bluuebunny/crossref_metadata_2025 huggingface dataset:
Single‐Crystal Elasticity of Antigorite at High Pressures and Seismic Detection of Serpentinized Slabs
Authors: Satta Niccolò , Grafulha Morales Luiz Fernando , Criniti Giacomo , Kurnosov Alexander , Boffa Ballaran Tiziana , Speziale Sergio , Marquardt Katharina , Capitani Gian Carlo , Marquardt Hauke
Published: August 2022

The subduction of serpentinized slabs is the dominant process to transport “water” into Earth's mantle, and plays a pivotal role for subduction dynamics. Antigorite, the most abundant serpentine mineral in subduction settings, may imprint a seismic signature on serpentinized slabs, making them seismically distinguishable from the dry, non‐serpentinized ones. However, the complete single‐crystal elasticity of antigorite has not been experimentally constrained at high pressures, hindering the use of seismological approaches to detect serpentinization in subducting slabs. Here, we report the full elastic stiffness tensor of antigorite by single‐crystal Brillouin spectroscopy and X‐ray diffraction up to 7.71(5) GPa. We use our results to model seismic properties of antigorite‐bearing rocks and show that their seismological detectability depends on the geometrical relation between seismic wave paths and foliation of serpentinized rocks. In particular, we demonstrate that seismic shear anisotropy shows low sensitivity to serpentinization for a range of relevant geometries.
Global Spectrum of Vegetation Light‐Use Efficiency
Authors: He Mingzhu , Chen Shaoyuan , Lian Xu , Wang Xuhui , Peñuelas Josep , Piao Shilong
Published: August 2022

Vegetation light‐use efficiency (LUE) is a critical parameter of vegetation photosynthesis, but its global variations and the drivers remain poorly understood. Here, we used data from 172 flux tower sites to characterize the global distribution of ecosystem‐level LUE spanning various vegetation and climate. The global growing season average LUE was 1.30 ± 0.55 g C MJ−1 for 2000–2014. The main factors driving LUE variations included environmental conditions (e.g., temperature), plant traits (e.g., foliar nitrogen concentration and isohydricity) and their interactions, which together accounted for about 76% of the observed global variations in LUE. However, an ensemble of 11 dynamic global vegetation models largely underestimated LUE, and hardly captured the key drivers. Our results highlight that a paradigm shift from vegetation functional type‐based scheme to trait‐climate spectrum‐based scheme is necessary for the next‐generation models to accurately simulate the response of vegetation carbon uptake to climate change.
Explosive Eruption of the Tonga Underwater Volcano Modulates the Ionospheric E‐Region Current on 15 January 2022
Authors: Sun Yang‐Yi , Chen Chieh‐Hung , Zhang Pengyu , Li Sheng , Xu Hui‐Ru , Yu Tao , Lin Kai , Mao Zhiqiang , Zhang Dixin , Lin Chi‐Yen , Liu Jann‐Yenq
Published: August 2022

The sudden eruption of the Tonga underwater volcano (20.53°S, 175.38°W) on 15 January 2022 generated explosions that triggered blast waves traveling away from the eruption. In this study, the analysis of the geomagnetic field observations on the ground shows that the eruption perturbed the E‐region current density by 22–55 mA/m within a radius of 8,000 km away from the eruption. The perturbation evolved into large scales of ∼5 hr and thousands of kilometers as it traveled away. The traveling speed of the leading front is ∼740 m/s that is near acoustic in the ionosphere. The magnetic fields and total electron content observations suggest that the dynamics changes further induced significant ionospheric disturbances that lasted ∼10 hr after the eruption. The examination of the Tonga volcanic eruption inspires us that a near‐surface perturbation can change the dynamics of the upper atmosphere.
First Synoptic Images of FUV Discrete Aurora and Discovery of Sinuous Aurora at Mars by EMM EMUS
Authors: Lillis Robert J. , Deighan Justin , Brain David , Fillingim Matthew , Jain Sonal , Chaffin Michael , England Scott , Holsclaw Greg , Chirakkil Krishnaprasad , Al Matroushi Hessa , Lootah Fatma , Al Mazmi Hoor , Thiemann Ed , Eparvier Frank , Schneider Nick , Curry Shannon
Published: August 2022

We present the first measurements of Mars discrete aurora in the extreme ultraviolet (<110 nm) and the first synoptic aurora images in the far ultraviolet (110–180 nm). Auroral emission is detected in >75% of nightside images, with patterns shifting visibly over 15–20 min. Aurora is observed most frequently in regions of open magnetic topology (where crustal magnetic fields are very weak and/or vertical), with the brightest aurora where crustal fields are strongest. We present the first disk‐averaged spectrum of discrete aurora, with several O, C, and CO features as expected for electron impact primarily on CO2. We categorize discrete auroral morphology into three types: crustal field aurora, non‐crustal field patchy aurora, and a new type we call “sinuous” aurora, an elongated serpentine structure that stretches thousands of kilometers into the nightside from near midnight in the northern hemisphere. These observations point to a highly dynamic environment in Mars' magnetotail.
Isotopic Evidence That Alkyl Nitrates Are Important to Aerosol Nitrate Formation in the Equatorial Pacific
Authors: Joyce Emily E. , Balint Sawyer J. , Hastings Meredith G.
Published: August 2022

