bluuebunny/crossref_metadata_2025 huggingface dataset:
Fuzzy C-Means and K-Means Methods Comparison for the Detection of Diabetes
Authors: Subarja Roy Efendi , Hendrik Billy
Published: August 2024

The necessity for precise and effective disease detection techniques has increased due to the rising incidence of diabetes. The main objective of this study is to assess how well the fuzzy C-Means and K-Means clustering algorithms detect diabetes. Based on pertinent medical data, the study attempts to examine how well these two clustering approaches identify cases of diabetes. For testing, a dataset with a variety of health and diagnostic indicator variables was used. Metrics including sensitivity, specificity, accuracy, and F1-score were used to evaluate the detection performance of the Fuzzy C-Means and K-Means algorithms that were used to cluster the dataset. Based on several evaluation criteria, the results show that both clustering approaches have promising potential for diabetes identification. However, their performance varies. This study sheds light on the advantages and disadvantages of clustering algorithms and advances our understanding of their suitability for diabetes identification. Improved diagnosis precision and early diabetes management intervention could result from more optimization and validation of these algorithms
Implementation of Neural Key Generation Algorithm For IoT Devices
Authors: Guitouni Zied , Zairi Aya , Zrigui Mounir
Published: August 2024

In the realm of Internet of Things (IoT) systems, the generation of cryptographic keys is crucial for ensuring secure data transmission and device authentication. However, traditional methods of generating random keys encounter challenges about security, efficiency, and scalability, particularly when applied to resource-constrained IoT devices. To address these issues, neural networks have emerged as a promising approach due to their ability to learn intricate patterns. Nonetheless, the architecture of neural networks significantly impacts their performance. This paper presents a comprehensive comparative analysis of three commonly employed neural network architectures for generating cryptographic keys on IoT devices. We propose a novel neural network-based algorithm for key generation and implement it using each architecture. The models are trained to generate cryptographic keys of various sizes from random input data. Performance evaluation is conducted based on key metrics such as accuracy, loss, key randomness, and model complexity. Experimental results indicate that the Feedforward Neural Network (FFNN) architecture achieves exceptional accuracy of over 99% and successfully passes all randomness tests, surpassing the alternatives. Convolutional Neural Networks (CNNs) demonstrate subpar performance as they emphasize spatial features that are irrelevant to key generation. Recurrent Neural Networks (RNNs) struggle with the complex long-range dependencies inherent in generating keys
Arduino-based Automatic Fish Feeding Device Prototype
Authors: Nugraha Muhammad Iqbal , Cahyono Bagus Dwi
Published: August 2024

Consuming fish food is an important part of the process of growing and maintaining fish. In general, fish food is given by conventionally throwing it by hand. However, this is not done at the same time every day. Based on the problems above, the researchers made a prototype of an Arduino-based automatic fish feeding device. The aim of this research is to determine the effectiveness of the automatic fish feeder prototype. In the prototype that the researchers made using several main components such as Arduino Uno as the system or brain of this prototype, servo motor, 20 x 4 LCD, buttons, Real Time Clock (RTC), and several jumper cables. The effectiveness of this tool can be seen from the test results, where the automatic fish feeder prototype succeeded in providing fish food according to a predetermined schedule.
Innovative Educational Game: Designing and Developing Interactive Web-Based Memory Card Games as an Educational Media for Children
Authors: Helda Nurul , Sanusi Sanusi , Suhendra Rivansyah
Published: August 2024

In the dynamic landscape of children’s education, innovation plays a pivotal role in shaping engaging and effective learning experiences. This research focuses on the design and development of an interactive web-based memory card game as an innovative educational tool. Grounded in the waterfall method, the development process prioritizes sequential stages to ensure robustness. Performance testing, using PageSpeed Insights, evaluates the game’s speed and efficiency, aiming to enhance user experience. The results, showcased by a remarkable score of 99, affirm the careful consideration given to optimization techniques. This research not only contributes to the broader understanding of game-based learning but also provides concrete insights for developers. The memory card game stands as a testament to the seamless integration of technological innovations into children’s education, promising enduring contributions to the future of learning.
Optimisation of Evacuation Route Determination in an Earthquake Natural Disaster Scenario Using an Excel Solver
Authors: Izzah Nurul , Jannah Asri Barokatul
Published: August 2024

Earthquake natural disasters can cause significant infrastructure damage, hindering community access and mobility. In such a situation, determining the shortest path for evacuation becomes very important. This research uses linear programming by utilising Excel Solver to determine the shortest evacuation route for earthquake natural disasters. Excel Solver is a feature in Microsoft Excel that serves as an analytical tool to solve linear optimisation problems. Excel solver can be used to find solutions that maximise or minimise the objective function, with respect to predetermined constraints. This research utilises relevant earthquake natural disaster simulation data as constraints in the optimisation model. The results show that the model can generate shortest paths that fulfil various constraints and criteria. The model can also be used to predict the time required to reach the destination. This research makes an important contribution to the development of tools and methods for shortest path optimisation in natural disaster scenarios. The optimisation model developed in this research can be used to assist decision makers in improving the efficiency and effectiveness of evacuation and disaster relief operations.
Optimisation of Fertiliser Delivery Distribution from Distributor to Farmer Group Using Excel Solver in Tanjung Village
Authors: Hasanah Uswatun , Halizah Siti Nur
Published: August 2024

