bluuebunny/crossref_metadata_2025 huggingface dataset:
On Internal Tides Driving Residual Currents and Upwelling on an Island
Authors: Rogers Justin S. , Mayer Frederick T. , Davis Kristen A. , Fringer Oliver B.
Published: June 2022

We present a modeling study of an idealized island with sloping sides in a stratified ocean with internal tides propagating through the domain, which transform into nonlinear internal waves as they encounter shallow depths. In the base condition, representative of a mid‐latitude island with relatively steep super critical slopes, the nonlinear internal waves shoaling on the island wrap around the island, scatter, and create an asymmetric wavefield. Radiation stress gradients from this wavefield and rotation are balanced by pressure gradients and turbulent vertical diffusion in the momentum equations which drive residual mean currents around the island. We explore the effects of different physical parameters including no rotation, higher Froude number, subcritical slope, addition of barotropic tides, larger excursion number, and addition of large‐scale mean currents. All simulations showed formation of residual currents of varying intensity, upwelled deep waters in shallow regions, and cooler waters on the side of the island consistent with the direction of incoming internal tides. While the no rotation and strong mean flow conditions created some upwelling, of all the modeled conditions, the subcritical slope has the greatest potential for creating favorable conditions for benthic organisms through enhanced upwelling. Areas of the world's oceans with stratified waters sufficient to sustain internal tide motions, strong internal tide energy, and local subcritical bottom slopes are likely to have cooler waters and more upwelled deep waters than the surrounding areas, and potentially serve as thermal refugia from future ocean warming.
Benthic Carbon Remineralization and Iron Cycling in Relation to Sea Ice Cover Along the Eastern Continental Shelf of the Antarctic Peninsula
Authors: Baloza M. , Henkel S. , Geibert W. , Kasten S. , Holtappels M.
Published: June 2022

Rapid and profound climatic and environmental changes have been predicted for the Antarctic Peninsula with so far unknown impact on the biogeochemistry of the continental shelves. In this study, we investigate benthic carbon sedimentation, remineralization and iron cycling using sediment cores retrieved on a 400 mile transect with contrasting sea ice conditions along the eastern shelf of the Antarctic Peninsula. Sediments at comparable water depths of 330–450 m showed sedimentation and remineralization rates of organic carbon, ranging from 2.5 to 13 and 1.8–7.2 mmol C m−2 d−1, respectively. Both rates were positively correlated with the occurrence of marginal sea ice conditions (5%–35% ice cover) along the transect, suggesting a favorable influence of the corresponding light regime and water column stratification on algae growth and sedimentation rates. From south to north, the burial efficiency of organic carbon decreased from 58% to 27%, while bottom water temperatures increased from −1.9 to −0.1°C. Net iron reduction rates, as estimated from pore‐water profiles of dissolved iron, were significantly correlated with carbon degradation rates and contributed 0.7%–1.2% to the total organic carbon remineralization. Tightly coupled phosphate‐iron recycling was indicated by significant covariation of dissolved iron and phosphate concentrations, which almost consistently exhibited P/Fe flux ratios of 0.26. Iron efflux into bottom waters of 0.6–4.5 μmol Fe m−2 d−1 was estimated from an empirical model. Despite the deep shelf waters, a clear bentho‐pelagic coupling is indicated, shaped by the extent and duration of marginal sea ice conditions during summer, and likely to be affected by future climate change.
High‐Resolution Thermophysical Analysis of the OSIRIS‐REx Sample Site and Three Other Regions of Interest on Bennu
Authors: Rozitis B. , Ryan A. J. , Emery J. P. , Nolan M. C. , Green S. F. , Christensen P. R. , Hamilton V. E. , Daly M. G. , Barnouin O. S. , Lauretta D. S.
Published: June 2022

The OSIRIS‐REx (Origins, Spectral Interpretation, Resource Identification, and Security–Regolith Explorer) spacecraft sampled asteroid (101955) Bennu on 20 October 2020 and will return the collected regolith to Earth in 2023. Before sample collection, spectral observations of four regions of interest on Bennu's surface were acquired at high spatial resolution (2–9 m per spectrometer spot) to identify the most suitable site for sampling and provide contextual information for the returned sample. In this study, we investigate thermal‐infrared (6–50 μm) observations of these four regions, including the site that OSIRIS‐REx ultimately sampled, using the Advanced Thermophysical Model with input digital terrain models derived from laser altimetry. From model‐to‐measurement comparisons, we find that the observed brightness temperatures depend strongly on small‐scale topography, local variations in thermal inertia, and the observation phase angle. Thermal inertia mapping reveals spatial variations that distinguish the different boulder types found on Bennu. A boulder bearing carbonate veins has higher thermal inertia than average, suggesting that cementation processes reduced its porosity. The thermal inertia of the site sampled is 190 ± 30 J m−2 K−1 s−1/2, which is consistent with observations of a fine‐grained regolith mixed with porous rocks. Thermophysical modeling of the site sampled predicts that the maximum temperatures experienced by the collected sample while on Bennu were 357 ± 3 and 261 ± 3 K for the surface and 50 cm depth, respectively. We predict that OSIRIS‐REx will return a sample with thermophysical properties unique from those of meteorites.
Antecedent Topography and Sediment Dispersal: The Influence of Geologically Instantaneous Events on Basin Fill Patterns
Authors: Sincavage Ryan , Liang Man , Pickering Jennifer , Goodbred Steven , Passalacqua Paola
Published: June 2022

