bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methodological Reconstruction of Historical Seismic Events From Anecdotal Accounts of Destructive Tsunamis: A Case Study for the Great 1852 Banda Arc Mega‐Thrust Earthquake and Tsunami
Authors: Ringer H. , Whitehead J. P. , Krometis J. , Harris R. A. , Glatt‐Holtz N. , Giddens S. , Ashcraft C. , Carver G. , Robertson A. , Harward M. , Fullwood J. , Lightheart K. , Hilton R. , Avery A. , Kesler C. , Morrise M. , Klein M. H. 
Published: March 2021

AbstractWe demonstrate the efficacy of a Bayesian statistical inversion framework for reconstructing the likely characteristics of large pre‐instrumentation earthquakes from historical records of tsunami observations. Our framework is designed and implemented for the estimation of the location and magnitude of seismic events from anecdotal accounts of tsunamis including shoreline wave arrival times, heights, and inundation lengths over a variety of spatially separated observation locations. The primary advantage of this approach is that all of the assumptions made in the inversion process are incorporated explicitly into the mathematical framework. As an initial test case we use our framework to reconstruct the great 1852 earthquake and tsunami of eastern Indonesia. Relying on the assumption that these observations were produced by a subducting thrust event, the posterior distribution indicates that the observables were the result of a massive mega‐thrust event with magnitude near 8.8 Mw and a likely rupture zone in the north‐eastern Banda arc. The distribution of predicted epicentral locations overlaps with the largest major seismic gap in the region as indicated by instrumentally recorded seismic events. These results provide a geologic and seismic context for hazard risk assessment in coastal communities experiencing growing population and urbanization in Indonesia. In addition, the methodology demonstrated here highlights the potential for applying a Bayesian approach to enhance understanding of the seismic history of other subduction zones around the world.
Distinct Mineralogy and Age of Individual Lava Flows in Atla Regio, Venus Derived From Magellan Radar Emissivity
Authors: Brossier J. , Gilmore M. S. , Toner K. , Stein A. J. 
Published: March 2021

AbstractNASA's Magellan mission revealed that many Venus highlands exhibit low radar emissivity values at higher altitudes. This phenomenon is ascribed to the presence of minerals having high dielectric constants, produced or stabilized by temperature‐dependent chemical weathering between the rocks and the atmosphere. Some large volcanoes on Venus have multiple reductions of radar emissivity at varying altitudes. The authors present morphological maps of major lava flow units at Maat, Ozza, and Sapas montes and compare them to radar emissivity. Sapas has a single reduction in emissivity values at 6,054.6 km, while Maat and Ozza have several reductions at altitudes of 6,052.5–6,056.7 km. Emissivity values are highly spatially correlated to individual lava flows indicating that minerals in the rocks control the emissivity signature. The emissivity patterns at these volcanoes require at least four individual ferroelectric mineral compositions in the rocks that are highly conductive at Curie temperatures of 693–731 K. These temperatures are compatible with chlorapatite and some perovskite oxides. Modeling the minimum volumes of ferroelectrics (10–100s ppm) shows the volume and type of ferroelectric may vary over the lifetime of a single volcano. The modeled volumes of ferroelectrics in Ozza and Sapas are greater than in Maat, consistent with the production of ferroelectrics via weathering over a longer period of time, and supporting the idea that Maat has younger volcanic activity. The stratigraphic relationship of Maat's youngest flows with impact craters may indicate the timeframe of the production of specific ferroelectrics via chemical weathering is over 9–60 Ma.
Can Land Surface Models Capture the Observed Soil Moisture Control of Water and Carbon Fluxes in Temperate‐To‐Boreal Forests?
Authors: dos Santos T. , Keppel‐Aleks G. , De Roo R. , Steiner A. L. 
Published: March 2021