Subsidised fertilisers are declared as goods that are monitored for distribution with a specific target, namely farmers. In the distribution process, the government cooperates with various components including the Ministry of Industry and Trade, the Ministry of Agriculture, the Ministry of State-Owned Enterprises and the Ministry of Home Affairs. At the same time, transportation and communication technologies continue to develop rapidly, such as mobile communications and the Internet, which drive the continuous development of the supply chain and technologies related to its regulatory management. This research aims to find out how to optimise the fertiliser transprortation Fertiliser Delivery Distribution and a series of fertiliser supply systems from Distributors to Farmer Groups Using Excel Solvers in Tanjung Village so as to provide better user control. The benefits of this research for distributors can help buffer distributor management to determine the quantity and time of delivery of subsidised fertiliser to official kiosks. The research method uses a case study which is a method of collecting and processing data through review / study of various research reports, flowsheets, research journals, as well as books and other relevant literature.
Determining the Shortest Path for Souvenir Delivery to Tourist Attractions in Pamekasan Using Excel Solver
Authors: Tamam Badrud , Dyana Motik Arisca
Published: August 2024

Pamekasan, as one of the districts in East Java, is famous for its various interesting tourist attractions. As the number of tourists increases, the need for typical Pamekasan souvenirs also increases. This encourages souvenir craftsmen to look for efficient ways to distribute their products to tourist attractions. One method that can be used is to use Solver Excel to determine the shortest path for sending souvenirs. This research aims to determine the shortest path for sending souvenirs from production sites to tourist attractions in Pamekasan using Solver Excel. The research method used is quantitative using Excel Solver. The data used is data on the distance between production sites and tourist attractions in Pamekasan. This data was obtained from the Pamekasan Regency Tourism and Culture Office. The research results show that Solver Excel can be used to determine the shortest route for sending souvenirs from production sites to tourist attractions in Pamekasan so that it can help souvenir craftsmen to save time and costs in distributing their products.
Geographic Information System for Shortest Route Search for Clinics in Pamekasan Regency Using the Djikstra Method
Authors: Fairil Ahan , Tobroni Imam
Published: August 2024

Earthquake natural disasters can cause significant infrastructure damage, hindering community access and mobility. In such a situation, determining the shortest path for evacuation becomes very important. This research uses linear programming by utilising Excel Solver to determine the shortest evacuation route for earthquake natural disasters. Excel Solver is a feature in Microsoft Excel that serves as an analytical tool to solve linear optimisation problems. Excel solver can be used to find solutions that maximise or minimise the objective function, with respect to predetermined constraints. This research utilises relevant earthquake natural disaster simulation data as constraints in the optimisation model. The results show that the model can generate shortest paths that fulfil various constraints and criteria. The model can also be used to predict the time required to reach the destination. This research makes an important contribution to the development of tools and methods for shortest path optimisation in natural disaster scenarios. The optimisation model developed in this research can be used to assist decision makers in improving the efficiency and effectiveness of evacuation and disaster relief operations.
The Impact of Parental Involvement in Online Learning on Student Academic Success
Authors: Rohmatillah Nur , Musmulyadin Musmulyadin , Maharaja Chandra Halim , Sabri Sabri , Ulwi Krim
Published: August 2024

Online learning is learning conducted through the internet. Online learning is also commonly referred to as e-learning, online learning, distance learning, virtual learning, and so on. Based on the explanation of online learning, parental involvement is also needed when students implement online learning. This study was conducted with the aim to find out how parental involvement can help students be more involved in online learning. In addition, it also aims to find out how parental involvement can impact on students’ academic success. The method used in this research is quantitative method. This method is a way of collecting numerical data that can be tested. Data is collected through the distribution of questionnaires addressed to students. Furthermore, the data that has been collected from the distribution of the questionnaire, will be accessible in Excel format which can then be processed with SPSS. From this study conducted, the researcher was able to obtain the results of the study on the impact of parental involvement in online learning on students’ academic success showed that parental involvement has a positive and significant influence on students’ academic achievement. In addition, parental involvement can help students in increasing students’ motivation to learn, improve students’ cognitive and psychomotor abilities, and help students face challenges in online learning. Based on the results of this study, it can be concluded that the impact of parental involvement in online learning on students’ academic success has a significant effect on students’ academic success. Parents play an active role in helping their children study at home, providing students with mobile phones and internet quota, and monitoring their academic progress. In addition, they provide supervision, incentives, and guidance which are very important for online learning.
Penyelesaian Sengketa Pertanahan Dalam Perspektif Reforma Agraria
Authors: Saputra Tri Eka
Published: August 2024

