bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Representations of Realistic Topography on Parameterized Oceanic Lee Wave Energy Flux
Authors: Baker L. E. , Mashayek A. 
Published: October 2022

AbstractOceanic lee waves are generated when quasi‐steady flows interact with rough topography at the bottom of the ocean, providing an important sink of energy and momentum from the mean flow and a source of turbulent kinetic energy. Linear theory with a spectral representation of topography is typically used to inform parameterizations of lee wave generation. Here, we use a realistic wave resolving simulation of the Drake Passage, a hot‐spot of lee wave generation, to investigate the utility of such parameterizations for areas of complex large scale topography. The flow is often blocked and split by large amplitude topographic features, creating an “effective topography,” and calling into question the spectral representation of small scale topography for lee wave generation. By comparing the resolved modeled wavefield to parameterizations employing various representations of topography, we show that spectral methods may not be appropriate in areas of rough topography. We develop a simple topographic representation consisting of an ensemble of topographic peaks, which allows physical treatment of flow blocking at finite amplitude topography. This method effectively predicts bottom vertical velocities and lee wave energy flux, whereas spectral methods overestimate the energy flux by approximately 4 times. Our results also imply that the nature of lee waves in such regions can be misrepresented by a spectral approach to topographic representation. This leads to both an overestimate of wave energy flux and an underestimate of wave nonlinearity, with implications for the mechanisms by which lee waves break and mix in the abyssal ocean.
CO2 Ocean Bistability on Terrestrial Exoplanets
Authors: Graham R. J. , Lichtenberg Tim , Pierrehumbert Raymond T. 
Published: October 2022

AbstractCycling of carbon dioxide between the atmosphere and interior of rocky planets can stabilize global climate and enable planetary surface temperatures above freezing over geologic time. However, variations in global carbon budget and unstable feedback cycles between planetary sub‐systems may destabilize the climate of rocky exoplanets toward regimes unknown in the Solar System. Here, we perform clear‐sky atmospheric radiative transfer and surface weathering simulations to probe the stability of climate equilibria for rocky, ocean‐bearing exoplanets at instellations relevant for planetary systems in the outer regions of the circumstellar habitable zone. Our simulations suggest that planets orbiting G‐ and F‐type stars (but not M‐type stars) may display bistability between an Earth‐like climate state with efficient carbon sequestration and an alternative stable climate equilibrium where CO2 condenses at the surface and forms a blanket of either clathrate hydrate or liquid CO2. At increasing instellation and with ineffective weathering, the latter state oscillates between cool, surface CO2‐condensing and hot, non‐condensing climates. CO2 bistable climates may emerge early in planetary history and remain stable for billions of years. The carbon dioxide‐condensing climates follow an opposite trend in pCO2 versus instellation compared to the weathering‐stabilized planet population, suggesting the possibility of observational discrimination between these distinct climate categories.
Hydraulic Sensitivity and Stomatal Regulation of Two Desert Riparian Species
Authors: Bai Yan , Liu Yanlan , Kueppers Lara M. , Li Engui , Zhang Cicheng , Yu Kailiang , Yang Xiaofan , Li Xiaoyan 
Published: October 2022

AbstractCharacterizing plant response to water stresses is among the keys to understanding ecosystem functions. Despite increasing recognition of plant hydraulic and stomatal dynamics not captured by isohydricity, defined as the sensitivity of leaf water potential Ψl to soil water potential, it remains unclear which plant traits are critical to improved representation of plant hydraulic and stomatal dynamics beyond isohydricity, especially in dryland ecosystems. Here, we examine eco‐physiological responses of two typical desert riparian species, Populus euphratica and Tamarix ramosissima, to hydro‐meteorological variations. Based on measured hydraulic traits, variations of Ψl, leaf gas exchange, groundwater table, and soil moisture across vertical profiles, we investigated how subsurface hydraulic conditions control plant hydraulic sensitivity and stomatal regulation. We found both species exhibited anisohydric behaviors, which, however, were attributed to drying soil at different depths because of root distributions. The similar anisohydric behaviors also led to distinct stomatal regulation, due to the impact of atmospheric dryness decoupled from soil moisture and different sensitivities of stomatal conductance (gs) to Ψl. The latter was found to be dynamic throughout the growing season, which dominated the seasonal variation of gs and thus should not be neglected. The results suggest similar anisohydric behaviors could imply diverging hydraulic behaviors as the evaporate demand and flow regime change. Root morphological trait and stomatal sensitivity to Ψl are identified as keys to characterize responses to water stresses in desert riparian ecosystems. Our findings highlight that improved measurements and representations of these traits could contribute to better assessments of dryland ecosystem functions.
Leaf Traits Predict Water‐Use Efficiency in U.S. Pacific Northwest Grasslands Under Rain Exclusion Treatment
Authors: Dawson Hilary Rose , Maxwell Toby M. , Reed Paul B. , Bridgham Scott D. , Silva Lucas C. R. 
Published: October 2022

