bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deformation in SW Anatolia (Turkey) Documented by Anisotropy of Magnetic Susceptibility Data
Authors: Özkaptan Murat , Gülyüz Erhan , Uzel Bora , Langereis Cor G. , Özacar A. Arda , Kaymakcı Nuretdin 
Published: November 2021

AbstractConvergence between the Eurasian and the African plates in the West Anatolian‐Aegean region results in a trench retreat due to slab roll‐back and tearing of the subducted African lithosphere. The upper plate response of this process gave way to back‐arc extension in the region. We have conducted a very detailed anisotropy of magnetic susceptibility (AMS) study on the Neogene rocks in SW Anatolia to unravel the style and magnitudes of deformation. For this purpose, from 83 sites in 11 structurally homogeneous domains, 1,680 paleomagnetic samples were analyzed. The results show that AMS fabrics are related to the tectonic deformation and that the magnetic lineation (maximum susceptibility axis, k1) is parallel to inferred maximum extension, while minimum susceptibility (k3) is typically normal to the bedding plane, corresponding to a preserved compaction associated with deposition fabric. The intermediate axis (k2) is parallel to a second extension direction and indicates that the region has been under the control of multi‐directional extension during the Neogene. Two main magnetic lineation directions are identified and represent Oligocene to middle Miocene E‐W, and late Miocene to Pliocene NW‐SE oriented extension. The magnetic lineation directions are dominantly parallel or perpendicular to the general strikes of the normal faults. The results show that the deformation in the region resembles two differentially stretched rubber sheets under the influence of SW oriented extension, exerted by the southward retreating Eastern Mediterranean subduction system.
Investigating Strike‐Slip Faulting Parallel to the Icelandic Plate Boundary Using Boundary Element Models
Authors: Pearson Anna E. R. , Loveless John P. 
Published: November 2021

AbstractMost faults in Iceland strike roughly parallel to the divergent plate boundary, a part of the North American‐Eurasian plate boundary, which would be expected to lead to primarily normal faulting. However, several studies have observed a significant component of rift‐parallel strike‐slip faulting in Iceland. To investigate these fault kinematics, we use the boundary element method to model fault slip and crustal stress patterns of the Icelandic tectonic system, including a spherical hotspot and uniaxial stress that represents rifting. On a network of faults, we estimate the slip required to relieve traction imposed by hotspot inflation and remote rifting stress and compare the model results with observed slip kinematics, crustal seismicity, and geodetic data. We note a good fit between model‐predicted and observed deformation metrics, with both indicating significant components of normal and strike‐slip faulting and consistency between recent data and longer‐term records of geologic fault slip. Possible stress permutations between steeply plunging σ1 and σ2 axes are common in our models, suggesting that localized stress perturbations may impact strike‐slip faulting. Some increases in model complexity, including older hotspot configurations and allowing fault opening to simulate dike intrusion, show improvement to model fit in select regions. This work provides new insight into the physical mechanisms driving faulting styles within Iceland away from the current active plate boundary, implying that a significant portion of observed strike‐slip faulting is likely caused by the combined effects of tectonic rifting, hotspot impacts, and mechanical interactions across the fault network.
Psychological and biological resilience modulates the effects of stress on epigenetic aging
Authors: Harvanek Zachary M. , Fogelman Nia , Xu Ke , Sinha Rajita 
Published: November 2021

AbstractOur society is experiencing more stress than ever before, leading to both negative psychiatric and physical outcomes. Chronic stress is linked to negative long-term health consequences, raising the possibility that stress is related to accelerated aging. In this study, we examine whether resilience factors affect stress-associated biological age acceleration. Recently developed “epigenetic clocks” such as GrimAge have shown utility in predicting biological age and mortality. Here, we assessed the impact of cumulative stress, stress physiology, and resilience on accelerated aging in a community sample (N = 444). Cumulative stress was associated with accelerated GrimAge (P = 0.0388) and stress-related physiologic measures of adrenal sensitivity (Cortisol/ACTH ratio) and insulin resistance (HOMA). After controlling for demographic and behavioral factors, HOMA correlated with accelerated GrimAge (P = 0.0186). Remarkably, psychological resilience factors of emotion regulation and self-control moderated these relationships. Emotion regulation moderated the association between stress and aging (P = 8.82e−4) such that with worse emotion regulation, there was greater stress-related age acceleration, while stronger emotion regulation prevented any significant effect of stress on GrimAge. Self-control moderated the relationship between stress and insulin resistance (P = 0.00732), with high self-control blunting this relationship. In the final model, in those with poor emotion regulation, cumulative stress continued to predict additional GrimAge Acceleration even while accounting for demographic, physiologic, and behavioral covariates. These results demonstrate that cumulative stress is associated with epigenetic aging in a healthy population, and these associations are modified by biobehavioral resilience factors.
Initiation of hepatic stellate cell activation extends into chronic liver disease
Authors: De Smet Vincent , Eysackers Nathalie , Merens Vincent , Kazemzadeh Dastjerd Mina , Halder Georg , Verhulst Stefaan , Mannaerts Inge , van Grunsven Leo A. 
Published: November 2021