Concentrations and the stable isotopic composition of bulk aerosol nitrate (NO3−) were quantified from two GEOTRACES cruises: (a) Alaska–Tahiti (GP15; n = 22) and (b) Peru–Tahiti (GP16; n = 17) to explore the hypothesis that a marine source influences aerosol NO3− in the equatorial Pacific. The δ15N‐NO3− ranged from −14.5‰–0.5‰, with lowest values furthest from the coast, primarily reflecting a shift in sources. The δ18O‐ and Δ17O‐NO3− were both relatively high (65.2‰–85.4‰ and 21.4‰–30.7‰, respectively) and decreased away from continental regions, reflecting a shift in the oxidants that influence the formation of NO3−. Transport modeling and co‐occurrence of low δ15N, δ18O and Δ17O provided evidence for an important influence of marine‐derived alkyl nitrates (RONO2) on aerosol NO3− formation. Based on the Δ17O, we quantified that the contribution of RONO2 to aerosol NO3− can be as high as 47.5% (range 7.5%–47.5%). We also estimate an average δ15N‐RONO2 of −27.8‰ ± 23.3‰.
A Rotation Procedure to Improve Seasonally Varying Empirical Orthogonal Function Bases for MJO Indices
Authors: Weidman Sarah , Kleiner Ned , Kuang Zhiming
Published: August 2022

Various indices have been defined to characterize the phase and amplitude of the Madden‐Julian oscillation (MJO). One widely used index is the outgoing longwave radiation (OLR) based MJO index (OMI), which is calculated using the spatial pattern of 30–96‐day eastward‐filtered OLR. The empirical orthogonal functions (EOFs) used to calculate the OMI in observations are prone to degeneracy and exhibit oscillations on the order of 10–20 days, despite initial filtering of the OLR. We propose a simple modification to the OMI that involves aligning the EOFs between neighboring days while retaining the spatial pattern described by the EOFs. This rotation method is implemented as a postprocessing procedure of the current OMI calculation and cleanly removes the spurious oscillations and degeneracy issues seen in the standard method. A similar rotation procedure can be implemented in calculations of other MJO indices.
Carbon Isotopic Constraints on Basin‐Scale Vertical and Lateral Particulate Organic Carbon Dynamics in the Northern South China Sea
Authors: Zhang Jingjing , Li Hongliang , Wiesner Martin G. , Eglinton Timothy I. , Haghipour Negar , Jian Zhimin , Chen Jianfang
Published: August 2022

Lateral particle transport in shelf/slope settings of marginal sea systems may potentially supply allochthonous particulate organic carbon (POC) to the ocean interior. The magnitude and prevalence of such processes has implications for our understanding of the functioning and efficiency of modern biological carbon pump processes, as well as for interpretation of deep ocean sediment records. Yet, ages and relative contribution of POC from different sources to deep ocean basins are much less understood. Here, based on radiocarbon (Fm, fraction modern), stable carbon (δ13Corg), and other geochemical analysis of particles intercepted by time‐series sediment traps deployed at three different depths (1,000, 2,150, and 3,200 m), we constrain the source of the sinking POC in the deep basin of northern South China Sea (SCS). The results show that the modern POC derived from surface ocean productivity, acting as the vertical vector, accounts for 87% ± 4% of sinking POC on average, while the lateral vector (aged POC hosted on resuspended sediment) comprises the remainder (13%). The contribution of laterally supplied POC increases with depth and is composed of aged POC derived from several sources. The majority stems from sediment resuspension of the northeastern SCS slope, that entrains aged marine POC (dominant), fossil OC, and soil OC (least significant). The diminished proportion of fossil OC in deep basin sinking POC relative to Taiwan‐proximal areas is likely due to its dispersion via resuspension–deposition loops and dilution by POC stemming from modern surface ocean productivity during the delivery.
Training Physics‐Based Machine‐Learning Parameterizations With Gradient‐Free Ensemble Kalman Methods
Authors: Lopez‐Gomez Ignacio , Christopoulos Costa , Langeland Ervik Haakon Ludvig , Dunbar Oliver R. A. , Cohen Yair , Schneider Tapio
Published: August 2022

Most machine learning applications in Earth system modeling currently rely on gradient‐based supervised learning. This imposes stringent constraints on the nature of the data used for training (typically, residual time tendencies are needed), and it complicates learning about the interactions between machine‐learned parameterizations and other components of an Earth system model. Approaching learning about process‐based parameterizations as an inverse problem resolves many of these issues, since it allows parameterizations to be trained with partial observations or statistics that directly relate to quantities of interest in long‐term climate projections. Here, we demonstrate the effectiveness of Kalman inversion methods in treating learning about parameterizations as an inverse problem. We consider two different algorithms: unscented and ensemble Kalman inversion. Both methods involve highly parallelizable forward model evaluations, converge exponentially fast, and do not require gradient computations. In addition, unscented Kalman inversion provides a measure of parameter uncertainty. We illustrate how training parameterizations can be posed as a regularized inverse problem and solved by ensemble Kalman methods through the calibration of an eddy‐diffusivity mass‐flux scheme for subgrid‐scale turbulence and convection, using data generated by large‐eddy simulations. We find the algorithms amenable to batching strategies, robust to noise and model failures, and efficient in the calibration of hybrid parameterizations that can include empirical closures and neural networks.
Biomonitoring of inorganic arsenic species in pregnancy
Authors: Ashley-Martin Jillian , Fisher Mandy , Belanger Patrick , Cirtiu Ciprian Mihai , Arbuckle Tye E.
Published: August 2022

