bluuebunny/crossref_metadata_2025 huggingface dataset:
CubeSat attitude determination with decomposed Kalman filters
Authors: Patrik Reizinger , Ferenc Vajda
Published: February 2023

CubeSats are the cost-effective entry to space research and applications. As mission requirements increase to carry out more complex tasks, the constraints on the satellite challenge how attitude estimation and control systems are designed. Limited energy, sensors, and computational capacity require compromises. In this paper, we propose a Kalman filter architecture to reduce the computational cost of attitude estimation, leveraging the conditional independence structure of its physical model. Our method decomposes attitude dynamics and kinematics, leading to a linear attitude quaternion and a nonlinear angular velocity filter. As accommodating all vector measurements would require a nonlinear filter, we propose the virtual sensor paradigm that transforms the nonlinear observation model into a linear one, without relying on approximations. Our numerical experiments showcase superior error dynamics and robustness to epistemic uncertainty compared to a nonlinear quaternionic filter, and we also investigate performance against star tracker measurement frequency and sensitivity to the angle between Sun and Earth magnetic field measurements.
Effects of post-printing heat treatment on microstructure, corrosion and wet wear behavior of CoCrW alloy produced by L-PBF process
Authors: Lanzutti A. , Andreatta F. , Vaglio E. , Sortino M. , Totis G. , Fedrizzi L.
Published: February 2023

CoCr alloys are widely used as human implants because of both their superior corrosion resistance and superior mechanical properties (fatigue, wear resistance, etc.) respect to other metal alloys used in biomedical field. In particular, CoCrW alloys are used mainly to produce dental implants. In this study, the effects of thermal treatment on the corrosion resistance and wet wear resistance of CoCrW alloys produced via Laser-Powder Bed Fusion (L-PBF) were investigated, and the corrosion resistance and wet wear resistance of the L-PBF specimens were compared with those of the specimens obtained after forging. The heat treatment involved the solubilization of the alloy at 1150 °C in an Ar-saturated atmosphere, followed by furnace cooling. A detailed microstructural characterization of the L-PBF specimens was carried out using a light microscope and a scanning electron microscope in both the horizontal and vertical growth directions. Scanning Kelvin probe measurements were performed on the heat-treated specimens obtained by three-dimensional printing and forging. The void contents of the specimens were evaluated using the Archimedes’ method and image analysis. Vickers (HV2) hardness measurements were performed to evaluate the mechanical properties of the specimens. The corrosion properties of the specimens were evaluated by carrying out potentiodynamic tests in two different corrosive media (aqueous solution (9 g/L NaCl) at pH = 2 and 7). The corroded areas of the specimens were then examined using scanning electron microscopy (SEM). Finally, tribological tests were performed using the pin (Ti counter material)-on-flat configuration under dry and wet conditions, using the same corrosive environments as those used in the potentiodynamic tests and two different stroke lengths. The worn samples were characterized using SEM to investigate their wear mechanisms, and a stylus profilometer was used to determine the wear rates of the materials. The experimental results showed that the additively manufactured CoCrW L-PBF alloy had higher corrosion resistance than the wrought material. In addition, the additively manufactured material showed better dry and wet wear performances than the wrought material. Nevertheless, the heat treatment did not affect the properties evaluated in this study.
Measurement and Processing of Road Irregularity for Surface Generation and Tyre Dynamics Simulation in NVH Context
Authors: Rapino Luca , La Paglia Ivano , Ripamonti Francesco , Corradi Roberto , Di Lione Riccardo , Baro Simone
Published: February 2023

Nowadays, finite element tyre models are often used to perform vehicle NVH (noise, vibration, harshness) simulations. To account for the specific operating conditions, a road surface must be properly included in the model. This paper deals with a methodology to experimentally evaluate and process road irregularity measurements, so as to generate a road surface input. These surfaces are used to simulate the tyre/road interaction at the footprint, which is modelled as a contact surface in finite element tyre models. For this reason, a linear profile of the road surface is not suitable for these simulations and the whole surface must be considered. Starting from the measurements taken through a test equipment specifically designed to carry laser sensors and scan road profiles, the Power Spectral Density (PSD) of a specific track is estimated and then interpolated considering piecewise functions. Finally, a model to generate a road surface starting from the measured PSD is developed, discussed and validated.
Molecular regulation of tomato male reproductive development
Authors: Yang Dandan , Wang Zhao , Huang Xiaozhen , Xu Cao
Published: February 2023

The reproductive success of flowering plants, which directly affects crop yield, is sensitive to environmental changes. A thorough understanding of how crop reproductive development adapts to climate changes is vital for ensuring global food security. In addition to being a high-value vegetable crop, tomato is also a model plant used for research on plant reproductive development. Tomato crops are cultivated under highly diverse climatic conditions worldwide. Targeted crosses of hybrid varieties have resulted in increased yields and abiotic stress resistance; however, tomato reproduction, especially male reproductive development, is sensitive to temperature fluctuations, which can lead to aborted male gametophytes, with detrimental effects on fruit set. We herein review the cytological features as well as genetic and molecular pathways influencing tomato male reproductive organ development and responses to abiotic stress. We also compare the shared features among the associated regulatory mechanisms of tomato and other plants. Collectively, this review highlights the opportunities and challenges related to characterizing and exploiting genic male sterility in tomato hybrid breeding programs.
Aspen Plus simulation of Chemical Looping Combustion of syngas and methane in fluidized beds
Authors: Jasper Micah , Shahbazi Abolghasem , Schimmel Keith , Li Fanxing , Wang Lijun
Published: February 2023