AbstractThe reservoir of soil water is exchanged with the atmosphere through evaporative processes, which are mediated via vegetation through transpiration. Carbon uptake is closely coupled to transpiration, and most process‐based models link transpiration and photosynthesis explicitly. Here, we evaluate the simulation of water and carbon fluxes in forested areas of North America using point‐based simulations of the Community Land Model version 5 (CLM5) with Soil Moisture Active/Passive (SMAP) satellite derived soil moisture measurements and in situ measurements at eight Fluxnet and two United States Climate Research Network (CRN) sites. Compared to observations, there is a broad site‐to‐site variability in simulated soil moisture, with some sites exhibiting wet biases and others dry biases. The bias sign does not depend on ecosystem or other environmental drivers such as radiation and temperature. Compared to Fluxnet latent heat (LH) and gross primary production (GPP) flux tower observations, simulated LH flux biases at deciduous broadleaf forests are linked with soil moisture biases, and the model captures the observed seasonal cycle and parabolic seasonal relationship with soil moisture. The parabolic shape is driven by high soil moisture and low LH fluxes in June, peak LH and drier soil conditions in July, followed by further soil moisture drawdown in August. GPP is underestimated at most sites, and the model exhibits a linear relationship between soil moisture and GPP. Because the photosynthesis parameterizations are similar in most Earth system models, further model development that incorporates observations and observed relationships is needed to accurately capture the GPP‐soil moisture relationship.
Comment on “Paleomagnetism of the Late Cretaceous Red Beds From the Far Western Lhasa Terrane: Inclination Discrepancy and Tectonic Implications” by Bian et al.
Authors: Zhao Qian , Huang Baochun , Tao Wei 
Published: March 2021

AbstractBian et al. (2020, https://doi.org/10.1029/2020TC006280) recently studied the paleomagnetism of the Late Cretaceous redbeds and summarized all the published paleomagnetic data obtained from the Lhasa terrane. A total of 25 poles from western and central‐eastern Lhasa terrane were collectively analyzed, of which they concluded 21 poles are reliable. These filtered directions, corrected for tilt and depositional biases following Tong et al. (2019, https://doi.org/10.1016/j.earscirev.2019.02.009), were then used to reconstruct the paleoposition and shape of the southern margin of the Asian continent. However, some of Bian et al.'s (2020, https://doi.org/10.1029/2020TC006280) interpretations are in conflict with the known geology of the Lhasa terrane. We argue that they have not applied the appropriate structural corrections to their data. The magnetic directions need to be corrected for a plunging fold axis and evaluated more thoroughly for post‐depositional strain. We recommend the data as presented in Bian et al. (2020, https://doi.org/10.1029/2020TC006280) should not be used for paleogeographic reconstructions. Moreover, cautions need to be given when applying paleomagnetic data with anisotropy of magnetic susceptibility analysis showing pencil structure to the deformational fabric to paleogeographic reconstructions.
Sex-specific genetic architecture in response to American and ketogenic diets
Authors: Salvador Anna C. , Arends Danny , Barrington William T. , Elsaadi Ahmed M. , Brockmann Gudrun A. , Threadgill David W. 
Published: March 2021

Abstract
Background/objectives
There is a growing appreciation for individual responses to diet. In a previous study, mouse strain-specific responses to American and ketogenic diets were observed. In this study, we searched for genetic variants underlying differences in the responses to American and ketogenic diets between C57BL/6J (B6) and FVB/NJ (FVB) mouse strains.

Results
Genetic mapping of fat and lean mass gain revealed QTLs on Chromosome (Chr) 1 at 191.6 Mb (Fmgq1) (P < 0.001, CI = 180.2–194.4 Mb), Chr5 at 73.7 Mb (Fmgq2, Lmgq1) (P < 0.001, CI = 66.1–76.6 Mb), and Chr7 at 40.5 Mb (Fmgq3) (P < 0.01, CI = 36.6–44.5 Mb). Analysis of serum HDL cholesterol concentration identified a significant (P < 0.001, CI = 160.6–176.1 Mb) QTL on Chr1 at 168.6 Mb (Hdlq1). Causal network inference suggests that HDL cholesterol and fat mass gain are both linked to Fmgq1.

