bluuebunny/crossref_metadata_2025 huggingface dataset:
Occurrence Probability of Magnetic Field Disturbances Measured With Swarm: Mapping the Dynamic Magnetosphere‐Ionosphere Coupling
Authors: Decotte Margot , Laundal Karl M. , Hatch Spencer M. , Reistad Jone P.
Published: February 2024

The exchange of kinetic and electromagnetic energy by precipitation and/or outflow and through field‐aligned currents are two aspects of the ionosphere‐magnetosphere coupling. A thorough investigation of these processes is required to better understand magnetospheric dynamics. Building on our previous study using the Defense Meteorological Satellite Program spectrometer data, here we use Swarm vector field magnetometer data to describe the auroral zone morphology in terms of east‐west magnetic field perturbations. We define a threshold for detecting magnetic fluctuations based on the power spectral density of ΔBEW, and derive the disturbed magnetic field occurrence probability (dBOP) at low [0.1–1 Hz] and high [2.5–5 Hz] frequencies. High‐frequency distributions of dBOP reveal a dayside‐nightside asymmetry, whereas low‐frequency dBOP exhibits a persistent morphological asymmetry between the dawn‐to‐noon and the dusk‐to‐midnight sectors, peaking at dawn. Notably, weak solar wind conditions are associated with an increase in the dBOP asymmetric patterns. At low frequency in particular, while the dBOP seems to be primarily constant at dawn, the dusk dBOP decreases during quiet times, inducing a relatively larger dawn‐dusk asymmetry in such conditions. Furthermore, based on a comparison analysis between low‐frequency dBOP and auroral electron precipitation occurrence probability, we suggest that both types of distribution offer a more comprehensive understanding of the large‐scale auroral zone when considered concurrently. Our interpretation is that the dBOP at low frequencies reflects a quasi‐steady state circulation of energy, while the high‐frequency dBOP reflects the regions of rapid changes in the magnetosphere. The dBOP is therefore a crucial source of information regarding the magnetosphere‐ionosphere coupling.
Evidence for a Current System and Potential Structure in the Martian Magnetotail
Authors: Nauth Murti , Mitchell David L. , Fowler Christopher M. , de Pater Imke , Azari Abigail R.
Published: February 2024

We present a case study of plasma and magnetic field observations in the Martian magnetotail using data from the Mars Atmosphere and Volatile EvolutioN (MAVEN) mission during an orbit when the spacecraft was in the optical shadow, past the dusk terminator and downstream of the strongest crustal magnetic fields. In this region, we observed multiple magnetic field rotations (a signature of currents) closely associated with energized (up to 100 eV) electron populations. Several transitions between closed and draped magnetic topologies also occur in this region, which are likely to be caused by magnetic reconnection between the interplanetary magnetic field (IMF) and crustal magnetic fields. We also observe two regions of energized, counter‐streaming electrons, which are rare in the magnetotail, but twice as likely to occur downstream of strong crustal magnetic fields when they are near the evening terminator. Together, the multiple magnetic field rotations, topological changes, and counter streaming electrons suggest the presence of an electric potential structure similar to those observed above the auroral arc regions at Earth.
Ionospheric Conductances Due To Electron and Ion Precipitations: A Comparison Between EISCAT and DMSP Estimates
Authors: Wang Xin , Cai Lei , Aikio Anita , Vanhamäki Heikki , Virtanen Ilkka , Zhang Yongliang , Luo Bingxian , Liu Siqing
Published: February 2024

Energetic particle precipitation is the major source of electron production that controls the ionospheric Pedersen and Hall conductances at high latitudes. Many studies use empirical formulas to estimate conductances. The particle precipitation spectra measured by the Defense Meteorological Satellite Program (DMSP) Special Sensor J are often used as the input to the empirical formulas. In this study, we evaluate the empirical formulas of ionospheric conductances during four different types of auroral precipitation conditions based on 63 conjugate events observed by DMSP and EISCAT. The conductances calculated from the DMSP data with the empirical formulas are compared with those based on EISCAT measurements with the standard equations. The best correlation between these two is found when the empirical Robinson formulas (Robinson et al., 1987, https://doi.org/10.1029/ja092ia03p02565) are used in the presence of diffuse electron precipitation without ions. In the presence of ion precipitation, the correlation coefficients are smaller, but the correlation improves when the Galand formulas (Galand & Richmond, 2001, https://doi.org/10.1029/1999ja002001) are used to estimate the contribution of ion precipitation to the conductances. We also found that pure ion precipitation can cause the increase of conductances up to 2–7 S for Pedersen and 2.5–10 S for Hall conductances, which is positively correlated with the auroral electrojet index. Overall, the empirical formulas applied to the DMSP particle spectra underestimate the ionospheric conductances.
Stable Zirconium Isotopic Compositions of the Metasomatized Mantle
Authors: Zou Zongqi , Xu Yi‐Gang , Wang Zaicong , Hu Chuyu , Feng Lanping , Guo Jing‐Liang , Zhang Wen , Ma Liang , Hu Zhaochu , Liu Yongsheng
Published: February 2024