Favorable topographic gradients and channel bed aggradation are often cited as primers for river channel avulsion. Sylhet Basin in Bangladesh subsides relatively rapidly and presents a topographically favorable channel course for the Brahmaputra River. Holocene occupations of this region remained routed along the basin's western margin, depositing tens of meters of amalgamated channel sands but leaving the central basin under‐filled. The localized backwater effect from a seasonal lake that forms in Sylhet Basin, referred to as a “hydraulic barrier,” has been proposed as a mechanism for keeping the channel pinned to the western margin. Using a 1‐D channel profile model and a 2‐D depth‐averaged hydrodynamic model, we test the preferred flow path between two possible channel courses under a range of physical conditions. Results show that the hydraulic barrier interpretation is implausible unless water depths are increased beyond the physical dimensions of Sylhet Basin. Reducing topographic slope along the two pathways does not sufficiently enhance the local backwater to steer the channel to the basin center. Only the introduction of a scoured antecedent channel along the western margin induces a strong preference for bypass of the central basin. These results corroborate field evidence that Holocene outburst floods scoured a paleochannel that became the preferred course for the Brahmaputra within Sylhet Basin in the mid to late Holocene. We conclude that modification of basin topography by large, infrequent flood events can exert a persistent influence on channel steering that is comparable to previously documented effects of monsoon variability and tectonic deformation.
Reclamation of Tidal Flats Within Tidal Basins Alters Centennial Morphodynamic Adaptation to Sea‐Level Rise
Authors: Guo Leicheng , Zhu Chunyan , Xu Fan , Xie Weiming , van der Wegen Mick , Townend Ian , Wang Zheng Bing , He Qing
Published: June 2022

Reclamation of low‐lying tidal flats and floodplains adjacent to present shorelines has been implemented worldwide for both coastal defense and development. While it is technically feasible to monitor the short‐term impact of tidal flat embankments, it is challenging to identify long‐term and cumulative morphodynamic impact, particularly considering centennial sea‐level rise (SLR). In this study, we construct a process‐based hydro‐morphodynamic model for a schematized tidal basin and examine its morphodynamic evolution under the combined influence of SLR and tidal flat embankments. We see that rising sea levels lead to inundation of low‐lying floodplains just above high water, creating new intertidal flats that mitigate the drowning impact of SLR. This mitigation effect is lost if the low‐lying floodplains and tidal flats are reclaimed, preventing any shoreline migration under SLR. Removing a large portion of intertidal flats within the tidal basin induces significant changes in basin hypsometry and potentially, a reversal of flood/ebb dominance. The resulting hydro‐morphodynamic impact of large‐scale tidal flat embankment is more significant than SLR at a centennial time scale. This suggests a need for much greater management awareness regarding the cumulative impact of human activities. These findings imply that allowing lateral shoreline migration under SLR sustains tidal basin's inherent morphodynamic buffering capacity, whereas reclaiming tidal flats significantly alters hydro‐morphodynamic adaptation at the decadal to centennial time scales. It highlights the importance of conserving low‐lying floodplains and tidal flats in tide‐dominated systems to counteract the drowning impact of SLR.
Modeling Spatial Distribution of Carbon Sequestration, CO2 Absorption, and O2 Production in an Urban Area: Integrating Ground‐Based Data, Remote Sensing Technique, and GWR Model
Authors: Khodakarami Loghman , Pourmanafi Saeid , Soffianian Ali Reza , Lotfi Ali
Published: June 2022

The main purpose of this research is to model the spatial distribution of carbon sequestration, CO2 absorption, and oxygen production by trees within Isfahan city, Iran, in 2020. To quantify carbon sequestration, we accessed a sample group of trees with measured biophysical attributes. First, we calculated the biomass and carbon sequestration of a tree using the allometric and photosynthesis equations. Then, to model the spatial distribution of carbon sequestration, we used geographic weighted regression (GWR) method. In this model, the amount of calculated carbon sequestration was the dependent variable, whereas the difference between vegetation indexes of Excess Green Plant Index minus Excess Red Plant Index (ΔExGR) from the Worldview image was the independent variable. Subsequently, the spatial distribution map of CO2 absorption and oxygen production was generated. The total value of annual carbon sequestration, CO2 absorption, and O2 production was about 7704.22, 28274.502, and 20570.16 tons, respectively. The results showed that there was a strong correlation between the ΔExGR index of the canopy with calculated carbon. Integrating the ΔExGR index from a high‐resolution image with calculated carbon can contribute to developing a fast, accurate, and low‐cost method in estimating carbon sequestration and modeling its spatial distribution in urban areas. In conclusion, the results of this research can be implemented by land‐use planners to integrate urban ecosystem service concept (i.e., carbon sequestration) in planning process toward sustainability of the cities.
Reevaluating Ecosystems on the Basis of Climate Change Vulnerability
Authors: Padmanaban Deepa
Published: June 2022

Climate change elevates the risk category of ecosystems across the United States, a new study finds.
After GRExit: Reducing Bias in Geoscience Graduate Admissions
Authors: Cooke Michele , Baranes Hannah , Casta�eda Isla , Woodruff Jonathan , Boutt David
Published: June 2022

Dropping the GRE is just a first step toward holistic admissions. To further reduce bias in applicant evaluations, the UMass-Amherst geosciences program has changed the way it assesses students.
Contrasting Volcanic Deformation in Arc and Ocean Island Settings Due To Exsolution of Magmatic Water
Authors: Yip Stanley Tze Hou , Biggs Juliet , Edmonds Marie , Liggins Philippa , Shorttle Oliver
Published: June 2022