Conclusions
Strong sex effects were identified at both Fmgq2 and Lmgq1, which are also diet-dependent. Interestingly, Fmgq2 and Fmgq3 affect fat gain directly, while Fmgq1 influences fat gain directly and via an intermediate change in serum cholesterol. These results demonstrate how precision nutrition will be advanced through the integration of genetic variation and sex in physiological responses to diets varied in carbohydrate composition.
Hepatic sinusoidal obstruction syndrome and short-term application of 6-thioguanine in pediatric acute lymphoblastic leukemia
Authors: Stanulla Martin , Schaeffeler Elke , Möricke Anja , Buchmann Swantje , Zimmermann Martin , Igel Svitlana , Schmiegelow Kjeld , Flotho Christian , Hartmann Hans , Illsinger Sabine , Sauerbrey Axel , Junk Stefanie V. , Schütte Peter , Hinze Laura , Lauten Melchior , Modlich Simon , Kolb Reinhard , Rossig Claudia , Schwabe Georg , Gnekow Astrid K. , Fleischhack Gudrun , Schlegel Paul Gerhard , Schünemann Holger J. , Kratz Christian P. , Cario Gunnar , Schrappe Martin , Schwab Matthias 
Published: March 2021

AbstractLong-term treatment with 6-thioguanine (6-TG) for pediatric acute lymphoblastic leukemia (ALL) is associated with high rates of hepatic sinusoidal obstruction syndrome (SOS). Nevertheless, current treatment continues to use short-term applications of 6-TG with only sparse information on toxicity. 6-TG is metabolized by thiopurine methyltransferase (TPMT) which underlies clinically relevant genetic polymorphism. We analyzed the association between hepatic SOS reported as a serious adverse event (SAE) and short-term 6-TG application in 3983 pediatric ALL patients treated on trial AIEOP-BFM ALL 2000 (derivation cohort) and defined the role of TPMT genotype in this relationship. We identified 17 patients (0.43%) with hepatic SOS, 13 of which with short-term exposure to 6-TG (P < 0.0001). Eight of the 13 patients were heterozygous for low-activity TPMT variants, resulting in a 22.4-fold (95% confidence interval 7.1–70.7; P ≤ 0.0001) increased risk of hepatic SOS for heterozygotes in comparison to TPMT wild-type patients. Results were supported by independent replication analysis. All patients with hepatic SOS after short-term 6-TG recovered and did not demonstrate residual symptoms. Thus, hepatic SOS is associated with short-term exposure to 6-TG during treatment of pediatric ALL and SOS risk is increased for patients with low-activity TPMT genotypes.
Effects of cancer screening restart strategies after COVID-19 disruption
Authors: Kregting Lindy M. , Kaljouw Sylvia , de Jonge Lucie , Jansen Erik E. L. , Peterse Elisabeth F. P. , Heijnsdijk Eveline A. M. , van Ravesteyn Nicolien T. , Lansdorp-Vogelaar Iris , de Kok Inge M. C. M. 
Published: March 2021

Abstract
Background
Many breast, cervical, and colorectal cancer screening programmes were disrupted due to the COVID-19 pandemic. This study aimed to estimate the effects of five restart strategies after the disruption on required screening capacity and cancer burden.

Methods
Microsimulation models simulated five restart strategies for breast, cervical, and colorectal cancer screening. The models estimated required screening capacity, cancer incidence, and cancer-specific mortality after a disruption of 6 months. The restart strategies varied in whether screens were caught up or not and, if so, immediately or delayed, and whether the upper age limit was increased.

Results
The disruption in screening programmes without catch-up of missed screens led to an increase of 2.0, 0.3, and 2.5 cancer deaths per 100 000 individuals in 10 years in breast, cervical, and colorectal cancer, respectively. Immediately catching-up missed screens minimised the impact of the disruption but required a surge in screening capacity. Delaying screening, but still offering all screening rounds gave the best balance between required capacity, incidence, and mortality.

Conclusions
Strategies with the smallest loss in health effects were also the most burdensome for the screening organisations. Which strategy is preferred depends on the organisation and available capacity in a country.
Achieving clinical success with BET inhibitors as anti-cancer agents
Authors: Shorstova Tatiana , Foulkes William D. , Witcher Michael 
Published: March 2021