Chemical Looping Combustion (CLC) is a technology that efficiently combines power generation and CO2 capture. In CLC, the fuel is oxidized by a metal oxide called an oxygen carrier (OC). CLC uses two reactors: a fuel reactor and an air reactor. The fuel reactor oxidizes the fuel and reduces the OC. The air reactor oxidizes the OC using air and then the OC is cycled back to the fuel reactor. It is typical for both the fuel and the air reactors to be fluidized beds (FBs). In this research, an Aspen Plus model was developed to simulate a CLC system. Aspen Plus has recently included a built-in FB unit operation module. To our knowledge, no literature has been reported using this FB module for simulating fluidized bed combustion or gasification. This FB unit process was investigated in Aspen Plus and a kinetic based model was used and compared the simulation results to experimental data and the commonly used Gibbs equilibrium model. The FB unit and the kinetic model well fit the experimental data for syngas and methane combustion within 2% of the molar composition of syngas combustion and within 4% for the methane combustion. An advantage of this model over other kinetic models in literature is that the core shrinking model kinetic rate equations have been converted into a power law form. This allows Aspen Plus to use a calculator instead of an external Fortran compiler. This greatly simplifies the modeling process. The reaction rate equations are given for all reactions. A sensitivity analysis of the reaction kinetics was conducted. All data, code, and simulation files are given.
The Present Clinical Treatment and Future Emerging Interdisciplinary for Heart Failure: Where we are and What we can do
Authors: Yang Yu , Gao Jiamin , Qin Zhen , Lu Yongzheng , Xu Yanyan , Guo Jiacheng , Cui Xiaolin , Zhang Jinying , Tang Junnan
Published: February 2023

Heart failure is a complex clinical syndrome caused by the progression to severe stages of various cardiac diseases, characterized by high morbidity and mortality. With the increasing aging of the population and the poor control of high-risk factors for heart failure such as hypertension and diabetes, the incidence of heart failure remains high. Therefore, there is widespread global attention regarding the various treatments for heart failure. Currently, pharmacological therapy, associated device therapy, interventional therapy, and end-stage surgical related therapy are the main clinical treatments for heart failure. Heart failure treatment is gradually evolving to be more precise, safe, and effective, as traditional therapies can no longer match clinical needs. A number of cutting-edge research studies are being conducted on the treatment of heart failure, based on the different pathogenesis and causes of heart failure, to treat patients with heart failure in a multifaceted and integrated way. This article summarizes the current clinical treatment of heart failure and the latest therapeutic advances in heart failure in current research to further promote the standardized management and treatment of heart failure and improve patient prognosis.
Parameter Dependencies of Early‐Stage Tangential Discontinuity‐Driven Foreshock Bubbles in Local Hybrid Simulations
Authors: Vu Andrew , Liu Terry Z. , Zhang Hui , Delamere Peter
Published: February 2023

Foreshock bubbles (FBs) are significant foreshock transients that can accelerate particles and disturb the magnetosphere‐ionosphere system. In the kinetic formation model, foreshock ions interact with the discontinuity by performing partial gyrations to generate currents that change the magnetic field topology around the discontinuity. However, how different foreshock ion properties affect the growth of the field variations is not well understood. Therefore, we use 2‐D local hybrid simulations to study the effects of different foreshock ion distributions and properties on the growth of tangential discontinuity (TD)‐driven FBs. We discover that for a gyrophase‐bunched distribution with an initial phase where the guiding center is on the other side of the TD, the foreshock ions gyrate together across the TD, causing more foreshock ions to cross the TD and leading to a faster expansion of the structure than for a Maxwellian distribution. A ring distribution also yields higher expansion speeds because of the higher projected velocity into the new perpendicular direction. For Maxwellian distributions, there are positive and linear correlations of the FB expansion speeds with the initial foreshock ion densities, thermal speeds, parallel speeds, and sine of the TD magnetic shear angles. These parameter dependencies grow in strength as the structures evolve with time. The foreshock ion distributions and properties that lead to stronger currents produce more significant magnetic field variations and higher expansion speeds. Our study helps quantify the formation and expansion of FBs to forecast their space weather effects and contribution to shock acceleration.
A Microphysical Model of Rock Friction and the Brittle‐Ductile Transition Controlled by Dislocation Glide and Backstress Evolution
Authors: Thom Christopher A. , Hansen Lars N. , Goldsby David L. , Brodsky Emily E.
Published: February 2023