AbstractActivated hepatic stellate cells (aHSC) are the main source of extra cellular matrix in liver fibrosis. Activation is classically divided in two phases: initiation and perpetuation. Currently, HSC-based therapeutic candidates largely focus on targeting the aHSCs in the perpetuation phase. However, the importance of HSC initiation during chronic liver disease (CLD) remains unclear. Here, we identified transcriptional programs of initiating and activated HSCs by RNA sequencing, using in vitro and in vivo mouse models of fibrosis. Importantly, we show that both programs are active in HSCs during murine and human CLD. In human cirrhotic livers, scar associated mesenchymal cells employ both transcriptional programs at the single cell level. Our results indicate that the transcriptional programs that drive the initiation of HSCs are still active in humans suffering from CLD. We conclude that molecules involved in the initiation of HSC activation, or in the maintenance of aHSCs can be considered equally important in the search for druggable targets of chronic liver disease.
MLK4 regulates DNA damage response and promotes triple-negative breast cancer chemoresistance
Authors: Mehlich Dawid , Łomiak Michał , Sobiborowicz Aleksandra , Mazan Alicja , Dymerska Dagmara , Szewczyk Łukasz M. , Mehlich Anna , Borowiec Agnieszka , Prełowska Monika K. , Gorczyński Adam , Jabłoński Paweł , Iżycka-Świeszewska Ewa , Nowis Dominika , Marusiak Anna A. 
Published: November 2021

AbstractChemoresistance constitutes a major challenge in the treatment of triple-negative breast cancer (TNBC). Mixed-Lineage Kinase 4 (MLK4) is frequently amplified or overexpressed in TNBC where it facilitates the aggressive growth and migratory potential of breast cancer cells. However, the functional role of MLK4 in resistance to chemotherapy has not been investigated so far. Here, we demonstrate that MLK4 promotes TNBC chemoresistance by regulating the pro-survival response to DNA-damaging therapies. We observed that MLK4 knock-down or inhibition sensitized TNBC cell lines to chemotherapeutic agents in vitro. Similarly, MLK4-deficient cells displayed enhanced sensitivity towards doxorubicin treatment in vivo. MLK4 silencing induced persistent DNA damage accumulation and apoptosis in TNBC cells upon treatment with chemotherapeutics. Using phosphoproteomic profiling and reporter assays, we demonstrated that loss of MLK4 reduced phosphorylation of key DNA damage response factors, including ATM and CHK2, and compromised DNA repair via non-homologous end-joining pathway. Moreover, our mRNA-seq analysis revealed that MLK4 is required for DNA damage-induced expression of several NF-кB-associated cytokines, which facilitate TNBC cells survival. Lastly, we found that high MLK4 expression is associated with worse overall survival of TNBC patients receiving anthracycline-based neoadjuvant chemotherapy. Collectively, these results identify a novel function of MLK4 in the regulation of DNA damage response signaling and indicate that inhibition of this kinase could be an effective strategy to overcome TNBC chemoresistance.
ONECUT2 facilitates hepatocellular carcinoma metastasis by transcriptionally upregulating FGF2 and ACLY
Authors: Liu Danfei , Zhang Tongyue , Chen Xiaoping , Zhang Bixiang , Wang Yijun , Xie Meng , Ji Xiaoyu , Sun Mengyu , Huang Wenjie , Xia Limin 
Published: November 2021

