bluuebunny/crossref_metadata_2025 huggingface dataset:
Information geometry of Wasserstein statistics on shapes and affine deformations
Authors: Amari Shun-ichi , Matsuda Takeru
Published: July 2024

Information geometry and Wasserstein geometry are two main structures introduced in a manifold of probability distributions, and they capture its different characteristics. We study characteristics of Wasserstein geometry in the framework of [32] for the affine deformation statistical model, which is a multi-dimensional generalization of the location-scale model. We compare merits and demerits of estimators based on information geometry and Wasserstein geometry. The shape of a probability distribution and its affine deformation are separated in the Wasserstein geometry, showing its robustness against the waveform perturbation in exchange for the loss in Fisher efficiency. We show that the Wasserstein estimator is the moment estimator in the case of the elliptically symmetric affine deformation model. It coincides with the information-geometrical estimator (maximum-likelihood estimator) when the waveform is Gaussian. The role of the Wasserstein efficiency is elucidated in terms of robustness against waveform change.
Indian Agriculture Under Climate Change: The Competing Effect of Temperature and Rainfall Anomalies
Authors: Gallé Johannes , Katzenberger Anja
Published: July 2024

The latest generation of global climate models robustly projects that monsoon rainfall anomalies in India will significantly increase in the 21st century due to global warming. This raises the question of the impact of these changes on the agricultural yield. Based on annual district data for the years 1966-2014, we estimate the relationship between weather indices (amount of seasonal rainfall, number of wet days, average temperature) and the most widely grown kharif crops, including rice, in a flexible non-parametric way. We use the empirical relationship in order to predict district-specific crop yield based on the climate projections of eight evaluated state-of-the-art climate models under two global warming scenarios for the years 2021-2100. We find that the loss in rice yield by the end of the 21st century lies on average between 3 - 22% depending on the underlying emission scenario. For the sustainable scenario impacts range from an increase of 3.2% to a decrease of 12.1% for individual districts. In the worst-case scenario, all districts are negatively affected, with a predicted decrease in rice yield ranging from 34% to a decrease of 11.5% in the long run. Potential gains due to increasing rainfall are more than offset by the negative impacts of increasing temperature. Adaptation efforts in the worst-case global warming scenario would need to cut the negative impacts of temperature by 50% in order to reach the outcome of the sustainable scenario.
Feeding Assistance Skill Score: development and verification of reliability and validity
Authors: Nagano Ayano , Maeda Keisuke , Matsumoto Tomohiro , Murotani Kenta , Wakabayashi Hidetaka , Koyama Tamami , Nagai Takako , Mori Naoharu
Published: July 2024

Purpose

Feeding assistance should be safe and improve the assisted individual’s ability to feed, yet objective tools for evaluating these skills are lacking. This study focuses on developing a tool for assessing feeding assistance skills.

Methods

A group consisting of 25 experts employed the Delphi method to achieve a consensus on the essential items necessary for assessing feeding assistance skills. Subsequently, a draft score using a three-point scale was developed. To test the reliability of the draft scores, a group of 20 patients and 20 nurses was matched to record a meal assistance scene, which were independently evaluated by three raters. We computed the AC1 statistic to assess both intra- and inter-rater reliability, and further examined correlations between the Feeding Assistance Skill Score (FASS) scores and outcome items to verify validity.

Results

Initially, an 18-item draft score was generated using the Delphi method. Subsequently, seven items were omitted from the intra- or inter-rater reliability analysis. Furthermore, after discussion, researchers removed one item that assessed food cognition, because the agreement score between the two items was 91%. Finally, the 10-item FASS was developed, showing a correlation with dietary intake upon validation.