Rate‐ and state‐friction (RSF) is an empirical framework that describes the complex velocity‐, time‐, and slip‐dependent phenomena observed during frictional sliding of rocks and gouge in the laboratory. Despite its widespread use in earthquake nucleation and recurrence models, our understanding of RSF, particularly its time‐ and/or slip‐dependence, is still largely empirical, limiting our confidence in extrapolating laboratory behavior to the seismogenic zone. While many microphysical models have been proposed over the past few decades, none have explicitly incorporated the effects of strain hardening, anelasticity, or transient elastoplastic rheology. Here we present a new model of rock friction that incorporates these phenomena directly from the microphysical behavior of lattice dislocations. This model of rock friction exhibits the same logarithmic dependence on sliding velocity (strain rate) as RSF and displays a dependence on the internal backstress caused by long‐range interactions among geometrically necessary dislocations (GNDs). Changes in the backstress (internal stress) evolve exponentially with plastic strain of asperities and are dependent on both the current backstress and previous deformation, which give rise to phenomena consistent with interpretations of the “critical slip distance,” “memory effect,” and “evolution effect” of RSF. The rate dependence of friction in this model is primarily controlled by the evolution of backstress and temperature. We provide several analytical predictions for RSF‐like behavior and the “brittle‐ductile” transition based on microphysical mechanisms and measurable parameters such as the GND density and strain‐dependent hardening modulus.
The Interaction Between Frictional Slip and Viscous Fault Root Produces Slow Slip Events
Authors: Perfettini Hugo , Molinari Alain
Published: February 2023

We consider a model where an unstable frictional region, governed by rate and state friction, interacts with a viscous zone with Newtonian rheology. The system is loaded at distance with a constant velocity. Pore pressure variations are considered and we show that the model of Segall and Rice (1995, https://doi.org/10.1029/95jb02403) relating porosity changes to variations of the state variable could be derived considering viscoplastic deformation of a population of identical asperities. We perform a linear stability analysis in the case of a constant pore pressure in agreement with the full numerical results. For a given value of the viscosity of the viscous region, stable slip is promoted at low normal stress and unstable slip at high normal stress. Near the transition from stable to unstable slip, modest acceleration of slip, resembling slow slip events (SSE) are observed. We show that our model can reproduce real SSE sequences in the Guerrero subduction zone which are the largest worldwide. The best fit parameters suggest that SSEs happen in areas of low effective normal stress (for the frictional region) and low viscosity (for the viscous region). In our model, SSEs happen in a regime where the viscous region is able to counteract the instability of the frictional one. We show that considering a rate strengthening rheology or a non newtonian one leads to the same linear stability results. Our work shows that a simple model with homogeneous spatial properties can lead to complex dynamics, covering a wide range of observed sliding modes, from steady‐state creep to seismic slip and SSEs.
Machine Learning Reveals Additional Hydraulic Fracture‐Induced Seismicity in the Eagle Ford Shale
Authors: Fasola Shannon L. , Brudzinski Michael R.
Published: February 2023

A recent study found ∼90% of earthquakes in the Eagle Ford shale in Texas from 2014 to 2018 were spatiotemporally related to hydraulic fracturing (HF) wells. Since then, earthquakes have remained prevalent, including a new region of seismicity in Live Oak county. We sought to perform a deeper exploration of how HF has contributed to recent seismicity using template matching and repeating signal detection (RSD), which employs machine learning to search for repeating earthquakes with the potential to find something different than the template catalog. RSD identified new bursts of seismicity with a shorter S‐P time (∼2 s) than the previous catalog (>4 s), which temporally correlated with HF near station N4 735B. The short S‐P events have smaller magnitudes (ML < 2.0), consistent with the idea that HF‐induced seismicity in the Eagle Ford is likely more pervasive than previously reported, but detection is limited by the density of stations. RSD and template matching identified 1,600 earthquakes correlated with HF from 2019 to February 2020. We confirmed newly detected HF‐induced seismicity in Live Oak county did not occur until January 2019. Despite similar cumulative volume prior to and after 2019, the onset of detectable seismicity did not occur until HF injection exceeded 2 million barrels per month over this area, supporting the notion that injection flux is a stronger influence on the seismicity occurrence than cumulative volume. When considering the full catalog, the likelihood of seismicity also correlated with proximity to mapped faults, with 13% of wells <2 km from faults having seismicity compared to only 3% of wells >2 km.
The Hydro‐Mechanical Properties of Fracture Intersections: Pressure‐Dependant Permeability and Effective Stress Law
Authors: Stanton‐Yonge Ashley , Mitchell Thomas M. , Meredith Philip G.
Published: February 2023

Fluid flow through the brittle crust is primarily controlled by the capability of fracture networks to provide pathways for fluid transport. The dominant permeability orientation within fractured rock masses has been consistently correlated with the development of fracture intersections; an observation also made at the meso‐regional scale. Despite the importance attributed to fracture intersections in promoting fluid flow, the magnitude of their enhancement of fractured rock permeability has not yet been quantified. Here, we characterize the hydro‐mechanical properties of intersections in samples of Seljadalur Basalt by generating two orthogonal, tensile fractures produced by two separate loadings using a Brazilian test apparatus, and measuring their permeability as a function of hydrostatic pressure. We observe that intersecting fractures are significantly more permeable and less compliant than two independent macro‐fractures. We formulate a model for fracture intersection permeability as a function of pressure by adding the contributions of two independent fractures plus a tube‐like cavity with an effective elastic compressibility determined by its geometry. Permeability measurements during cyclic loading allowed determination of the effective stress coefficient (α in pe = pc − αpp) for fracture and intersection permeability. We observe a trend of lower αintersection values with respect to αfracture, which suggests that the channels controlling fluid flow have a higher aspect ratio (are more tubular) for the intersections relative to independent fractures. Our results suggest that fracture intersections play a critical role in maintaining permeability at depth, which has significant implications for the quantification and upscaling of fracture permeability toward reservoir‐scale simulations.
Tectonic Controls on Magmatic Tempo in an Active Continental Margin: Insights From the Early Cretaceous Syn‐Tectonic Magmatism in the Changle‐Nan’ao Belt, South China
Authors: Wei Wei , Lin Wei , Chen Yan , Faure Michel , Ji Wenbin , Hou Quanlin , Yan Quanren , Wang Qingchen
Published: February 2023