Exposure assessment of inorganic arsenic is challenging due to the existence of multiple species, complexity of arsenic metabolism, and variety of exposure sources. Exposure assessment of arsenic during pregnancy is further complicated by the physiological changes that occur to support fetal growth. Given the well-established toxicity of inorganic arsenic at high concentrations, continued research into the potential health effects of low-level exposure on maternal and fetal health is necessary. Our objectives were to review the value of and challenges inherent in measuring inorganic arsenic species in pregnancy and highlight related research priorities. We discussed how the physiological changes of pregnancy influence arsenic metabolism and necessitate the need for pregnancy-specific data. We reviewed the biomonitoring challenges according to common and novel biological matrices and discussed how each matrix differs according to half-life, bioavailability, availability of laboratory methods, and interpretation within pregnancy. Exposure assessment in both established and novel matrices that accounts for the physiological changes of pregnancy and complexity of speciation is a research priority. Standardization of laboratory method for novel matrices will help address these data gaps. Research is particularly lacking in contemporary populations of pregnant women without naturally elevated arsenic drinking water concentrations (i.e. <10 µg/l).
Tumor-derived miR-130b-3p induces cancer-associated fibroblast activation by targeting SPIN90 in luminal A breast cancer
Authors: Ahn Suyeon , Kwon Ahreum , Huh Yun Hyun , Rhee Sangmyung , Song Woo Keun
Published: August 2022

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) interact closely with cancer cells to promote tumor development. Downregulation of SPIN90 in CAFs has been reported to facilitate breast cancer progression, but the underlying mechanism has not been elucidated. Here, we demonstrate that miR-130b-3p directly downregulates SPIN90 in stromal fibroblasts, leading to their differentiation into CAFs. As the decrease of SPIN90 in CAFs was shown to be more prominent in estrogen receptor (ER)-positive breast tumors in this study, miR-130b-3p was selected by bioinformatics analysis of data from patients with ER-positive breast cancer. Ectopic expression of miR-130b-3p in fibroblasts accelerated their differentiation to CAFs that promote cancer cell motility; this was associated with SPIN90 downregulation. We also found that miR-130b-3p was generated in luminal A-type cancer cells and activated fibroblasts after being secreted via exosomes from cancer cells. Finally, miR-130b-3p increased in SPIN90-downregulated tumor stroma of luminal A breast cancer patients and MCF7 cell-xenograft model mice. Our data demonstrate that miR-130b-3p is a key modulator that downregulates SPIN90 in breast CAFs. The inverse correlation between miR-130b-3p and SPIN90 in tumor stroma suggests that the miR-130b-3p/SPIN90 axis is clinically significant for CAF activation during breast cancer progression.
Cell-type-specific epigenetic effects of early life stress on the brain
Authors: Rahman Mouly F. , McGowan Patrick O.
Published: August 2022

Early life stress (ELS) induces long-term phenotypic adaptations that contribute to increased vulnerability to a host of neuropsychiatric disorders. Epigenetic mechanisms, including DNA methylation, histone modifications and non-coding RNA, are a proposed link between environmental stressors, alterations in gene expression, and phenotypes. Epigenetic modifications play a primary role in shaping functional differences between cell types and can be modified by environmental perturbations, especially in early development. Together with contributions from genetic variation, epigenetic mechanisms orchestrate patterns of gene expression within specific cell types that contribute to phenotypic variation between individuals. To date, many studies have provided insights into epigenetic changes resulting from ELS. However, most of these studies have examined heterogenous brain tissue, despite evidence of cell-type-specific epigenetic modifications in phenotypes associated with ELS. In this review, we focus on rodent and human studies that have examined epigenetic modifications induced by ELS in select cell types isolated from the brain or associated with genes that have cell-type-restricted expression in neurons, microglia, astrocytes, and oligodendrocytes. Although significant challenges remain, future studies using these approaches can enable important mechanistic insight into the role of epigenetic variation in the effects of ELS on brain function.
Molecular characterization of the missing electron pathways for butanol synthesis in Clostridium acetobutylicum
Authors: Foulquier Céline , Rivière Antoine , Heulot Mathieu , Dos Reis Suzanna , Perdu Caroline , Girbal Laurence , Pinault Mailys , Dusséaux Simon , Yoo Minyeong , Soucaille Philippe , Meynial-Salles Isabelle
Published: August 2022

Clostridium acetobutylicum is a promising biocatalyst for the renewable production of n-butanol. Several metabolic strategies have already been developed to increase butanol yields, most often based on carbon pathway redirection. However, it has previously demonstrated that the activities of both ferredoxin-NADP+ reductase and ferredoxin-NAD+ reductase, whose encoding genes remain unknown, are necessary to produce the NADPH and the extra NADH needed for butanol synthesis under solventogenic conditions. Here, we purify, identify and partially characterize the proteins responsible for both activities and demonstrate the involvement of the identified enzymes in butanol synthesis through a reverse genetic approach. We further demonstrate the yield of butanol formation is limited by the level of expression of CA_C0764, the ferredoxin-NADP+ reductase encoding gene and the bcd operon, encoding a ferredoxin-NAD+ reductase. The integration of these enzymes into metabolic engineering strategies introduces opportunities for developing a homobutanologenic C. acetobutylicum strain.
Evidence for a HURP/EB free mixed-nucleotide zone in kinetochore-microtubules
Authors: Castrogiovanni Cédric , Inchingolo Alessio V. , Harrison Jonathan U. , Dudka Damian , Sen Onur , Burroughs Nigel J. , McAinsh Andrew D. , Meraldi Patrick
Published: August 2022