Two of the most widely observed co‐eruptive volcanic phenomena—Ground deformation and volcanic outgassing—Are fundamentally linked via the mechanism of magma degassing and the development of compressibility, which controls how the volume of magma changes in response to a change in pressure. Here we use thermodynamic models—Constrained by petrological data—To reconstruct volatile exsolution and the consequent changes in magma properties. We use the fraction of SO2 exsolved during decompression to predict co‐eruptive SO2 flux and magma compressibility to predict co‐eruptive surface deformation (both normalized by erupted volume). We conduct sensitivity tests using properties of typical basalts to assess how varying magma volatile content, crustal properties, and chamber geometry affect co‐eruptive deformation and degassing. We find that magmatic H2O content has the most impact on both SO2 flux and volume change. Our findings have general implications for typical basaltic systems in arc and ocean island settings. The higher water content of arc magmas makes them more compressible than ocean island magmas and leads to muted or non‐existent deformation being observed during arc eruptions. Our models are consistent with observation: Deformation has been detected during 48% of basaltic eruptions in ocean island settings (16/33) during the satellite era (2005–2020), but only 11% of basaltic eruptions in arc settings (7/61).
Illuminating the Motions of Jupiter's Auroral Dawn Storms
Authors: Rutala M. J. , Clarke J. T. , Mullins J. D. , Nichols J. D.
Published: June 2022

Jupiter's auroral main emission (ME) has long been considered to be the result of currents keeping plasma corotating with the surrounding magnetosphere. As a result, the ME corotates with the planet, and individual auroral features making up the ME roughly follow suit. Jupiter's dawn storms, some of the rarest and brightest auroral features within the ME, are an exception, as they do not corotate but instead remain fixed near local dawn. The causes of this enigmatic motion are not fully understood. To test the significance of this motion, we have developed a process to identify auroral features and measure their degree of corotational motion, including dawn storms, in archival Hubble Space Telescope images of the Jovian ultraviolet aurorae. We compare motions of features inside and outside the dawn sector, characterizing the exact motions of dawn storms and providing context for these motions for the first time. In keeping with previous studies, we expected to identify features fixed near local dawn in 10% of observations; instead, we find that half of all features near local dawn lag corotation. We show that subcorotating dawn emissions are far more common than previously thought, and that the drivers of this motion must be similarly common. Corotational motion must be considered when identifying the processes driving all dawn aurorae, including the dawn storms. We explore the consistency of this result with various theories of dawn ME formation and propose that aspects of the known current system relating to the Sun‐Jupiter geometry can explain this behavior.
Evolved Gas Analyses of Sedimentary Rocks From the Glen Torridon Clay‐Bearing Unit, Gale Crater, Mars: Results From the Mars Science Laboratory Sample Analysis at Mars Instrument Suite
Authors: McAdam A. C. , Sutter B. , Archer P. D. , Franz H. B. , Wong G. M. , Lewis J. M. T. , Clark J. V. , Millan M. , Williams A. J. , Eigenbrode J. L. , Knudson C. A. , Freissinet C. , Glavin D. P. , Stern J. C. , Navarro‐González R. , Achilles C. N. , Ming D. W. , Morris R. V. , Bristow T. F. , Rampe E. B. , Thorpe M. T. , House C. H. , Andrejkovičová S. , Bryk A. B. , Fox V. K. , Johnson S. S. , Mahaffy P. R. , Malespin C. A.
Published: June 2022

Evolved gas analysis (EGA) data from the Sample Analysis at Mars (SAM) instrument suite indicated Fe‐rich smectite, carbonate, oxidized organics, Fe/Mg sulfate, and chloride in sedimentary rocks from the Glen Torridon (GT) region of Gale crater that displayed phyllosilicate spectral signatures from orbit. SAM evolved H2O data indicated that the primary phyllosilicate in all GT samples was an Fe‐rich dioctahedral smectite (e.g., nontronite) with lesser amounts of a phyllosilicate such as mixed layer talc‐serpentine or greenalite‐minnesotaite. CO2 data supported the identification of siderite in several samples, and CO2 and CO data was also consistent with trace oxidized organic compounds such as oxalate salts. SO2 data indicated trace and/or amorphous Fe sulfates in all samples and one sample may contain Fe sulfides. SO2 data points to significant Mg sulfates in two samples, and lesser amounts in several other samples. A lack of evolved O2 indicated the absence of oxychlorine salts and Mn3+/Mn4+ oxides. The lack of, or very minor, evolved NO revealed absent or very trace nitrate/nitrite salts. HCl data suggested chloride salts in GT samples. Constraints from EGA data on mineralogy and chemistry indicated that the environmental history of GT involved alteration with fluids of variable redox potential, chemistry and pH under a range of fluid‐to‐rock ratio conditions. Several of the fluid episodes could have provided habitable environmental conditions and carbon would have been available to any past microbes though the lack of significant N could have been a limiting factor for microbial habitability in the GT region.
Association of day-of-injury plasma glial fibrillary acidic protein concentration and six-month posttraumatic stress disorder in patients with mild traumatic brain injury
Authors: Kulbe Jacqueline R. , Jain Sonia , Nelson Lindsay D. , Korley Frederick K. , Mukherjee Pratik , Sun Xiaoying , Okonkwo David O. , Giacino Joseph T. , Vassar Mary J. , Robertson Claudia S. , McCrea Michael A. , Wang Kevin K. W. , Temkin Nancy , Mac Donald Christine L. , Taylor Sabrina R. , Ferguson Adam R. , Markowitz Amy J. , Diaz-Arrastia Ramon , Manley Geoffrey T. , Stein Murray B. ,   TRACK-TBI Investigators, Badjatia Neeraj , Duhaime Ann-Christine , Feeser V. Ramana , Keene C. Dirk , Madden Christopher , Merchant Randall , Puccio Ava , Schnyer David , Taylor Sabrina R. , Valadka Alex , Yue John K. , Yuh Esther L. , Zafonte Ross
Published: June 2022