Penelitian ini bertujuan untuk mengetahui dan menganalisis bentuk penyelesaian sengketa pertanahan berdasarkan peraturan perundang-undangan. Metode penelitian yang digunakan adalah hukum normatif dengan mengamati realitas hukum dalam berbagai norma-norma hukum yang berkaitan dengan artikel ini. Hasil penelitian menunjukan bahwa bentuk penyelesaian sengketa pertanahan berdasarkan Peraturan Presiden Nomor 86 Tahun 2018 tidak dijelaskan secara khusus tetapi hanya mengatur mekanisme pembentukan Gugus Tugas Reforma Agraria. Pengaturan mengenai mekanisme penyelesaian sengketa pertanahan menggunakan Peraturan Menteri Agraria/Kepala Badan Pertanahan Nomor 21 Tahun 2020.
ATUAÇÃO DA CIRURGIA PLÁSTICA NO TRATAMENTO DE FERIDAS COMPLEXAS: UMA REVISÃO DE LITERATURA
Authors: Silva Carlos Daniel , Jacobson Dyefferson Henrique , Alencar Ingrid Gomes , Santos Gabriele Arja de Abreu dos , Silveira Viviane Almeida da , Silva Júnior Ned Augusto Rocha da , Lacerda Ingrid Peixoto , Borges Luana Dias , Rocha Márllon Cardozo Vieira , Bimbatti Maria Alice Silva , Pazini Alice Pontara , Moura Dávinna Nyara Lima , Marques João Vitor Almeida , Amaral Letícia Bittencourt , Lima Luan Cardoso Silva , Bastos Isabella Rodrigues dos Santos , Filho e Lira Carlos Vinicio Carvalho , Souza Natália Campos Vieira Freitas de , Molinar Maria Paula Cury
Published: August 2024

A cirurgia plástica é essencial no tratamento de feridas complexas, e enfrentadesafios que afetam diretamente a qualidade de vida dos pacientes. Com o avanço de técnicascomo a microcirurgia reconstrutiva e a utilização de enxertos e retalhos, essa especialidade alémde melhorar a cicatrização, também aprimora os resultados estéticos e funcionais. Ainterdisciplinaridade e as novas tecnologias, como nanotecnologia e engenharia de tecidos, temtransformado o sucesso no tratamento dessas feridas, ao promover uma recuperação maiscompleta. Objetivo: Avaliar o papel da cirurgia plástica no tratamento de feridas complexas eseus efeitos nos desfechos clínicos. Métodos: Uma revisão sistemática de literatura foi realizadanas bases de dados Pubmed e Scopus, com um filtro de 6 anos e estudos de alta qualidademetodológica em língua inglesa. Resultados e Discussão: Foram selecionados 7 artigos paracompor essa pesquisa. A cirurgia plástica tem se destacado no tratamento de feridas complexas,mostrando-se essencial para melhorar os desfechos clínicos e a qualidade de vida dos pacientes.Diversas técnicas avançadas, como o uso de enxertos, retalhos e tecnologias emergentes, comoimpressão 3D e terapias celulares, demonstram eficácia no controle de complicações e napromoção da regeneração tecidual. Estudos recentes suportam a superioridade das abordagensplásticas em cenários em que métodos tradicionais falham. Conclusão: A cirurgia plástica écrucial no tratamento de feridas complexas, ao utilizar técnicas avançadas que melhoram acicatrização e os resultados funcionais e estéticos. Inovações como a bioengenharia e tecnologiasemergentes ampliam as possibilidades terapêuticas, e ressalta a necessidade de diretrizespadronizadas para otimizar esses benefícios. Desse modo, redefine o sucesso no tratamento deferidas ao focar na cura e na restauração funcional e estética, fundamental para o bem-estar dospacientes.
Allosteric inhibition of trypanosomatid pyruvate kinases by a camelid single-domain antibody
Authors: Pinto Torres Joar Esteban , Claes Mathieu , Hendrickx Rik , Yuan Meng , Smiejkowska Natalia , Van Wielendaele Pieter , Hacisuleyman Aysima , De Winter Hans , Muyldermans Serge , Michels Paul A , Walkinshaw Malcolm D , Versées Wim , Caljon Guy , Magez Stefan , Sterckx Yann G.-J
Published: August 2024

African trypanosomes are the causative agents of neglected tropical diseases affecting both humans and livestock. Disease control is highly challenging due to an increasing number of drug treatment failures. African trypanosomes are extracellular, blood-borne parasites that mainly rely on glycolysis for their energy metabolism within the mammalian host. Trypanosomal glycolytic enzymes are therefore of interest for the development of trypanocidal drugs. Here, we report the serendipitous discovery of a camelid single-domain antibody (sdAb aka Nanobody) that selectively inhibits the enzymatic activity of trypanosomatid (but not host) pyruvate kinases through an allosteric mechanism. By combining enzyme kinetics, biophysics, structural biology, and transgenic parasite survival assays, we provide a proof-of-principle that the sdAb-mediated enzyme inhibition negatively impacts parasite fitness and growth.
Allosteric inhibition of trypanosomatid pyruvate kinases by a camelid single-domain antibody
Authors: Torres Joar Esteban Pinto , Claes Mathieu , Hendrickx Rik , Yuan Meng , Smiejkowska Natalia , Wielendaele Pieter Van , Winter Hans De , Muyldermans Serge , Michels Paul A , Walkinshaw Malcolm D , Versées Wim , Caljon Guy , Magez Stefan , Sterckx Yann G.-J
Published: August 2024