Mantle metasomatism, which affects the geochemical and lithological properties of the Earth, is crucial to the evolution and modification of the Earth's interior. Variations in chemical proxy of metasomatism, including high‐field strength elements (HFSE, e.g., Zr‐Ti isotopes and isovalent Zr‐Hf), have been commonly utilized as a tool to unravel the processes associated with the evolution of the Earth. However, the impact of mantle metasomatism by diverse agents on the Zr isotopic compositions of metasomatized mantle remains poorly understood. Here we carried out high‐precision double‐spike δ94/90Zr measurements for a suite of basalts, which were derived from the mantle sources metasomatized by typical metasomatic agents of fluid, silicate melt and carbonate melt originating from the deep mantle or recycled crustal materials. Mantle metasomatism results in lithological diversities within the mantle, ranging from hybridized peridotites to pyroxenite/eclogite and carbonated eclogite, which can significantly fractionate the isovalent HFSEs. However, our data show that these basalts have primitive mantle‐like δ94ZrNIST values (−0.033–0.043 ‰), regardless of their superchondritic Zr/Hf. The primitive mantle‐like δ94ZrNIST, irrelevant to any proxy of metasomatism (e.g., Sr‐Nd isotopes, Zr/Hf and La/Sm), indicate that mantle metasomatism and subsequence melting produce no measurable Zr isotopic variations in metasomatized mantle‐derived basalts. The δ94ZrNIST of basalts thus can be representative of the mean metasomatized mantle compositions. Combined with previously reported komatiites and oceanic basalts, we show that the Earth's mantle displays consistent δ94ZrNIST (−0.013 ± 0.053 ‰), even if it has a secular dynamic evolution with the interaction between Earth's exterior and interior.
Hydrology Controls Dissolved Organic Carbon and Nitrogen Export and Post‐Storm Recovery in Two Arctic Headwaters
Authors: Shogren Arial J. , Zarnetske Jay P. , Abbott Benjamin W. , Grose Amelia L. , Rec Abigail F. , Nipko Jansen , Song Chao , O’Donnell Jonathan A. , Bowden William B.
Published: February 2024

Climate change is rapidly altering hydrological processes and consequently the structure and functioning of Arctic ecosystems. Predicting how these alterations will shape biogeochemical responses in rivers remains a major challenge. We measured [C]arbon and [N]itrogen concentrations continuously from two Arctic watersheds capturing a wide range of flow conditions to assess understudied event‐scale C and N concentration‐discharge (C‐Q) behavior and post‐event recovery of stoichiometric conditions. The watersheds represent low‐gradient, tundra landscapes typical of the eastern Brooks Range on the North Slope of Alaska and are part of the Arctic Long‐Term Ecological Research sites: the Kuparuk River and Oksrukuyik Creek. In both watersheds, we deployed high‐frequency optical sensors to measure dissolved organic carbon (DOC), nitrate (), and total dissolved nitrogen (TDN) for five consecutive thaw seasons (2017–2021). Our analyses revealed a lag in DOC: stoichiometric recovery after a hydrologic perturbation: while DOC was consistently elevated after high flows, diluted during rainfall events and consequently, recovery in post‐event concentration was delayed. Conversely, the co‐enrichment of TDN at high flows, even in watersheds with relatively high N‐demand, represents a potential “leak” of hydrologically available organic N to downstream ecosystems. Our use of high‐frequency, long‐term optical sensors provides an improved method to estimate carbon and nutrient budgets and stoichiometric recovery behavior across event and seasonal timescales, enabling new insights and conceptualizations of a changing Arctic, such as assessing ecosystem disturbance and recovery across multiple timescales.
Using Stochastic Point Pattern Analysis to Track Regional Orientations of Magmatism During the Transition to Cenozoic Extension and Rio Grande Rifting, Southern Rocky Mountains
Authors: Rosera J. M. , Gaynor S. P. , Ulianov A. , Schaltegger U.
Published: February 2024

The southern Rocky Mountains in Colorado and northern New Mexico hosted intracontinental magmatism that developed during a tectonic transition from shortening (Laramide orogeny, ca. 75 to 40 Ma) through extension and rifting. We present a novel approach that uses stochastic weighted bootstrap simulations of a large set of new and historical geochronology data to better understand how regional anisotropies responsible for focusing magma emplacement evolved through time. This technique can detect subtle trends in directional distributions, including multi‐modal orientations, and can be filtered from regional to local scales. Our results indicate that magmatism followed first the northeast trend of the Colorado mineral belt between 75 and 40 Ma and deviated afterward. These deviations vary depending on the scale of the analysis. At the smallest scale we evaluated (<75 km), the orientation of magmatism from 45 to 30 Ma rotated counter‐clockwise before aligning with the north‐south trend of the modern Rio Grande rift. Larger, regional‐scale analyses indicate magma centers between 40 to 35 Ma and 25 to 20 Ma were dominantly oriented southwest‐northeast, whereas magmatism between 35 and 25 Ma had north‐south orientation. The large areal footprint of magmatism and shifting regional patterns suggest that ancient zones of weakness in the North American lithosphere accommodated magma flow at different moments in time, rather than controlled by a retreating interface of the Farallon and North American plates.
Predicting Imminent Cyanobacterial Blooms in Lakes Using Incomplete Timely Data
Authors: Heggerud Christopher M. , Xu Jingjing , Wang Hao , Lewis Mark A. , Zurawell Ron W. , Loewen Charlie J. G. , Vinebrooke Rolf D. , Ramazi Pouria
Published: February 2024