Several proteins have proven useful as blood-based biomarkers to assist in evaluation and management of traumatic brain injury (TBI). The objective of this study was to determine whether two day-of-injury blood-based biomarkers are predictive of posttraumatic stress disorder (PTSD). We used data from 1143 individuals with mild TBI (mTBI; defined as admission Glasgow Coma Scale [GCS] score 13–15) enrolled in TRACK-TBI, a prospective longitudinal study of level 1 trauma center patients. Plasma glial fibrillary acidic protein (GFAP) and serum high sensitivity C-reactive protein (hsCRP) were measured from blood collected within 24 h of injury. Two hundred and twenty-seven (19.9% of) patients had probable PTSD (PCL-5 score ≥ 33) at 6 months post-injury. GFAP levels were positively associated (Spearman’s rho = 0.35, p < 0.001) with duration of posttraumatic amnesia (PTA). There was an inverse association between PTSD and (log)GFAP (adjusted OR = 0.85, 95% CI 0.77–0.95 per log unit increase) levels, but no significant association with (log)hsCRP (adjusted OR = 1.11, 95% CI 0.98–1.25 per log unit increase) levels. Elevated day-of-injury plasma GFAP, a biomarker of glial reactivity, is associated with reduced risk of PTSD after mTBI. This finding merits replication and additional studies to determine a possible neurocognitive basis for this relationship.
The TIP60-ATM axis regulates replication fork stability in BRCA-deficient cells
Authors: Schleicher Emily M. , Dhoonmoon Ashna , Jackson Lindsey M. , Khatib Jude B. , Nicolae Claudia M. , Moldovan George-Lucian
Published: June 2022

Maintenance of replication fork stability is essential for genome preservation. Stalled replication forks can be reversed by translocases such as SMARCAL1, and unless protected through the activity of the BRCA pathway, are subsequently subjected to nucleolytic degradation. The ATM and ATR kinases are master regulators of the DNA damage response. ATM activation upon DNA damage is mediated by the acetyltransferase TIP60. Here, we show that the TIP60-ATM pathway promotes replication fork reversal by recruiting SMARCAL1 to stalled forks. This enables fork degradation in BRCA-deficient cells. We also show that this ATM activity is not shared by ATR. Moreover, we performed a series of genome-wide CRISPR knockout genetic screens to identify genetic determinants of the cellular sensitivity to ATM inhibition in wildtype and BRCA2-knockout cells, and validated the top hits from multiple screens. We provide a valuable list of common genes which regulate the response to multiple ATM inhibitors. Importantly, we identify a differential response of wildtype and BRCA2-deficient cells to these inhibitors. In BRCA2-knockout cells, DNA repair genes (including RAD17, MDC1, and USP28) were essential for survival upon ATM inhibitor treatment, which was not the case in wild-type cells. These findings may eventually help guide the way for rational deployment of ATM inhibitors in the clinic.
Dynamic metabolic interactions and trophic roles of human gut microbes identified using a minimal microbiome exhibiting ecological properties
Authors: Shetty Sudarshan A , Kostopoulos Ioannis , Geerlings Sharon Y , Smidt Hauke , de Vos Willem M , Belzer Clara
Published: June 2022

Microbe–microbe interactions in the human gut are influenced by host-derived glycans and diet. The high complexity of the gut microbiome poses a major challenge for unraveling the metabolic interactions and trophic roles of key microbes. Synthetic minimal microbiomes provide a pragmatic approach to investigate their ecology including metabolic interactions. Here, we rationally designed a synthetic microbiome termed Mucin and Diet based Minimal Microbiome (MDb-MM) by taking into account known physiological features of 16 key bacteria. We combined 16S rRNA gene-based composition analysis, metabolite measurements and metatranscriptomics to investigate community dynamics, stability, inter-species metabolic interactions and their trophic roles. The 16 species co-existed in the in vitro gut ecosystems containing a mixture of complex substrates representing dietary fibers and mucin. The triplicate MDb-MM’s followed the Taylor’s power law and exhibited strikingly similar ecological and metabolic patterns. The MDb-MM exhibited resistance and resilience to temporal perturbations as evidenced by the abundance and metabolic end products. Microbe-specific temporal dynamics in transcriptional niche overlap and trophic interaction network explained the observed co-existence in a competitive minimal microbiome. Overall, the present study provides crucial insights into the co-existence, metabolic niches and trophic roles of key intestinal microbes in a highly dynamic and competitive in vitro ecosystem.
Early-life stress exposure and large-scale covariance brain networks in extremely preterm-born infants
Authors: Lammertink Femke , van den Heuvel Martijn P. , Hermans Erno J. , Dudink Jeroen , Tataranno Maria L. , Benders Manon J. N. L. , Vinkers Christiaan H.
Published: June 2022