AbstractDoes drought stress in temperate grasslands alter the relationship between plant structure and function? Here we report data from an experiment focusing on growth form and species traits that affect the critical functions of water‐ and nutrient‐use efficiency in prairie and pasture plant communities. A total of 139 individuals of 12 species (11 genera and four families) were sampled in replicated plots maintained for three years across a 520 km latitudinal gradient in the Pacific Northwest, USA. Rain exclusion did not alter the interspecific relationship between foliar traits and stoichiometry or intrinsic water‐use efficiency (iWUE). Rain exclusion reduced iWUE in grasses, an effect was primarily species‐specific, although leaf morphology, life history strategy, and phylogenetic distance predicted iWUE for all 12 species when analyzed together. Variation in specific leaf area explained most of the variation in iWUE between different functional groups, with annual forbs and annual grasses at opposite ends of the resource‐use spectrum. Our findings are consistent with expected trait‐driven tradeoffs between productivity and resource‐use efficiency, and provide insight into strategies for the sustainable use and conservation of temperate grasslands.
Global Barotropic Tide Modeling Using Inline Self‐Attraction and Loading in MPAS‐Ocean
Authors: Barton Kristin N. , Pal Nairita , Brus Steven R. , Petersen Mark R. , Arbic Brian K. , Engwirda Darren , Roberts Andrew F. , Westerink Joannes J. , Wirasaet Damrongsak , Schindelegger Michael 
Published: October 2022

AbstractWe examine ocean tides in the barotropic version of the Model for Prediction Across Scales (MPAS‐Ocean), the ocean component of the Department of Energy Earth system model. We focus on four factors that affect tidal accuracy: self‐attraction and loading (SAL), model resolution, details of the underlying bathymetry, and parameterized topographic wave drag. The SAL term accounts for the tidal loading of Earth's crust and the self‐gravitation of the ocean and the load‐deformed Earth. A common method for calculating SAL is to decompose mass anomalies into their spherical harmonic constituents. Here, we compare a scalar SAL approximation versus an inline SAL using a fast spherical harmonic transform package. Wave drag accounts for energy lost by breaking internal tides that are produced by barotropic tidal flow over topographic features. We compare a series of successively finer quasi‐uniform resolution meshes (62.9, 31.5, 15.7, and 7.87 km) to a variable resolution (45 to 5 km) configuration. We ran MPAS‐Ocean in a single‐layer barotropic mode forced by five tidal constituents. The 45 to 5 km variable resolution mesh obtained the best total root‐mean‐square error (5.4 cm) for the deep ocean (1,000 m) tide compared to TPXO8 and ran twice as fast as the quasi‐uniform 8 km mesh, which had an error of 5.8 cm. This error is comparable to those found in other forward (non‐assimilative) ocean tide models. In future work, we plan to use MPAS‐Ocean to study tidal interactions with other Earth system components, and the tidal response to climate change.
Clinical Considerations for Behavioral Pain Management in Co-Occurring Acute and Chronic Pain Presentations
Authors: Connolly Megan E. , Hardy Steven J. 
Published: October 2022