AbstractThe transcriptional upregulation of oncogenes is a driving force behind the progression of many tumours. However, until a decade ago, the concept of ‘switching off’ these oncogenic pathways represented a formidable challenge. Research has revealed that members of the bromo- and extra-terminal domain (BET) motif family are key activators of oncogenic networks in a spectrum of cancers; their function depends on their recruitment to chromatin through two bromodomains (BD1 and BD2). The advent of potent inhibitors of BET proteins (BETi), which target either one or both bromodomains, represents an important step towards the goal of suppressing oncogenic networks within tumours. Here, we discuss the biology of BET proteins, advances in BETi design and highlight potential biomarkers predicting their activity. We also outline the logic of incorporating BETi into combination therapies to enhance its efficacy. We suggest that understanding mechanisms of activity, defining predictive biomarkers and identifying potent synergies represents a roadmap for clinical success using BETi.
BMP4 overexpression induces the upregulation of APP/Tau and memory deficits in Alzheimer’s disease
Authors: Zhang Xiaoqing , Li Juan , Ma Li , Xu Hui , Cao Yun , Liang Wei , Ma Jia , Wang Z. Peter , Li Yuyun 
Published: March 2021

AbstractAlzheimer’s disease (AD) is a chronic progressive degenerative disease of the nervous system. Its pathogenesis is complex and is related to the abnormal expression of the amyloid β (Aβ), APP, and Tau proteins. Evidence has demonstrated that bone morphogenetic protein 4 (BMP4) is highly expressed in transgenic mouse models of AD and that endogenous levels of BMP4 mainly affect hippocampal function. To determine whether BMP4 participates in AD development, transgenic mice were constructed that overexpress BMP4 under the control of the neuron-specific enolase (NSE) promoter. We also performed MTT, FACS, transfection, TUNEL, and Western blotting assays to define the role of BMP4 in cells. We found that middle-aged BMP4 transgenic mice exhibited impaired memory via the Morris water maze experiment. Moreover, their hippocampal tissues exhibited high expression levels of AD-related proteins, including APP, Aβ, PSEN-1, Tau, P-Tau (Thr181), and P-Tau (Thr231). Furthermore, in multiple cell lines, the overexpression of BMP4 increased the expression of AD-related proteins, whereas the downregulation of BMP4 demonstrated opposing effects. Consistent with these results, BMP4 modulation affected cell apoptosis via the regulation of BAX and Bcl-2 expression in cells. Our findings indicate that BMP4 overexpression might be a potential factor to induce AD.
Umbilical cord-derived mesenchymal stromal cells immunomodulate and restore actin dynamics and phagocytosis of LPS-activated microglia via PI3K/Akt/Rho GTPase pathway
Authors: Mukai Takeo , Di Martino Elena , Tsuji Shunichiro , Blomgren Klas , Nagamura-Inoue Tokiko , Ådén Ulrika 
Published: March 2021

AbstractMicroglia are the immune cells in the central nervous system surveying environment and reacting to various injuries. Activated microglia may cause impaired synaptic plasticity, therefore modulating and restoring them to neutral phenotype is crucial to counteract a pro-inflammatory, neurotoxic state. In this study, we focused on elucidating whether human umbilical cord (UC) -derived mesenchymal stromal cells (MSCs) can exert immunomodulatory effect and change the phenotype of activated microglia. Primary culture of microglia was activated by lipopolysaccharide (LPS) and was co-cultured with three lots of MSCs. We investigated immunomodulation, actin dynamics and phagocytic capacity of activated microglia, and examined change of Rho GTPase in microglia as the mechanism. MSCs suppressed the expression of IL-1β and pNFκB in LPS-activated microglia, and conversely elevated the expression of IL-1β in resting-surveying microglia with lot-to-lot variation. Morphological and phagocytotic analyses revealed that LPS stimulation significantly increased active Rho GTPase, Rac1, and Cdc42 levels in the microglia, and their morphology changed to amoeboid in which F-actin spread with ruffle formation. The F-actin spreading persisted after removal of LPS stimulation and reduced phagocytosis. On the other hand, MSC co-culture induced bimodal increase in active Rac1 and Cdc42 levels in LPS-activated microglia. Moreover, extended ruffles of F-actin shrinked and concentrated to form an actin ring, thereby restoring phagocytosis. We confirmed inhibition of the PI3K/Akt pathway attenuated F-actin dynamics and phagocytosis restored by MSCs. Overall, we demonstrated that MSCs immunomodulated microglia with lot-to-lot variation, and changed the phenotype of LPS-activated microglia restoring actin dynamics and phagocytosis by increase of active Rho GTPase.
Role of interleukins in the pathogenesis of pulmonary fibrosis
Authors: She Yi Xin , Yu Qing Yang , Tang Xiao Xiao 
Published: March 2021

