bluuebunny/crossref_metadata_2025 huggingface dataset:
Processing code-blending beyond the lexical level: evidence for a double syntactic derivation?
Authors: Giustolisi Beatrice , Jaber Angélique , Branchini Chiara , Geraci Carlo , Donati Caterina
Published: January 2024

Bimodal bilinguals master languages in two modalities, spoken and signed, and can use them simultaneously due to the independence of the articulators. This behavior, named code-blending, is one of the hallmarks of bimodal bilingualism. Lexical experiments on production and comprehension in American Sign Language/English showed that blending is not cognitively costly and facilitates lexical access. In this work, we replicated the blending advantage in lexical comprehension for hearing bimodal bilinguals with two other language pairs, French Sign Language (LSF)–French and Italian Sign Language (LIS)–Italian, and we explored whether the facilitation is also found at the sentential level. Results show that blended utterances for languages with incongruent word order like LIS–Italian were processed slower than monolingual utterances, while no difference was found when the word orders were congruent (LSF–French). We discuss these findings in light of linguistic theories of syntactic structure derivation in bimodal bilinguals.
Cycling Rates of Particulate Organic Carbon Along the GEOTRACES Pacific Meridional Transect GP15
Authors: Amaral Vinícius J. , Lam Phoebe J. , Marchal Olivier , Kenyon Jennifer A.
Published: January 2024

Understanding particle cycling processes in the ocean is critical for predicting the response of the biological carbon pump to external perturbations. Here, measurements of particulate organic carbon (POC) concentration in two size fractions (1–51 and >51 μm) from GEOTRACES Pacific meridional transect GP15 are combined with a POC cycling model to estimate rates of POC production, (dis)aggregation, sinking, remineralization, and vertical transport mediated by migrating zooplankton, in the euphotic zone (EZ) and upper mesopelagic zone (UMZ) of distinct environments. We find coherent variations in POC cycling parameters and fluxes throughout the transect. Thus, the settling speed of POC in the >51 μm fraction increased with depth in the UMZ, presumably due to higher particle densities at depth. The settling flux of total POC (>1 μm) out of the EZ was positively correlated with primary production integrated over the EZ; the highest export occurred in the subarctic gyre while the lowest occurred in the subtropical gyres. The ratio of POC settling flux to integrated primary production was low (<5%) along GP15, which suggests an efficient recycling of POC in the EZ in all trophic regimes. Specific rates of POC remineralization did not show clear variations with temperature or dissolved oxygen concentration, that is, POC recycling was apparently controlled by other factors such as microbial colonization and substrate lability. Particle cohesiveness, as approximated by the second‐order rate constant for particle aggregation, was negatively correlated with trophic regime: particles appeared more cohesive in low‐productivity regions than in high‐productivity regions.
Africa's Crustal Architecture Inferred From Probabilistic and Perturbational Inversion of Ambient Noise: ADAMA
Authors: Olugboji Tolulope , Xue Siyu , Legre Jean‐Joel , Tamama Yuri
Published: January 2024

Africa's continental crust hosts a variety of geologic terrains and is crucial for understanding the evolution of its longest‐lived cratons. However, few of its seismological models are yet to incorporate the largest continent‐wide noise dispersion data sets. Here, we report on new insights into Africa's crustal architecture obtained using a new data set and model assessment product, ADAMA, which comprises a large ensemble of short‐period surface wave dispersion measurements: 5–40 s. We construct a continent‐wide model of Africa's Crust Evaluated with ADAMA's Rayleigh Phase maps (ACE‐ADAMA‐RP). Dispersion maps, and uncertainties, are obtained with a probabilistic approach. This model update, and a crustal taxonomy derived from unsupervised machine learning, reveals that the architecture of Africa's crust can be classified into two main types: primitive (C1: faster velocities with little gradients) and modified (C2–C4: slower velocities in the shallow crust with more pronounced gradients). The Archean shields are “primitive,” showing little variation or secular evolution. The basins, orogens, and continental margins are “modified” and retain imprints of surface deformation. The crustal taxonomy is obtained without a‐priori geological information and differs from previous classification schemes. While most of our reported features are robust, probabilistic modeling suggests caution in the quantitative interpretations where illumination is compromised by low‐quality measurements, sparse coverage or both. Future extension of our approach to other complementary seismological and geophysical data sets—for example, multimode earthquake dispersion, receiver functions, gravity, and mineral physics, will enable continent‐wide lithospheric modeling that extends resolution to the upper mantle.
Quasiperiodic Emissions: Fine Structure Corresponding to a Bouncing Wave
Authors: Němec F. , Santolík O. , Hospodarsky G. B. , Kurth W. S.
Published: January 2024

Quasiperiodic (QP) emissions are whistler‐mode electromagnetic waves observed in the Earth's inner magnetosphere whose intensity has a nearly periodic time modulation with typical modulation periods on the order of minutes. Some events exhibit, on top of the main modulation period, an additional fine inner modulation with modulation periods on the order of seconds. We use high‐resolution multi‐component electromagnetic wave data obtained by the Van Allen Probes spacecraft to investigate one such event. Detailed wave analysis demonstrates that the fine inner modulation is due to a wave packet bouncing back and forth between the hemispheres. The presence of a density duct is important for the formation of the event, as demonstrated by the increased ratio of wave power propagating away from the equator (a tentative source region) within the duct. The main QP modulation period corresponds to the plasma number density modulation observed just outside the plasmasphere.
Effects of Stratospheric Warming on Ural blocking Events in Winter
Authors: Li Zhihao , Dai Guokun , Mu Mu
Published: January 2024