The cause of magmatic tempo in an active plate margin remains controversial, partly due to lack of structural analysis. During 130–105 Ma, the magmatism in the South China Block (SCB) was significantly reduced (lull) and restricted around the Changle‐Nan'ao Belt (CNB) while the magmatism was highly active (flare‐up) in North China. For unveiling the tectonic role on magmatism, a multidisciplinary study including field and microscopic structural observations, magnetic fabric measurement (AMS), and zircon/monazite dating was conducted on the plutons with oriented minerals in the CNB. Structural analysis and AMS results show a highly clustered NE‐striking vertical foliation developed during the emplacement indicating a syn‐emplacement NW‐SE shortening regime. The geochronology results confirm that the emplacement occurred during 130–105 Ma. Regional geologic correlation indicates that the collision between the Dangerous Grounds‐West Philippines Block and SCB was responsible for this shortening regime. The collected depleted zircon εHf(t) data suggest that a possible collision‐triggered slab break‐off caused the syn‐collisional magmatic activity around the CNB. This study shows that the magmatic lull in the SCB was coeval with a crustal shortening regime due to the arrival of a microcontinent carried by the subduction slab, while the magmatic flare‐up was coeval with an extensional regime due to the subduction roll‐back and retreat as evidenced by the Cretaceous evolution of the SCB before and after the collision and that of North China which is unaffected by the collision. The cause of magmatic tempo in the continental margin is largely due to the tectonic evolution of underlain subduction slabs.
Convectively Transported Water Vapor Plumes in the Midlatitude Lower Stratosphere
Authors: Wang Xun , Huang Yi , Qu Zhipeng , Vaillancourt Paul A. , Yau Man‐Kong , Feng Jing , Langille Jeffery , Bourassa Adam
Published: February 2023

Deep convective overshooting has been shown to transport water vapor into the midlatitude lower stratosphere. However, it has not been demonstrated how the convective water vapor plumes evolve after the overshoots collapse. Furthermore, there is a lack of characterization of the convective water vapor plumes, nor is it clear whether satellite instruments can observe the characteristics. We use a high‐resolution numerical weather prediction model to study a convective system over North America. Multiple overshoots transport water vapor in the overworld stratosphere, forming a moist layer between 16.2 and 16.8 km (389.8–399.7 K), with horizontal diameters of about 300–400 km, and a maximum water vapor mixing ratio of 10.0 ppmv (4.3 ppmv anomaly). Lagrangian trajectories and mass integrations show the overworld water vapor plumes are maintained after the convective system weakens. In the lowermost stratosphere (LMS), water vapor plumes are less stable and ice is present, because there is perturbation by ongoing convection. Lagrangian trajectories and mass integrations show the LMS parcels partly return to the troposphere, and that the LMS water vapor mass is reduced by half after the convection weakens. On average, the LMS moistening is between 15.0 and 15.8 km (362.6–382.0 K), with horizontal diameters of about 150 km, and a maximum water vapor mixing ratio of 31.1 ppmv (18.4 ppmv anomaly). Although current satellites have difficulty observing the fine structure of the convective water vapor plumes, a new satellite instrument under development (SHOW) with 1‐km vertical and 100‐km horizontal resolution will be able to verify the plume characteristics.
Cloud Condensation Nuclei Closure Study Using Airborne Measurements Over the Southern Great Plains
Authors: Kulkarni Gourihar , Mei Fan , Shilling John E. , Wang Jian , Reveggino Renato Pinto , Flynn Connor , Zelenyuk Alla , Fast Jerome
Published: February 2023

Airborne measurements of non‐refractory bulk aerosol chemical composition, aerosol size distributions, and cloud condensation nuclei (CCN) were conducted onboard a research aircraft during the Holistic Interactions of Shallow Clouds, Aerosols and Land Ecosystems field campaign in the spring and summer of 2016. A CCN closure study for the entire campaign period was performed where measured CCN concentrations at 0.24% and 0.46% supersaturation were compared with the predicted CCN concentrations calculated using κ‐Köhler theory, three different assumptions of aerosol mixing state, and various assumptions about hygroscopicity, density, and the insoluble fraction of organic particles. We found that the Closure Ratio (CR), calculated as the ratio of predicted to measured CCN concentrations, was equal to one under two different aerosol mixing state assumptions: (a) all particles are composed of 100% organic particles, and (b) particles are externally mixed and composed of pure sulfates, nitrates, and organic particles assuming hygroscopicity values for organic particles () between 0.04 and 0.17. The use of internal mixing state assumption often led to overprediction of CCN concentrations but the agreement within ±20% with the measured CCN concentrations was observed under certain closure permutations. A similar agreement, that is, within ±20%, was also observed using permuted parameters concerning density (1 and 1.5 g cm−3) and an insoluble fraction (0% and 20%) of organic particles. These findings may provide constraints on to predict CCN concentrations at a remote continental Southern Great Plains site.
Effect of Slope Aspect on Plant Above‐ and Belowground Functional Traits of Alpine Meadow on the Qinghai‐Tibet Plateau, China
Authors: Pan Yingping , Ren Liang , Xiang Xiang , Huo Jiaxuan , Meng Dehui , Wang Yuanyuan , Yu Cheng , Huang Yongmei
Published: February 2023