AbstractInterleukins, a group of cytokines participating in inflammation and immune response, are proved to be involved in the formation and development of pulmonary fibrosis. In this article, we reviewed the relationship between interleukins and pulmonary fibrosis from the clinical, animal, as well as cellular levels, and discussed the underlying mechanisms in vivo and in vitro. Despite the effects of interleukin-targeted treatment on experimental pulmonary fibrosis, clinical applications are lacking and unsatisfactory. We conclude that intervening in one type of interleukins with similar functions in IPF may not be enough to stop the development of fibrosis as it involves a complex network of regulation mechanisms. Intervening interleukins combined with other existing therapy or targeting interleukins affecting multiple cells/with different functions at the same time may be one of the future directions. Furthermore, the intervention time is critical as some interleukins play different roles at different stages. Further elucidation on these aspects would provide new perspectives on both the pathogenesis mechanism, as well as the therapeutic strategy and drug development.
Semi-device-independent random number generation with flexible assumptions
Authors: Pivoluska Matej , Plesch Martin , Farkas Máté , Ružičková Natália , Flegel Clara , Valencia Natalia Herrera , McCutcheon Will , Malik Mehul , Aguilar Edgar A. 
Published: March 2021

AbstractOur ability to trust that a random number is truly random is essential for fields as diverse as cryptography and fundamental tests of quantum mechanics. Existing solutions both come with drawbacks—device-independent quantum random number generators (QRNGs) are highly impractical and standard semi-device-independent QRNGs are limited to a specific physical implementation and level of trust. Here we propose a framework for semi-device-independent randomness certification, using a source of trusted vacuum in the form of a signal shutter. It employs a flexible set of assumptions and levels of trust, allowing it to be applied in a wide range of physical scenarios involving both quantum and classical entropy sources. We experimentally demonstrate our protocol with a photonic setup and generate secure random bits under three different assumptions with varying degrees of security and resulting data rates.
Stability of filament-wound hyperbolic flexible pipes under internal pressure based on non-geodesic winding
Authors: Xu Guo-min , Shuai Chang-geng 
Published: March 2021

AbstractFilament-wound flexible pipes are widely used to transport fluid in pipeline systems, proved extremely useful in marine engineering. The hyperbolic flexible pipes have good vibration suppression performance, but they are easily deformed under internal pressure. This paper focuses on the stability of hyperbolic flexible pipes based on the composite Reissner shell theory and the transfer-matrix method. The nonlinear stretch of the reinforced filament and the fiber bridge effect are considered in the model. The calculation results show that a large winding angle reduces the deformation and the meridional stress. The available initial winding angle is limited by the geometry and the slippage coefficient of flexible pipe. The reinforced filament of high tensile modulus will reduce the deformation of the pipe. Compared with the geodesic winding trajectory, non-geodesic winding trajectories improves the stability of the pipe. The theoretical result is verified by the finite element analysis. The investigation method and results present in this paper will guide the design and optimization of more novel flexible pipes in the future.
Non-specific interactions of antibody-oligonucleotide conjugates with living cells
Authors: Lehot Victor , Kuhn Isabelle , Nothisen Marc , Erb Stéphane , Kolodych Sergii , Cianférani Sarah , Chaubet Guilhem , Wagner Alain 
Published: March 2021

AbstractAntibody-Oligonucleotide Conjugates (AOCs) represent an emerging class of functionalized antibodies that have already been used in a wide variety of applications. While the impact of dye and drug conjugation on antibodies’ ability to bind their target has been extensively studied, little is known about the effect caused by the conjugation of hydrophilic and charged payloads such as oligonucleotides on the functions of an antibody. Previous observations of non-specific interactions of nucleic acids with untargeted cells prompted us to further investigate their impact on AOC binding abilities and cell selectivity. We synthesized a series of single- and double-stranded AOCs, as well as a human serum albumin-oligonucleotide conjugate, and studied their interactions with both targeted and non-targeted living cells using a time-resolved analysis of ligand binding assay. Our results indicate that conjugation of single strand oligonucleotides to proteins induce consistent non-specific interactions with cell surfaces while double strand oligonucleotides have little or no effect, depending on the preparation method.