Utilizing the Open Integrated Forecasting System, the responses of Ural blocking (UB) to different stratospheric warming scenarios are investigated. Numerical results show that stratospheric warming with moderate strength in minor patterns prolongs the UB duration and enhances its intensity, while strong stratospheric warming in minor patterns tends to shorten its duration and weaken its intensity, even leading to the collapse of the UB events. Further diagnosis reveals that the planetary wave activity flux propagates downward from the stratosphere to the troposphere after stratospheric warming. Moreover, the convergence of planetary wave activity flux is a key factor for UB enhancement and maintenance. In addition, the weakened meridional temperature gradients, decelerated zonal westerly winds, and a reduced meridional potential vorticity gradient (PVy) result in UB enhancement in response to stratospheric warming with moderate strength. As stratospheric warming strengthens, planetary wave activity flux diverges, westerly winds in the tropospheric mid‐latitudes accelerate and the PVy in the Ural sector enlarges, which further weakens UB. Regarding the stratospheric perturbations in major patterns, they have similar influences on UB events, that is, UB enhances with moderate stratospheric warming and weakens with strong warming. However, the strengthened warming would trigger UB re‐enhancement, which is closely associated with anomalous activities of tropospheric synoptic‐scale waves induced by stratospheric perturbations. These results reveal UB events respond differently to stratospheric warming with various intensities and patterns in the short term, which makes a contribution to understanding stratosphere‐troposphere coupling.
GRDL: A New Global Reservoir Area‐Storage‐Depth Data Set Derived Through Deep Learning‐Based Bathymetry Reconstruction
Authors: Hao Zhen , Chen Fang , Jia Xiaofeng , Cai Xiaobin , Yang Chao , Du Yun , Ling Feng
Published: January 2024

Reservoirs play a critical role in the global water cycle by regulating the flow of water from the environment into human systems. Accurate estimation of the area‐storage‐depth relationships for global reservoirs is essential for effective hydrological modeling and reservoir storage monitoring. Bathymetry reconstruction presents a promising approach to derive this information. Current bathymetry methods either rely on simple approximations or are constrained by dependence on altimetry data or field survey data. To overcome these limitations, this study presents a pioneering approach involving training a deep learning model to reconstruct bathymetry and establish precise area‐storage‐depth relationships. We trained the deep learning model with approximately 160,000 simulated reservoirs derived from Shuttle Radar Topography Mission (SRTM) and fine‐tuned the model based on hundreds of reservoirs with bathymetry data. By employing the trained model and SRTM, the bathymetry of 7,250 reservoirs in the Global Reservoir and Dam Database were subsequently reconstructed. The method is validated against comprehensive reference data sets, including 54 test reservoirs with bathymetry data, 118 satellite altimetry‐based reservoirs, and 68 LiDAR‐based reservoirs. The reconstructed bathymetry achieves a mean absolute error of 7.87 m and a mean error of +2.05 m for the test reservoirs. The validation against satellite altimetry and LiDAR‐based references significantly outperforms previous geometric approximation techniques, with median normalized root mean square error (NRMSE) values of 20.6% for area‐storage and 22.1% for area‐level curves. Additionally, the reservoir storage variations are estimated with precision, outperforming previous methods. The proposed deep learning‐based approach presents a robust solution for accurate reservoir bathymetry estimation and establishes more reliable area‐storage‐depth relationships for reservoirs worldwide.
Hedgehog signalling is involved in acquired resistance to KRASG12C inhibitors in lung cancer cells
Authors: Lee Chaeyoung , Yi Jawoon , Park Jihwan , Ahn Byungyong , Won Young-Wook , Jeon JiHeung , Lee Byung Ju , Cho Wha Ja , Park Jeong Woo
Published: January 2024

Although KRASG12C inhibitors have shown promising activity in lung adenocarcinomas harbouring KRASG12C, acquired resistance to these therapies eventually occurs in most patients. Re-expression of KRAS is thought to be one of the main causes of acquired resistance. However, the mechanism through which cancer cells re-express KRAS is not fully understood. Here, we report that the Hedgehog signal is induced by KRASG12C inhibitors and mediates KRAS re-expression in cancer cells treated with a KRASG12C inhibitor. Further, KRASG12C inhibitors induced the formation of primary cilia and activated the Hedgehog-GLI-1 pathway. GLI-1 binds to the KRAS promoter region, enhancing KRAS promoter activity and KRAS expression. Inhibition of GLI using siRNA or the smoothened (Smo) inhibitor suppressed re-expression of KRAS in cells treated with a KRASG12C inhibitor. In addition, we demonstrate that KRASG12C inhibitors decreased Aurora kinase A (AURKA) levels in cancer cells, and inhibition of AURKA using siRNA or inhibitors led to increased expression levels of GLI-1 and KRAS even in the absence of KRAS inhibitor. Ectopic expression of AURKA attenuated the effect of KRASG12C inhibitors on the expression of GLI-1 and re-expression of KRAS. Together, these findings demonstrate the important role of AURKA, primary cilia, and Hedgehog signals in the re-expression of KRAS and therefore the induction of acquired resistance to KRASG12C inhibitors, and provide a rationale for targeting Hedgehog signalling to overcome acquired resistance to KRASG12C inhibitors.
Targeting POLRMT by a first-in-class inhibitor IMT1 inhibits osteosarcoma cell growth in vitro and in vivo
Authors: Kong Yang , Li Xiangrong , Zhang Huanle , Fu Bin , Jiang Hua-Ye , Yang Hui-Lin , Dai Jin
Published: January 2024