Toxic cyanobacterial blooms (CBs) are becoming more frequent globally, posing a threat to freshwater ecosystems. While making long‐range forecasts is overly challenging, predicting imminent CBs is possible from precise monitoring data of the underlying covariates. It is, however, infeasibly costly to conduct precise monitoring on a large scale, leaving most lakes unmonitored or only partially monitored. The challenge is hence to build a predictive model that can use the incomplete, partially‐monitored data to make near‐future CB predictions. By using 30 years of monitoring data for 78 water bodies in Alberta, Canada, combined with data of watershed characteristics (including natural land cover and anthropogenic land use) and meteorological conditions, we train a Bayesian network that predicts future 2‐week CB with an area under the curve (AUC) of 0.83. The only monitoring data that the model needs to reach this level of accuracy are whether the cell count and Secchi depth are low, medium, or high, which can be estimated by advanced high‐resolution imaging technology or trained local citizens. The model is robust against missing values as in the absence of any single covariate, it performs with an AUC of at least 0.78. While taking a major step toward reduced‐cost, less data‐intensive CB forecasting, our results identify those key covariates that are worth the monitoring investment for highly accurate predictions.
A Semi‐Analytical Solution for the Equivalent Permeability Coefficient of the Multilayered Porous Medium With Continuous Fracture
Authors: Zhang Shuai , Liu Xiaoli
Published: February 2024

Fractures significantly alter the permeability characteristics of the natural porous media, especially for the multilayered porous medium system. The most direct and effective approach to assess the hydraulic conductivity of a multilayered porous medium with continuous fracture is to determine its equivalent permeability coefficient (EPC). A mathematical model with second‐order accuracy is established to analysis the permeability characteristics of the multilayered porous medium incorporating a continuous fracture. The Navier‒Stokes equation is used to govern the clear fluid motion in the continuous fracture, and the seepage fluid motion in the multilayered porous matrix is governed by the Brinkman‒Darcy equation. The semi‐analytical solutions for the velocity profile and EPC of the present model are derived under the conditions of the jumping stress at the fracture‐matrix interface and the continuous velocity at the matrix(i)‐matrix(i +1) interface. The Lattice Boltzmann method, finite element method, and one domain method simulations are conducted to verify the deduced semi‐analytical solutions of the velocity profile. Furthermore, the calculated EPC of the present multilayered model is in good agreement with that of the existing classic models (i.e., one region: fracture, two regions: fracture‐matrix, three regions: fracture‐matrix1‐matrix2, and multilayered porous medium without fracture). Parameter sensitivity reveals that increasing the thickness, dip angle, and porosity of the fractured porous media increases the flow velocity, while an increase in the stress jump coefficient can result in the opposite effect. This implies that porous layers containing fracture are more susceptible to erosion, particularly under conditions of steep dip angle and strong permeability.
Finding a balance in reduced toxicity hematopoietic stem cell transplantation for thalassemia: role of infused CD3+ cell count and immunosuppression
Authors: Meissner Barbara , Lang Peter , Bader Peter , Hoenig Manfred , Müller Ingo , Meisel Roland , Greil Johann , Sauer Martin G. , Metzler Markus , Corbacioglu Selim , Burkhardt Birgit , Wölfl Matthias , Strahm Brigitte , Kafa Kinan , Basu Oliver , Lode Holger N. , Gruhn Bernd , Cario Holger , Ozga Ann-Kathrin , Zimmermann Martin , Jarisch Andrea , Beier Rita
Published: February 2024

We performed a retrospective analysis on 124 patients with transfusion-dependent thalassemia who were registered in the German pediatric registry for stem cell transplantation. All patients underwent first allogeneic hematopoietic stem cell transplantation (HSCT) between 2011 and 2020 and belonged mainly to Pesaro risk class 1–2. Four-year overall (OS) and thalassemia-free survival (TFS) were 94.5% ± 2.9% and 88.0% ± 3.4% after treosulfan-fludarabine-thiotepa- and 96.9% ± 3.1% (P = 0.763) and 96.9% ± 3.1% (P = 0.155) after busulfan-fludarabine-based conditioning. Mixed chimerism below 75% occurred predominantly in treosulfan-based regimens (27.5% versus 6.2%). OS and TFS did not differ significantly between matched sibling, other matched family and matched unrelated donor (UD) HSCTs (OS: 100.0%, 100.0%, 96.3% ± 3.6%; TFS: 96.5% ± 2.4%, 90.0% ± 9.5%, 88.9% ± 6.0%). However, mismatched UD-HSCTs performed less favorable (OS: 84.7% ± 7.3% (P = 0.029); TFS: 79.9% ± 7.4% (P = 0.082)). We generated a scoring system reflecting the risk to develop mixed chimerism in our cohort. The main risk-reducing factors were a high CD3+ cell count (≥6 × 107/kg) in the graft, busulfan-conditioning, pre-conditioning therapy and low-targeted ciclosporin A trough levels. Acute GvHD grade III-IV in treosulfan-based concepts predominantly occurred in patients with UD and reduced GvHD prophylaxis but not in the context of high CD3+ cell doses. Taken together, this information might be used to develop more risk-adapted HSCT regimens for thalassemia patients.
Serum NY-ESO-1 antibody as a predictive biomarker for postoperative recurrence of gastric cancer: a multicenter prospective observational study
Authors: Saito Takuro , Kurokawa Yukinori , Fujitani Kazumasa , Kawabata Ryohei , Takeno Atsushi , Mikami Jota , Endo Shunji , Matsuyama Jin , Akamaru Yusuke , Hirota Masashi , Kishi Kentaro , Urakawa Shinya , Yamamoto Kei , Tanaka Koji , Takahashi Tsuyoshi , Oka Mikio , Wada Hisashi , Eguchi Hidetoshi , Doki Yuichiro
Published: February 2024

Background

No reliable marker has been identified to predict postoperative recurrence of gastric cancer. We designed a clinical trial to investigate the utility of serum NY-ESO-1 antibody responses as a predictive marker for postoperative recurrence in gastric cancer.

Methods

A multicenter prospective study was conducted between 2012 and 2021. Patients with resectable cT3-4 gastric cancer were included. Postoperative NY-ESO-1 and p53 antibody responses were serially evaluated every 3 months for 1 year in patients with positive preoperative antibody responses. The recurrence rate was assessed by the positivity of antibody responses at 3 and 12 months postoperatively.