AbstractMetastasis is the predominant reason for high mortality of hepatocellular carcinoma (HCC) patients. It is critical to explore the molecular mechanism underlying HCC metastasis. Here, we reported that transcription factor One Cut homeobox 2 (ONECUT2) functioned as an oncogene to facilitate HCC metastasis. Elevated ONECUT2 expression was positively correlated with increased tumor number, tumor encapsulation loss, microvascular invasion, poor tumor differentiation, and advanced TNM stage. Mechanistically, ONECUT2 directly bound to the promoters of fibroblast growth factor 2 (FGF2) and ATP citrate lyase (ACLY) and transcriptionally upregulated their expression. Knockdown of FGF2 and ACLY inhibited ONECUT2-mediated HCC metastasis, whereas upregulation of FGF2 and ACLY rescued ONECUT2 knockdown-induced suppression of HCC metastasis. ONECUT2 expression was positively correlated with FGF2 and ACLY expression in human HCC tissues. HCC patients with positive coexpression of ONECUT2/FGF2 or ONECUT2/ACLY exhibited the worst prognosis. In addition, FGF2 upregulated ONECUT2 expression through the FGFR1/ERK/ELK1 pathway, which formed an FGF2-FGFR1-ONECUT2 positive feedback loop. Knockdown of ONECUT2 inhibited FGF2-induced HCC metastasis. Furthermore, the combination of FGFR1 inhibitor PD173074 with ACLY inhibitor ETC-1002 markedly suppressed ONECUT2-mediated HCC metastasis. In summary, ONECUT2 was a potential prognostic biomarker in HCC and targeting this oncogenic signaling pathway may provide an efficient therapeutic strategy against HCC metastasis.
The METTL3/MALAT1/PTBP1/USP8/TAK1 axis promotes pyroptosis and M1 polarization of macrophages and contributes to liver fibrosis
Authors: Shu Bo , Zhou Ying-Xia , Li Hao , Zhang Rui-Zhi , He Chao , Yang Xin 
Published: November 2021

AbstractPro-inflammatory M1 macrophages, via activating hepatic stellate cells, contribute to liver fibrosis. In this study, we examined the mechanism and the significance of a signaling axis, METTL3/MALAT1/PTBP1/USP8/TAK1, in regulating pyroptosis and M1 polarization of hepatic macrophages. Liver fibrosis model was established in vivo by CCl4 treatment; M1 polarization was induced in vitro by treating macrophages with lipopolysaccharide or interferon γ. Expressions of METTL3, MALAT1, PTBP1, USP8, and TAK1 were measured by RT-PCR and/or Western blot in Kupffer cells (KCs) isolated from in vivo model or in vitro activated macrophages. Macrophage phenotypes including inflammation (RT-qPCR analysis of a panel of proinflammatory cytokines and ELISA on productions of interleukin (IL)−1β and IL-18) and pyroptosis (Western blot of NLRP3, Caspase-1, and GSDMD) were investigated. The impact of METTL3 on m6A methylation of MALAT1 was examined by methylated RNA immunoprecipitation (RIP), the interaction between PTBP1 and MALAT1 or USP8 mRNA by combining RNA pull-down, RIP, and RNA stability assays, and the crosstalk between USP8 and TAK1 by co-immunoprecipitation and protein degradation assays. Functional significance of individual component of METTL3/MALAT1/PTBP1/USP8/TAK1 axis was assessed by combining gain-of-function and loss-of-function approaches. In KCs isolated from in vivo liver fibrosis model or in vitro M1-polarized macrophages, METTL3 was up-regulated, and sequentially, it increased MALAT1 level via m6A methylation, which promoted USP8 mRNA degradation through the interaction with PTBP1. Reduced USP8 expression regulated the ubiquitination and protein stability of TAK1, which promoted pyroptosis and inflammation of macrophages. The signaling cascade METTL3/MALAT1/PTBP1/USP8/TAK1, by essentially stimulating pyroptosis and inflammation of macrophages, aggravates liver fibrosis. Therefore, targeting individual components of this axis may benefit the treatment of liver fibrosis.
Against the NEER principle: the third type of photochromism for GFP chromophore derivatives
Authors: Liao Jun-Wei , Sung Robert , Sung Kuangsen 
Published: November 2021

The third type of photochromism does not follow Z–E photoisomerization by τ-torsion, but undergoes light-driven φ-torsion, followed by ESIPT; it's against NEER principle since light-driven φ-torsion involves equilibration of excited-state rotamers.
Intelligent task migration with deep Qlearning in multi‐access edge computing
Authors: Huang Sheng‐Zhi , Lin Kun‐Yu , Hu Chin‐Lin 
Published: November 2021