African trypanosomes are the causative agents of neglected tropical diseases affecting both humans and livestock. Disease control is highly challenging due to an increasing number of drug treatment failures. African trypanosomes are extracellular, blood-borne parasites that mainly rely on glycolysis for their energy metabolism within the mammalian host. Trypanosomal glycolytic enzymes are therefore of interest for the development of trypanocidal drugs. Here, we report the serendipitous discovery of a camelid single-domain antibody (sdAb aka Nanobody) that selectively inhibits the enzymatic activity of trypanosomatid (but not host) pyruvate kinases through an allosteric mechanism. By combining enzyme kinetics, biophysics, structural biology, and transgenic parasite survival assays, we provide a proof-of-principle that the sdAb-mediated enzyme inhibition negatively impacts parasite fitness and growth. We propose that these results pinpoint a site of vulnerability on trypanosomatid pyruvate kinases that may be exploited for the design of novel chemotherapeutics.
The evolutionary modifications of a GoLoco motif in the AGS protein facilitate micromere formation in the sea urchin embryo
Authors: Emura Natsuko , Wavreil Florence DM , Fries Annaliese , Yajima Mamiko
Published: August 2024

The evolutionary introduction of asymmetric cell division (ACD) into the developmental program facilitates the formation of a new cell type, contributing to developmental diversity and, eventually, to species diversification. The micromere of the sea urchin embryo may serve as one of those examples: An ACD at the 16-cell stage forms micromeres unique to echinoids among echinoderms. We previously reported that a polarity factor, Activator of G-protein Signaling (AGS), plays a crucial role in micromere formation. However, AGS and its associated ACD factors are present in all echinoderms and across most metazoans, leaving a question of what evolutionary modification of AGS protein or its surrounding molecular environment contributed to the evolutionary acquisition of micromeres only in echinoids. In this study, we learned that the GoLoco motifs at the AGS C-terminus play critical roles in regulating micromere formation in sea urchin embryos. Further, other echinoderms’ AGS or chimeric AGS that contain the C-terminus of AGS orthologs from various organisms showed varied localization and function in micromere formation. In contrast, the sea star or the pencil urchin orthologs of other ACD factors were consistently localized at the vegetal cortex in the sea urchin embryo, suggesting that AGS may be a unique variable factor that facilitates ACD diversity among echinoderms. Consistently, sea urchin AGS appears to facilitate micromere-like cell formation and accelerate the enrichment timing of the germline factor Vasa during early embryogenesis of the pencil urchin, an ancestral type of sea urchin. Based on these observations, we propose that the molecular evolution of a single polarity factor facilitates ACD diversity while preserving the core ACD machinery among echinoderms and beyond during evolution.
Distinct Activation Mechanisms of CXCR4 and ACKR3 Revealed by Single-Molecule Analysis of their Conformational Landscapes
Authors: Schafer Christopher T , Pauszek Raymond F , Gustavsson Martin , Handel Tracy M , Millar David P
Published: August 2024

The canonical chemokine receptor CXCR4 and atypical receptor ACKR3 both respond to CXCL12 but induce different effector responses to regulate cell migration. While CXCR4 couples to G proteins and directly promotes cell migration, ACKR3 is G protein- independent and scavenges CXCL12 to regulate extracellular chemokine levels and maintain CXCR4 responsiveness, thereby indirectly influencing migration. The receptors also have distinct activation requirements. CXCR4 only responds to wild-type CXCL12 and is sensitive to mutation of the chemokine. By contrast, ACKR3 recruits GPCR kinases (GRKs) and β-arrestins and promiscuously responds to CXCL12, CXCL12 variants, other peptides and proteins, and is relatively insensitive to mutation. To investigate the role of conformational dynamics in the distinct pharmacological behaviors of CXCR4 and ACKR3, we employed single-molecule FRET to track discrete conformational states of the receptors in real-time. The data revealed that apo-CXCR4 preferentially populates a high- FRET inactive state, while apo-ACKR3 shows little conformational preference and high transition probabilities among multiple inactive, intermediate and active conformations, consistent with its propensity for activation. Multiple active-like ACKR3 conformations are populated in response to agonists, compared to the single CXCR4 active-state. This and the markedly different conformational landscapes of the receptors suggest that activation of ACKR3 may be achieved by a broader distribution of conformational states than CXCR4. Much of the conformational heterogeneity of ACKR3 is linked to a single residue that differs between ACKR3 and CXCR4. The dynamic properties of ACKR3 may underly its inability to form productive interactions with G proteins that would drive canonical GPCR signaling.
Deuterium Metabolic Imaging Phenotypes Mouse Glioblastoma Heterogeneity Through Glucose Turnover Kinetics
Authors: Simões Rui V , Henriques Rafael N , Olesen Jonas L , Cardoso Beatriz M , Fernandes Francisca F , Monteiro Mariana AV , Jespersen Sune N , Carvalho Tânia , Shemesh Noam
Published: August 2024

