reveals the basis of flexibility
Authors: Li Jinfeng , Chen Bao , Fu Zunyun , Mao Jingjing , Liu Lijun , Chen Xiaochen , Zheng Mingyue , Wang Chang-Yun , Wang Chengyuan , Guo Yue-Wei , Xu Baofu 
Published: July 2024

AbstractEunicellane diterpenoids, containing a typical 6,10-bicycle, are bioactive compounds widely present in marine corals, but rarely found in bacteria and plants. The intrinsic macrocycle exhibits innate structural flexibility resulting in dynamic conformational changes. However, the mechanisms controlling flexibility remain unknown. The discovery of a terpene synthase, MicA, that is responsible for the biosynthesis of a nearly non-flexible eunicellane skeleton, enable us to propose a feasible theory about the flexibility in eunicellane structures. Parallel studies of all eunicellane synthases in nature discovered to date, including 2Z-geranylgeranyl diphosphate incubations and density functional theory-based Boltzmann population computations, reveale that a trans-fused bicycle with a 2Z-configuration alkene restricts conformational flexibility resulting in a nearly non-flexible eunicellane skeleton. The catalytic route and the enzymatic mechanism of MicA are also elucidated by labeling experiments, density functional theory calculations, structural analysis of the artificial intelligence-based MicA model, and mutational studies.
Socio-economic and environmental trade-offs in Amazonian protected areas and Indigenous territories revealed by assessing competing land uses
Authors: den Braber Bowy , Oldekop Johan A. , Devenish Katie , Godar Javier , Nolte Christoph , Schmoeller Marina , Evans Karl L. 
Published: July 2024

AbstractProtected area (PA) assessments rarely evaluate socio-economic and environmental impacts relative to competing land uses, limiting understanding of socio-environmental trade-offs from efforts to protect 30% of the globe by 2030. Here we assess deforestation and poverty outcomes (fiscal income, income inequality, sanitation and literacy) between 2000 and 2010 of strict PAs (SPAs), sustainable-use PAs (SUPAs) and Indigenous territories (ITs) compared with different land uses (agriculture and mining concessions) across ~5,500 census tracts in the Brazilian Legal Amazon. ITs reduced deforestation relative to all alternative land uses (48–83%) but had smaller socio-economic benefits compared with other protection types and land uses (18–36% depending on outcome), indicating that Indigenous communities experience socio-economic trade-offs. By contrast, SUPAs, and potentially SPAs, did not reduce deforestation relative to small-scale agriculture (landholdings <10 ha) but did so relative to larger agricultural landholdings (70–82%). Critically, these reductions in deforestation frequently occurred without negative socio-economic outcomes. By contrast, ITs and SUPAs protected against deforestation from mining, but at the cost of smaller improvements in income and inequality. Our results suggest that although PAs in the Brazilian Legal Amazon substantially reduced deforestation without compromising local socio-economic development, efforts to secure Indigenous rights need additional interventions to ensure these communities are not further disadvantaged.
Terahertz spectroscopy of collective charge density wave dynamics at the atomic scale
Authors: Sheng Shaoxiang , Abdo Mohamad , Rolf-Pissarczyk Steffen , Lichtenberg Kurt , Baumann Susanne , Burgess Jacob A. J. , Malavolti Luigi , Loth Sebastian 
Published: July 2024

AbstractCharge density waves are wave-like modulations of a material’s electron density that display collective amplitude and phase dynamics. The interaction with atomic impurities induces strong spatial heterogeneity of the charge-ordered phase. Direct real-space observation of phase excitation dynamics of such defect-induced charge modulation is absent. Here, by utilizing terahertz pump–probe spectroscopy in a scanning tunnelling microscope, we measure the ultrafast collective dynamics of the charge density wave in the transition metal dichalcogenide 2H-NbSe2 with atomic spatial resolution. The tip-enhanced electric field of the terahertz pulses excites oscillations of the charge density wave that vary in magnitude and frequency on the scale of individual atomic impurities. Overlapping phase excitations originating from the randomly distributed atomic defects in the surface create this spatially structured response of the charge density wave. This ability to observe collective charge order dynamics with local probes makes it possible to study the dynamics of correlated materials at the intrinsic length scale of their underlying interactions.
Phylogenetic relationships and genetic diversity of the Korean endemic Phedimus latiovalifolius (Crassulaceae) and its close relatives
Authors: Cho Myong-Suk , Kim Yongsung , Kim Seon-Hee , Jeon Ji-Hyeon , Yang JiYoung , Kim Seung-Chul 
Published: July 2024