Conclusions

We successfully developed a scoring system for peer evaluation of feeding assistance skills. Future studies should aim to validate the FASS. The implementation of the FASS aims to assess the effectiveness of feeding assistance training and care quality, potentially improving safety and satisfaction for those receiving feeding assistance.
Predicting irrigation water quality indices in a typical mining dominated area in the Upper West region of Ghana using multiple machine learning techniques
Authors: Kazapoe Raymond Webrah , Sagoe Samuel Dzidefo , Abu Mahamuda
Published: July 2024

The quality of groundwater resources in artisanal mining districts in Ghana is under threat due to pollution; rendering the resource unsafe for drinking and irrigation purposes. This makes the assessment of the quality of groundwater resources a relevant aspect of groundwater studies as it informs decision making and monitoring. This study adopts 3 Machine Learning (ML) models, Support Vector Regression (SVR), Gradient Boost Regression (GBR), and Artificial Neural Network (ANN), to evaluate a variety of irrigation water quality metrics such as Sodium Percentage (Na%), Soluble Sodium Percentage (SSP), Sodium Adsorption Ratio (SAR), Residual Sodium Carbonate (RSC), Permeability Index (PI), Pollution Index of Groundwater (PIG), Kelly’s Ratio (KR), and Magnesium Hazard (MH). 105 samples were collected from a mining area in Northern Ghana and analysed through traditional methods. The Irrigation Water Quality Indices (IWQIs) demonstrate that all water samples are suitable for use as irrigable water with the exception of MH, Na%, PI, and PIG which revealed that 69.52%, 8.57%, 29.52%, and 3.81% are inappropriate for irrigation. SVR, GBR and ANN were used to establish important factors that may influence IWQIs in the area. The measured data was used as independent variables, and the derived IWQIs, the dependent variables. The results revealed that ANN, GBR, and SVR are all viable options for the prediction of IWQIs, but GBR exhibited variable performance in some indices making it lack consistency and thus falls a bit short compared to ANN and SVR. SVR models overall performed best with SVR-RSC having the highest accuracy.
CommentClass: A Robust Ensemble Machine Learning Model for Comment Classification
Authors: Rahman Md. Mostafizer , Shiplu Ariful Islam , Watanobe Yutaka
Published: July 2024

Enormous amounts of data are generated in the form of feedback or comments from online platforms such as social media, e-commerce, education, and programming. This feedback and comments hold significant value for making important strategic decisions; therefore, effectively analyzing them poses a major challenge. This research addresses the imperative need for an efficient comment classification model. To fill this research gap, we propose a robust ensemble machine learning (ML) model called CommentClass (RF+AdaBoost+SVM+Soft-Voting), specifically designed for the comment classification task. First, we developed eight (08) pipelines using various combinations of ML algorithms. Next, the fundamental ensemble techniques such as stacking, blending, hard-voting, soft-voting, and averaging are incorporated into these pipelines to improve comment classification performance. These ensemble models are able to discern the latent characteristics of diverse text comments, classifying them to achieve superior accuracy. The proposed CommentClass ensemble model achieved an impressive accuracy and F1-score of approximately 98% for comment classification on the YouTube dataset. This result represents an improvement in accuracy by approximately +3% compared to prior research on the same dataset. Moreover, the proposed CommentClass model obtained higher F1-scores of 90.26%, 87.04%, and 75.74%, on the Spambase, IMDB, and Twitter datasets, respectively, compared to other sophisticated models. Furthermore, the proposed CommentClass model exhibited significant accuracy on the SMS dataset and two distinct synthetic datasets.
Entrepreneurship education in East, West and North Africa Higher Education Institutions (HEIs): mapping agripreneurship curriculum and lecturers’ competencies
Authors: Okello Dickson , Mshenga Patience , Saidi Mwanarusi , Juma Fahad , Maria Sassi , Egeru Antony , Gogo Elisha
Published: July 2024

This study focused on mapping agripreneurship curriculum and lecturers’ competencies in 8 African Higher Education Institutions (HEIs), participating in the Strengthening Agri-Entrepreneurship and Community Engagement Training in East, West and North Africa (AgriENGAGE) joint Project. A sample of 194 lecturers from East, West, and North Africa participated in the study. The study employed a mixed method approach with concurrent nested research design methodology to collect information. Among the main results found in this study, the key aspects that were implemented in curricula were; business plan development (µ = 3.57), business opportunities identification (µ = 3.56), and communicating with value chain actors (= 3.51). Concerning the forms of entrepreneurship taught, most institutions focused on subsistence agripreneurship (µ = 3.23) with growth-oriented agripreneurship (µ = 2.50) and innovative-oriented agripreneurship (µ = 2.50) having the lowest rating. Regarding teaching methods within the provision of entrepreneurship education, most of the institutions were using traditional teaching methodologies with the common ones being formal lectures, field trips, in-class group discussions, and group project-based learning. Most lecturers had low teaching competencies concerning instructional quality and a moderate/average level of entrepreneurial competencies. The study recommends that universities should implement more professional development and pedagogical training over and above the subject competency to improve lecturers’ entrepreneurial competency.
Exploring the challenges of RNAi-based strategies for crop protection
Authors: Zhao Jian-Hua , Liu Qing-Yan , Xie Zong-Ming , Guo Hui-Shan
Published: July 2024