Results

Among 1001 patients, preoperative NY-ESO-1 and p53 antibody responses were positive in 12.6% and 18.1% of patients, respectively. NY-ESO-1 antibody responses became negative postoperatively in non-recurrent patients (negativity rates; 45% and 78% at 3 and 12 months, respectively), but remained positive in recurrent patients (negativity rates; 9% and 8%, respectively). p53 antibody responses remained positive in non-recurrent patients. In multivariate analysis, NY-ESO-1 antibody positivity at 3 months (P  < 0.03) and 12 months (P  < 0.001) were independent prognostic factors for a shorter recurrence-free interval.

Conclusions

Serum NY-ESO-1 antibodies may be a useful predictive marker for postoperative recurrence in gastric cancer.

Clinical trial registration

UMIN000007925.
Process-evaluation of forest aerosol-cloud-climate feedback shows clear evidence from observations and large uncertainty in models
Authors: Blichner Sara M. , Yli-Juuti Taina , Mielonen Tero , Pöhlker Christopher , Holopainen Eemeli , Heikkinen Liine , Mohr Claudia , Artaxo Paulo , Carbone Samara , Meller Bruno Backes , Quaresma Dias-Júnior Cléo , Kulmala Markku , Petäjä Tuukka , Scott Catherine E. , Svenhag Carl , Nieradzik Lars , Sporre Moa , Partridge Daniel G. , Tovazzi Emanuele , Virtanen Annele , Kokkola Harri , Riipinen Ilona
Published: February 2024

Natural aerosol feedbacks are expected to become more important in the future, as anthropogenic aerosol emissions decrease due to air quality policy. One such feedback is initiated by the increase in biogenic volatile organic compound (BVOC) emissions with higher temperatures, leading to higher secondary organic aerosol (SOA) production and a cooling of the surface via impacts on cloud radiative properties. Motivated by the considerable spread in feedback strength in Earth System Models (ESMs), we here use two long-term observational datasets from boreal and tropical forests, together with satellite data, for a process-based evaluation of the BVOC-aerosol-cloud feedback in four ESMs. The model evaluation shows that the weakest modelled feedback estimates can likely be excluded, but highlights compensating errors making it difficult to draw conclusions of the strongest estimates. Overall, the method of evaluating along process chains shows promise in pin-pointing sources of uncertainty and constraining modelled aerosol feedbacks.
Visualization-enhanced under-oil open microfluidic system for in situ characterization of multi-phase chemical reactions
Authors: Chen Qiyuan , Zhai Hang , Beebe David J. , Li Chao , Wang Bu
Published: February 2024

Under-oil open microfluidic system, utilizing liquid-liquid boundaries for confinements, offers inherent advantages including clogging-free flow channels, flexible access to samples, and adjustable gas permeation, making it well-suited for studying multi-phase chemical reactions that are challenging for closed microfluidics. However, reports on the novel system have primarily focused on device fabrication and functionality demonstrations within biology, leaving their application in broader chemical analysis underexplored. Here, we present a visualization-enhanced under-oil open microfluidic system for in situ characterization of multi-phase chemical reactions with Raman spectroscopy. The enhanced system utilizes a semi-transparent silicon (Si) nanolayer over the substrate to enhance visualization in both inverted and upright microscope setups while reducing Raman noise from the substrate. We validated the system’s chemical stability and capability to monitor gas evolution and gas-liquid reactions in situ. The enhanced under-oil open microfluidic system, integrating Raman spectroscopy, offers a robust open-microfluidic platform for label-free molecular sensing and real-time chemical/biochemical process monitoring in multi-phase systems.
The role of extracellular vesicle fusion with target cells in triggering systemic inflammation
Authors: Papareddy Praveen , Tapken Ines , Kroh Keshia , Varma Bhongir Ravi Kiran , Rahman Milladur , Baumgarten Maria , Cim Eda Irem , Györffy Lilla , Smeds Emanuel , Neumann Ariane , Veerla Srinivas , Olinder Jon , Thorlacus Henrik , Ryden Cecilia , Bartakova Eva , Holub Michal , Herwald Heiko
Published: February 2024

Extracellular vesicles (EVs) play a crucial role in intercellular communication by transferring bioactive molecules from donor to recipient cells. As a result, EV fusion leads to the modulation of cellular functions and has an impact on both physiological and pathological processes in the recipient cell. This study explores the impact of EV fusion on cellular responses to inflammatory signaling. Our findings reveal that fusion renders non-responsive cells susceptible to inflammatory signaling, as evidenced by increased NF-κB activation and the release of inflammatory mediators. Syntaxin-binding protein 1 is essential for the merge and activation of intracellular signaling. Subsequent analysis show that EVs transfer their functionally active receptors to target cells, making them prone to an otherwise unresponsive state. EVs in complex with their agonist, require no further stimulation of the target cells to trigger mobilization of NF-κB. While receptor antagonists were unable to inhibit NF-κB activation, blocking of the fusion between EVs and their target cells with heparin mitigated inflammation in mice challenged with EVs.
Hormonal steroids induce multidrug resistance and stress response genes in Neisseria gonorrhoeae by binding to MtrR
Authors: Hooks Grace M. , Ayala Julio C. , Holley Concerta L. , Dhulipala Vijaya , Beggs Grace A. , Perfect John R. , Schumacher Maria A. , Shafer William M. , Brennan Richard G.
Published: February 2024