Current models infer that the microtubule-based mitotic spindle is built from GDP-tubulin with small GTP caps at microtubule plus-ends, including those that attach to kinetochores, forming the kinetochore-fibres. Here we reveal that kinetochore-fibres additionally contain a dynamic mixed-nucleotide zone that reaches several microns in length. This zone becomes visible in cells expressing fluorescently labelled end-binding proteins, a known marker for GTP-tubulin, and endogenously-labelled HURP - a protein which we show to preferentially bind the GDP microtubule lattice in vitro and in vivo. We find that in mitotic cells HURP accumulates on the kinetochore-proximal region of depolymerising kinetochore-fibres, whilst avoiding recruitment to nascent polymerising K-fibres, giving rise to a growing “HURP-gap”. The absence of end-binding proteins in the HURP-gaps leads us to postulate that they reflect a mixed-nucleotide zone. We generate a minimal quantitative model based on the preferential binding of HURP to GDP-tubulin to show that such a mixed-nucleotide zone is sufficient to recapitulate the observed in vivo dynamics of HURP-gaps.
mTORC1 controls Golgi architecture and vesicle secretion by phosphorylation of SCYL1
Authors: Kaeser-Pebernard Stéphanie , Vionnet Christine , Mari Muriel , Sankar Devanarayanan Siva , Hu Zehan , Roubaty Carole , Martínez-Martínez Esther , Zhao Huiyuan , Spuch-Calvar Miguel , Petri-Fink Alke , Rainer Gregor , Steinberg Florian , Reggiori Fulvio , Dengjel Jörn
Published: August 2022

The protein kinase mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth and proliferation, supporting anabolic reactions and inhibiting catabolic pathways like autophagy. Its hyperactivation is a frequent event in cancer promoting tumor cell proliferation. Several intracellular membrane-associated mTORC1 pools have been identified, linking its function to distinct subcellular localizations. Here, we characterize the N-terminal kinase-like protein SCYL1 as a Golgi-localized target through which mTORC1 controls organelle distribution and extracellular vesicle secretion in breast cancer cells. Under growth conditions, SCYL1 is phosphorylated by mTORC1 on Ser754, supporting Golgi localization. Upon mTORC1 inhibition, Ser754 dephosphorylation leads to SCYL1 displacement to endosomes. Peripheral, dephosphorylated SCYL1 causes Golgi enlargement, redistribution of early and late endosomes and increased extracellular vesicle release. Thus, the mTORC1-controlled phosphorylation status of SCYL1 is an important determinant regulating subcellular distribution and function of endolysosomal compartments. It may also explain the pathophysiology underlying human genetic diseases such as CALFAN syndrome, which is caused by loss-of-function of SCYL1.
Determination of the asymptotic limits of adaptive photon counting measurements for coherent-state optical phase estimation
Authors: Rodríguez-García M. A. , DiMario M. T. , Barberis-Blostein P. , Becerra F. E.
Published: August 2022

Physical realizations of the canonical phase measurement for the optical phase are unknown. Single-shot phase estimation, which aims to determine the phase of an optical field in a single shot, is critical in quantum information processing and metrology. Here we present a family of strategies for single-shot phase estimation of coherent states based on adaptive non-Gaussian, photon counting, measurements with coherent displacements that maximize information gain as the measurement progresses, which have higher sensitivities over the best known adaptive Gaussian strategies. To gain understanding about their fundamental characteristics and demonstrate their superior performance, we develop a comprehensive statistical analysis based on Bayesian optimal design of experiments, which provides a natural description of these non-Gaussian strategies. This mathematical framework, together with numerical analysis and Monte Carlo methods, allows us to determine the asymptotic limits in sensitivity of strategies based on photon counting designed to maximize information gain, which up to now had been a challenging problem. Moreover, we show that these non-Gaussian phase estimation strategies have the same functional form as the canonical phase measurement in the asymptotic limit differing only by a scaling factor, thus providing the highest sensitivity among physically-realizable measurements for single-shot phase estimation of coherent states known to date. This work shines light into the potential of optimized non-Gaussian measurements based on photon counting for optical quantum metrology and phase estimation.
Towards understanding the magnetic properties of the breathing pyrochlore compound Ba3Yb2Zn5O11through single-crystal studies
Authors: Dissanayake Sachith , Shi Zhenzhong , Rau Jeffrey G. , Bag Rabindranath , Steinhardt William , Butch Nicholas P. , Frontzek Matthias , Podlesnyak Andrey , Graf David , Marjerrison Casey , Liu Jue , Gingras Michel J. P. , Haravifard Sara
Published: August 2022

Ba3Yb2Zn5O11 is exceptional among breathing pyrochlore compounds for being in the nearly-decoupled limit where inter-tetrahedron interactions are weak, hosting isolated clusters or molecular magnet-like tetrahedra of magnetic ytterbium (Yb3+) ions. In this work, we present the study carried out on single-crystal samples of the breathing pyrochlore Ba3Yb2Zn5O11, using a variety of magnetometry and neutron scattering techniques along with theoretical modeling. We employ inelastic neutron scattering to investigate the magnetic dynamics as a function of applied field (with respect to both magnitude and direction) down to a temperature of 70 mK, where inelastic scattering reveals dispersionless bands of excitations as found in earlier powder sample studies, in good agreement with a single-tetrahedron model. However, diffuse neutron scattering at zero field and dc-susceptibility at finite field exhibit features suggesting the presence of excitations at low-energy that are not captured by the single tetrahedron model. Analysis of the local structure down to 2 K via pair distribution function analysis finds no evidence of structural disorder. We conclude that effects beyond the single tetrahedron model are important in describing the low-energy, low-temperature physics of Ba3Yb2Zn5O11, but their nature remains undetermined.
The effects of the voglibose on non-alcoholic fatty liver disease in mice model
Authors: Bae Jaehyun , Lee Ji Young , Shin Eugene , Lee Minyoung , Lee Yong-ho , Lee Byung-Wan , Kang Eun Seok , Cha Bong-Soo
Published: August 2022