Osteosarcoma (OS) is a highly aggressive form of bone cancer that predominantly affects adolescents and young adults. In this study, we have undertaken an investigation into the potential anti-OS cell activity of IMT1 (inhibitor of mitochondrial transcription 1), a first-in-class inhibitor of RNA polymerase mitochondrial (POLRMT). IMT1 exhibited a profound inhibitory effect on cell survival, proliferation, cell cycle progression, and migration in primary and immortalized OS cells. Furthermore, this POLRMT inhibitor elicited apoptosis in the OS cells, without, however, inducing cytotoxicity in human osteoblasts or osteoblastic cells. IMT1 disrupted mitochondrial functions in OS cells, resulting in mitochondrial depolarization, oxidative injury, lipid peroxidation, and ATP reduction in OS cells. Silencing POLRMT using targeted shRNA closely mimicked the actions of IMT1 and exerted potent anti-OS cell activity. Importantly, IMT1’s effectiveness was diminished in POLRMT-silenced OS cells. Subsequent investigations revealed that IMT1 suppressed the activation of the Akt-mammalian target of rapamycin (mTOR) cascade in OS cells. IMT1 treatment or POLRMT silencing in primary OS cells led to a significant reduction in Akt1-S6K-S6 phosphorylation. Conversely, it was enhanced upon POLRMT overexpression. The restoration of Akt-mTOR activation through the introduction of a constitutively active S473D mutant Akt1 (caAkt1) mitigated IMT1-induced cytotoxicity in OS cells. In vivo, oral administration of IMT1 robustly curtailed the growth of OS xenografts in nude mice. Furthermore, IMT1 suppressed POLRMT activity, impaired mitochondrial function, repressed Akt-mTOR activation, and induced apoptosis within xenograft tissues. Collectively, these findings underscore the potent growth-inhibitory effects attributed to IMT1 via targeted POLRMT inhibition. The utilization of this POLRMT inhibitor carries substantial therapeutic promise in the context of OS treatment.
Antibody-dependent enhancement of toxicity of myotoxin II from Bothrops asper
Authors: Sørensen Christoffer V. , Fernández Julián , Adams Anna Christina , Wildenauer Helen H. K. , Schoffelen Sanne , Ledsgaard Line , Pucca Manuela B. , Fiebig Michael , Cerni Felipe A. , Tulika Tulika , Voldborg Bjørn G. , Karatt-Vellatt Aneesh , Morth J. Preben , Ljungars Anne , Grav Lise M. , Lomonte Bruno , Laustsen Andreas H.
Published: January 2024

Improved therapies are needed against snakebite envenoming, which kills and permanently disables thousands of people each year. Recently developed neutralizing monoclonal antibodies against several snake toxins have shown promise in preclinical rodent models. Here, we use phage display technology to discover a human monoclonal antibody and show that this antibody causes antibody-dependent enhancement of toxicity (ADET) of myotoxin II from the venomous pit viper, Bothrops asper, in a mouse model of envenoming that mimics a snakebite. While clinical ADET related to snake venom has not yet been reported in humans, this report of ADET of a toxin from the animal kingdom highlights the necessity of assessing even well-known antibody formats in representative preclinical models to evaluate their therapeutic utility against toxins or venoms. This is essential to avoid potential deleterious effects as exemplified in the present study.
Microscopic mechanisms of pressure-induced amorphous-amorphous transitions and crystallisation in silicon
Authors: Fan Zhao , Tanaka Hajime
Published: January 2024

Some low-coordination materials, including water, silica, and silicon, exhibit polyamorphism, having multiple amorphous forms. However, the microscopic mechanism and kinetic pathway of amorphous-amorphous transition (AAT) remain largely unknown. Here, we use a state-of-the-art machine-learning potential and local structural analysis to investigate the microscopic kinetics of AAT in silicon after a rapid pressure change. We find that the transition from low-density-amorphous (LDA) to high-density-amorphous (HDA) occurs through nucleation and growth, resulting in non-spherical interfaces that underscore the mechanical nature of AAT. In contrast, the reverse transition occurs through spinodal decomposition. Further pressurisation transforms LDA into very-high-density amorphous (VHDA), with HDA serving as an intermediate state. Notably, the final amorphous states are inherently unstable, transitioning into crystals. Our findings demonstrate that AAT and crystallisation are driven by joint thermodynamic and mechanical instabilities, assisted by preordering, occurring without diffusion. This unique mechanical and diffusion-less nature distinguishes AAT from liquid-liquid transitions.
A Machine Learning-Driven Virtual Biopsy System For Kidney Transplant Patients
Authors: Yoo Daniel , Divard Gillian , Raynaud Marc , Cohen Aaron , Mone Tom D. , Rosenthal John Thomas , Bentall Andrew J. , Stegall Mark D. , Naesens Maarten , Zhang Huanxi , Wang Changxi , Gueguen Juliette , Kamar Nassim , Bouquegneau Antoine , Batal Ibrahim , Coley Shana M. , Gill John S. , Oppenheimer Federico , De Sousa-Amorim Erika , Kuypers Dirk R. J. , Durrbach Antoine , Seron Daniel , Rabant Marion , Van Huyen Jean-Paul Duong , Campbell Patricia , Shojai Soroush , Mengel Michael , Bestard Oriol , Basic-Jukic Nikolina , Jurić Ivana , Boor Peter , Cornell Lynn D. , Alexander Mariam P. , Toby Coates P. , Legendre Christophe , Reese Peter P. , Lefaucheur Carmen , Aubert Olivier , Loupy Alexandre
Published: January 2024