Glioblastomas are aggressive brain tumors with dismal prognosis. One of the main bottlenecks for developing more effective therapies for glioblastoma stems from their histologic and molecular heterogeneity, leading to distinct tumor microenvironments and disease phenotypes. Effectively characterizing these features would improve the clinical management of glioblastoma. Glucose flux rates through glycolysis and mitochondrial oxidation have been recently shown to quantitatively depict glioblastoma proliferation in mouse models (GL261 and CT2A tumors, 38±3 mm
3
) using dynamic glucose-enhanced (DGE) deuterium spectroscopy. However, the spatial features of tumor microenvironment phenotypes remain hitherto unresolved. Here, we develop a DGE Deuterium Metabolic Imaging (DMI) approach for profiling tumor microenvironments through glucose conversion kinetics. Using a multimodal combination of tumor mouse models, novel strategies for spectroscopic imaging and noise attenuation, and histopathological correlations, we show that tumor lactate turnover mirrors phenotype differences between GL261 and CT2A mouse glioblastoma (59±7 mm
3
), whereas peritumoral glutamate-glutamine recycling is a potential marker of invasion capacity in pooled cohorts, linked to secondary brain lesions. Our findings were validated by histopathological characterization of each tumor, including cell density and proliferation, peritumoral infiltration, and distant migration. Our study bodes well for precision neuro-oncology, highlighting the importance of mapping glucose flux rates to better understand the metabolic heterogeneity of glioblastoma and its links to disease phenotypes.
Switching on lysosomes
Authors: Adhikari Deepak , Carroll John
Published: August 2024

The formation of large endolysosomal structures in unfertilized eggs ensures that lysosomes remain dormant before fertilization, and then shift into clean-up mode after the egg-to-embryo transition.
Il-6 signaling exacerbates hallmarks of chronic tendon disease by stimulating reparative fibroblasts
Authors: Stauber Tino , Moschini Greta , Hussien Amro A , Jaeger Patrick K , De Bock Katrien , Snedeker Jess G
Published: August 2024

Tendinopathies are debilitating diseases currently increasing in prevalence and associated costs. There is a need to deepen our understanding of the underlying cell signaling pathways to unlock effective treatments. In this work, we screen cell signaling pathways in human tendinopathies and find positively enriched IL-6/JAK/STAT signaling alongside signatures of cell populations typically activated by IL-6 in other tissues. In human tendinopathic tendons, we also confirm the strong presence and co-localization of IL-6, IL6R, and CD90, an established marker of reparative fibroblasts. To dissect the underlying causalities, we combine IL-6 knock-out mice with an explant-based assembloid model of tendon damage to successfully connect IL-6 signaling to reparative fibroblast activation and recruitment. Vice versa, we show that these reparative fibroblasts promote the development of tendinopathy hallmarks in the damaged explant upon IL-6 activation. We conclude that IL-6 activates tendon fibroblast populations which then initiate and deteriorate tendinopathy hallmarks.
Functional Implications of the Exon 9 Splice Insert in GluK1 Kainate Receptors
Authors: Dhingra Surbhi , Chopade Prachi M , Vinnakota Rajesh , Kumar Janesh
Published: August 2024

Kainate receptors are key modulators of synaptic transmission and plasticity in the central nervous system. Different kainate receptor isoforms with distinct spatiotemporal expressions have been identified in the brain. The GluK1-1 splice variant receptors, which are abundant in the adult brain, have an extra fifteen amino acids inserted in the amino-terminal domain (ATD) of the receptor resulting from alternative splicing of exon 9. However, the functional implications of this post-transcriptional modification are not yet clear. We employed a multi-pronged approach using cryogenic electron microscopy, electrophysiology, and other biophysical and biochemical tools to understand the structural and functional impact of this splice insert in the extracellular domain of GluK1 receptors. Our study reveals that the splice insert alters the key gating properties of GluK1 receptors and their modulation by the cognate auxiliary Neuropilin and tolloid-like (Neto) proteins 1 and 2. Mutational analysis identified the role of crucial splice residues that influence receptor properties and their modulation. Furthermore, the cryoEM structure of the variant shows that the presence of exon 9 in GluK1 does not affect the receptor architecture or domain arrangement in the desensitized state. Our study thus provides the first detailed structural and functional characterization of GluK1-1a receptors, highlighting the role of the splice insert in modulating receptor properties and their modulation.
Transformation of valence signaling in a striatopallidal circuit
Authors: Lee Donghyung , Lau Nathan , Liu Lillian , Root Cory M
Published: August 2024

The ways in which sensory stimuli acquire motivational valence through association with other stimuli is one of the simplest forms of learning. Though we have identified many brain nuclei that play various roles in reward processing, a significant gap remains in understanding how valence encoding transforms through the layers of sensory processing. To address this gap, we carried out a comparative investigation of the anteromedial olfactory tubercle (OT), and the ventral pallidum (VP) - 2 connected nuclei of the basal ganglia which have both been implicated in reward processing. First, using anterograde and retrograde tracing, we show that both D1 and D2 neurons of the anteromedial OT project primarily to the VP and minimally elsewhere. Using 2-photon calcium imaging, we then investigated how the identity of the odor and reward contingency of the odor are differently encoded by neurons in either structure during a classical conditioning paradigm. We find that VP neurons robustly encode reward contingency, but not identity, in low-dimensional space. In contrast, the OT neurons primarily encode odor identity in high-dimensional space. Although D1 OT neurons showed larger responses to rewarded odors than other odors, consistent with prior findings, we interpret this as identity encoding with enhanced contrast. Finally, using a novel conditioning paradigm that decouples reward contingency and licking vigor, we show that both features are encoded by non-overlapping VP neurons. These results provide a novel framework for the striatopallidal circuit in which a high-dimensional encoding of stimulus identity is collapsed onto a low-dimensional encoding of motivational valence.
AI-driven Automated Discovery Tools Reveal Diverse Behavioral Competencies of Biological Networks
Authors: Etcheverry Mayalen , Moulin-Frier Clément , Oudeyer Pierre-Yves , Levin Michael
Published: August 2024