Transcriptional regulator MtrR inhibits the expression of the multidrug efflux pump operon mtrCDE in the pathogenic bacterium Neisseria gonorrhoeae. Here, we show that MtrR binds the hormonal steroids progesterone, β-estradiol, and testosterone, which are present at urogenital infection sites, as well as ethinyl estrogen, a component of some hormonal contraceptives. Steroid binding leads to the decreased affinity of MtrR for cognate DNA, increased mtrCDE expression, and enhanced antimicrobial resistance. Furthermore, we solve crystal structures of MtrR bound to each steroid, thus revealing their binding mechanisms and the conformational changes that induce MtrR.
Realization of large-area ultraflat chiral blue phosphorene
Authors: Song Ye-Heng , Muzaffar M. U. , Wang Qi , Wang Yunhui , Jia Yu , Cui Ping , Zhang Weifeng , Wang Xue-Sen , Zhang Zhenyu
Published: February 2024

Blue phosphorene (BlueP), a theoretically proposed phosphorous allotrope with buckled honeycomb lattice, has attracted considerable interest due to its intriguing properties. Introducing chirality into BlueP can further enrich its physical and chemical properties, expanding its potential for applications. However, the synthesis of chiral BlueP remains elusive. Here, we demonstrate the growth of large-area BlueP films on Cu(111), with lateral size limited by the wafer dimensions. Importantly, we discovered that the BlueP is characterized by an ultraflat honeycomb lattice, rather than the prevailing buckled structure, and develops highly ordered spatial chirality plausibly resulting from the rotational stacking with the substrate and interface strain release, as further confirmed by the geometric phase analysis. Moreover, spectroscopic measurements reveal its intrinsic metallic nature and different characteristic quantum oscillations in the image-potential states, which can be exploited for a range of potential applications including polarization optics, spintronics, and chiral catalysis.
Memristor-based storage system with convolutional autoencoder-based image compression network
Authors: Feng Yulin , Zhang Yizhou , Zhou Zheng , Huang Peng , Liu Lifeng , Liu Xiaoyan , Kang Jinfeng
Published: February 2024

The exponential growth of various complex images is putting tremendous pressure on storage systems. Here, we propose a memristor-based storage system with an integrated near-storage in-memory computing-based convolutional autoencoder compression network to boost the energy efficiency and speed of the image compression/retrieval and improve the storage density. We adopt the 4-bit memristor arrays to experimentally demonstrate the functions of the system. We propose a step-by-step quantization aware training scheme and an equivalent transformation for transpose convolution to improve the system performance. The system exhibits a high (>33 dB) peak signal-to-noise ratio in the compression and decompression of the ImageNet and Kodak24 datasets. Benchmark comparison results show that the 4-bit memristor-based storage system could reduce the latency and energy consumption by over 20×/5.6× and 180×/91×, respectively, compared with the server-grade central processing unit-based/the graphics processing unit-based processing system, and improve the storage density by more than 3 times.
A multicenter clinical AI system study for detection and diagnosis of focal liver lesions
Authors: Ying Hanning , Liu Xiaoqing , Zhang Min , Ren Yiyue , Zhen Shihui , Wang Xiaojie , Liu Bo , Hu Peng , Duan Lian , Cai Mingzhi , Jiang Ming , Cheng Xiangdong , Gong Xiangyang , Jiang Haitao , Jiang Jianshuai , Zheng Jianjun , Zhu Kelei , Zhou Wei , Lu Baochun , Zhou Hongkun , Shen Yiyu , Du Jinlin , Ying Mingliang , Hong Qiang , Mo Jingang , Li Jianfeng , Ye Guanxiong , Zhang Shizheng , Hu Hongjie , Sun Jihong , Liu Hui , Li Yiming , Xu Xingxin , Bai Huiping , Wang Shuxin , Cheng Xin , Xu Xiaoyin , Jiao Long , Yu Risheng , Lau Wan Yee , Yu Yizhou , Cai Xiujun
Published: February 2024

Early and accurate diagnosis of focal liver lesions is crucial for effective treatment and prognosis. We developed and validated a fully automated diagnostic system named Liver Artificial Intelligence Diagnosis System (LiAIDS) based on a diverse sample of 12,610 patients from 18 hospitals, both retrospectively and prospectively. In this study, LiAIDS achieved an F1-score of 0.940 for benign and 0.692 for malignant lesions, outperforming junior radiologists (benign: 0.830-0.890, malignant: 0.230-0.360) and being on par with senior radiologists (benign: 0.920-0.950, malignant: 0.550-0.650). Furthermore, with the assistance of LiAIDS, the diagnostic accuracy of all radiologists improved. For benign and malignant lesions, junior radiologists’ F1-scores improved to 0.936-0.946 and 0.667-0.680 respectively, while seniors improved to 0.950-0.961 and 0.679-0.753. Additionally, in a triage study of 13,192 consecutive patients, LiAIDS automatically classified 76.46% of patients as low risk with a high NPV of 99.0%. The evidence suggests that LiAIDS can serve as a routine diagnostic tool and enhance the diagnostic capabilities of radiologists for liver lesions.
Protein degradation by human 20S proteasomes elucidates the interplay between peptide hydrolysis and splicing
Authors: Soh Wai Tuck , Roetschke Hanna P. , Cormican John A. , Teo Bei Fang , Chiam Nyet Cheng , Raabe Monika , Pflanz Ralf , Henneberg Fabian , Becker Stefan , Chari Ashwin , Liu Haiyan , Urlaub Henning , Liepe Juliane , Mishto Michele
Published: February 2024