In kidney transplantation, day-zero biopsies are used to assess organ quality and discriminate between donor-inherited lesions and those acquired post-transplantation. However, many centers do not perform such biopsies since they are invasive, costly and may delay the transplant procedure. We aim to generate a non-invasive virtual biopsy system using routinely collected donor parameters. Using 14,032 day-zero kidney biopsies from 17 international centers, we develop a virtual biopsy system. 11 basic donor parameters are used to predict four Banff kidney lesions: arteriosclerosis, arteriolar hyalinosis, interstitial fibrosis and tubular atrophy, and the percentage of renal sclerotic glomeruli. Six machine learning models are aggregated into an ensemble model. The virtual biopsy system shows good performance in the internal and external validation sets. We confirm the generalizability of the system in various scenarios. This system could assist physicians in assessing organ quality, optimizing allograft allocation together with discriminating between donor derived and acquired lesions post-transplantation.
Towards estimating the number of strains that make up a natural bacterial population
Authors: Viver Tomeu , Conrad Roth E. , Rodriguez-R Luis M. , Ramírez Ana S. , Venter Stephanus N. , Rocha-Cárdenas Jairo , Llabrés Mercè , Amann Rudolf , Konstantinidis Konstantinos T. , Rossello-Mora Ramon
Published: January 2024

What a strain is and how many strains make up a natural bacterial population remain elusive concepts despite their apparent importance for assessing the role of intra-population diversity in disease emergence or response to environmental perturbations. To advance these concepts, we sequenced 138 randomly selected Salinibacter ruber isolates from two solar salterns and assessed these genomes against companion short-read metagenomes from the same samples. The distribution of genome-aggregate average nucleotide identity (ANI) values among these isolates revealed a bimodal distribution, with four-fold lower occurrence of values between 99.2% and 99.8% relative to ANI >99.8% or <99.2%, revealing a natural “gap” in the sequence space within species. Accordingly, we used this ANI gap to define genomovars and a higher ANI value of >99.99% and shared gene-content >99.0% to define strains. Using these thresholds and extrapolating from how many metagenomic reads each genomovar uniquely recruited, we estimated that –although our 138 isolates represented about 80% of the Sal. ruber population– the total population in one saltern pond is composed of 5,500 to 11,000 genomovars, the great majority of which appear to be rare in-situ. These data also revealed that the most frequently recovered isolate in lab media was often not the most abundant genomovar in-situ, suggesting that cultivation biases are significant, even in cases that cultivation procedures are thought to be robust. The methodology and ANI thresholds outlined here should represent a useful guide for future microdiversity surveys of additional microbial species.
Selective CK1α degraders exert antiproliferative activity against a broad range of human cancer cell lines
Authors: Nishiguchi Gisele , Mascibroda Lauren G. , Young Sarah M. , Caine Elizabeth A. , Abdelhamed Sherif , Kooijman Jeffrey J. , Miller Darcie J. , Das Sourav , McGowan Kevin , Mayasundari Anand , Shi Zhe , Barajas Juan M. , Hiltenbrand Ryan , Aggarwal Anup , Chang Yunchao , Mishra Vibhor , Narina Shilpa , Thomas Melvin , Loughran Allister J. , Kalathur Ravi , Yu Kaiwen , Zhou Suiping , Wang Xusheng , High Anthony A. , Peng Junmin , Pruett-Miller Shondra M. , Daniels Danette L. , Urh Marjeta , Shelat Anang A. , Mullighan Charles G. , Riching Kristin M. , Zaman Guido J. R. , Fischer Marcus , Klco Jeffery M. , Rankovic Zoran
Published: January 2024

Molecular-glue degraders are small molecules that induce a specific interaction between an E3 ligase and a target protein, resulting in the target proteolysis. The discovery of molecular glue degraders currently relies mostly on screening approaches. Here, we describe screening of a library of cereblon (CRBN) ligands against a panel of patient-derived cancer cell lines, leading to the discovery of SJ7095, a potent degrader of CK1α, IKZF1 and IKZF3 proteins. Through a structure-informed exploration of structure activity relationship (SAR) around this small molecule we develop SJ3149, a selective and potent degrader of CK1α protein in vitro and in vivo. The structure of SJ3149 co-crystalized in complex with CK1α + CRBN + DDB1 provides a rationale for the improved degradation properties of this compound. In a panel of 115 cancer cell lines SJ3149 displays a broad antiproliferative activity profile, which shows statistically significant correlation with MDM2 inhibitor Nutlin-3a. These findings suggest potential utility of selective CK1α degraders for treatment of hematological cancers and solid tumors.
Enhancing aortic valve drug delivery with PAR2-targeting magnetic nano-cargoes for calcification alleviation
Authors: Chen Jinyong , Ren Tanchen , Xie Lan , Hu Haochang , Li Xu , Maitusong Miribani , Zhou Xuhao , Hu Wangxing , Xu Dilin , Qian Yi , Cheng Si , Yu Kaixiang , Wang Jian`an , Liu Xianbao
Published: January 2024