Many applications in biomedicine and synthetic bioengineering depend on the ability to understand, map, predict, and control the complex, context-sensitive behavior of chemical and genetic networks. The emerging field of diverse intelligence has offered frameworks with which to investigate and exploit surprising problem-solving capacities of unconventional agents. However, for systems that are not conventional animals used in behavior science, there are few quantitative tools that facilitate exploration of their competencies, especially when their complexity makes it infeasible to use unguided exploration. Here, we formalize and investigate a view of gene regulatory networks as agents navigating a problem space. We develop automated tools to efficiently map the repertoire of robust goal states that GRNs can reach despite perturbations. These tools rely on two main contributions that we make in this paper: (1) Using curiosity-driven exploration algorithms, originating from the AI community to explore the range of behavioral abilities of a given system, that we adapt and leverage to automatically discover the range of reachable goal states of GRNs and (2) Proposing a battery of empirical tests inspired by implementation-agnostic behaviorist approaches to assess their navigation competencies. Our data reveal that models inferred from real biological data can reach a surprisingly wide spectrum of steady states, while showcasing various competencies that living agents often exhibit, in physiological network dynamics and that do not require structural changes of network properties or connectivity. Furthermore, we investigate the applicability of the discovered “behavioral catalogs” for comparing the evolved competencies across classes of evolved biological networks, as well as for the design of drug interventions in biomedical contexts or for the design of synthetic gene networks in bioengineering. Altogether, these automated tools and the resulting emphasis on behaviorshaping and exploitation of innate competencies open the path to better interrogation platforms for exploring the complex behavior of biological networks in an efficient and cost-effective manner. To read the interactive version of this paper, please visit https://developmentalsystems.org/curious-exploration-of-gm-competencies.
A model-based factorization method for scRNA data unveils bifurcating transcriptional modules underlying cell fate determination
Authors: Ren Jun , Zhou Ying , Hu Yudi , Yang Jing , Fang Hongkun , Lyu Xuejing , Guo Jintao , Shi Xiaodong , Li Qiyuan
Published: August 2024

Manifold-learning is particularly useful to resolve the complex cellular state space from single-cell RNA sequences. While current manifold-learning methods provide insights into cell fate by inferring graph-based trajectory at cell level, challenges remain to retrieve interpretable biology underlying the diverse cellular states. Here, we described MGPfactXMBD, a model-based manifold-learning framework and capable to factorize complex development trajectories into independent bifurcation processes of gene sets, and thus enables trajectory inference based on relevant features. MGPfactXMBD offers a more nuanced understanding of the biological processes underlying cellular trajectories with potential determinants. When bench-tested across 239 datasets, MGPfactXMBD showed advantages in major quantity-control metrics, such as branch division accuracy and trajectory topology, outperforming most established methods. In real datasets, MGPfactXMBD recovered the critical pathways and cell types in microglia development with experimentally valid regulons and markers. Furthermore, MGPfactXMBD discovered evolutionary trajectories of tumor-associated CD8+ T cells and yielded new subtypes of CD8+ T cells with gene expression signatures significantly predictive of the responses to immune checkpoint inhibitor in independent cohorts. In summary, MGPfactXMBD offers a manifold-learning framework in scRNA-seq data which enables feature selection for specific biological processes and contributing to advance our understanding of biological determination of cell fate.
Bridging verbal coordination and neural dynamics
Authors: Schwab-Mohamed Isaïh , Mercier Manuel R , Trébuchon Agnès , Morillon Benjamin , Lancia Leonardo , Schön Daniele
Published: August 2024

Our use of language, which is profoundly social in nature, essentially takes place in interactive contexts and is shaped by precise coordination dynamics that interlocutors must observe. Thus language interaction is high demanding on fast adjustment of speech production. Here, we developed a real-time coupled-oscillators virtual partner that allows - by changing the coupling strength parameters - to modulate the ability to synchronise speech with a speaker. Then, we recorded the intracranial brain activity of 16 patients with drug-resistant epilepsy while they performed a verbal coordination task with the virtual partner (VP). More precisely, patients had to repeat short sentences synchronously with the VP. This synchronous speech task is efficient to highlight both the dorsal and ventral language pathways. Importantly, combining time-resolved verbal coordination and neural activity shows more spatially differentiated patterns and different types of neural sensitivity along the dorsal pathway. More precisely, high-frequency activity in secondary auditory regions is highly sensitive to verbal coordinative dynamics, while primary regions are not. Finally, the high-frequency activity of the IFG BA44 seems to specifically index the online coordinative adjustments that are continuously required to compensate deviation from synchronisation. These findings illustrate the possibility and value of using a fully dynamic, adaptive and interactive language task to gather deeper understanding of the subtending neural dynamics involved in speech perception, production as well as their interaction.
H2A.Z deposition at meiotic prophase I underlies homologous recombination and pachytene genome activation during male meiosis
Authors: Sun Shenfei , Jiang Yamei , Jiang Ning , Zhang Qiaoli , Pan Hongjie , Huang Fujing , Zhang Xinna , Guo Yuxuan , You Xiaoyu , Gong Kai , Wei Wei , Liu Hanmin , Song Zhenju , Song Yuanlin , Tang Xiaofang , Yu Miao , Li Runsheng , Lin Xinhua
Published: August 2024