Slope aspects could cause significant differences in microclimate (e.g., radiation and moisture) and edaphic properties (e.g., soil nutrients content) in rugged landscapes. Therefore, understanding the variations of the above‐ and belowground functional traits on hillslope scales and their driving factors are essential for disentangling the plant adaptive strategies to local environmental factors. Based on the measurements of community weighted mean traits of alpine meadow from 15 hillslopes (eight south‐facing and seven north‐facing) in the Qinghai Lake watershed, northeastern Qinghai‐Tibet Plateau, China, we found that the aboveground morphological traits that is, specific leaf area and leaf dry matter content, and belowground stoichiometric traits, that is, root carbon content (RCC), root nitrogen content (RNC), root phosphorus content (RPC) and RCC: RNC, varied significantly between slope aspects. Hierarchical partitioning indicated that the slope aspect contributed the most to the variations of aboveground morphological and belowground stoichiometric traits, whereas soil properties were the major contributor to aboveground phosphorous‐related traits and belowground morphological traits. Both above‐ and belowground traits displayed a two‐dimensional variation on the hillslope scale. Additionally, the above‐ and belowground traits were weakly coordinated. In general, alpine meadow on the south‐facing slopes tended to adopt the conservative strategy, while acquisitive strategy was preferred by that on the north‐facing slopes. These findings can improve our understanding of spatial variations of functional traits at fine scales, and we highlighted that it is helpful to integrate both above‐ and belowground traits dimensions in disentangling the ecological process and predicting ecosystem function under changing climate.
Cre recombinase expression cooperates with homozygous FLT3 internal tandem duplication knockin mouse model to induce acute myeloid leukemia
Authors: Straube Jasmin , Eifert Theresa , Vu Therese , Janardhanan Yashaswini , Haldar Rohit , von Eyss Björn , Cooper Leanne , Bruedigam Claudia , Ling Victoria Y. , Cooper Emily , Patch Ann-Marie , Bullinger Lars , Schnoeder Tina M. , Bywater Megan , Heidel Florian H. , Lane Steven W.
Published: February 2023

Murine models offer a valuable tool to recapitulate genetically defined subtypes of AML, and to assess the potential of compound mutations and clonal evolution during disease progression. This is of particular importance for difficult to treat leukemias such as FLT3 internal tandem duplication (ITD) positive AML. While conditional gene targeting by Cre recombinase is a powerful technology that has revolutionized biomedical research, consequences of Cre expression such as lack of fidelity, toxicity or off-target effects need to be taken into consideration. We report on a transgenic murine model of FLT3-ITD induced disease, where Cre recombinase expression alone, and in the absence of a conditional allele, gives rise to an aggressive leukemia phenotype. Here, expression of various Cre recombinases leads to polyclonal expansion of FLT3ITD/ITD progenitor cells, induction of a differentiation block and activation of Myc-dependent gene expression programs. Our report is intended to alert the scientific community of potential risks associated with using this specific mouse model and of unexpected effects of Cre expression when investigating cooperative oncogenic mutations in murine models of cancer.
Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia
Authors: Larrue Clement , Mouche Sarah , Lin Shan , Simonetta Federico , Scheidegger Nastassja K. , Poulain Laury , Birsen Rudy , Sarry Jean-Emmanuel , Stegmaier Kimberly , Tamburini Jerome
Published: February 2023

Mitochondrial metabolism recently emerged as a critical dependency in acute myeloid leukemia (AML). The shape of mitochondria is tightly regulated by dynamin GTPase proteins, which drive opposing fusion and fission forces to consistently adapt bioenergetics to the cellular context. Here, we showed that targeting mitochondrial fusion was a new vulnerability of AML cells, when assayed in patient-derived xenograft (PDX) models. Genetic depletion of mitofusin 2 (MFN2) or optic atrophy 1 (OPA1) or pharmacological inhibition of OPA1 (MYLS22) blocked mitochondrial fusion and had significant anti-leukemic activity, while having limited impact on normal hematopoietic cells ex vivo and in vivo. Mechanistically, inhibition of mitochondrial fusion disrupted mitochondrial respiration and reactive oxygen species production, leading to cell cycle arrest at the G0/G1 transition. These results nominate the inhibition of mitochondrial fusion as a promising therapeutic approach for AML.
Spindle function and Wnt pathway inhibition by PBX1 to suppress tumor progression via downregulating DCDC2 in colorectal cancer
Authors: Dai Weigang , Liu Yinan , Zhang Tianhao , Huang Zhixin , Xu Xiang , Zhao Zeyu , Liu Jianqiu , Zhai Ertao , Cai Shirong , Chen Jianhui
Published: February 2023