Objective: Behavioral pain management treatments are typically provided after a multidisciplinary assessment determining whether the nature of pain is expected to be short-term (i.e., acute) or whether the pain is persistent (i.e., chronic). However, many of the standard ways clinicians approach pain management are challenged by the presentation of co-occurring acute and chronic pain experiences, such as can be the case in sickle cell disease (SCD), headache management (migraines and daily persisting headaches), chronic musculoskeletal pain with reinjury, and juvenile idiopathic arthritis, among others. Such overlapping pain presentations can involve conflicting treatment approaches for pain management. Currently, there is burgeoning, yet still limited, understanding of the complexity of co-occurring acute and chronic pain presentations. Methods: Given the unique pain presentation common in SCD, among other conditions, we review how behavioral pain management strategies can utilize complementary approaches to address the experience of co-occurring acute and chronic pain. Results: This commentary provides a brief historical review of the evolution of our understanding of pain perception and psychological treatments for pain. We propose an innovative clinical framework for behavioral pain management of co-occurring acute and chronic pain. Conclusions: We hope to enhance the current dialogue around pain perception and pain burden to address the unique needs of co-occurring acute and chronic pain presentations. Ongoing areas for research and clinical considerations are also discussed. Implications for Impact Statement There is increasing awareness of the heterogeneity of pain conditions involving both acute and chronic pain. This commentary proposes a new care model for behavioral pain management for individuals experiencing co-occurring acute and chronic pain. Behavioral pain management strategies should consider complementary and flexible approaches that address the cumulative experience of both acute and chronic pain.
Chlorine redox chemistry is widespread in microbiology
Authors: Barnum Tyler P , Coates John D 
Published: October 2022

Abstract
Chlorine is abundant in cells and biomolecules, yet the biology of chlorine oxidation and reduction is poorly understood. Some bacteria encode the enzyme chlorite dismutase (Cld), which detoxifies chlorite (ClO2−) by converting it to chloride (Cl−) and molecular oxygen (O2). Cld is highly specific for chlorite and aside from low hydrogen peroxide activity has no known alternative substrate. Here, we reasoned that because chlorite is an intermediate oxidation state of chlorine, Cld can be used as a biomarker for oxidized chlorine species. Cld was abundant in metagenomes from various terrestrial habitats. About 5% of bacterial and archaeal genera contain a microorganism encoding Cld in its genome, and within some genera Cld is highly conserved. Cld has been subjected to extensive horizontal gene transfer. Genes found to have a genetic association with Cld include known genes for responding to reactive chlorine species and uncharacterized genes for transporters, regulatory elements, and putative oxidoreductases that present targets for future research. Cld was repeatedly co-located in genomes with genes for enzymes that can inadvertently reduce perchlorate (ClO4−) or chlorate (ClO3−), indicating that in situ (per)chlorate reduction does not only occur through specialized anaerobic respiratory metabolisms. The presence of Cld in genomes of obligate aerobes without such enzymes suggested that chlorite, like hypochlorous acid (HOCl), might be formed by oxidative processes within natural habitats. In summary, the comparative genomics of Cld has provided an atlas for a deeper understanding of chlorine oxidation and reduction reactions that are an underrecognized feature of biology.
Altered language network lateralization in euthymic bipolar patients: a pilot study
Authors: Romeo Zaira , Marino Marco , Angrilli Alessandro , Semenzato Ilaria , Favaro Angela , Magnolfi Gianna , Padovan Giordano Bruno , Mantini Dante , Spironelli Chiara 
Published: October 2022

AbstractBipolar patients (BD) in the euthymic phase show almost no symptoms, nevertheless possibility of relapse is still present. We expected to find a psychobiological trace of their vulnerability by analyzing a specific network—the Language Network (LN)—connecting many high-level processes and brain regions measured at rest. According to Crow’s hypothesis on the key role of language in the origin of psychoses, we expected an altered asymmetry of the LN in euthymic BDs. Eighteen euthymic BD patients (10 females; age = 54.50 ± 11.38 years) and 16 healthy controls (HC) (8 females; age = 51.16 ± 11.44 years) underwent a functional magnetic resonance imaging scan at rest. The LN was extracted through independent component analysis. Then, LN time series was used to compute the fractional amplitude of the low-frequency fluctuation (fALFF) index, which was then correlated with clinical scales. Compared with HC, euthymic patients showed an altered LN with greater activation of Broca’s area right homologous and anterior insula together with reduced activation of left middle temporal gyrus. The normalized fALFF analysis on BD patients’ LN time series revealed that the Slow-5 fALFF band was positively correlated with residual mania symptoms but negatively associated with depression scores. In line with Crow’s hypothesis postulating an altered language hemispheric asymmetry in psychoses, we revealed, in euthymic BD patients, a right shift involving both the temporal and frontal linguistic hubs. The fALFF applied to LN allowed us to highlight a number of significant correlations of this measure with residual mania and depression psychiatric symptoms.
Inhibition of mTOR signaling protects human glioma cells from hypoxia-induced cell death in an autophagy-independent manner
Authors: Divé Iris , Klann Kevin , Michaelis Jonas B. , Heinzen Dennis , Steinbach Joachim P. , Münch Christian , Ronellenfitsch Michael W. 
Published: October 2022