Calcific aortic valve disease is a prevalent cardiovascular disease with no available drugs capable of effectively preventing its progression. Hence, an efficient drug delivery system could serve as a valuable tool in drug screening and potentially enhance therapeutic efficacy. However, due to the rapid blood flow rate associated with aortic valve stenosis and the lack of specific markers, achieving targeted drug delivery for calcific aortic valve disease has proved to be challenging. Here we find that protease-activated-receptor 2 (PAR2) expression is up-regulated on the plasma membrane of osteogenically differentiated valvular interstitial cells. Accordingly, we develop a magnetic nanocarrier functionalized with PAR2-targeting hexapeptide for dual-active targeting drug delivery. We show that the nanocarriers effectively deliver XCT790—an anti-calcification drug—to the calcified aortic valve under extra magnetic field navigation. We demonstrate that the nano-cargoes consequently inhibit the osteogenic differentiation of valvular interstitial cells, and alleviate aortic valve calcification and stenosis in a high-fat diet-fed low-density lipoprotein receptor-deficient (Ldlr−/−) mouse model. This work combining PAR2- and magnetic-targeting presents an effective targeted drug delivery system for treating calcific aortic valve disease in a murine model, promising future clinical translation.
Acceleration of the ocean warming from 1961 to 2022 unveiled by large-ensemble reanalyses
Authors: Storto Andrea , Yang Chunxue
Published: January 2024

Long-term changes in ocean heat content (OHC) represent a fundamental global warming indicator and are mostly caused by anthropogenic climate-altering gas emissions. OHC increases heavily threaten the marine environment, therefore, reconstructing OHC before the well-instrumented period (i.e., before the Argo floats deployment in the mid-2000s) is crucial to understanding the multi-decadal climate change in the ocean. Here, we shed light on ocean warming and its uncertainty for the 1961-2022 period through a large ensemble reanalysis system that spans the major sources of uncertainties. Results indicate a 62-year warming of 0.43 ± 0.08 W m−2, and a statistically significant acceleration rate equal to 0.15 ± 0.04 W m−2 dec−1, locally peaking at high latitudes. The 11.6% of the global ocean area reaches the maximum yearly OHC in 2022, almost doubling any previous year. At the regional scale, major OHC uncertainty is found in the Tropics; at the global scale, the uncertainty represents about 40% and 15% of the OHC variability, respectively before and after the mid-2000s. The uncertainty of regional trends is mostly affected by observation calibration (especially at high latitudes), and sea surface temperature data uncertainty (especially at low latitudes).
An artificial intelligence-based model for optimal conjunctive operation of surface and groundwater resources
Authors: Akbarifard Saeid , Madadi Mohamad Reza , Zounemat-Kermani Mohammad
Published: January 2024

A hybrid simulation-optimization model is proposed for the optimal conjunctive operation of surface and groundwater resources. This second-level model is created by finding and combining the best aspects of two resilient metaheuristics, the moth swarm algorithm and the symbiotic organization search algorithm, and then connecting the resulting algorithm to an artificial neural network simulator. For assessment of the developed model efficiency, its results are compared with two first-level simulation-optimization models. The comparisons reveal that the operation policies obtained by the developed second-level model can reliably supply more than 99% of the total demands in the study regions, indicating its superior efficiency compared to the two other first-level models. In addition, the highest sustainability index in the study regions belongs to the proposed model. Comparing the results of this research with those of other recent studies confirm the supremacy of the developed second-level model over several previously developed models.
Spin-resolved topology and partial axion angles in three-dimensional insulators
Authors: Lin Kuan-Sen , Palumbo Giandomenico , Guo Zhaopeng , Hwang Yoonseok , Blackburn Jeremy , Shoemaker Daniel P. , Mahmood Fahad , Wang Zhijun , Fiete Gregory A. , Wieder Benjamin J. , Bradlyn Barry
Published: January 2024

Symmetry-protected topological crystalline insulators (TCIs) have primarily been characterized by their gapless boundary states. However, in time-reversal- ($${{{{{{{\mathcal{T}}}}}}}}$$
T
-) invariant (helical) 3D TCIs—termed higher-order TCIs (HOTIs)—the boundary signatures can manifest as a sample-dependent network of 1D hinge states. We here introduce nested spin-resolved Wilson loops and layer constructions as tools to characterize the intrinsic bulk topological properties of spinful 3D insulators. We discover that helical HOTIs realize one of three spin-resolved phases with distinct responses that are quantitatively robust to large deformations of the bulk spin-orbital texture: 3D quantum spin Hall insulators (QSHIs), “spin-Weyl” semimetals, and $${{{{{{{\mathcal{T}}}}}}}}$$
T
-doubled axion insulator (T-DAXI) states with nontrivial partial axion angles indicative of a 3D spin-magnetoelectric bulk response and half-quantized 2D TI surface states originating from a partial parity anomaly. Using ab-initio calculations, we demonstrate that β-MoTe2 realizes a spin-Weyl state and that α-BiBr hosts both 3D QSHI and T-DAXI regimes.
High-speed and energy-efficient non-volatile silicon photonic memory based on heterogeneously integrated memresonator
Authors: Tossoun Bassem , Liang Di , Cheung Stanley , Fang Zhuoran , Sheng Xia , Strachan John Paul , Beausoleil Raymond G.
Published: January 2024