The stressful extrauterine environment following premature birth likely has far-reaching and persistent adverse consequences. The effects of early “third-trimester” ex utero stress on large-scale brain networks’ covariance patterns may provide a potential avenue to understand how early-life stress following premature birth increases risk or resilience. We evaluated the impact of early-life stress exposure (e.g., quantification of invasive procedures) on maturational covariance networks (MCNs) between 30 and 40 weeks of gestational age in 180 extremely preterm-born infants (<28 weeks of gestation; 43.3% female). We constructed MCNs using covariance of gray matter volumes between key nodes of three large-scale brain networks: the default mode network (DMN), executive control network (ECN), and salience network (SN). Maturational coupling was quantified by summating the number of within- and between-network connections. Infants exposed to high stress showed significantly higher SN but lower DMN maturational coupling, accompanied by DMN-SN decoupling. Within the SN, the insula, amygdala, and subthalamic nucleus all showed higher maturational covariance at the nodal level. In contrast, within the DMN, the hippocampus, parahippocampal gyrus, and fusiform showed lower coupling following stress. The decoupling between DMN-SN was observed between the insula/anterior cingulate cortex and posterior parahippocampal gyrus. Early-life stress showed longitudinal network-specific maturational covariance patterns, leading to a reprioritization of developmental trajectories of the SN at the cost of the DMN. These alterations may enhance the ability to cope with adverse stimuli in the short term but simultaneously render preterm-born individuals at a higher risk for stress-related psychopathology later in life.
Designed Ankyrin Repeat Proteins as a tool box for analyzing p63
Authors: Strubel Alexander , Münick Philipp , Chaikuad Apirat , Dreier Birgit , Schaefer Jonas , Gebel Jakob , Osterburg Christian , Tuppi Marcel , Schäfer Birgit , Knapp Stefan , Plückthun Andreas , Dötsch Volker
Published: June 2022

The function of the p53 transcription factor family is dependent on several folded domains. In addition to a DNA-binding domain, members of this family contain an oligomerization domain. p63 and p73 also contain a C-terminal Sterile α-motif domain. Inhibition of most transcription factors is difficult as most of them lack deep pockets that can be targeted by small organic molecules. Genetic knock-out procedures are powerful in identifying the overall function of a protein, but they do not easily allow one to investigate roles of individual domains. Here we describe the characterization of Designed Ankyrin Repeat Proteins (DARPins) that were selected as tight binders against all folded domains of p63. We determine binding affinities as well as specificities within the p53 protein family and show that DARPins can be used as intracellular inhibitors for the modulation of transcriptional activity. By selectively inhibiting DNA binding of the ΔNp63α isoform that competes with p53 for the same promoter sites, we show that p53 can be reactivated. We further show that inhibiting the DNA binding activity stabilizes p63, thus providing evidence for a transcriptionally regulated negative feedback loop. Furthermore, the ability of DARPins to bind to the DNA-binding domain and the Sterile α-motif domain within the dimeric-only and DNA-binding incompetent conformation of TAp63α suggests a high structural plasticity within this special conformation. In addition, the developed DARPins can also be used to specifically detect p63 in cell culture and in primary tissue and thus constitute a very versatile research tool for studying the function of p63.
Implementation of a combined CDK inhibition and arginine-deprivation approach to target arginine-auxotrophic glioblastoma multiforme cells
Authors: Riess Christin , del Moral Katharina , Fiebig Adina , Kaps Philipp , Linke Charlotte , Hinz Burkhard , Rupprecht Anne , Frank Marcus , Fiedler Tomas , Koczan Dirk , Troschke-Meurer Sascha , Lode Holger N. , Engel Nadja , Freitag Thomas , Classen Carl Friedrich , Maletzki Claudia
Published: June 2022

Constitutive activation of cyclin-dependent kinases (CDKs) or arginine auxotrophy are hallmarks of Glioblastoma multiforme (GBM). The latter metabolic defect renders tumor cells vulnerable to arginine-depleting substances, such as arginine deiminase from Streptococcus pyogenes (SpyADI). Previously, we confirmed the susceptibility of patient-derived GBM cells towards SpyADI as well as CDK inhibitors (CDKis). To improve therapeutic effects, we here applied a combined approach based on SpyADI and CDKis (dinaciclib, abemaciclib). Three arginine-auxotrophic patient-derived GBM lines with different molecular characteristics were cultured in 2D and 3D and effects of this combined SpyADI/CDKi approach were analyzed in-depth. All CDKi/SpyADI combinations yielded synergistic antitumoral effects, especially when given sequentially (SEQ), i.e., CDKi in first-line and most pronounced in the 3D models. SEQ application demonstrated impaired cell proliferation, invasiveness, and viability. Mitochondrial impairment was demonstrated by increasing mitochondrial membrane potential and decreasing oxygen consumption rate and extracellular acidification rate after SpyADI/abemaciclib monotherapy or its combination regimens. The combined treatment even induced autophagy in target cells (abemaciclib/SpyADI > dinaciclib/SpyADI). By contrast, the unfolded protein response and p53/p21 induced senescence played a minor role. Transmission electron microscopy confirmed damaged mitochondria and endoplasmic reticulum together with increased vacuolization under CDKi mono- and combination therapy. SEQ-abemaciclib/SpyADI treatment suppressed the DSB repair system via NHEJ and HR, whereas SEQ-dinaciclib/SpyADI treatment increased γ-H2AX accumulation and induced Rad51/Ku80. The latter combination also activated the stress sensor GADD45 and β-catenin antagonist AXIN2 and induced expression changes of genes involved in cellular/cytoskeletal integrity. This study highlights the strong antitumoral potential of a combined arginine deprivation and CDK inhibition approach via complex effects on mitochondrial dysfunction, invasiveness as well as DNA-damage response. This provides a good starting point for further in vitro and in vivo proof-of-concept studies to move forward with this strategy.
Ct-OATP1B3 promotes high-grade serous ovarian cancer metastasis by regulation of fatty acid beta-oxidation and oxidative phosphorylation
Authors: Huang Yutang , Du Yan , Zheng Yujie , Wen Chunjie , Zou Hecun , Huang Jiafeng , Zhou Honghao , Zhao Hongbo , Wu Lanxiang
Published: June 2022