The α-glucosidase inhibitor (α-GI) delays the intestinal absorption of glucose, which reduces postprandial hepatic glucose intake. This mechanism is considered to be effective in treating non-alcoholic fatty liver disease (NAFLD). Here, we investigated the effect of voglibose, an α-glucosidase inhibitor, on high-fat, high-fructose (HFHFr) diet-induced NAFLD models. Seven-week-old male C57BL/6J mice were randomly placed in a chow diet group or an HFHFr diet group. After 10 weeks, mice in the HFHFr group were randomly assigned to one of three groups: HFHFr diet with vehicle, HFHFr with voglibose, or HFHFr with pioglitazone. Each diet and treatment was continued for 10 weeks. The HFHFr diet induced severe NAFLD in terms of steatosis, hepatitis, and fibrosis. Administration of voglibose improved all aspects of NAFLD, comparable to those of pioglitazone, a positive control. In voglibose-treated mice, gene expressions of hepatic lipogenesis markers were significantly downregulated. In the in vitro experiment, reducing the influx of glucose into hepatocytes significantly reduced steatosis and de novo lipogenesis even in the presence of sufficient fructose and fat, demonstrating that the mechanism of voglibose could be effective in treating HFHFr diet-induced NAFLD. These results indicate that voglibose improves HFHFr diet-induced NAFLD by suppressing hepatic de novo lipogenesis.
Experimental study on compression mechanical characteristics of filled rock joints after multiple pre-impacts
Authors: Chai Shaobo , Jia Yongsheng , Du Yuxiang , Hu Bo , Li Xianpeng
Published: August 2022

The prefabricated artificial filled jointed rock specimens are impacted by a self-made drop hammer impact device for many times, and the specimens with different degrees of cumulative damage characteristics are obtained. Then, the static and dynamic compression mechanical properties are studied by using universal testing machine and SHPB device. Through the static compression test, the strength and deformation characteristics of jointed rock specimens after multiple impacts are obtained, and the influence of the damage degree of jointed rock specimens characterized by wave velocity on the compressive strength of filled joints is analysed. Based on the results of SHPB impact test, the dynamic strength and deformation evolution, wave propagation law and energy dissipation law of filled joints after multiple impacts are analysed. During the SHPB test, the impact failure process of rock specimens is recorded by a high-speed camera. The experimental results show that the damage degree of jointed rock samples increases nonlinearly after multiple impacts. The attenuation laws of static strength and dynamic strength of rock samples under the same damage evolution conditions are different. With the increase of impact times, the failure mode of jointed rock samples after damage is simpler and tends to compression failure.
Exploring the brachistochrone (shortest-time) path in fire spread
Authors: Sun Peiyi , Liu Yanhui , Huang Xinyan
Published: August 2022

The brachistochrone (shortest-time) curve is the path connecting two points that enables the shortest travel time. This work explores the “brachistochrone path” of fire spread connecting two points at the same altitude and with a fixed path length. The starting and ending points are connected by both thermally thin fuels (thin wires) and thermally thick fuels (PMMA bars). Flame-spread paths of triangular, rectangular, and circular shapes with different heights and inclinations are explored. Results show that having a local maximum flame-spread rate does not result in the shortest overall travel time. For thin-wire paths, the fastest overall-path fire spread occurs, when the upward spread path is vertical, and the path height reaches a maximum, as demonstrated by the theoretical analysis. Differently, for thick PMMA-bar paths, the brachistochrone condition occurs when the path length of the vertical upward spread reaches the maximum, because the upward spread is about ten times faster than the downward spread. This study extends the conventional problem of the fastest fire spread to the shortest-time problem of the whole fire path, and it may help optimize the fuel distribution inside the built environment and estimate available safe egress time in building and wildland fires.
Absolute binding free energy calculations improve enrichment of actives in virtual compound screening
Authors: Feng Mudong , Heinzelmann Germano , Gilson Michael K.
Published: August 2022

We determined the effectiveness of absolute binding free energy (ABFE) calculations to refine the selection of active compounds in virtual compound screening, a setting where the more commonly used relative binding free energy approach is not readily applicable. To do this, we conducted baseline docking calculations of structurally diverse compounds in the DUD-E database for three targets, BACE1, CDK2 and thrombin, followed by ABFE calculations for compounds with high docking scores. The docking calculations alone achieved solid enrichment of active compounds over decoys. Encouragingly, the ABFE calculations then improved on this baseline. Analysis of the results emphasizes the importance of establishing high quality ligand poses as starting points for ABFE calculations, a nontrivial goal when processing a library of diverse compounds without informative co-crystal structures. Overall, our results suggest that ABFE calculations can play a valuable role in the drug discovery process.
Validation of droplet digital PCR for cytokeratin 19 mRNA detection in canine peripheral blood and mammary gland
Authors: Tanvetthayanont Potsawat , Yata Teerapong , Boonnil Jiranun , Temisak Sasithon , Ponglowhapan Suppawiwat
Published: August 2022