RNA silencing (or RNA interference, RNAi) initiated by double-stranded RNAs is a conserved mechanism for regulating gene expression in eukaryotes. RNAi-based crop protection strategies, including host-induced gene silencing (HIGS), spray-induced gene silencing (SIGS) and microbe-induced gene silencing (MIGS), have been successfully used against various pests and pathogens. Here, we highlight the challenges surrounding dsRNA design, large-scale production of dsRNA and dsRNA delivery systems. Addressing these questions will accelerate the lab-to-field transition of RNAi-based strategies. Moreover, based on studies of exogenous dsRNA-induced RNAi inheritance in Caenorhabditis elegans, we speculate that RNAi-based strategies would confer longer-lasting protection for crops against pests or fungal pathogens.
A Rare Simultaneous Detection of a Mid‐Latitude Plasma Depleted Structure in O(1D) 630.0 and O(1S) 557.7 nm All‐Sky Airglow Images on a Geomagnetically Quiet Night
Authors: Patgiri D. , Rathi R. , Yadav V. , Chakrabarty D. , Sunil Krishna M. V. , Kannaujiya S. , Pavan Chaitanya P. , Patra A. K. , Liu Jann‐Yenq , Sarkhel S.
Published: July 2024

This letter reports first simultaneous detection of F‐region plasma‐depleted structure in O(1D) 630.0 and O(1S) 557.7 nm airglow images on a geomagnetically quiet‐night (Ap = 3) of 26 June 2021 from mid‐latitude station (Hanle, India) due to enhanced thermospheric 557.7 nm emission. Since nighttime thermospheric 557.7 nm emission over mid‐latitudes is predominantly masked by significantly larger mesospheric component, F‐region plasma structures are rarely observed in 557.7 nm images. Interestingly, thermospheric 557.7 nm emission was not significant on the following geomagnetically quiet‐night as bands of medium‐scale traveling ionospheric disturbance were only observed in 630.0 nm images. Poleward wind generated by Equatorial Temperature and Wind Anomaly transported plasma from the boundary of equatorial ionization anomaly, causing significant electron density enhancement around 250 km and descent of F‐layer peak over Hanle on 26 June 2021. This amplified the dissociative recombination enabling the simultaneous detection of plasma‐depleted structure in 557.7 and 630.0 nm images.
Observing and Modeling Short‐Term Changes in Basal Friction During Rain‐Induced Speed‐Ups on an Alpine Glacier
Authors: Togaibekov Anuar , Gimbert Florent , Gilbert Adrien , Walpersdorf Andrea
Published: July 2024

Basal shear stress on hard‐bedded glaciers results from normal stress against bed roughness, which depends on basal water pressure and cavity size. These quantities are related in a steady state but are expected to behave differently under rapid changes in water input, which may lead to a transient frictional response not captured by existing friction laws. Here, we investigate transient friction using Global Positioning System vertical displacement and horizontal velocity observations, basal water pressure measurements, and cavitation model predictions during rain‐induced speed‐up events at Glacier d'Argentière, French Alps. We observe up to a threefold increase in horizontal surface velocity, spatially migrating at rates consistent with subglacial flow drainage, and associated with surface uplift and increased water pressure. We show that frictional changes are mainly driven by changes in water pressure at nearly constant cavity size. We propose a generalized friction law capable of capturing observations in both the transient and steady‐state regimes.
Time Sequence of Magnetospheric Responses to a Southward IMF Turning
Authors: Samsonov Andrey , Milan Stephen , Buzulukova Natalia , Sibeck David , Forsyth Colin , Branduardi‐Raymont Graziella , Dai Lei
Published: July 2024