AbstractMulti‐access edge computing provides computation and network resources in proximity to user applications in mobile environments. Deploying edge servers in network boundary can not only offload the heavy task loading on the cloud, but also alleviate resource‐limited capabilities of mobile devices. Rather than many stand‐alone edge servers, the concept of multi‐server edge computing is recently advocated to contend with the issues of system scalability and service quality against dynamic task workload. This study exploits collaborative computing resources and designs a task migration strategy for multiple edge servers in mobile networks. This study formulates a queueing optimization problem of minimizing the overall service time in a multi‐server system. An intelligent task migration scheme is then developed using the deep reinforcement learning and Q‐learning techniques. With a variety of numerical attributes derived from the queueing model, this intelligent scheme can arrange the task distribution among edge servers to enhance the task processing capability. Simulation‐based results show that the proposed task migration scheme can sustain service efficiency and resource utilization, which is promising as compared with conventional designs without collaborative intelligence in mobile environments.
Distributed deep reinforcement learning for integrated generation‐control and power‐dispatch of interconnected power grid with various renewable units
Authors: Li Jiawen , Yao Jianguo , Yu Tao , Zhang Xiaoshun 
Published: November 2021

AbstractTo mismatch various power disturbances of interconnected power grid, an integrated generation‐control and power‐dispatch (IGCPD) for performance‐based frequency regulation market is proposed. Unlike the conventional automatic generation control with an independent controller and a power distributor, IGCPD can significantly improve the dynamic control performance via combining these two parts into an integrated decision agent. The IGCPD eliminates the waste of frequency regulation resources and repeated regulation of the units caused by the mismatch of the controller and power distributor. In addition, by setting the reward function reasonably, IGCPD can save regulatable capacity of fast units for regulation in the next large‐scale disturbance. In order to enhance the decision ability, a swarm intelligence‐based deep deterministic policy gradient (SI‐DDPG) algorithm is proposed to acquire the control knowledge and implement a high‐quality decision for this agent. Moreover, the swarm intelligence‐based training sample can achieve a high learning robustness for SI‐DDPG which solve the problem of low robustness in conventional deep reinforcement learning. The proposed technique is verified on an England two‐area load frequency control model and the west China two‐area LFC model. IGCPD improves the area control error control performance and reduce the frequency regulation mileage payment of the interconnected power grid.
Large-scale magnetic field in the Monoceros OB 1 east molecular cloud
Authors: Alina D. , Montillaud J. , Hu Y. , Lazarian A. , Ristorcelli I. , Abdikamalov E. , Sagynbayeva S. , Juvela M. , Liu T. , Carrière J.-S. 
Published: November 2021

Context. The role of large-scale magnetic fields in the evolution of star-forming regions remains elusive. Its investigation requires the observational characterization of well-constrained molecular clouds. The Monoceros OB 1 molecular cloud is a large complex containing several structures that have been shown to be engaged in an active interaction and to have a rich star formation history. However, the magnetic fields in this region have only been studied on small scales.
Aims. We study the large-scale magnetic field structure and its interplay with the gas dynamics in the Monoceros OB 1 east molecular cloud.
Methods. We combined observations of dust polarized emission from the Planck telescope and CO molecular line emission observations from the Taeduk Radio Astronomy Observatory 14-metre telescope. We calculated the strength of the plane-of-sky magnetic field using a modified Chandrasekhar-Fermi method and estimated the mass-over-flux ratios in different regions of the cloud. We used the comparison of the velocity and intensity gradients of the molecular line observations with the polarimetric observations to trace dynamically active regions.
Results. The molecular complex shows an ordered large-scale plane-of-sky magnetic field structure. In the northern part, it is mostly orientated along the filamentary structures, while the southern part shows at least two regions with distinct magnetic field orientations. Our analysis reveals a shock region in the northern part right between two filamentary clouds that, in previous studies, were suggested to be involved in a collision. The magnetic properties of the north-main and north-eastern filaments suggest that these filaments once formed a single one, and that the magnetic field evolved together with the material and did not undergo major changes during the evolution of the cloud. In the southern part, we find that either the magnetic field guides the accretion of interstellar matter towards the cloud or it is dragged by the matter falling towards the main cloud.
Conclusions. The large-scale magnetic field in the Monoceros OB 1 east molecular cloud is tightly connected to the global structure of the complex. In the northern part, it seems to serve a dynamically important role by possibly providing support against gravity in the direction perpendicular to the field and to the filament. In the southern part, it is probably the most influential factor governing the morphological structure by guiding possible gas inflow. A study of the whole Monoceros OB 1 molecular complex at large scales is necessary to form a global picture of the formation and evolution of the Monoceros OB 1 east cloud and the role of the magnetic field in this process.
ESASky SSOSS: Solar System Object Search Service and the case of Psyche
Authors: Racero E. , Giordano F. , Carry B. , Berthier J. , Müller T. , Mahlke M. , Valtchanov I. , Baines D. , Kruk S. , Merín B. , Besse S. , Küppers M. , Puga E. , González Núñez J. , Rodríguez P. , de la Calle I. , López-Marti B. , Norman H. , Wångblad M. , López-Caniego M. , Álvarez Crespo N. 
Published: November 2021