In humans, peripheral blood cytokeratin 19 (CK19) mRNA-positive circulating tumor cells (CTCs) was utilized to identify early-stage breast cancer patients with micrometastatic disease who are at risk for disease progression and monitor treatment response in patients with advanced disease. To our knowledge, there has been little research regarding CK19 in canine mammary tumors (CMTs) using molecular methods. A droplet digital PCR (ddPCR) is proposed as a precise and sensitive quantification of nucleic acid targets. Hence, this study aimed to validate a newly designed assay for CK19 detection in canine blood and mammary tissue, along with the reference gene HPRT, by ddPCR. All primers and probes showed a precise match with the exon region of target genes. The assay exhibited PCR efficacy of 90.4% and 91.0% for CK19 and HPRT amplifications with linearity, respectively. The annealing temperature (Ta) for duplex ddPCR was 55 °C, providing the highest concentrations of both genes tested by the synthetic plasmid DNA. The limit of detection (LOD) of CK19 and HPRT were 2.16 ± 1.27 and 2.44 ± 1.31 copies/µL, respectively. Finally, the ddPCR assay was validated with canine peripheral blood, non-neoplastic mammary tissues and spiked samples. Our findings provide a new platform for CK19 studies in CMT diagnosis through blood and mammary tissues.
Neoadjuvant chemotherapy or upfront surgery in localized pancreatic cancer: a contemporary analysis
Authors: Uson Junior Pedro Luiz Serrano , Carvalho Leonardo , Fernandes Milena Lourenço Coleta , Botrus Gehan , de Souza Martins Rodrigo , da Silva Elaine Ferreira , dos Santos Sarah Silva Mello Batista , Taniwaki Leticia , Taranto Patrícia , Dutra Ana Carolina Pereira , de Oliveira Filho João Bosco , Araujo Sergio Eduardo Alonso , Moura Fernando
Published: August 2022

Neoadjuvant chemotherapy is considered a new treatment option for potentially resectable pancreatic cancer. However, data are not well established on overall survival and delaying surgery in resectable pancreatic cancer, as well as on those patients that ultimately cannot undergo surgery. We analyzed pancreatic cancer patients treated in a tertiary hospital from January 2016 to December 2020. Patients with resectable stage I and II pancreatic cancer were evaluated regarding surgery, neoadjuvant treatment, and other clinical demographics. The survival function was estimated using the Kaplan–Meier method, and the relationship between the variables of interest and the overall survival (OS) was assessed by adopting the proportional regression Cox models. A total of 216 patients were evaluated. 81 of them with resectable/borderline resectable disease and 135 with unresectable /metastatic disease at diagnosis. Median OS for stage I and II disease were 36 and 28 months, respectively. For resectable pancreatic cancer median OS was 28 months, for borderline resectable pancreatic cancer median OS was 11 months. Median OS for stage III (locally advanced) and stage IV (metastatic) were 10 and 7 months, respectively (p < 0.0001). Median OS of 9 months were obtained for patients with stage I and II that did not undergo surgery compared to 25 months in patients that underwent surgery in any time (p < 0.001). Comparing patients with localized disease, median OS for patients treated with upfront surgery was 28 months, compared to 15 months in patients treated with neoadjuvant approach (p = 0.04). Most patients that did not undergo surgery have decline of performance status or disease progression on neoadjuvant treatment. On multivariable analysis in pancreatic cancer stages I and II, including age, sex, borderline or resectable disease, CA 19–9, positive lymph nodes and neoadjuvant treatment, the surgery was the only factor associated with improved overall survival (p = 0.04). Upfront surgery should still be considered a standard of care approach for resectable pancreatic cancer. Biomarker driven studies and randomized trials with combination therapies are necessary to address neoadjuvant chemotherapy and delaying surgery in purely resectable pancreatic cancer.
Spin revolution breaks time reversal symmetry of rolling magnets
Authors: Vedmedenko Elena Y. , Wiesendanger Roland
Published: August 2022

The classical laws of physics are usually invariant under time reversal. Here, we reveal a novel class of magnetomechanical effects rigorously breaking time-reversal symmetry. These effects are based on the mechanical rotation of a hard magnet around its magnetization axis in the presence of friction and an external magnetic field, which we call spin revolution. The spin revolution leads to a variety of symmetry breaking phenomena including upward propulsion on vertical surfaces defying gravity as well as magnetic gyroscopic motion that is perpendicular to the applied force. The angular momentum of spin revolution differs from those of the magnetic field, the magnetic torque, the rolling axis, and the net torque about the rolling axis. The spin revolution emerges spontaneously, without external rotations, and offers various applications in areas such as magnetism, robotics and energy harvesting.
Transcriptional dynamics of colorectal cancer risk associated variation at 11q23.1 correlate with tuft cell abundance and marker expression in silico
Authors: Harris Bradley T. , Rajasekaran Vidya , Blackmur James P. , O’Callaghan Alan , Donnelly Kevin , Timofeeva Maria , Vaughan-Shaw Peter G. , Din Farhat V. N. , Dunlop Malcolm G. , Farrington Susan M.
Published: August 2022

Colorectal cancer (CRC) is characterised by heritable risk that is not well understood. Heritable, genetic variation at 11q23.1 is associated with increased colorectal cancer (CRC) risk, demonstrating eQTL effects on 3 cis- and 23 trans-eQTL targets. We sought to determine the relationship between 11q23.1 cis- and trans-eQTL target expression and test for potential cell-specificity. scRNAseq from 32,361 healthy colonic epithelial cells was aggregated and subject to weighted gene co-expression network analysis (WGCNA). One module (blue) included 19 trans-eQTL targets and was correlated withPOU2AF2expression only. Following unsupervised clustering of single cells, the expression of 19 trans-eQTL targets was greatest and most variable in cluster number 11, which transcriptionally resembled tuft cells. 14 trans-eQTL targets were found to demarcate this cluster, 11 of which were corroborated in a second dataset. Intra-cluster WGCNA and module preservation analysis then identified twelve 11q23.1 trans-eQTL targets to comprise a network that was specific to cluster 11. Finally, linear modelling and differential abundance testing showed 11q23.1 trans-eQTL target expression was predictive of cluster 11 abundance. Our findings suggest 11q23.1 trans-eQTL targets comprise aPOU2AF2-related network that is likely tuft cell-specific and reduced expression of these genes correlates with reduced tuft cell abundance in silico.
Drinking hydrogen water improves photoreceptor structure and function in retinal degeneration 6 mice
Authors: Igarashi Tsutomu , Ohsawa Ikuroh , Kobayashi Maika , Miyazaki Kai , Igarashi Toru , Kameya Shuhei , Shiozawa Asaka Lee , Ikeda Yasuhiro , Miyagawa Yoshitaka , Sakai Mashito , Okada Takashi , Sakane Iwao , Takahashi Hiroshi
Published: August 2022