AbstractAlthough malignant gliomas frequently show aberrant activation of the mammalian target of rapamycin (mTOR), mTOR inhibitors have performed poorly in clinical trials. Besides regulating cell growth and translation, mTOR controls the initiation of autophagy. By recycling cellular components, autophagy can mobilize energy resources, and has thus been attributed cancer-promoting effects. Here, we asked whether the activation of autophagy represents an escape mechanism to pharmacological mTOR inhibition in glioma cells, and explored co-treatment with mTOR and autophagy inhibitors as a therapeutic strategy. Mimicking conditions of the glioma microenvironment, glioma cells were exposed to nutrient starvation and hypoxia. We analyzed autophagic activity, cell growth, viability and oxygen consumption following (co-)treatment with the mTOR inhibitors torin2 or rapamycin, and autophagy inhibitors bafilomycin A1 or MRT68921. Changes in global proteome were quantified by mass spectrometry. In the context of hypoxia and starvation, autophagy was strongly induced in glioma cells and further increased by mTOR inhibition. While torin2 enhanced glioma cell survival, co-treatment with torin2 and bafilomycin A1 failed to promote cell death. Importantly, treatment with bafilomycin A1 alone also protected glioma cells from cell death. Mechanistically, both compounds significantly reduced cell growth and oxygen consumption. Quantitative proteomics analysis showed that bafilomycin A1 induced broad changes in the cellular proteome. More specifically, proteins downregulated by bafilomycin A1 were associated with the mitochondrial respiratory chain and ATP synthesis. Taken together, our results show that activation of autophagy does not account for the cytoprotective effects of mTOR inhibition in our in vitro model of the glioma microenvironment. Our proteomic findings suggest that the pharmacological inhibition of autophagy induces extensive changes in the cellular proteome that can support glioma cell survival under nutrient-deplete and hypoxic conditions. These findings provide a novel perspective on the complex role of autophagy in gliomas.
A VEGFR targeting peptide-drug conjugate (PDC) suppresses tumor angiogenesis in a TACE model for hepatocellular carcinoma therapy
Authors: Wang Dongyuan , Liu Jiacheng , Li Tongqiang , Wang Yingliang , Liu Xiaoming , Bai Yaowei , Wang Chaoyang , Ju Shuguang , Huang Songjiang , Yang Chongtu , Zhou Chen , Zhang Yu , Xiong Bin 
Published: October 2022

AbstractTranscatheter arterial chemoembolization (TACE) has become the preferred therapy for unresectable advanced hepatocellular carcinoma (HCC). However, the embolization of tumor-feeding arteries by TACE always leads to hypoxia-related tumor angiogenesis, which limited the therapeutic effect for HCC. In this paper, we used a VEGFR targeting peptide VEGF125 − 136 (QKRKRKKSRYKS) to conjugate with a lytic peptide (KLUKLUKKLUKLUK) to form a peptide-drug conjugate (PDC). We used cell affinity assay to detect the peptide binding ability to VEGFR highly expressed cell lines, and CCK8, cell apoptosis to confirm the cellular toxicity for different cell lines. Meanwhile, we created a VX2 tumor-bearing rabbit model to assess the in vivo anti-tumor effect of the peptide conjugate in combination with TAE. HE staining was used to verify the in vivo safety of the peptide conjugate. IHC was used to assess the anti-angiogenesis and cell toxicity of the peptide conjugate in tumor tissues. The peptide conjugate could not only target VEGFR in cell surface and inhibit VEGFR function, but also have potent anti-cancer effect. We luckily found the peptide conjugate showed potent cytotoxicity for liver cancer cell Huh7 (IC50 7.3 ± 0.74 μM) and endothelial cell HUVEC (IC50 10.7 ± 0.292 μM) and induced cell apoptosis of these two cell lines. We also found the peptide conjugate inhibited cell migration of HUVEC through wound healing assay. Besides, these peptides also showed better in vivo anti-tumor effect than traditional drug DOX through TACE in VX2 rabbit tumor model, and efficiently inhibit angiogenesis in tumor tissues with good safety. In conclusion, our work may provide an alternative option for clinical HCC therapy via TACE combination.
Role of K63-linked ubiquitination in cancer
Authors: Cao Liangzi , Liu Xiaofang , Zheng Bowen , Xing Chengzhong , Liu Jingwei 
Published: October 2022