Recently, interest in programmable photonics integrated circuits has grown as a potential hardware framework for deep neural networks, quantum computing, and field programmable arrays (FPGAs). However, these circuits are constrained by the limited tuning speed and large power consumption of the phase shifters used. In this paper, we introduce the memresonator, a metal-oxide memristor heterogeneously integrated with a microring resonator, as a non-volatile silicon photonic phase shifter. These devices are capable of retention times of 12 hours, switching voltages lower than 5 V, and an endurance of 1000 switching cycles. Also, these memresonators have been switched using 300 ps long voltage pulses with a record low switching energy of 0.15 pJ. Furthermore, these memresonators are fabricated on a heterogeneous III-V-on-Si platform capable of integrating a rich family of active and passive optoelectronic devices directly on-chip to enable in-memory photonic computing and further advance the scalability of integrated photonic processors.
Site-specific metal-support interaction to switch the activity of Ir single atoms for oxygen evolution reaction
Authors: Wei Jie , Tang Hua , Sheng Li , Wang Ruyang , Fan Minghui , Wan Jiale , Wu Yuheng , Zhang Zhirong , Zhou Shiming , Zeng Jie
Published: January 2024

The metal-support interactions (MSI) could greatly determine the electronic properties of single-atom catalysts, thus affecting the catalytic performance. However, the typical approach to regulating MSI usually suffers from interference of the variation of supports or sacrificing the stability of catalysts. Here, we effectively regulate the site-specific MSI of Ir single atoms anchored on Ni layered double hydroxide through an electrochemical deposition strategy. Cathodic deposition drives Ir atoms to locate at three-fold facial center cubic hollow sites with strong MSI, while anodic deposition drives Ir atoms to deposit onto oxygen vacancy sites with weak MSI. The mass activity and intrinsic activity of Ir single-atom catalysts with strong MSI towards oxygen evolution reaction are 19.5 and 5.2 times that with weak MSI, respectively. Mechanism study reveals that the strong MSI between Ir atoms and the support stimulates the activity of Ir sites by inducing the switch of active sites from Ni sites to Ir sites and optimizes the adsorption strength of intermediates, thereby enhancing the activity.
Mesoscale simulation of biomembranes with FreeDTS
Authors: Pezeshkian Weria , Ipsen John H.
Published: January 2024

We present FreeDTS software for performing computational research on biomembranes at the mesoscale. In this software, a membrane is represented by a dynamically triangulated surface equipped with vertex-based inclusions to integrate the effects of integral and peripheral membrane proteins. Several algorithms are included in the software to simulate complex membranes at different conditions such as framed membranes with constant tension, vesicles and high-genus membranes with various fixed volumes or constant pressure differences and applying external forces to membrane regions. Furthermore, the software allows the user to turn off the shape evolution of the membrane and focus solely on the organization of proteins. As a result, we can take realistic membrane shapes obtained from, for example, cryo-electron tomography and backmap them into a finer simulation model. In addition to many biomembrane applications, this software brings us a step closer to simulating realistic biomembranes with molecular resolution. Here we provide several interesting showcases of the power of the software but leave a wide range of potential applications for interested users.
HHV-6B detection and host gene expression implicate HHV-6B as pulmonary pathogen after hematopoietic cell transplant
Authors: Hill Joshua A. , Lee Yeon Joo , Vande Vusse Lisa K. , Xie Hu , Chung E. Lisa , Waghmare Alpana , Cheng Guang-Shing , Zhu Haiying , Huang Meei-Li , Hill Geoffrey R. , Jerome Keith R. , Leisenring Wendy M. , Zerr Danielle M. , Gharib Sina A. , Dadwal Sanjeet , Boeckh Michael
Published: January 2024

Limited understanding of the immunopathogenesis of human herpesvirus 6B (HHV-6B) has prevented its acceptance as a pulmonary pathogen after hematopoietic cell transplant (HCT). In this prospective multicenter study of patients undergoing bronchoalveolar lavage (BAL) for pneumonia after allogeneic HCT, we test blood and BAL fluid (BALF) for HHV-6B DNA and mRNA transcripts associated with lytic infection and perform RNA-seq on paired blood. Among 116 participants, HHV-6B DNA is detected in 37% of BALs, 49% of which also have HHV-6B mRNA detection. We establish HHV-6B DNA viral load thresholds in BALF that are highly predictive of HHV-6B mRNA detection and associated with increased risk for overall mortality and death from respiratory failure. Participants with HHV-6B DNA in BALF exhibit distinct host gene expression signatures, notable for enriched interferon signaling pathways in participants clinically diagnosed with idiopathic pneumonia. These data implicate HHV-6B as a pulmonary pathogen after allogeneic HCT.
Optimizing drug combination and mechanism analysis based on risk pathway crosstalk in pan cancer
Authors: Hu Congxue , Mi Wanqi , Li Feng , Zhu Lun , Ou Qi , Li Maohao , Li Tengyue , Ma Yuheng , Zhang Yunpeng , Xu Yingqi
Published: January 2024

Combination therapy can greatly improve the efficacy of cancer treatment, so identifying the most effective drug combination and interaction can accelerate the development of combination therapy. Here we developed a computational network biological approach to identify the effective drug which inhibition risk pathway crosstalk of cancer, and then filtrated and optimized the drug combination for cancer treatment. We integrated high-throughput data concerning pan-cancer and drugs to construct miRNA-mediated crosstalk networks among cancer pathways and further construct networks for therapeutic drug. Screening by drug combination method, we obtained 687 optimized drug combinations of 83 first-line anticancer drugs in pan-cancer. Next, we analyzed drug combination mechanism, and confirmed that the targets of cancer-specific crosstalk network in drug combination were closely related to cancer prognosis by survival analysis. Finally, we save all the results to a webpage for query (http://bio-bigdata.hrbmu.edu.cn/oDrugCP/). In conclusion, our study provided an effective method for screening precise drug combinations for various cancer treatments, which may have important scientific significance and clinical application value for tumor treatment.
Multi-cohort shotgun metagenomic analysis of oral and gut microbiota overlap in healthy adults
Authors: Rashidi Armin , Gem Hakan , McLean Jeffrey S. , Kerns Kristopher , Dean David R. , Dey Neelendu , Minot Samuel
Published: January 2024