Retinitis pigmentosa (RP) is a genetically heterogeneous group of inherited retinal disorders involving the progressive dysfunction of photoreceptors and the retinal pigment epithelium, for which there is currently no treatment. The rd6 mouse is a natural model of autosomal recessive retinal degeneration. Given the known contributions of oxidative stress caused by reactive oxygen species (ROS) and selective inhibition of potent ROS peroxynitrite and OH·by H2 gas we have previously demonstrated, we hypothesized that ingestion of H2 water may delay the progression of photoreceptor death in rd6 mice. H2 mice showed significantly higher retinal thickness as compared to controls on optical coherence tomography. Histopathological and morphometric analyses revealed higher thickness of the outer nuclear layer for H2 mice than controls, as well as higher counts of opsin red/green-positive cells. RNA sequencing (RNA-seq) analysis of differentially expressed genes in the H2 group versus control group revealed 1996 genes with significantly different expressions. Gene and pathway ontology analysis showed substantial upregulation of genes responsible for phototransduction in H2 mice. Our results show that drinking water high in H2 (1.2–1.6 ppm) had neuroprotective effects and inhibited photoreceptor death in mice, and suggest the potential of H2 for the treatment of RP.
Research on collapse ultimate load of fabricated reinforced concrete column and steel beam composite frame structure
Authors: Liu Youquan , Xiong Jingang , Wen Jiancong , Xiong Moqiang
Published: August 2022

In this work, the collapse ultimate load of a prefabricated reinforced concrete column–steel beam composite frame structure was studied. During the study, the “new RCS beam-to-column joint” was used as the beam-to-column connection in the experimental model. Further, the half-scale fabricated RCS space frame structure (2-story, 1 × 2 bay) was subjected to instantaneous failure experiments twice at the bottom of the side column under various load levels and the 2A column was quickly pulled out by the traction force of the vehicle. The experimental results demonstrated that the method of dismantling the failure column provided a relatively true response to the condition of progressive collapse. The remaining RCS structure was found to be in the elastic stage during various load level tests. Moreover, the displacement time history curve did not have a vibration phenomenon during the first experimentation. The SAP2000 finite element program was used to verify that the test results were similar to that of the numerical simulation results, and it was further explored and found that the collapse ultimate load value was 10.25 times the structure design load value.
Synthesis of vacant graphitic carbon nitride in argon atmosphere and its utilization for photocatalytic hydrogen generation
Authors: Praus Petr , Řeháčková Lenka , Čížek Jakub , Smýkalová Aneta , Koštejn Martin , Pavlovský Jiří , Filip Edelmannová Miroslava , Kočí Kamila
Published: August 2022

Graphitic carbon nitride (C3N4) was synthesised from melamine at 550 °C for 4 h in the argon atmosphere and then was reheated for 1–3 h at 500 °C in argon. Two band gaps of 2.04 eV and 2.47 eV were observed in all the synthetized materials. Based on the results of elemental and photoluminescence analyses, the lower band gap was found to be caused by the formation of vacancies. Specific surface areas of the synthetized materials were 15–18 m2g−1 indicating that no thermal exfoliation occurred. The photocatalytic activity of these materials was tested for hydrogen generation. The best photocatalyst showed 3 times higher performance (1547 μmol/g) than bulk C3N4 synthetized in the air (547 μmol/g). This higher activity was explained by the presence of carbon (VC) and nitrogen (VN) vacancies grouped in their big complexes 2VC + 2VN (observed by positron annihilation spectroscopy). The effect of an inert gas on the synthesis of C3N4 was demonstrated using Graham´s law of ammonia diffusion. This study showed that the synthesis of C3N4 from nitrogen-rich precursors in the argon atmosphere led to the formation of vacancy complexes beneficial for hydrogen generation, which was not referred so far.
Longitudinal association of atopic dermatitis progression and keratin 6A
Authors: Zhu Angela Y. , Mitra Nandita , Margolis David J.
Published: August 2022

Atopic dermatitis is a common skin disease characterized by loss of skin integrity. Risk and severity have been associated with genetic variation especially with respect to the filaggrin gene, suggesting the importance of skin barrier function in atopic dermatitis pathogenesis. The keratin protein plays a role in epithelial health but its relationship with disease severity would benefit from further exploration. In this study, we evaluate the association between common keratin 6 variants and severity of atopic dermatitis over time using a Bayesian generalized linear mixed model to account for repeated measures. We identify groups of variants within which individual variants have similar effects on skin repair. Further assessment of the biological mechanisms by which these contribute to repair of epidermis may inform treatment of atopic dermatitis.
Effectiveness of splitter plate to control fluid forces on a circular obstacle in a transient flow: FEM computations
Authors: Ain Qurrat ul , Mahmood Rashid , Awrejcewicz Jan , Siddique Imran , Majeed Afraz Hussain , Pawłowski Witold
Published: August 2022