If and how proteasomes catalyze not only peptide hydrolysis but also peptide splicing is an open question that has divided the scientific community. The debate has so far been based on immunopeptidomics, in vitro digestions of synthetic polypeptides as well as ex vivo and in vivo experiments, which could only indirectly describe proteasome-catalyzed peptide splicing of full-length proteins. Here we develop a workflow—and cognate software - to analyze proteasome-generated non-spliced and spliced peptides produced from entire proteins and apply it to in vitro digestions of 15 proteins, including well-known intrinsically disordered proteins such as human tau and α-Synuclein. The results confirm that 20S proteasomes produce a sizeable variety of cis-spliced peptides, whereas trans-spliced peptides are a minority. Both peptide hydrolysis and splicing produce peptides with well-defined characteristics, which hint toward an intricate regulation of both catalytic activities. At protein level, both non-spliced and spliced peptides are not randomly localized within protein sequences, but rather concentrated in hotspots of peptide products, in part driven by protein sequence motifs and proteasomal preferences. At sequence level, the different peptide sequence preference of peptide hydrolysis and peptide splicing suggests a competition between the two catalytic activities of 20S proteasomes during protein degradation.
Integrating leiomyoma genetics, epigenomics, and single-cell transcriptomics reveals causal genetic variants, genes, and cell types
Authors: Buyukcelebi Kadir , Duval Alexander J. , Abdula Fatih , Elkafas Hoda , Seker-Polat Fidan , Adli Mazhar
Published: February 2024

Uterine fibroids (UF), that can disrupt normal uterine function and cause significant physical and psychological health problems, are observed in nearly 70% of women of reproductive age. Although heritable genetics is a significant risk factor, specific genetic variations and gene targets causally associated with UF are poorly understood. Here, we performed a meta-analysis on existing fibroid genome-wide association studies (GWAS) and integrated the identified risk loci and potentially causal single nucleotide polymorphisms (SNPs) with epigenomics, transcriptomics, 3D chromatin organization from diverse cell types as well as primary UF patient’s samples. This integrative analysis identifies 24 UF-associated risk loci that potentially target 394 genes, of which 168 are differentially expressed in UF tumors. Critically, integrating this data with single-cell gene expression data from UF patients reveales the causal cell types with aberrant expression of these target genes. Lastly, CRISPR-based epigenetic repression (dCas9-KRAB) or activation (dCas9-p300) in a UF disease-relevant cell type further refines and narrows down the potential gene targets. Our findings and the methodological approach indicate the effectiveness of integrating multi-omics data with locus-specific epigenetic editing approaches for identifying gene- and celt type-targets of disease-relevant risk loci.
Capacitive tendency concept alongside supervised machine-learning toward classifying electrochemical behavior of battery and pseudocapacitor materials
Authors: Deebansok Siraprapha , Deng Jie , Le Calvez Etienne , Zhu Yachao , Crosnier Olivier , Brousse Thierry , Fontaine Olivier
Published: February 2024

In recent decades, more than 100,000 scientific articles have been devoted to the development of electrode materials for supercapacitors and batteries. However, there is still intense debate surrounding the criteria for determining the electrochemical behavior involved in Faradaic reactions, as the issue is often complicated by the electrochemical signals produced by various electrode materials and their different physicochemical properties. The difficulty lies in the inability to determine which electrode type (battery vs. pseudocapacitor) these materials belong to via simple binary classification. To overcome this difficulty, we apply supervised machine learning for image classification to electrochemical shape analysis (over 5500 Cyclic Voltammetry curves and 2900 Galvanostatic Charge-Discharge curves), with the predicted confidence percentage reflecting the shape trend of the curve and thus defined as a manufacturer. It’s called “capacitive tendency”. This predictor not only transcends the limitations of human-based classification but also provides statistical trends regarding electrochemical behavior. Of note, and of particular importance to the electrochemical energy storage community, which publishes over a hundred articles per week, we have created an online tool to easily categorize their data.
Challenging thermodynamics: combining immiscible elements in a single-phase nano-ceramic
Authors: Liu Shuo , Dun Chaochao , Jiang Qike , Xuan Zhengxi , Yang Feipeng , Guo Jinghua , Urban Jeffrey J. , Swihart Mark T.
Published: February 2024

The Hume-Rothery rules governing solid-state miscibility limit the compositional space for new inorganic material discovery. Here, we report a non-equilibrium, one-step, and scalable flame synthesis method to overcome thermodynamic limits and incorporate immiscible elements into single phase ceramic nanoshells. Starting from prototype examples including (NiMg)O, (NiAl)Ox, and (NiZr)Ox, we then extend this method to a broad range of Ni-containing ceramic solid solutions, and finally to general binary combinations of elements. Furthermore, we report an “encapsulated exsolution” phenomenon observed upon reducing the metastable porous (Ni0.07Al0.93)Ox to create ultra-stable Ni nanoparticles embedded within the walls of porous Al2O3 nanoshells. This nanoconfined structure demonstrated high sintering resistance during 640 h of catalysis of CO2 reforming of methane, maintaining constant 96% CH4 and CO2 conversion at 800 °C and dramatically outperforming conventional catalysts. Our findings could greatly expand opportunities to develop novel inorganic energy, structural, and functional materials.
Steep-slope vertical-transport transistors built from sub-5 nm Thin van der Waals heterostructures
Authors: Yang Qiyu , Luo Zheng-Dong , Duan Huali , Gan Xuetao , Zhang Dawei , Li Yuewen , Tan Dongxin , Seidel Jan , Chen Wenchao , Liu Yan , Hao Yue , Han Genquan
Published: February 2024