The multitude of barriers between the mouth and colon may eliminate swallowed oral bacteria. Ascertaining the presence of the same bacteria in the mouth and colon is methodologically challenging partly because 16S rRNA gene sequencing – the most commonly used method to characterize the human microbiota – has low confidence in taxonomic assignments deeper than genus for most bacteria. As different species of the same genus can have low-level variation across the same 16S rRNA gene region, shotgun sequencing is needed to identify a true overlap. We analyzed a curated, multi-cohort, shotgun metagenomic database with species-level taxonomy and clade-specific marker genes to fill this knowledge gap. Using 500 paired fecal/oral (4 oral sites) samples from 4 healthy adult cohorts, we found a minute overlap between the two niches. Comparing marker genes between paired oral and fecal samples with species-level overlap, the pattern of overlap in only 7 individuals was consistent with same-strain colonization. These findings argue against ectopic colonization of oral bacteria in the distal gut in healthy adults.
National-scale remotely sensed lake trophic state from 1984 through 2020
Authors: Meyer Michael F. , Topp Simon N. , King Tyler V. , Ladwig Robert , Pilla Rachel M. , Dugan Hilary A. , Eggleston Jack R. , Hampton Stephanie E. , Leech Dina M. , Oleksy Isabella A. , Ross Jesse C. , Ross Matthew R. V. , Woolway R. Iestyn , Yang Xiao , Brousil Matthew R. , Fickas Kate C. , Padowski Julie C. , Pollard Amina I. , Ren Jianning , Zwart Jacob A.
Published: January 2024

Lake trophic state is a key ecosystem property that integrates a lake’s physical, chemical, and biological processes. Despite the importance of trophic state as a gauge of lake water quality, standardized and machine-readable observations are uncommon. Remote sensing presents an opportunity to detect and analyze lake trophic state with reproducible, robust methods across time and space. We used Landsat surface reflectance data to create the first compendium of annual lake trophic state for 55,662 lakes of at least 10 ha in area throughout the contiguous United States from 1984 through 2020. The dataset was constructed with FAIR data principles (Findable, Accessible, Interoperable, and Reproducible) in mind, where data are publicly available, relational keys from parent datasets are retained, and all data wrangling and modeling routines are scripted for future reuse. Together, this resource offers critical data to address basic and applied research questions about lake water quality at a suite of spatial and temporal scales.
Genesis of ectosymbiotic features based on commensalistic syntrophy
Authors: Krishnan Nandakishor , Csiszár Villő , Móri Tamás F. , Garay József
Published: January 2024

The symbiogenetic origin of eukaryotes with mitochondria is considered a major evolutionary transition. The initial interactions and conditions of symbiosis, along with the phylogenetic affinity of the host, are widely debated. Here, we focus on a possible evolutionary path toward an association of individuals of two species based on unidirectional syntrophy. With the backing of a theoretical model, we hypothesize that the first step in the evolution of such symbiosis could be the appearance of a linking structure on the symbiont’s membrane, using which it forms an ectocommensalism with its host. We consider a commensalistic model based on the syntrophy hypothesis in the framework of coevolutionary dynamics and mutant invasion into a monomorphic resident system (evolutionary substitution). We investigate the ecological and evolutionary stability of the consortium (or symbiotic merger), with vertical transmissions playing a crucial role. The impact of the ‘effectiveness of vertical transmission’ on the dynamics is also analyzed. We find that the transmission of symbionts and the additional costs incurred by the mutant determine the conditions of fixation of the consortia. Additionally, we observe that small and highly metabolically active symbionts are likely to form the consortia.
An analysis of national media coverage of a parental leave reform investigating sentiment, semantics and contributors
Authors: Vermillet Arnault-Quentin , Krejberg Sara Engsig , Nielsen Julie Svinth , Parsons Christine E.
Published: January 2024

While paid leave for fathers after the birth of a child has become increasingly available, mothers still take most of the parental leave. A recent European Union (EU) reform addresses the unequal sharing of leave between parents via earmarking of paid, non-shareable leave to each parent. Given that the reform’s success will depend on uptake by families, we analysed Danish national media coverage to understand how journalists were writing about the reform. We assessed the sentiment and semantics of leave reform coverage compared to general news from the same period, also considering the inferred journalist gender and newspaper political orientation. Parental leave reform articles were slightly more emotional than general news, independent of who authored the article, or the newspaper where it was published. We found a robust difference in the semantics of how female journalists wrote about the reform, relative to male journalists, and that female journalists contributed to media coverage at a higher-than-expected rate. The tendency for media coverage to be written with a non-neutral sentiment can be understood in terms of the enduring political tensions over gender equality, the role of the EU and families’ rights to self-organization. That female journalists over-contributed to media coverage is interesting in understanding topic assignments or interest in parental leave.
Physical, mechanical, and microstructural characterisation of tungsten carbide-based polymeric composites for radiation shielding application
Authors: Abualroos Nadin Jamal , Idris Mohd Idzat , Ibrahim Haidi , Kamaruzaman Muhammad Izzat , Zainon Rafidah
Published: January 2024