PBX1 is a transcription factor that regulates a variety of genes, involved in intracellular lipid metabolism, cell proliferation, and other pathways. The promoting and inhibiting function of PBX1 in various cancer types was extensively discussed, however, there have been no studies on PBX1 proteins in colorectal cancer (CRC). This study aimed to reveal the anti-tumor function of PBX1 in CRC and the underlying molecular mechanism. Bioinformatics analysis revealed that PBX1 is downregulated in CRC, indicating that is a potential antioncogene in CRC. Overexpression of PBX1 suppresses tumor growth and metastasis in vitro and in vivo. Mechanistically, we found that PBX1 acted as a transcription factor that suppressed DCDC2 expression and inhibited spindle function. Moreover, the PBX1-DCDC2 axis controlled the Wnt pathway in CRC cells. Overexpression of DCDC2 restored CRC proliferation, metastasis abilities and Wnt pathway. In conclusion, this study suggests that PBX1 acts as a transcription factor to suppress DCDC2 expression and inhibit cell proliferation and metastasis by disrupting spindle function and the Wnt pathway in CRC.
Blood glutamate scavenging as a novel glutamate-based therapeutic approach for post-traumatic brain injury anxiety and social impairment
Authors: Frank Dmitry , Gruenbaum Benjamin F. , Shelef Ilan , Zvenigorodsky Vladislav , Severynovska Olena , Fleidervish Ilya , Knyazer Boris , Frenkel Amit , Zlotnik Alexander , Kofman Ora , Boyko Matthew
Published: February 2023

Traumatic brain injury (TBI) is a serious condition that is associated with an increased risk of severe, long-term psychiatric consequences. Drugs that target the glutamatergic system have proven successful in treating both TBI and many of its psychiatric sequelae. Blood glutamate scavengers (BGS) cause a decrease in blood glutamate levels, leading to a reduction in glutamate’s concentration gradient from the brain to the blood and decreased levels of brain glutamate. This study evaluated the BGS pyruvate as a treatment for TBI-related neuropsychiatric conditions in a rat model. 213 rats were divided into four groups in a 2 × 2 design: Sham or TBI rats treated with pyruvate or control treatment. Magnetic resonance imaging, neurological status, brain glutamate and blood glutamate levels were assessed following the injury. Four weeks after the start of treatment, all rats underwent behavioral tests to assess anxious behavior and social impairment (aggressive and hierarchical behavior). Rats responded positively to pyruvate in several tasks, lowering brain glutamate levels and reducing anxiety and depression, as well as modulating TBI-related changes in social behavior. Glutamate scavenging with pyruvate may be an effective therapeutic option for post-TBI behavioral changes by reducing associated elevations in brain glutamate levels.
Oxytocin vs. placebo effects on intrusive memory consolidation using a trauma film paradigm: a randomized, controlled experimental study in healthy women
Authors: Maslahati Tolou , Wingenfeld Katja , Hellmann-Regen Julian , Kraft Julia , Lyu Jing , Keinert Marie , Voß Aline , Cho An Bin , Ripke Stephan , Otte Christian , Schultebraucks Katharina , Roepke Stefan
Published: February 2023

Oxytocin administration during a trauma analogue has been shown to increase intrusive memories, which are a core symptom of post-traumatic stress disorder (PTSD). However, it is unknown whether oxytocin influences the acquisition or the consolidation of the trauma. The current study investigates the effect of the activation of the oxytocin system during the consolidation of an analogue trauma on the formation of intrusive memories over four consecutive days and whether this effect is influenced by individual neurobiological, genetic, or psychological factors. We conducted a randomized double-blind placebo-controlled study in 217 healthy women. They received either a single dose of intranasal oxytocin (24 IU) or placebo after exposure to a trauma film paradigm, which reliably induces intrusive memories. We used a general random forest to examine a potential heterogeneous treatment effect of oxytocin on the consolidation of intrusive memories. Furthermore, we used a poisson regression to examine whether salivary alpha amylase activity (sAA) as a marker of noradrenergic activity and cortisol response to the film, polygenic risk score (PRS) for psychiatric disorders, and psychological factors influence the number of intrusive memories. We found no significant effect of oxytocin on the formation of intrusive memories (F(2, 543.16) = 0.75, p = 0.51, ηp2 = 0.00) and identified no heterogeneous treatment effect. We replicated previous associations of the PRS for PTSD, sAA and the cortisol response on intrusive memories. We further found a positive association between high trait anxiety and intrusive memories, and a negative association between the emotion regulation strategy reappraisal and intrusive memories. Data of the present study suggest that the consolidation of intrusive memories in women is modulated by genetic, neurobiological and psychological factors, but is not influenced by oxytocin. Trial registration: NCT03875391.
Use of methotrexate and risk of skin cancer: a nationwide case–control study
Authors: Polesie Sam , Gillstedt Martin , Schmidt Sigrún Alba Jóhannesdóttir , Egeberg Alexander , Pottegård Anton , Kristensen Kasper
Published: February 2023

Background

Methotrexate (MTX) use has been suspected of increasing the risk of skin cancer. The aim of this investigation was to examine the association between the use of MTX and the risk of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC) and cutaneous malignant melanoma (CMM).

Methods

In a nationwide Danish case–control study, we identified incident, histologically verified cases of BCC (n = 131,447), cSCC (n = 18,661) or CMM (26,068) from 2004 to 2018. We matched 10 controls to each case on sex and birth year using risk-set sampling and computed crude and adjusted odds ratios (ORs) using conditional logistic regression for the use of MTX (≥2.5 g) compared with never-use.