High-grade serous ovarian cancer (HGSOC) is the most lethal gynecologic malignancy mainly due to its extensive metastasis. Cancer-type organic anion transporting polypeptide 1B3 (Ct-OATP1B3), a newly discovered splice variant of solute carrier organic anion transporter family member 1B3 (SLCO1B3), has been reported to be overexpressed in several types of cancer. However, the biological function of Ct-OATP1B3 remains largely unknown. Here, we reveal that Ct-OATP1B3 is overexpressed in HGSOC and promotes the metastasis of HGSOC in vivo and in vitro. Mechanically, Ct-OATP1B3 directly interacts with insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), an RNA-binding protein, which results in enhancement of the mRNA stability and expression of carnitine palmitoyltransferase 1A (CPT1A) and NADH:Ubiquinone Oxidoreductase Subunit A2 (NDUFA2), leading to increased mitochondrial fatty acid beta-oxidation (FAO) and oxidative phosphorylation (OXPHOS) activities. The increased FAO and OXPHOS activities further facilitate adenosine triphosphate (ATP) production and cellular lamellipodia formation, which is the initial step in the processes of tumor cell migration and invasion. Taken together, our study provides an insight into the function and underlying mechanism of Ct-OATP1B3 in HGSOC metastasis, and highlights Ct-OATP1B3 as a novel prognostic marker as well as therapeutic target in HGSOC.
Bioorthogonally activatable cyanine dye with torsion-induced disaggregation for in vivo tumor imaging
Authors: Zhang Xianghan , Gao Jingkai , Tang Yingdi , Yu Jie , Liew Si Si , Qiao Chaoqiang , Cao Yutian , Liu Guohuan , Fan Hongyu , Xia Yuqiong , Tian Jie , Pu Kanyi , Wang Zhongliang
Published: June 2022

Advancement of bioorthogonal chemistry in molecular optical imaging lies in expanding the repertoire of fluorophores that can undergo fluorescence signal changes upon bioorthogonal ligation. However, most available bioorthogonally activatable fluorophores only emit shallow tissue-penetrating visible light via an intramolecular charge transfer mechanism. Herein, we report a serendipitous “torsion-induced disaggregation (TIDA)” phenomenon in the design of near-infrared (NIR) tetrazine (Tz)-based cyanine probe. The TIDA of the cyanine is triggered upon Tz-transcyclooctene ligation, converting its heptamethine chain from S-trans to S-cis conformation. Thus, after bioorthogonal reaction, the tendency of the resulting cyanine towards aggregation is reduced, leading to TIDA-induced fluorescence enhancement response. This Tz-cyanine probe sensitively delineates the tumor in living mice as early as 5 min post intravenous injection. As such, this work discovers a design mechanism for the construction of bioorthogonally activatable NIR fluorophores and opens up opportunities to further exploit bioorthogonal chemistry in in vivo imaging.
Neuromorphic object localization using resistive memories and ultrasonic transducers
Authors: Moro Filippo , Hardy Emmanuel , Fain Bruno , Dalgaty Thomas , Clémençon Paul , De Prà Alessio , Esmanhotto Eduardo , Castellani Niccolò , Blard François , Gardien François , Mesquida Thomas , Rummens François , Esseni David , Casas Jérôme , Indiveri Giacomo , Payvand Melika , Vianello Elisa
Published: June 2022

Real-world sensory-processing applications require compact, low-latency, and low-power computing systems. Enabled by their in-memory event-driven computing abilities, hybrid memristive-Complementary Metal-Oxide Semiconductor neuromorphic architectures provide an ideal hardware substrate for such tasks. To demonstrate the full potential of such systems, we propose and experimentally demonstrate an end-to-end sensory processing solution for a real-world object localization application. Drawing inspiration from the barn owl’s neuroanatomy, we developed a bio-inspired, event-driven object localization system that couples state-of-the-art piezoelectric micromachined ultrasound transducer sensors to a neuromorphic resistive memories-based computational map. We present measurement results from the fabricated system comprising resistive memories-based coincidence detectors, delay line circuits, and a full-custom ultrasound sensor. We use these experimental results to calibrate our system-level simulations. These simulations are then used to estimate the angular resolution and energy efficiency of the object localization model. The results reveal the potential of our approach, evaluated in orders of magnitude greater energy efficiency than a microcontroller performing the same task.
Simulated co-optimization of renewable energy and desalination systems in Neom, Saudi Arabia
Authors: Riera Jefferson A. , Lima Ricardo M. , Hoteit Ibrahim , Knio Omar
Published: June 2022

The interdependence between the water and power sectors is a growing concern as the need for desalination increases globally. Therefore, co-optimizing interdependent systems is necessary to understand the impact of one sector on another. We propose a framework to identify the optimal investment mix for a co-optimized water-power system and apply it to Neom, Saudi Arabia. Our results show that investment strategies that consider the co-optimization of both systems result in total cost savings for the power sector compared to independent approaches. Analysis results suggest that systems with higher shares of non-dispatchable renewables experience the most significant cost reductions.
A practical fluorosulfonylating platform via photocatalytic imidazolium-based SO2F radical reagent
Authors: Zhang Weigang , Li Heyin , Li Xiaojuan , Zou Zhenlei , Huang Mengjun , Liu Jiyang , Wang Xiaochen , Ni Shengyang , Pan Yi , Wang Yi
Published: June 2022