Accurate meiotic progression is important for gamete formation and the generation of genetic diversity. However, little is known about the identity of chromatin regulators that underlie mammalian meiosis in vivo. Here, we identify the multifaceted functions of the chromatin remodeler Znhit1 in governing meiosis. We observe a gradual increase in
Znhit1
expression during the meiotic prophase. Znhit1 deficiency in spermatocytes results in arrested pachytene development, impaired DNA double-strand break repair, and defective homologous recombination. Single-cell RNA sequencing and transcriptome analysis reveal that Znhit1 loss downregulates the transcription of pachytene genome activation (PGA) genes globally. Chromatin immunoprecipitation data show that Znhit1 is needed for the incorporation of the histone variant H2A.Z into pachytene chromatin. Moreover, we find that H2A.Z cooperates with the transcription factor A-MYB to co-bind DNA elements and control enhancer activity. Our findings provide insights into the regulatory mechanisms governing meiotic progression and highlight Znhit1 as a critical regulator of meiotic recombination and PGA.
Van Allen probes, NOAA, GOES, and ground observations of an intense EMIC wave event extending over 12 h in magnetic local time
Authors: Engebretson M. J. , Posch J. L. , Wygant J. R. , Kletzing C. A. , Lessard M. R. , Huang C.‐L. , Spence H. E. , Smith C. W. , Singer H. J. , Omura Y. , Horne R. B. , Reeves G. D. , Baker D. N. , Gkioulidou M. , Oksavik K. , Mann I. R. , Raita T . , Shiokawa K.
Published: June 2015

Although most studies of the effects of electromagnetic ion cyclotron (EMIC) waves on Earth's outer radiation belt have focused on events in the afternoon sector in the outer plasmasphere or plume region, strong magnetospheric compressions provide an additional stimulus for EMIC wave generation across a large range of local times and L shells. We present here observations of the effects of a wave event on 23 February 2014 that extended over 8 h in UT and over 12 h in local time, stimulated by a gradual 4 h rise and subsequent sharp increases in solar wind pressure. Large‐amplitude linearly polarized hydrogen band EMIC waves (up to 25 nT p‐p) appeared for over 4 h at both Van Allen Probes, from late morning through local noon, when these spacecraft were outside the plasmapause, with densities ~5–20 cm−3. Waves were also observed by ground‐based induction magnetometers in Antarctica (near dawn), Finland (near local noon), Russia (in the afternoon), and in Canada (from dusk to midnight). Ten passes of NOAA‐POES and METOP satellites near the northern foot point of the Van Allen Probes observed 30–80 keV subauroral proton precipitation, often over extended L shell ranges; other passes identified a narrow L shell region of precipitation over Canada. Observations of relativistic electrons by the Van Allen Probes showed that the fluxes of more field‐aligned and more energetic radiation belt electrons were reduced in response to both the emission over Canada and the more spatially extended emission associated with the compression, confirming the effectiveness of EMIC‐induced loss processes for this event.
Electrical properties of methane hydrate + sediment mixtures
Authors: Du Frane Wyatt L. , Stern Laura A. , Constable Steven , Weitemeyer Karen A. , Smith Megan M. , Roberts Jeffery J.
Published: June 2015

Knowledge of the electrical properties of multicomponent systems with gas hydrate, sediments, and pore water is needed to help relate electromagnetic (EM) measurements to specific gas hydrate concentration and distribution patterns in nature. Toward this goal, we built a pressure cell capable of measuring in situ electrical properties of multicomponent systems such that the effects of individual components and mixing relations can be assessed. We first established the temperature‐dependent electrical conductivity (σ) of pure, single‐phase methane hydrate to be ~5 orders of magnitude lower than seawater, a substantial contrast that can help differentiate hydrate deposits from significantly more conductive water‐saturated sediments in EM field surveys. Here we report σ measurements of two‐component systems in which methane hydrate is mixed with variable amounts of quartz sand or glass beads. Sand by itself has low σ but is found to increase the overall σ of mixtures with well‐connected methane hydrate. Alternatively, the overall σ decreases when sand concentrations are high enough to cause gas hydrate to be poorly connected, indicating that hydrate grains provide the primary conduction path. Our measurements suggest that impurities from sand induce chemical interactions and/or doping effects that result in higher electrical conductivity with lower temperature dependence. These results can be used in the modeling of massive or two‐phase gas‐hydrate‐bearing systems devoid of conductive pore water. Further experiments that include a free water phase are the necessary next steps toward developing complex models relevant to most natural systems.
New paleomagnetic results from Late Ordovician rocks of the Yangtze Block, South China, and their paleogeographic implications
Authors: Han Zhirui , Yang Zhenyu , Tong Yabo , Jing Xianqing
Published: June 2015