Polymeric based composites have gained considerable attention as potential candidates for advanced radiation shielding applications due to their unique combination of high-density, radiation attenuation properties and improved mechanical strength. This study focuses on the comprehensive characterisation of polymeric based composites for radiation shielding applications. The objective of this study was to evaluate the physical, mechanical and microstructural properties of tungsten carbide-based epoxy resin and tungsten carbide cobalt-based epoxy resin for its efficiency in shielding against gamma-rays ranging from 0.6 up to 1.33 MeV. Polymeric composites with different weight percentages of epoxy resin (40 wt%, 35 wt%, 30 wt%, 25 wt%, 20 wt%, 15 wt% and 10 wt%) were fabricated, investigated and compared to conventional lead shield. The attenuation of the composites was performed using NaI (Tl) gamma-ray spectrometer to investigate the linear and mass attenuation coefficients, half value layer, and mean free path. High filler loadings into epoxy resin matrix (90% filler/10% epoxy) exhibited excellent gamma shielding properties. Mechanical properties, such as hardness were examined to assess the structural integrity and durability of the composites under various conditions. The fabricated composites showed a good resistance, the maximum hardness was attributed to composites with small thickness. The high loading of fillers in the epoxy matrix improved the microhardness of the composites. The distribution of the filler powder within the epoxy matrix was investigated using FESEM/EDX. The results revealed the successful incorporation of tungsten carbide and cobalt particles into the polymer matrix, leading to increased composite density and enhanced radiation attenuation. The unique combination of high-density, radiation attenuation, and improved mechanical properties positions polymeric based composites as promising candidates for radiation protection field.
Novel species of Triatoma (Hemiptera: Reduviidae) identified in a case of vectorial transmission of Chagas disease in northern Belize
Authors: Gunter Sarah M. , Nelson Alisa , Kneubehl Alexander R. , Justi Silvia A. , Manzanero Russell , Zielinski-Gutierrez Emily , Herrera Claudia , Thompson Julie , Mandage Rajendra , Desale Hans , Maliga Adrianna , Bautista Kim , Ronca Shannon E. , Morey Francis , Fuentes Rafael Chacon , Lopez Beatriz , Dumonteil Eric , Morazan Gerhaldine H. , Murray Kristy O.
Published: January 2024

Chagas disease is a leading cause of non-ischemic cardiomyopathy in endemic regions of Central and South America. In Belize, Triatoma dimidiata sensu lato has been identified as the predominate taxon but vectorial transmission of Chagas disease is considered to be rare in the country. We recently identified an acute case of vector-borne Chagas disease in the northern region of Belize. Here we present a subsequent investigation of triatomines collected around the case-patient’s home. We identified yet undescribed species, closely related to Triatoma huehuetenanguensis vector by molecular systematics methods occurring in the peridomestic environment. The identification of a T. cruzi-positive, novel species of Triatoma in Belize indicates an increased risk of transmission to humans in the region and warrants expanded surveillance and further investigation.
Dynamics of technology emergence in innovation networks
Authors: Ho Martin , Price Henry C. W. , Evans Tim S. , O’Sullivan Eoin
Published: January 2024

To create the next innovative product, participants in science need to understand which existing technologies can be combined, what new science must be discovered, and what new technologies must be invented. Knowledge of these often arrives by means of expert consensus or popularity metrics, masking key information on how intellectual efforts accumulate into technological progress. To address this shortcoming, we first present a method to establish a mathematical link between technological evolution and complex networks: a path of events that narrates innovation bottlenecks. Next, we quantify the position and proximity of documents to these innovation paths. The result is an innovation network that more exhaustively captures deterministic knowledge flows with respect to a marketed innovative product. Our dataset, containing over three million biomedical citations, demonstrates the possibility of quantifying the accumulation, speed, and division of labour in innovation over a sixty-year time horizon. The significance of this study includes the (i) use of a purpose-generated dataset showing causal paths from research to development to product; (ii) analysis of the innovation process as a directed acyclic graph; (iii) comparison between calendar time and network time; (iv) ordering of science funders along technology lifecycles; (v) quantification of innovative activities’ importance to an innovative outcome; and (vi) integration of publication, patent, clinical trial, regulatory data to study innovation holistically.
Transcriptional profile of ribosome-associated quality control components and their associated phenotypes in mammalian cells
Authors: Dos Santos Otávio Augusto Leitão , Carneiro Rodolfo L. , Requião Rodrigo D. , Ribeiro-Alves Marcelo , Domitrovic Tatiana , Palhano Fernando L.
Published: January 2024

During protein synthesis, organisms detect translation defects that induce ribosome stalling and result in protein aggregation. The Ribosome-associated Quality Control (RQC) complex, comprising TCF25, LTN1, and NEMF, is responsible for identifying incomplete protein products from unproductive translation events, targeting them for degradation. Although RQC disruption causes adverse effects on vertebrate neurons, data regarding mRNA/protein expression and regulation across tissues are lacking. Employing high-throughput methods, we analyzed public datasets to explore RQC gene expression and phenotypes. Our findings revealed widespread expression of RQC components in human tissues; however, silencing of RQC yielded only mild negative effects on cell growth. Notably, TCF25 exhibited elevated mRNA levels that were not reflected in the protein content. We experimentally demonstrated that this disparity arose from post-translational protein degradation by the proteasome. Additionally, we observed that cellular aging marginally influenced RQC expression, leading to reduced mRNA levels in specific tissues. Our results suggest the necessity of RQC expression in all mammalian tissues. Nevertheless, when RQC falters, alternative mechanisms seem to compensate, ensuring cell survival under nonstress conditions.