Sulfonyl fluorides are key components in the fields of chemical biology, materials science and drug discovery. In this line, the highly active SO2F radical has been employed for the construction of sulfonyl fluorides, but the utilization of gaseous ClSO2F as radical precursor is limited due to the tedious and hazardous preparation. Meanwhile, the synthesis of sulfonyl fluorides from inert SO2F2 gas through a fluorosulfonyl radical (·SO2F) process has met with inevitable difficulties due to the high homolytic bond dissociation energy of the S(VI)-F bond. Here we report a radical fluorosulfonylation strategy for the stereoselective synthesis of alkenyl sulfonyl fluorides and functional alkyl sulfonyl fluorides with an air-stable crystalline benzimidazolium fluorosulfonate cationic salt reagent. This bench-stable redox-active reagent offers a useful and operational protocol for the radical fluorosulfonylation of unsaturated hydrocarbons with good yield and high stereoselectivity, which can be further transformed into valuable functional SO2F moieties.
Daily precipitation dataset at 0.1° for the Yarlung Zangbo River basin from 2001 to 2015
Authors: Zhao Keke , Peng Dingzhi , Gu Yu , Pang Bo , Zhu Zhongfan
Published: June 2022

In order to obtain higher precision regional precipitation dataset in the Yarlung Zangbo River basin, two different schemes were proposed on the basis of the two most application potential satellite-based precipitation products, IMERG and CMORPH_BLD. The first method aimed to correct the positive error of IMERG based on high correlation (CC > 0.9) between IMERG and gauges. The second algorithm was developed to merge IMERG with CMORPH_BLD by the stepwise linear regression. As the reference, IMERG played a key role in correction of precipitation ratio determination and precipitation event detection. Two daily datasets with 0.1° resolution (BRD_IMERG and IGREA_IMERG-CMORPH) performed better than IMERG in CC, RMSE, ME, FAR and CSI, and streamflow simulation in the whole basin (NS: 0.86 and 0.87; RBIAS: −19% and −11%) and sub-basins. The two proposed methods were relatively simple and efficient for reconstructing higher precision regional precipitation, and the datasets provided a good application demonstration in the alpine region.
Possible role of insulin resistance in activation of plasma xanthine oxidoreductase in health check-up examinees
Authors: Kurajoh Masafumi , Fukumoto Shinya , Akari Seigo , Murase Takayo , Nakamura Takashi , Takahashi Kanae , Yoshida Hisako , Nakatani Shinya , Tsuda Akihiro , Morioka Tomoaki , Mori Katsuhito , Imanishi Yasuo , Hirata Kazuto , Emoto Masanori
Published: June 2022

We previously found an association of insulin resistance (IR) with plasma xanthine oxidoreductase (XOR) activity in a cross-sectional study. However, whether IR induces increased XOR activity has not been elucidated. This retrospective longitudinal observational study included 347 participants (173 males, 174 females) who underwent annual health examinations and were medication naïve. Homeostasis model assessment of IR (HOMA-IR) index, and physical and laboratory measurements were determined at the baseline. At baseline and 12-month follow-up examinations, plasma XOR activity was determined using our novel assay based on [13C2,15N2] xanthine and liquid chromatography/triple quadrupole mass spectrometry. Subjects with IR, defined as HOMA-IR index ≥ 1.7 (n = 92), exhibited significantly (p < 0.001) higher plasma XOR activity levels than those without IR (n = 255), with an increase in that activity seen in 180 (51.9%) after 12 months. Multivariable linear and logistic regression analyses showed that IR, but not BMI or waist circumference, at baseline was significantly associated with plasma XOR activity (β = 0.094,p = 0.033) and increased plasma XOR activity over the 12-month period (odds ratio, 1.986; 95% confidence interval, 1.048–3.761;p = 0.035), after adjustments for various clinical parameters, including plasma XOR activity at baseline. These results suggest that IR induces increased plasma XOR activity in a manner independent of adiposity.
Combining host and vector data informs emergence and potential impact of an Usutu virus outbreak in UK wild birds
Authors: Lawson Becki , Robinson Robert A. , Briscoe Andrew G. , Cunningham Andrew A. , Fooks Anthony R. , Heaver Joseph P. , Hernández-Triana Luis M. , John Shinto K. , Johnson Nicholas , Johnston Colin , Lean Fabian Z. X. , Macgregor Shaheed K. , Masters Nicholas J. , McCracken Fiona , McElhinney Lorraine M. , Medlock Jolyon M. , Pearce-Kelly Paul , Seilern-Moy Katharina , Spiro Simon , Vaux Alexander G. C. , Folly Arran J.
Published: June 2022

Following the first detection in the United Kingdom of Usutu virus (USUV) in wild birds in 2020, we undertook a multidisciplinary investigation that combined screening host and vector populations with interrogation of national citizen science monitoring datasets to assess the potential for population impacts on avian hosts. Pathological findings from six USUV-positive wild passerines were non-specific, highlighting the need for molecular and immunohistochemical examinations to confirm infection. Mosquito surveillance at the index site identified USUV RNA in Culex pipiens s.l. following the outbreak. Although the Eurasian blackbird (Turdus merula) is most frequently impacted by USUV in Europe, national syndromic surveillance failed to detect any increase in occurrence of clinical signs consistent with USUV infection in this species. Furthermore, there was no increase in recoveries of dead blackbirds marked by the national ringing scheme. However, there was regional clustering of blackbird disease incident reports centred near the index site in 2020 and a contemporaneous marked reduction in the frequency with which blackbirds were recorded in gardens in this area, consistent with a hypothesis of disease-mediated population decline. Combining results from multidisciplinary schemes, as we have done, in real-time offers a model for the detection and impact assessment of future disease emergence events.
Rupture pressure values of cerebral arteries in the presence of unruptured intracranial aneurysm
Authors: Lombarski Leszek , Kunert Przemysław , Tarka Sylwia , Piechna Adam , Kujawski Sławomir , Marchel Andrzej
Published: June 2022