The paleogeographic relationship between South China and Australia during the Ordovician is important for understanding the configuration of South China in Gondwana. However, high‐quality Ordovician paleomagnetic results for the Yangtze Block are scarce. Here we report the results of a new paleomagnetic study of the Late Ordovician limestones of Wangcang County in the northern Yangtze Block, performed in order to constrain the paleoposition of South China. Two magnetic components were isolated by detailed stepwise thermal demagnetization. The low‐temperature component falls close to the local current Earth's field direction. The site‐mean direction obtained from the high‐temperature component (HTC) carried by magnetite is D/I = 132.6°/−35.2° (α95 = 3.6°) after bedding correction, yielding a paleomagnetic pole at 45.8°S, 191.3°E (dp = 2.4°, dm = 4.2°). The HTC direction passed reversal and fold tests, and its corresponding pole differs from the available paleomagnetic poles since the Silurian of the South China Block. These results suggest that the remanent magnetization was probably acquired during the earliest stage of sedimentation. The high‐temperature component yields a paleolatitude of 19.5°S, implying that the Yangtze Block was at tropic latitudes during the Late Ordovician. These new and reliable paleomagnetic results bridge the Ordovician data gap and favor the proximity between South China and Australia during the Late Ordovician.
The air‐water CO2 exchange of a coastal sea—A sensitivity study on factors that influence the absorption and outgassing of CO2 in the Baltic Sea
Authors: Gustafsson Erik , Omstedt Anders , Gustafsson Bo G.
Published: June 2015

In this study, the BALTSEM model is used to estimate how air‐water CO2 fluxes in the Baltic Sea respond to parameterizations of organic alkalinity (Aorg), gas transfer, and phytoplankton growth, and further to changes in river loads. The forcing data include the most complete compilation of Baltic river loads for dissolved inorganic and organic carbon (DIC and DOC) and total alkalinity (TA). In addition, we apply the most recent estimates of internal TA generation in the system. Our results clearly demonstrate how air‐water CO2 fluxes of a coastal sea depend on river loads of carbon, TA, and nutrients as well the freshwater import itself. Long‐term changes in DIC loads are shown to be compensated by corresponding changes in air‐water CO2 exchange. By adding Aorg, a discrepancy in the carbonate system calculations was removed, and the simulated net CO2 absorption of the system decreased by 11%. A new parameterization for cyanobacteria growth significantly improved the seasonal development of pCO2 in the central Baltic Sea, although the net effect on CO2 fluxes was below 5%. By applying either a linear, quadratic, or cubic wind speed dependence for gas transfer, the long‐term net CO2 exchange was adjusted by less than 5%. There is no clear indication that any one of these parameterizations provides a more accurate estimate of CO2 fluxes than the other two. Our findings are applicable in other coastal areas that are heavily influenced by river loads of TA, DIC, and DOC.
White water: Fifty years of snow research in WRR and the outlook for the future
Authors: Sturm Matthew
Published: June 2015

Over the past 50 years, 239 papers related to snow have been published in Water Resources Research (WRR). Seminal papers on virtually every facet of snow physics and snow water resources have appeared in the journal. These include papers on drifting snow, the snow surface energy balance, the effect of grain size on albedo, chemical elution, water movement through snow, and canopy interception. In particular, papers in WRR have explored the distribution of snow across different landscapes, providing data, process knowledge, and the basis for virtually all of the distributed snow models in use today. In this paper, I review these key contributions and provide some personal thoughts on what is likely to be the focus and nature of papers published in the next few decades, a period that is likely to see an increasing ability to map snow cover in detail, which should serve as a basis for the further development and improvement of snow models. It will also be an uncertain future, with profound changes in snow climatology predicted. I expect WRR will continue to play a key role in documenting and understanding these important cryospheric changes.
Copper‐Promoted Coupling of Carbon Dioxide and Propargylic Alcohols: Expansion of Substrate Scope and Trapping of Vinyl Copper Intermediate
Authors: Ouyang Lu , Tang Xiaodong , He Haitao , Qi Chaorong , Xiong Wenfang , Ren Yanwei , Jiang Huanfeng
Published: June 2015

We have successfully demonstrated that in the presence of N,N‐diisopropylethylamine, copper iodide could efficiently catalyze the coupling of internal propargylic alcohols with carbon dioxide to afford the corresponding α‐alkylidene cyclic carbonates in moderate to excellent yields. Moreover, we have developed a new and versatile protocol for the chemo‐ and stereoselective synthesis of a wide range of (E)‐α‐iodoalkylidene cyclic carbonates from carbon dioxide, propargylic alcohols and potassium iodide using copper salt as the promoter. The process is proposed to proceed through the trapping of the vinyl copper intermediate by in situ generated triiodide ion as electrophile.

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