We use MHD simulations to study the time sequence of magnetospheric responses to a synthetic event with a southward interplanetary magnetic field (IMF) turning. The onset of dayside magnetopause reconnection launches a weak rarefaction wave and sunward flow in the equatorial magnetosphere simultaneously with a tailward flow through the polar cap. This convection results in the accumulation of magnetic flux in the tail lobes and thinning of the tail current layer which provides favorable conditions for the onset of nightside reconnection. The onset of nightside reconnection about 40 min later closes the Dungey convection cycle, resulting in a second increase in the sunward flow in the equatorial plane. Variations of the magnetopause standoff distance as well as the size of the polar cap (PC) may indicate the onsets of the dayside and nightside reconnections. We compare the results of two MHD models and discuss their differences.
Downscaled‐GRACE Data Reveal Anthropogenic and Climate‐Induced Water Storage Decline Across the Indus Basin
Authors: Arshad Arfan , Mirchi Ali , Taghvaeian Saleh , AghaKouchak Amir
Published: July 2024

GRACE (Gravity Recovery and Climate Experiment) has been widely used to evaluate terrestrial water storage (TWS) and groundwater storage (GWS). However, the coarse‐resolution of GRACE data has limited the ability to identify local vulnerabilities in water storage changes associated with climatic and anthropogenic stressors. This study employs high‐resolution (1 km2) GRACE data generated through machine learning (ML) based statistical downscaling to illuminate TWS and GWS dynamics across twenty sub‐regions in the Indus Basin. Monthly TWS and GWS anomalies obtained from a geographically weighted random forest (RFgw) model maintained good consistency with original GRACE data at the 25 km2 grid scale. The downscaled data at 1 km2 resolution illustrate the spatial heterogeneity of TWS and GWS depletion within each sub‐region. Comparison with in‐situ GWS from 2,200 monitoring wells shows that downscaling of GRACE data significantly improves agreement with in‐situ data, evidenced by higher Kling‐Gupta Efficiency (0.50–0.85) and correlation coefficients (0.60–0.95). Hotspots with the highest TWS and GWS decline rate between 2002 and 2023 were Dehli Doab (−442, −585 mm/year), BIST Doab (−367, −556 mm/year), Rajasthan (−242, −381 mm/year), and BARI (−188, −333 mm/year). Based on a general additive model, 47%–83% of the TWS decline was associated with anthropogenic stressors mainly due to increasing trends of crop sown area, water consumption, and human settlements. The decline rate of TWS and GWS anomalies was lower (i.e., −25 to −75 mm/year) in upstream sub‐regions (e.g., Yogo, Gilgit, Khurmong, Kabul) where climatic factors (downward shortwave radiations, air temperature, and sea surface temperature) explained 72%–91% of TWS/GWS changes. The relative influences of climatic and anthropogenic stressors varied across sub‐regions, underscoring the complex interplay of natural‐human activities in the basin. These findings inform place‐based water resource management in the Indus Basin by advancing the understanding of local vulnerabilities.
Snow Depth Extraction From Time‐Lapse Imagery Using a Keypoint Deep Learning Model
Authors: Breen C. M. , Currier W. R. , Vuyovich C. , Miao Z. , Prugh L. R.
Published: July 2024

Snow pole time‐lapse photography, in which a snow pole of a known height is installed in front of a camera and photographed repeatedly over the course of a snow season, allows a large network of sites to be established relatively quickly and affordably. However, current approaches for extracting snow depth from snow poles typically relies on time intensive manual photo processing. By integrating computer vision algorithms with snow pole photography, we present a method that uses a keypoint detection model to automatically observe snow height across a network of sites. At 20 snow pole locations from Grand Mesa, CO (n = 9,722 images), our model successfully predicts the top and bottom of the pole with a mean absolute error (MAE) of 1.30 cm. To assess model generalizability, we tested the model on 12 sites in Washington State (n = 1,770 images). When the Colorado trained model was fine‐tuned using a subset of Washington images, the model predicted snow depth with a MAE of 4.0 cm. Best performance was achieved when both data sets were included during training, with a MAE of 2.05 cm for Colorado images and a MAE of 1.14 cm for Washington images. We demonstrate that, especially when trained using a subset of site‐specific data, a keypoint detection model can accelerate snow pole automation. This algorithm brings the hydrology community one step closer to a generalized snow pole detection model, and we call for a future model that integrates across time‐lapse images from additional locations.
Replaying the Tape of Academia: Fourteen Alternative Practices for the Physical Sciences
Authors: Kemeny Preston Cosslett , Phillips Alexandra Atlee , Johnson Daniel Lee
Published: July 2024