AbstractPhedimus latiovalifolius (Y.N.Lee) D.C.Son & H.J.Kim is exclusively distributed in the high mountains in the Korean Peninsula, mainly along the Baekdudaegan mountain range. Despite its morphological and distributional distinction from other Phedimus Raf. species, its taxonomic identity and phylogenetic relationship with congeneric species remain unclear. This study employs genotyping-by-sequencing-derived genome-wide single nucleotide polymorphisms to establish the monophyly of P. latiovalifolius and its relationship with closely related species. Genetic diversity and population differentiation of P. latiovalifolius are also assessed to provide baseline genetic information for future conservation and management strategies. Our phylogenetic analyses robustly demonstrate the monophyletic nature of P. latiovalifolius, with P. aizoon (L.) ‘t Hart identified as its closest sister lineage. There is no genetic evidence supporting a hybrid origin of P. latiovalifolius from P. aizoon involving either P. ellacombeanus (Praeger) ‘t Hart or P. kamtschaticus (Fisch.) ‘t Hart. Population genetic analyses reveal two major groups within P. latiovalifolius. A higher genetic variation is observed in P. ellacombeanus than in the congeneric species. Notably, most of the genetic variation exists within P. latiovalifolius populations. Given its distribution and the potential role of Baekdudaegan as an East Asian Pleistocene refugia, P. latiovalifolius could be considered rare and endemic, persisting in the refugium across glacial/interglacial cycles.
Prediction of damage intensity to masonry residential buildings with convolutional neural network and support vector machine
Authors: Jędrzejczyk Adrian , Firek Karol , Rusek Janusz , Alibrandi Umberto 
Published: July 2024

AbstractDuring their life cycle, buildings are subjected to damage that reduces their performance and can pose a significant threat to structural safety. This paper presents the results of research into the creation of a model for predicting damage intensity of buildings located in mining terrains. The basis for the research was a database of technical and mining impact data for 185 masonry residential buildings. The intensity of damage to buildings was negligible and ranged from 0 to 6%. The Convolutional Neural Network (CNN) methodology was used to create the model. The Support Vector Machine (SVM) methodology, which is commonly used for analysis of this type of issue, was used for comparisons. The resulting models were evaluated by comparing parameters such as accuracy, precision, recall, and F1 score. The comparisons revealed only minor differences between the models. Despite the small range of damage intensity, the models created were able to achieve prediction results of around 80%. The SVM model had better results for training set accuracy, while the CNN model achieved higher values for F1 score and average precision for the test set. The results obtained justify the adoption of the CNN methodology as effective in the context of predicting the damage intensity of masonry residential buildings located in mining terrains.
Effect of ABCB1 most frequent polymorphisms on the accumulation of bictegravir in recombinant HEK293 cell lines
Authors: De Greef Julien , Akue Mathilde , Panin Nadtha , Delongie Kévin-Alexandre , André Marina , Mahieu Gwenaëlle , Hoste Emilia , Elens Laure , Belkhir Leïla , Haufroid Vincent 
Published: July 2024

AbstractBictegravir, a key second-generation integrase strand transfer inhibitor in the treatment of HIV, is subject to active efflux transport mediated by ABCB1 (P-glycoprotein). Several coding variants of ABCB1 have been described and associated with variable effects on substrate drugs pharmacokinetics. Here, we investigated the effect of the four most common coding ABCB1 single nucleotide polymorphisms (i.e., c.1199G > A, c.1236C > T, c.2677G > T and c.3435C > T) on the intracellular accumulation of bictegravir. Using a previously validated HEK293 recombinant cell line model, we found decreased bictegravir intracellular concentrations in cell lines overexpressing ABCB1 as compared to control cell lines, in line with the known role of ABCB1 in bictegravir transport. However, we were unable to demonstrate any significant difference in bictegravir intracellular accumulation when comparing HEK293 cells overexpressing the wild type (1236C-2677G-3435C, 1199G) or the variant (1236C-2677G-3435T, 1236T-2677T-3435T or 1199A) proteins. These findings suggest that the ABCB1 c.1199G > A and c.1236C > T-c.2677G > T-c.3435C > T variants have no or at least limited impact on the active transport of bictegravir by ABCB1.
Efficient leather spreading operations by dual-arm robotic systems
Authors: Huan Yuan , Ren Gongchang , Sun Jiangong , Jin Guang , Ding Xujiang , Du Wenhao 
Published: July 2024