Results

Use of MTX was associated with increased risk of BCC, cSCC and CMM with adjusted ORs of (95% confidence interval) 1.29 (1.20–1.38), 1.61 (1.37–1.89) and 1.35 (1.13–1.61), respectively. For BCC and cSCC, ORs increased with higher cumulative doses. When restricting the study population to patients with psoriasis, the ORs were 1.43 (1.23–1.67), 1.18 (0.80–1.74) and 1.15 (0.77–1.72), respectively.

Conclusions

We observed an increased risk of BCC and cSCC associated with the use of MTX with evidence of a dose–response pattern; however, the association was not consistent when restricting the study population to patients with psoriasis.
Different pathways for engulfment and endocytosis of liquid droplets by nanovesicles
Authors: Ghosh Rikhia , Satarifard Vahid , Lipowsky Reinhard
Published: February 2023

During endocytosis of nanoparticles by cells, the cellular membranes engulf the particles, thereby forming a closed membrane neck that subsequently undergoes fission. For solid nanoparticles, these endocytic processes have been studied in some detail. Recently, such processes have also been found for liquid and condensate droplets, both in vitro and in vivo. These processes start with the spreading of the droplet onto the membrane followed by partial or complete engulfment of the droplet. Here, we use molecular dynamics simulations to study these processes at the nanoscale, for nano-sized droplets and vesicles. For both partial and complete engulfment, we observe two different endocytic pathways. Complete engulfment leads to a closed membrane neck which may be formed in a circular or strongly non-circular manner. A closed circular neck undergoes fission, thereby generating two nested daughter vesicles whereas a non-circular neck hinders the fission process. Likewise, partial engulfment of larger droplets leads to open membrane necks which can again have a circular or non-circular shape. Two key parameters identified here for these endocytic pathways are the transbilayer stress asymmetry of the vesicle membrane and the positive or negative line tension of the membrane-droplet contact line.
Evolutionary route of nasopharyngeal carcinoma metastasis and its clinical significance
Authors: Lin Mei , Zhang Xiao-Long , You Rui , Liu You-Ping , Cai Hong-Min , Liu Li-Zhi , Liu Xue-Fei , Zou Xiong , Xie Yu-Long , Zou Ru-Hai , Zhang Yi-Nuan , Sun Rui , Feng Wei-Yi , Wang Hai-Yan , Tao Gui-Hua , Li Hao-Jiang , Huang Wen-Jie , Zhang Chao , Huang Pei-Yu , Wang Jin , Zhao Qi , Yang Qi , Zhang Hong-Wan , Liu Ting , Li Hui-Feng , Jiang Xiao-Bing , Tang Jun , Gu Yang-Kui , Yu Tao , Wang Zhi-Qiang , Feng Lin , Kang Tie-Bang , Zuo Zhi-Xiang , Chen Ming-Yuan
Published: February 2023

It is critical to understand factors associated with nasopharyngeal carcinoma (NPC) metastasis. To track the evolutionary route of metastasis, here we perform an integrative genomic analysis of 163 matched blood and primary, regional lymph node metastasis and distant metastasis tumour samples, combined with single-cell RNA-seq on 11 samples from two patients. The mutation burden, gene mutation frequency, mutation signature, and copy number frequency are similar between metastatic tumours and primary and regional lymph node tumours. There are two distinct evolutionary routes of metastasis, including metastases evolved from regional lymph nodes (lymphatic route, 61.5%, 8/13) and from primary tumours (hematogenous route, 38.5%, 5/13). The hematogenous route is characterised by higher IFN-γ response gene expression and a higher fraction of exhausted CD8+ T cells. Based on a radiomics model, we find that the hematogenous group has significantly better progression-free survival and PD-1 immunotherapy response, while the lymphatic group has a better response to locoregional radiotherapy.
Estimation of cell lineages in tumors from spatial transcriptomics data
Authors: Ru Beibei , Huang Jinlin , Zhang Yu , Aldape Kenneth , Jiang Peng
Published: February 2023

Spatial transcriptomics (ST) technology through in situ capturing has enabled topographical gene expression profiling of tumor tissues. However, each capturing spot may contain diverse immune and malignant cells, with different cell densities across tissue regions. Cell type deconvolution in tumor ST data remains challenging for existing methods designed to decompose general ST or bulk tumor data. We develop the Spatial Cellular Estimator for Tumors (SpaCET) to infer cell identities from tumor ST data. SpaCET first estimates cancer cell abundance by integrating a gene pattern dictionary of copy number alterations and expression changes in common malignancies. A constrained regression model then calibrates local cell densities and determines immune and stromal cell lineage fractions. SpaCET provides higher accuracy than existing methods based on simulation and real ST data with matched double-blind histopathology annotations as ground truth. Further, coupling cell fractions with ligand-receptor coexpression analysis, SpaCET reveals how intercellular interactions at the tumor-immune interface promote cancer progression.
Cell surface-bound La protein regulates the cell fusion stage of osteoclastogenesis
Authors: Whitlock Jarred M. , Leikina Evgenia , Melikov Kamran , De Castro Luis Fernandez , Mattijssen Sandy , Maraia Richard J. , Collins Michael T. , Chernomordik Leonid V.
Published: February 2023