Context. The store of data collected in public astronomical archives across the world is continuously expanding and, thus, providing a convenient interface for accessing this information is a major concern for ensuring a second life for the data. In this context, Solar System objects (SSOs) are often difficult or even impossible to query, owing to their ever-changing sky coordinates.
Aims. Our study is aimed at providing the scientific community with a search service for all potential detections of SSOs among the ESA astronomy archival imaging data, called the Solar System Object Search Service (SSOSS). We illustrate its functionalities using the case of asteroid (16) Psyche, for which no information in the far-IR (70–500 μm) has previously been reported, to derive its thermal properties in preparation for the upcoming NASA Psyche mission.
Methods. We performed a geometrical cross-match of the orbital path of each object, as seen by the satellite reference frame, with respect to the public high-level imaging footprints stored in the ESA archives. There are about 800 000 asteroids and 2000 comets included in the SSOSS, available through ESASky, providing both targeted and serendipitous observations. For this first release, three missions were chosen: XMM-Newton, the Hubble Space Telescope (HST), and Herschel.
Results. We present a catalog listing all potential detections of asteroids within estimated limiting magnitude or flux limit in Herschel, XMM-Newton, and HST archival imaging data, including 909 serendipitous detections in Herschel images, 985 in XMM-Newton Optical Monitor camera images, and over 32 000 potential serendipitous detections in HST images. We also present a case study: the analysis of the thermal properties of Psyche from four serendipitous Herschel detections, combined with previously published thermal IR measurements. We see strong evidence for an unusual drop in (hemispherical spectral) emissivity, from 0.9 at 100 μm down to about 0.6 at 350 μm, followed by a possible but not well-constrained increase towards 500 μm, comparable to what was found for Vesta. The combined thermal data set puts a strong constraint on Psyche’s thermal inertia (between 20 to 80 J m−2 s−1/2 K−1) and favors an intermediate to low level surface roughness (below 0.4 for the rms of surface slopes).
Conclusions. Using the example of Psyche, we show how the SSOSS provides fast access to observations of SSOs from the ESA astronomical archives, regardless of whether the particular object was the actual target. This greatly simplifies the task of searching, identifying and retrieving such data for scientific analysis.
KDIGO-Leitlinien 2021 zur Glomerulonephritis – Focus ANCA-assoziierte Vaskulitiden und antiglomeruläre Basalmembran-Nephritis
Authors: de Groot Kirsten , Haubitz Marion , Rupprecht Harald D. , Schönermarck Ulf 
Published: November 2021

Was ist neu?
Klinische, serologische, histopathologische Diagnostik der ANCA-assoziierten Vaskulitis Zentraler Bestandteil der Diagnostik der AAV mit renaler Manifestation sind die Bestimmung von PR3- und MPO-ANCA sowie die Nierenbiopsie. Die Behandlung sollte in einem in AAV erfahrenen Zentrum erfolgen und rasch begonnen werden.
Remissionsinduktion Die Remissionsinduktion bei ANCA-assoziierter GN erfolgt mit Cyclophosphamid oder Rituximab in Kombination mit Kortikosteroiden. Die Leitlinie gibt Hilfestellung zur Therapieauswahl. Studienbasiert wird eine schnellere Steroidreduktion empfohlen.
Remissionserhaltung Zur Remissionserhaltung stehen Rituximab und Azathioprin zur Verfügung. Die Leitlinie gibt Hilfestellung zu Auswahl und Dauer der Therapie, die sich insbesondere nach dem Rezidivrisiko richtet.
Anti-GBM-Erkrankung Die Plasmapherese gehört zur Standardtherapie der Anti-GBM-Erkrankung, ist jedoch bei der ANCA-assoziierten GN einer Einzelfallentscheidung bei fulminantem Verlauf vorbehalten.
Transplantation Eine Nierentransplantation kann bei ANCA-assoziierter GN nach mindestens 6-monatiger Remission unabhängig vom ANCA-Status erfolgen, bei Patienten mit Anti-GBM-Erkrankung nur nach negativem Antikörpernachweis.