Cerebral arteries (CAs) are prone to the saccular aneurysm formation. Since aneurysms may be considered as balloon-like dilations of the locally weakened arterial wall, it should be determined whether the presence of intracranial aneurysm is related to the generalized weakening of CAs. Among 184 consecutive forensic autopsies, eight brains with a single unruptured saccular aneurysm were identified. Aneurysms with adjacent CAs and specific CA segments were excised, namely: the anterior communicating artery complex, and bifurcations of the basilar artery, internal carotid arteries, and middle cerebral arteries. Then, aneurysm and CA specimens were subjected to pressure-inflation tests until rupture occurred at the arterial bifurcation or at the wall of the CA or aneurysm. The same protocol was applied to the control group composed of CAs excised from eight brains without aneurysm. No significant differences were noted between the experimental and control groups, depending on the mean rupture pressure (1054 vs. 1048 mmHg) and rupture site (bifurcation vs. wall) of the analyzed specimens. These findings indicate that the presence of unruptured saccular aneurysm is not related to generalized weakening of CAs among autopsy subjects. Moreover, the CA bifurcations do not represent regions of decreased wall strength.
Machine learning-enabled cancer diagnostics with widefield polarimetric second-harmonic generation microscopy
Authors: Mirsanaye Kamdin , Uribe Castaño Leonardo , Kamaliddin Yasmeen , Golaraei Ahmad , Augulis Renaldas , Kontenis Lukas , Done Susan J. , Žurauskas Edvardas , Stambolic Vuk , Wilson Brian C. , Barzda Virginijus
Published: June 2022

The extracellular matrix (ECM) collagen undergoes major remodeling during tumorigenesis. However, alterations to the ECM are not widely considered in cancer diagnostics, due to mostly uniform appearance of collagen fibers in white light images of hematoxylin and eosin-stained (H&E) tissue sections. Polarimetric second-harmonic generation (P-SHG) microscopy enables label-free visualization and ultrastructural investigation of non-centrosymmetric molecules, which, when combined with texture analysis, provides multiparameter characterization of tissue collagen. This paper demonstrates whole slide imaging of breast tissue microarrays using high-throughput widefield P-SHG microscopy. The resulting P-SHG parameters are used in classification to differentiate tumor from normal tissue, resulting in 94.2% for both accuracy and F1-score, and 6.3% false discovery rate. Subsequently, the trained classifier is employed to predict tumor tissue with 91.3% accuracy, 90.7% F1-score, and 13.8% false omission rate. As such, we show that widefield P-SHG microscopy reveals collagen ultrastructure over large tissue regions and can be utilized as a sensitive biomarker for cancer diagnostics and prognostics studies.
Comparing cross-sectional and longitudinal tracking to establish percentile data and assess performance progression in swimmers
Authors: Born Dennis-Peter , Rüeger Eva , Beaven C. Martyn , Romann Michael
Published: June 2022

To provide percentile curves for short-course swimming events, including 5 swimming strokes, 6 race distances, and both sexes, as well as to compare differences in race times between cross-sectional analysis and longitudinal tracking, a total of 31,645,621 race times of male and female swimmers were analyzed. Two percentile datasets were established from individual swimmers’ annual best times and a two-way analysis of variance (ANOVA) was used to determine differences between cross-sectional analysis and longitudinal tracking. A software-based percentile calculator was provided to extract the exact percentile for a given race time. Longitudinal tracking reduced the number of annual best times that were included in the percentiles by 98.35% to 262,071 and showed faster mean race times (P < 0.05) compared to the cross-sectional analysis. This difference was found in the lower percentiles (1st to 20th) across all age categories (P < 0.05); however, in the upper percentiles (80th to 99th), longitudinal tracking showed faster race times during early and late junior age only (P < 0.05), after which race times approximated cross-sectional tracking. The percentile calculator provides quick and easy data access to facilitate practical application of percentiles in training or competition. Longitudinal tracking that accounts for drop-out may predict performance progression towards elite age, particularly for high-performance swimmers.
Genistein induces long-term expression of progesterone receptor regardless of estrogen receptor status and improves the prognosis of endometrial cancer patients
Authors: Yoriki Kaori , Mori Taisuke , Aoyama Kohei , Tarumi Yosuke , Kataoka Hisashi , Kokabu Tetsuya , Kitawaki Jo
Published: June 2022

Progesterone is used to treat uterine endometrial cancer in young patients wishing to preserve their fertility as well as in advanced or recurrent patients, but its response rate is limited. The antitumor effect of progesterone is mediated by progesterone receptor (PR) binding. Hence, loss of progesterone’s therapeutic effect, i.e., development of progesterone resistance, is mainly due to decreased PR expression. However, little is known about underlying mechanisms that regulate PR expression. Immunohistochemistry analysis of specimens from 31 young, endometrial cancer patients showed that elevated PR expression significantly increased (P < 0.05) rates of progression-free and overall survival. We investigated mechanisms of regulating PR expression and suppressing cell proliferation using genistein, a chemotherapeutic agent against different cancers. Genistein inhibits cell growth by inducing cell cycle arrest in G2 and apoptosis; moreover, it upregulates prolonged expression of PR-B and forkhead box protein O1, regardless of estrogen receptor alpha expression in endometrial cancer cells. Genistein-induced PR expression decreases CCAAT/enhancer binding protein beta expression and activates c-Jun N-terminal kinase pathway, rather than causing epigenetic alterations of the PR promoter. Therefore, increased PR expression is an important antitumor effect of genistein. This may help to improve the response rates of fertility-sparing treatments for young patients.