Two-dimensional (2D) semiconductor-based vertical-transport field-effect transistors (VTFETs) – in which the current flows perpendicularly to the substrate surface direction – are in the drive to surmount the stringent downscaling constraints faced by the conventional planar FETs. However, low-power device operation with a sub-60 mV/dec subthreshold swing (SS) at room temperature along with an ultra-scaled channel length remains challenging for 2D semiconductor-based VTFETs. Here, we report steep-slope VTFETs that combine a gate-controllable van der Waals heterojunction and a metal-filamentary threshold switch (TS), featuring a vertical transport channel thinner than 5 nm and sub-thermionic turn-on characteristics. The integrated TS-VTFETs were realised with efficient current switching behaviours, exhibiting a current modulation ratio exceeding 1 × 108 and an average sub-60 mV/dec SS over 6 decades of drain current. The proposed TS-VTFETs with excellent area- and energy-efficiency could help to tackle the performance degradation-device downscaling dilemma faced by logic transistor technologies.
Spatial transcriptomics reveal neuron–astrocyte synergy in long-term memory
Authors: Sun Wenfei , Liu Zhihui , Jiang Xian , Chen Michelle B. , Dong Hua , Liu Jonathan , Südhof Thomas C. , Quake Stephen R.
Published: February 2024

Memory encodes past experiences, thereby enabling future plans. The basolateral amygdala is a centre of salience networks that underlie emotional experiences and thus has a key role in long-term fear memory formation1. Here we used spatial and single-cell transcriptomics to illuminate the cellular and molecular architecture of the role of the basolateral amygdala in long-term memory. We identified transcriptional signatures in subpopulations of neurons and astrocytes that were memory-specific and persisted for weeks. These transcriptional signatures implicate neuropeptide and BDNF signalling, MAPK and CREB activation, ubiquitination pathways, and synaptic connectivity as key components of long-term memory. Notably, upon long-term memory formation, a neuronal subpopulation defined by increased Penk and decreased Tac expression constituted the most prominent component of the memory engram of the basolateral amygdala. These transcriptional changes were observed both with single-cell RNA sequencing and with single-molecule spatial transcriptomics in intact slices, thereby providing a rich spatial map of a memory engram. The spatial data enabled us to determine that this neuronal subpopulation interacts with adjacent astrocytes, and functional experiments show that neurons require interactions with astrocytes to encode long-term memory.
Circulating myeloid-derived MMP8 in stress susceptibility and depression
Authors: Cathomas Flurin , Lin Hsiao-Yun , Chan Kenny L. , Li Long , Parise Lyonna F. , Alvarez Johana , Durand-de Cuttoli Romain , Aubry Antonio V. , Muhareb Samer , Desland Fiona , Shimo Yusuke , Ramakrishnan Aarthi , Estill Molly , Ferrer-Pérez Carmen , Parise Eric M. , Wilk C. Matthias , Kaster Manuella P. , Wang Jun , Sowa Allison , Janssen William G. , Costi Sara , Rahman Adeeb , Fernandez Nicolas , Campbell Matthew , Swirski Filip K. , Nestler Eric J. , Shen Li , Merad Miriam , Murrough James W. , Russo Scott J.
Published: February 2024

Psychosocial stress has profound effects on the body, including the immune system and the brain1,2. Although a large number of pre-clinical and clinical studies have linked peripheral immune system alterations to stress-related disorders such as major depressive disorder (MDD)3, the underlying mechanisms are not well understood. Here we show that expression of a circulating myeloid cell-specific proteinase, matrix metalloproteinase 8 (MMP8), is increased in the serum of humans with MDD as well as in stress-susceptible mice following chronic social defeat stress (CSDS). In mice, we show that this increase leads to alterations in extracellular space and neurophysiological changes in the nucleus accumbens (NAc), as well as altered social behaviour. Using a combination of mass cytometry and single-cell RNA sequencing, we performed high-dimensional phenotyping of immune cells in circulation and in the brain and demonstrate that peripheral monocytes are strongly affected by stress. In stress-susceptible mice, both circulating monocytes and monocytes that traffic to the brain showed increased Mmp8 expression following chronic social defeat stress. We further demonstrate that circulating MMP8 directly infiltrates the NAc parenchyma and controls the ultrastructure of the extracellular space. Depleting MMP8 prevented stress-induced social avoidance behaviour and alterations in NAc neurophysiology and extracellular space. Collectively, these data establish a mechanism by which peripheral immune factors can affect central nervous system function and behaviour in the context of stress. Targeting specific peripheral immune cell-derived matrix metalloproteinases could constitute novel therapeutic targets for stress-related neuropsychiatric disorders.
Structural basis of ribosomal 30S subunit degradation by RNase R
Authors: Dimitrova-Paternoga Lyudmila , Kasvandik Sergo , Beckert Bertrand , Granneman Sander , Tenson Tanel , Wilson Daniel N. , Paternoga Helge
Published: February 2024

Protein synthesis is a major energy-consuming process of the cell that requires the controlled production1–3 and turnover4,5 of ribosomes. Although the past few years have seen major advances in our understanding of ribosome biogenesis, structural insight into the degradation of ribosomes has been lacking. Here we present native structures of two distinct small ribosomal 30S subunit degradation intermediates associated with the 3′ to 5′ exonuclease ribonuclease R (RNase R). The structures reveal that RNase R binds at first to the 30S platform to facilitate the degradation of the functionally important anti-Shine–Dalgarno sequence and the decoding-site helix 44. RNase R then encounters a roadblock when it reaches the neck region of the 30S subunit, and this is overcome by a major structural rearrangement of the 30S head, involving the loss of ribosomal proteins. RNase R parallels this movement and relocates to the decoding site by using its N-terminal helix-turn-helix domain as an anchor. In vitro degradation assays suggest that head rearrangement poses a major kinetic barrier for RNase R, but also indicate that the enzyme alone is sufficient for complete degradation of 30S subunits. Collectively, our results provide a mechanistic basis for the degradation of 30S mediated by RNase R, and reveal that RNase R targets orphaned 30S subunits using a dynamic mechanism involving an anchored switching of binding sites.
Transforming a head direction signal into a goal-oriented steering command
Authors: Westeinde Elena A. , Kellogg Emily , Dawson Paul M. , Lu Jenny , Hamburg Lydia , Midler Benjamin , Druckmann Shaul , Wilson Rachel I.
Published: February 2024