AbstractUbiquitination is a critical type of post-translational modifications, of which K63-linked ubiquitination regulates interaction, translocation, and activation of proteins. In recent years, emerging evidence suggest involvement of K63-linked ubiquitination in multiple signaling pathways and various human diseases including cancer. Increasing number of studies indicated that K63-linked ubiquitination controls initiation, development, invasion, metastasis, and therapy of diverse cancers. Here, we summarized molecular mechanisms of K63-linked ubiquitination dictating different biological activities of tumor and highlighted novel opportunities for future therapy targeting certain regulation of K63-linked ubiquitination in tumor.
Lineage-coupled clonal capture identifies clonal evolution mechanisms and vulnerabilities of BRAFV600E inhibition resistance in melanoma
Authors: Zhang Ze-Yan , Ding Yingwen , Ezhilarasan Ravesanker , Lhakhang Tenzin , Wang Qianghu , Yang Jie , Modrek Aram S. , Zhang Hua , Tsirigos Aristotelis , Futreal Andrew , Draetta Giulio F. , Verhaak Roel G. W. , Sulman Erik P. 
Published: October 2022

AbstractTargeted cancer therapies have revolutionized treatment but their efficacies are limited by the development of resistance driven by clonal evolution within tumors. We developed “CAPTURE”, a single-cell barcoding approach to comprehensively trace clonal dynamics and capture live lineage-coupled resistant cells for in-depth multi-omics analysis and functional exploration. We demonstrate that heterogeneous clones, either preexisting or emerging from drug-tolerant persister cells, dominated resistance to vemurafenib in BRAFV600E melanoma. Further integrative studies uncovered diverse resistance mechanisms. This includes a previously unrecognized and clinically relevant mechanism, chromosome 18q21 gain, which leads to vulnerability of the cells to BCL2 inhibitor. We also identified targetable common dependencies of captured resistant clones, such as oxidative phosphorylation and E2F pathways. Our study provides new therapeutic insights into overcoming therapy resistance in BRAFV600E melanoma and presents a platform for exploring clonal evolution dynamics and vulnerabilities that can be applied to study treatment resistance in other cancers.
High-quality microresonators in the longwave infrared based on native germanium
Authors: Ren Dingding , Dong Chao , Addamane Sadhvikas J. , Burghoff David 
Published: October 2022

AbstractThe longwave infrared (LWIR) region of the spectrum spans 8 to 14 μm and enables high-performance sensing and imaging for detection, ranging, and monitoring. Chip-scale LWIR photonics has enormous potential for real-time environmental monitoring, explosive detection, and biomedicine. However, realizing technologies such as precision sensors and broadband frequency combs requires ultra low-loss and low-dispersion components, which have so far remained elusive in this regime. Here, we use native germanium to demonstrate the first high-quality microresonators in the LWIR. These microresonators are coupled to partially-suspended Ge waveguides on a separate glass chip, allowing for the first unambiguous measurements of isolated linewidths. At 8 μm, we measured losses of 0.5 dB/cm and intrinsic quality (Q) factors of 2.5 × 105, nearly two orders of magnitude higher than prior LWIR resonators. Our work portends the development of novel sensing and nonlinear photonics in the LWIR regime.