The evolution of modern academic practices, analogous to the evolution of biological systems, reflects the influence of both contingency and determinism. From a theoretical perspective, how then could academic practices differ from those that were inherited? Would any alternative outcomes be more just, equitable, diverse, or inclusive? Here we present 14 alternative academic practices that might be attained upon replaying the tape of academia and evaluate their benefits and drawbacks. Oriented primarily around the physical sciences within the United States, these alternative practices reconsider common activities within the broad categories of the graduate student experience, faculty careers, evaluation methods, peer review and publication, and conference norms. Consideration of these alternative practices can guide within‐system change and large‐scale restructuring of academia to address the myriad challenges facing researchers and students. Conversely, alternative practices may introduce new issues or exacerbate existing problems. These alternative practices are meant to be imaginative, not prescriptive, and we hope their underlying ideas spur reflection and conversation on the existing practices embedded within academic culture. Readers are encouraged to complete a brief survey regarding their impressions of the alternative practices, available at the following link: rebrand.ly/AlternativePractices2024.
Cloud Radiative Feedback to the Large‐Scale Atmospheric Circulation Greatly Reduces Monsoon‐Season Wet Bias Over the Tibetan Plateau in Climate Modeling
Authors: Liu Jiarui , Yang Kun , Zhao Dingchi , Wu Peili , Wang Jiamin , Zhou Xu , Lin Yanluan , Lu Hui , Jiang Yaozhi , Shi Jiancheng
Published: July 2024

Over‐estimation of summer precipitation over the Tibetan Plateau (TP) is a well‐known and persistent problem in most climate models. This study demonstrates the impact of a Gaussian Probability Density Function cloud fraction scheme on rainfall simulations using the Weather Research and Forecasting model. It is found that this scheme in both 0.1° and 0.05° resolutions significantly reduces the wet bias through both local feedbacks and large‐scale dynamic process. Specifically, increased cloud water/ice content with this scheme reduces surface shortwave radiation, and consequently surface heat fluxes and evapotranspiration. This, in turn, dampens the large‐scale thermal effect of the TP and weakens the exaggerated monsoon circulation and low‐level moisture convergence. It is this large‐scale dynamic process that contributes the most (∼70%) to the wet bias reduction. Although this paper presents a modeling study, it highlights the cloud radiative feedback to the large‐scale dynamics and precipitation over the TP.
Widening Multi‐Beam Scan Angle of Conventional Waveguide Lens Antennas by Increasing Focal Points for Multi‐Feed Excitations
Authors: Panigrahi S. , Kawdungta S. , Torrungrueng D. , Chou H.‐T.
Published: July 2024

This paper presents an alternative approach to improve the achievable beam scan angle of a traditional multi‐beam waveguide lens antenna. Due to the focusing mechanism by manipulating the geometrical curvatures of the waveguide lens, the angular scan range is limited in the conventional waveguide lens design using dual‐focal points of excitations because the geometrical curvatures of the waveguide lens only provide two design freedoms. To overcome this limitation, a solution of treating the waveguide lens as a transmit array consisting of non‐identical elements is proposed so that each element of the antenna array can be well calibrated to improve the maximum scan angular range, where a third focus point of excitation can be created by adding another design freedom from the differentiation between non‐identical elements. Each element of this new transmitting array can be well calibrated with the help of a mathematical expression to improve the maximum angular scan range. Numerical simulations show that the proposed antenna architecture exhibits better radiation characteristics than the traditional waveguide lens antenna. Radiation characteristics are studied and compared for both types of lens antennas to validate the design concept. The proposed triple‐focal point provides a higher gain than the traditional lens antenna with fewer antenna elements. The gains of the beams at ±10°, ±20°, ±30°, and ±40° are found to be 27.78, 26.94, 26.19, and 24.04 dBi, respectively. From the comparison, it is seen that the variation in gain by the proposed triple‐focal array design is more stable than the conventional dual‐focal point design.
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

Stochastic 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

The 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

A 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

Inherited 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

The 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

Eunicellane 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

Protected 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

Charge 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

Phedimus 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

During 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

Bictegravir, 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

To 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

Hard-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

Direct 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.