AbstractTo achieve precise grasping and spreading of irregular sheet-like soft objects (such as leather) by robots, this study addresses several challenges, including the irregularity of leather edges and the ambiguity of feature recognition points. To tackle these issues, this paper proposes an innovative method that involves alternately grasping the lowest point twice and using planar techniques to effectively spread the leather. We improved the YOLOV8 algorithm by incorporating the BIFPN network structure and the WIOU loss function, and trained a dedicated dataset for the lowest grasping points and planar grasping points, thereby achieving high-precision recognition. Additionally, we determined the optimal posture for grasping the lowest point and constructed an experimental platform, successfully conducting multiple rounds of leather grasping and spreading experiments with a success rate of 72%. Through an in-depth analysis of the failed experiments, this study reveals the limitations of the current methods and provides valuable guidance for future research.
Genomic surveillance of malaria parasites in an indigenous community in the Peruvian Amazon
Authors: Cabrera-Sosa Luis , Nolasco Oscar , Kattenberg Johanna H. , Fernandez-Miñope Carlos , Valdivia Hugo O. , Barazorda Keare , Arévalo de los Rios Silvia , Rodriguez-Ferrucci Hugo , Vinetz Joseph M. , Rosanas-Urgell Anna , Van geertruyden Jean-Pierre , Gamboa Dionicia , Delgado-Ratto Christopher 
Published: July 2024

AbstractHard-to-reach communities represent Peru's main challenge for malaria elimination, but information about transmission in these areas is scarce. Here, we assessed Plasmodium vivax (Pv) and P. falciparum (Pf) transmission dynamics, resistance markers, and Pf hrp2/3 deletions in Nueva Jerusalén (NJ), a remote, indigenous community in the Peruvian Amazon with high population mobility. We collected samples from November 2019 to May 2020 by active (ACD) and passive case detection (PCD) in NJ. Parasites were identified with microscopy and PCR. Then, we analyzed a representative set of positive-PCR samples (Pv = 68, Pf = 58) using highly-multiplexed deep sequencing assays (AmpliSeq) and compared NJ parasites with ones from other remote Peruvian areas using population genetics indexes. The ACD intervention did not reduce malaria cases in the short term, and persistent malaria transmission was observed (at least one Pv infection was detected in 96% of the study days). In Nueva Jerusalen, the Pv population had modest genetic diversity (He = 0.27). Pf population had lower diversity (He = 0.08) and presented temporal clustering, one of these clusters linked to an outbreak in February 2020. Moreover, Pv and Pf parasites from NJ exhibited variable levels of differentiation (Pv Fst = 0.07–0.52 and Pf Fst = 0.11–0.58) with parasites from other remote areas. No artemisin resistance mutations but chloroquine (57%) and sulfadoxine-pyrimethamine (35–67%) were detected in NJ's Pf parasites. Moreover, pfhrp2/3 gene deletions were common (32–50% of parasites with one or both genes deleted). The persistent Pv transmission and the detection of a Pf outbreak with parasites genetically distinct from the local ones highlight the need for tailored interventions focusing on mobility patterns and imported infections in remote areas to eliminate malaria in the Peruvian Amazon.
Simultaneous production of syngas and carbon nanotubes from CO2/CH4 mixture over high-performance NiMo/MgO catalyst
Authors: Sae-tang Nonthicha , Saconsint Supanida , Srifa Atthapon , Koo-Amornpattana Wanida , Assabumrungrat Suttichai , Fukuhara Choji , Ratchahat Sakhon 
Published: July 2024

AbstractDirect conversion of biogas via the integrative process of dry reforming of methane (DRM) and catalytic methane decomposition (CDM) has received a great attention as a promising green catalytic process for simultaneous production of syngas and carbon nanotubes (CNTs). In this work, the effects of reaction temperature of 700–1100 °C and CH4/CO2 ratio of biogas were investigated over NiMo/MgO catalyst in a fixed bed reactor under industrial feed condition of pure biogas. The reaction at 700 °C showed a rapid catalyst deactivation within 3 h due to the formation of amorphous carbon on catalyst surface. At higher temperature of 800–900 °C, the catalyst can perform the excellent performance for producing syngas and carbon nanotubes. Interestingly, the smallest diameter and the highest graphitization of CNTs was obtained at high temperature of 1000 °C, while elevating temperature to 1100 °C leads to agglomeration of Ni particles, resulting in a larger size of CNTs. The reaction temperature exhibits optimum at 800 °C, providing the highest CNTs yield with high graphitization, high syngas purity up to 90.04% with H2/CO ratio of 1.1, and high biogas conversion (XCH4 = 86.44%, XCO2 = 95.62%) with stable performance over 3 h. The typical composition biogas (CH4/CO2 = 1.5) is favorable for the integration process, while the CO2 rich biogas caused a larger grain size of catalyst and a formation of molybdenum oxide nanorods (MoO3). The long-term stability of NiMo/MgO catalyst at 800 °C showed a stable trend (> 20 h). The experimental findings confirm that NiMo/MgO can perform the excellent activity and high stability at the optimum condition, allowing the process to be more promising for practical applications.