To navigate, we must continuously estimate the direction we are headed in, and we must correct deviations from our goal1. Direction estimation is accomplished by ring attractor networks in the head direction system2,3. However, we do not fully understand how the sense of direction is used to guide action. Drosophila connectome analyses4,5 reveal three cell populations (PFL3R, PFL3L and PFL2) that connect the head direction system to the locomotor system. Here we use imaging, electrophysiology and chemogenetic stimulation during navigation to show how these populations function. Each population receives a shifted copy of the head direction vector, such that their three reference frames are shifted approximately 120° relative to each other. Each cell type then compares its own head direction vector with a common goal vector; specifically, it evaluates the congruence of these vectors via a nonlinear transformation. The output of all three cell populations is then combined to generate locomotor commands. PFL3R cells are recruited when the fly is oriented to the left of its goal, and their activity drives rightward turning; the reverse is true for PFL3L. Meanwhile, PFL2 cells increase steering speed, and are recruited when the fly is oriented far from its goal. PFL2 cells adaptively increase the strength of steering as directional error increases, effectively managing the tradeoff between speed and accuracy. Together, our results show how a map of space in the brain can be combined with an internal goal to generate action commands, via a transformation from world-centric coordinates to body-centric coordinates.
Telomere-to-telomere gapless genome assembly of the Chinese sea bass (Lateolabrax maculatus)
Authors: Sun Zhilong , Li Shuo , Liu Yuyan , Li Weijing , Liu Kaiqiang , Cao Xuebin , Lin Jiliang , Wang Hongyan , Wang Qian , Shao Changwei
Published: February 2024

Chinese sea bass (Lateolabrax maculatus) is a highly sought-after commercial seafood species in Asian regions due to its excellent nutritional value. With the rapid advancement of bioinformatics, higher standards for genome analysis compared to previously published reference genomes are now necessary. This study presents a gapless assembly of the Chinese sea bass genome, which has a length of 632.75 Mb. The sequences were assembled onto 24 chromosomes with a coverage of over 99% (626.61 Mb), and telomeres were detected on 34 chromosome ends. Analysis using Merqury indicated a high level of accuracy, with an average consensus quality value of 54.25. The ONT ultralong and PacBio HiFi data were aligned with the assembly using minimap2, resulting in a mapping rate of 99.9%. The study also identified repeating elements in 20.90% (132.25 Mb) of the genome and inferred 22,014 protein-coding genes. These results establish meaningful groundwork for exploring the evolution of the Chinese sea bass genome and advancing molecular breeding techniques.
Chromosome level genome assembly of the Etruscan shrew Suncus etruscus
Authors: Bukhman Yury V. , Meyer Susanne , Chu Li-Fang , Abueg Linelle , Antosiewicz-Bourget Jessica , Balacco Jennifer , Brecht Michael , Dinatale Erica , Fedrigo Olivier , Formenti Giulio , Fungtammasan Arkarachai , Giri Swagarika Jaharlal , Hiller Michael , Howe Kerstin , Kihara Daisuke , Mamott Daniel , Mountcastle Jacquelyn , Pelan Sarah , Rabbani Keon , Sims Ying , Tracey Alan , Wood Jonathan M. D. , Jarvis Erich D. , Thomson James A. , Chaisson Mark J. P. , Stewart Ron
Published: February 2024

Suncus etruscus is one of the world’s smallest mammals, with an average body mass of about 2 grams. The Etruscan shrew’s small body is accompanied by a very high energy demand and numerous metabolic adaptations. Here we report a chromosome-level genome assembly using PacBio long read sequencing, 10X Genomics linked short reads, optical mapping, and Hi-C linked reads. The assembly is partially phased, with the 2.472 Gbp primary pseudohaplotype and 1.515 Gbp alternate. We manually curated the primary assembly and identified 22 chromosomes, including X and Y sex chromosomes. The NCBI genome annotation pipeline identified 39,091 genes, 19,819 of them protein-coding. We also identified segmental duplications, inferred GO term annotations, and computed orthologs of human and mouse genes. This reference-quality genome will be an important resource for research on mammalian development, metabolism, and body size control.
Correlations between ADL in patients with SCI and caregiver burden, quality of life, and presenteeism in South Korea
Authors: Kim Sung Shin , Kim On Yoo , Kim Sun Hong , Heo Jae Eun , Ho Seung Hee , Kim Ju Hee , Bae Young-Hyeon
Published: February 2024

The correlations between activities of daily living (ADL) among patients with spinal cord injury (SCI) and their caregivers’ burden, quality of life (QoL), and presenteeism was investigated. Participants included outpatients and inpatients with SCI at a rehabilitation center and their caregivers, recruited between March 2020 and April 2021. Eighty-seven valid responses were analysed using independent t-tests and Pearson’s correlations. There was a difference in caregiver burden according to patients’ ADL performance. QoL was negatively correlated with caregiver burden and presenteeism. Caregiver burden and presenteeism were positively correlated. Social support can improve caregivers’ QoL and reduce caregiver burden and presenteeism-induced work impairment.