Multinucleated osteoclasts, essential for skeletal remodeling in health and disease, are formed by the fusion of osteoclast precursors, where each fusion event raises their bone-resorbing activity. Here we show that the nuclear RNA chaperone, La protein has an additional function as an osteoclast fusion regulator. Monocyte-to-osteoclast differentiation starts with a drastic decrease in La levels. As fusion begins, La reappears as a low molecular weight species at the osteoclast surface, where it promotes fusion. La’s role in promoting osteoclast fusion is independent of canonical La-RNA interactions and involves direct interactions between La and Annexin A5, which anchors La to transiently exposed phosphatidylserine at the surface of fusing osteoclasts. Disappearance of cell-surface La, and the return of full length La to the nuclei of mature, multinucleated osteoclasts, acts as an off switch of their fusion activity. Targeting surface La in a novel explant model of fibrous dysplasia inhibits excessive osteoclast formation characteristic of this disease, highlighting La’s potential as a therapeutic target.
Antiferromagnetism-driven two-dimensional topological nodal-point superconductivity
Authors: Bazarnik Maciej , Lo Conte Roberto , Mascot Eric , von Bergmann Kirsten , Morr Dirk K. , Wiesendanger Roland
Published: February 2023

Magnet/superconductor hybrids (MSHs) hold the promise to host emergent topological superconducting phases. Both one-dimensional (1D) and two-dimensional (2D) magnetic systems in proximity to s-wave superconductors have shown evidence of gapped topological superconductivity with zero-energy end states and chiral edge modes. Recently, it was proposed that the bulk transition-metal dichalcogenide 4Hb-TaS2 is a gapless topological nodal-point superconductor (TNPSC). However, there has been no experimental realization of a TNPSC in a MSH system yet. Here we present the discovery of TNPSC in antiferromagnetic (AFM) monolayers on top of an s-wave superconductor. Our calculations show that the topological phase is driven by the AFM order, resulting in the emergence of a gapless time-reversal invariant topological superconducting state. Using low-temperature scanning tunneling microscopy we observe a low-energy edge mode, which separates the topological phase from the trivial one, at the boundaries of antiferromagnetic islands. As predicted by the calculations, we find that the relative spectral weight of the edge mode depends on the edge’s atomic configuration. Our results establish the combination of antiferromagnetism and superconductivity as a novel route to design 2D topological quantum phases.
Mystery of fatal ‘staggering disease’ unravelled: novel rustrela virus causes severe meningoencephalomyelitis in domestic cats
Authors: Matiasek Kaspar , Pfaff Florian , Weissenböck Herbert , Wylezich Claudia , Kolodziejek Jolanta , Tengstrand Sofia , Ecke Frauke , Nippert Sina , Starcky Philip , Litz Benedikt , Nessler Jasmin , Wohlsein Peter , Baumbach Christina , Mundhenk Lars , Aebischer Andrea , Reiche Sven , Weidinger Pia , Olofsson Karin M. , Rohdin Cecilia , Weissenbacher-Lang Christiane , Matt Julia , Rosati Marco , Flegel Thomas , Hörnfeldt Birger , Höper Dirk , Ulrich Rainer G. , Nowotny Norbert , Beer Martin , Ley Cecilia , Rubbenstroth Dennis
Published: February 2023

‘Staggering disease’ is a neurological disease entity considered a threat to European domestic cats (Felis catus) for almost five decades. However, its aetiology has remained obscure. Rustrela virus (RusV), a relative of rubella virus, has recently been shown to be associated with encephalitis in a broad range of mammalian hosts. Here, we report the detection of RusV RNA and antigen by metagenomic sequencing, RT-qPCR, in-situ hybridization and immunohistochemistry in brain tissues of 27 out of 29 cats with non-suppurative meningoencephalomyelitis and clinical signs compatible with’staggering disease’ from Sweden, Austria, and Germany, but not in non-affected control cats. Screening of possible reservoir hosts in Sweden revealed RusV infection in wood mice (Apodemus sylvaticus). Our work indicates that RusV is the long-sought cause of feline ‘staggering disease’. Given its reported broad host spectrum and considerable geographic range, RusV may be the aetiological agent of neuropathologies in further mammals, possibly even including humans.
Orientated crystallization of FA-based perovskite via hydrogen-bonded polymer network for efficient and stable solar cells
Authors: Li Mubai , Sun Riming , Chang Jingxi , Dong Jingjin , Tian Qiushuang , Wang Hongze , Li Zihao , Yang Pinghui , Shi Haokun , Yang Chao , Wu Zichao , Li Renzhi , Yang Yingguo , Wang Aifei , Zhang Shitong , Wang Fangfang , Huang Wei , Qin Tianshi
Published: February 2023

Incorporating mixed ion is a frequently used strategy to stabilize black-phase formamidinum lead iodide perovskite for high-efficiency solar cells. However, these devices commonly suffer from photoinduced phase segregation and humidity instability. Herein, we find that the underlying reason is that the mixed halide perovskites generally fail to grow into homogenous and high-crystalline film, due to the multiple pathways of crystal nucleation originating from various intermediate phases in the film-forming process. Therefore, we design a multifunctional fluorinated additive, which restrains the complicated intermediate phases and promotes orientated crystallization of α-phase of perovskite. Furthermore, the additives in-situ polymerize during the perovskite film formation and form a hydrogen-bonded network to stabilize α-phase. Remarkably, the polymerized additives endow a strongly hydrophobic effect to the bare perovskite film against liquid water for 5 min. The unencapsulated devices achieve 24.10% efficiency and maintain >95% of the initial efficiency for 1000 h under continuous sunlight soaking and for 2000 h at air ambient of ~50% humid, respectively.