The reliability of the usage of a splitter plate (passive control device) downstream of the obstacle, in suppressing the fluid forces on a circular obstacle of diameter$$D = 0.1\;\;{\text{m}}$$D=0.1mis studied in this paper. The first parameter of the current study is the attachment of a splitter plate of various lengths$$(L_{i} )$$(Li)with the obstacle, whereas the gap separation$$(G_{i} )$$(Gi)between the splitter plate and the obstacle, is used as a second parameter. The control elements of the first and second parameters are varied from$$0.1$$0.1to$$0.3$$0.3. For the attached splitter plates of lengths$$0.2$$0.2and$$0.3$$0.3, the oscillatory behavior of transient flow at$$Re = 100$$Re=100is successfully controlled. For the gap separation,$$0.1$$0.1and$$0.2$$0.2similar results are obtained. However, it is observed that a splitter plate of too short length and a plate located at the inappropriate gap from the obstacle, are worthless. A computational strategy based on the finite element method is utilized due to the complicated representative equations. For a clear physical depiction of the problem, velocity and pressure plots have been provided. Drag and lift coefficients the hydrodynamic benchmark values are also evaluated in a graphical representation surrounding the obstacle’s peripheral surface as well as the splitter plate. In a conclusion, a splitter plate can function to control fluid forces whether it is attached or detached, based on plate length and gap separation between obstacle and plate, respectively.
Clinical staging and genetic profiling of Korean patients with primary lymphedema using targeted gene sequencing
Authors: Seo Soo Hyun , Lee Seungjun , Park Joseph Kyu-hyung , Yang Eun Joo , Kim Boram , Lee Jee-Soo , Kim Man Jin , Park Sung Sup , Seong Moon-Woo , Nam Sun-Young , Heo Chan-Yeong , Myung Yujin
Published: August 2022

Lymphedema is a progressive disease caused by lymphatic flow blockage in the lymphatic pathway. Primary (hereditary) lymphedema is caused by genetic mutations without secondary causes. We performed clinical profiling on Korean primary lymphedema patients based on their phenotypes using lymphoscintigraphy and made genetic diagnoses using a next-generation sequencing panel consisting of 60 genes known to be related to primary lymphedema and vascular anomalies. Of 27 patients included in this study, 14.8% of the patients had lymphedema of the upper extremities, 77.8% had lymphedema of the lower extremities and 7.4% had 4-limbs lymphedema. Based on the International Society of Lymphology staging, 14, 10, and 3 patients had stage 3, 2, and 1 lymphedema, respectively. Only one family was genetically confirmed to harbor likely pathogenic variants in CELSR1. The proband was carrying two likely pathogenic variants in CELSR1, while her symptomatic mother was confirmed to carry only one of the variants. Furthermore, two other variants of uncertain significance in CELSR1 were detected in other patients, making CELSR1 the most commonly altered gene in our study. The clinical and genetic profile of hereditary lymphedema reported here is the first such data series reported for South Korea.
A non-invasive system to monitor in vivo neural graft activity after spinal cord injury
Authors: Ago Kentaro , Nagoshi Narihito , Imaizumi Kent , Kitagawa Takahiro , Kawai Momotaro , Kajikawa Keita , Shibata Reo , Kamata Yasuhiro , Kojima Kota , Shinozaki Munehisa , Kondo Takahiro , Iwano Satoshi , Miyawaki Atsushi , Ohtsuka Masanari , Bito Haruhiko , Kobayashi Kenta , Shibata Shinsuke , Shindo Tomoko , Kohyama Jun , Matsumoto Morio , Nakamura Masaya , Okano Hideyuki
Published: August 2022

Expectations for neural stem/progenitor cell (NS/PC) transplantation as a treatment for spinal cord injury (SCI) are increasing. However, whether and how grafted cells are incorporated into the host neural circuit and contribute to motor function recovery remain unknown. The aim of this project was to establish a novel non-invasive in vivo imaging system to visualize the activity of neural grafts by which we can simultaneously demonstrate the circuit-level integration between the graft and host and the contribution of graft neuronal activity to host behaviour. We introduced Akaluc, a newly engineered luciferase, under the control of enhanced synaptic activity-responsive element (E-SARE), a potent neuronal activity-dependent synthetic promoter, into NS/PCs and engrafted the cells into SCI model mice. Through the use of this system, we found that the activity of grafted cells was integrated with host behaviour and driven by host neural circuit inputs. This non-invasive system is expected to help elucidate the therapeutic mechanism of cell transplantation treatment for SCI.
3D printed heterogeneous hybrid hydrogel scaffolds for sequential tumor photothermal-chemotherapy and wound healing
Authors: Xu Langtao , Chen You , Zhang Peng , Tang Junjie , Xue Yifan , Luo Hongsheng , Dai Rui , Jin Jinlong , Liu Jie
Published: August 2022

A 3D printed heterogeneous hybrid hydrogel scaffold was fabricated for sequential tumor photothermal-chemotherapy and wound healing, which could be a potential technique for preventing tumor recurrence and promoting wound healing following surgery.
Solar energy-driven electrolysis with molecular catalysts for the reduction of carbon dioxide coupled with the oxidation of 5-hydroxymethylfurfural
Authors: Yang Zhi-Wen , Chen Jin-Mei , Qiu Li-Qi , Xie Wen-Jun , He Liang-Nian
Published: August 2022

The electrocatalytic reduction of CO2coupled with the oxidation of 5-hydroxymethylfurfural in a single cell based on molecular catalysts was successfully conducted with high faradaic efficiency, which could successfully be driven by solar energy.