bluuebunny/crossref_metadata_2025 huggingface dataset:
A Reconstruction Algorithm for Temporally Aliased Seismic Signals Recorded by the InSight Mars Lander
Authors: Sollberger David , Schmelzbach Cedric , Andersson Fredrik , Robertsson Johan O. A. , Brinkman Nienke , Kedar Sharon , Banerdt William B. , Clinton John , van Driel Martin , Garcia Raphael , Giardini Domenico , Grott Matthias , Haag Thomas , Hudson Troy L. , Lognonné Philippe , Pierick Jan ten , Pike William , Spohn Tilman , Stähler Simon C. , Zweifel Peter
Published: July 2021

In December 2018, the NASA InSight lander successfully placed a seismometer on the surface of Mars. Alongside, a hammering device was deployed at the landing site that penetrated into the ground to attempt the first measurements of the planetary heat flow of Mars. The hammering of the heat probe generated repeated seismic signals that were registered by the seismometer and can potentially be used to image the shallow subsurface just below the lander. However, the broad frequency content of the seismic signals generated by the hammering extends beyond the Nyquist frequency governed by the seismometer's sampling rate of 100 samples per second. Here, we propose an algorithm to reconstruct the seismic signals beyond the classical sampling limits. We exploit the structure in the data due to thousands of repeated, only gradually varying hammering signals as the heat probe slowly penetrates into the ground. In addition, we make use of the fact that repeated hammering signals are sub‐sampled differently due to the unsynchronized timing between the hammer strikes and the seismometer recordings. This allows us to reconstruct signals beyond the classical Nyquist frequency limit by enforcing a sparsity constraint on the signal in a modified Radon transform domain. In addition, the proposed method reduces uncorrelated noise in the recorded data. Using both synthetic data and actual data recorded on Mars, we show how the proposed algorithm can be used to reconstruct the high‐frequency hammering signal at very high resolution.
Characteristics of Negative Cloud‐To‐Ground Flashes Observed in the Brazilian Amazon Region
Authors: Leal Adonis F. R. , Matos Wendler L. N. , Ferreira Eduardo R. , Ferreira Gabriel A. V. S. , Lopes Marcio N. G. , Rocha Brigida
Published: July 2021

Features of negative cloud‐to‐ground (CG) flashes in the eastern Amazon region of Brazil, near the equator line, were analyzed from their wideband (160 Hz–10 MHz) electric field records acquired at the UFPA‐Lightning Research Laboratory in Belem, Para, Brazil in the rainy season of 2020. Records of CG flashes were synchronized in time with the Geostationary Lightning Mapper (GLM) data. We found that the GLM relative detection efficiency for negative CG flashes in the region of study is 78.5%. For a subset of 613 flashes that were detected by the GLM, we segregate the events into three categories (close‐, intermediate‐ and distant‐range) according to the GLM reported locations. Flash multiplicity, interstroke time interval, flash duration, leader duration, preliminary‐breakdown (PB) pulse train duration, PB to first return‐stroke (RS) time interval, and the ratio of PB to first RS are determined for 781 negative CG flashes containing 2,383 strokes. The results were compared with previous results obtained in different parts of the globe with an emphasis on studies performed in similar regions such as in the tropics. For all flashes, the average number of strokes per flash is 3.1 and the percentage of single‐stroke flash is 30%. The geometric mean of interstroke intervals, flash duration, PB to first RS time interval, and PB pulse train duration are 63, 186, 10, and 1.5 ms, respectively.
Robust Meteorological Drought Prediction Using Antecedent SST Fluctuations and Machine Learning
Authors: Li Jun , Wang Zhaoli , Wu Xushu , Xu Chong‐Yu , Guo Shenglian , Chen Xiaohong , Zhang Zhenxing
Published: July 2021

While reliable drought prediction is fundamental for drought mitigation and water resources management, it is still a challenge to develop robust drought prediction models due to complex local hydro‐climatic conditions and various predictors. Sea surface temperature (SST) is considered as the fundamental predictor to develop drought prediction models. However, traditional models usually extract SST signals from one or several specific sea zones within a given time span, which limits full use of SST signals for drought prediction. Here, we introduce a new meteorological drought prediction approach by using the antecedent SST fluctuation pattern (ASFP) and machine learning techniques (e.g., support vector regression (SVR), random forest (RF), and extreme learning machine (ELM)). Three models (i.e., ASFP‐SVR, ASFP‐ELM, and ASFP‐RF) are developed for ensemble, probability, and deterministic drought predictions. The Colorado, Danube, Orange, and Pearl River basins with frequent droughts over different continents are selected, as the cases, where standardized precipitation evapotranspiration index (SPEI) are predicted at the 1° × 1° resolution with 1‐ and 3‐month lead times. Results show that the ASFP‐ELM model can effectively predict space‐time evolutions of drought events with satisfactory skills, outperforming the ASFP‐SVR and ASFP‐RF models. Our study has potential to provide a reliable tool for drought prediction, which further supports the development of drought early warning systems.
Glaciers and Nutrients in the Canadian Arctic Archipelago Marine System
Authors: Bhatia Maya P. , Waterman Stephanie , Burgess David O. , Williams Patrick L. , Bundy Randelle M. , Mellett Travis , Roberts Megan , Bertrand Erin M.
Published: July 2021

The Canadian Arctic Archipelago (CAA) is vulnerable to climate warming, and with over 300 tidewater glaciers, is a hotspot for enhanced glacial retreat and meltwater runoff to the ocean. In contrast to Greenlandic and Antarctic systems, CAA glaciers and their impact on the marine environment remain largely unexplored. Here, we investigate how CAA glaciers impact nutrient delivery to surface waters. We compare water column properties in the nearshore coastal zone along a continuum of locations, spanning those with glaciers (glacierized) to those without (non‐glacierized), in Jones Sound, eastern CAA. We find that surface waters of glacierized regions contain significantly more macronutrients (nitrogen, silica, phosphorus) and micronutrients (iron, manganese) than their non‐glacierized counterparts. Water column structure and chemical composition suggest that macronutrient enrichments are a result of upwelling induced by rising submarine discharge plumes, while micronutrient enrichments are delivered directly by glacial discharge. Generally, the strength of upwelling and associated macronutrient delivery scales with the subglacial meltwater discharge. Glacier‐driven delivery of the limiting macronutrient, nitrate, is of particular importance for local productivity, while metal delivery may have consequences for regional micronutrient cycling given Jones Sound's important role in modifying water masses flowing into the North Atlantic. Finally, we use the natural variability in glacier characteristics observed in Jones Sound to consider, how nutrient delivery may be affected as glaciers retreat. The impacts of melting glaciers on marine ecosystems through both these mechanisms will likely be amplified with increased meltwater fluxes in the short term, but eventually muted as CAA ice masses diminish.
Biogeochemical Cycling of Colloidal Trace Metals in the Arctic Cryosphere
Authors: Jensen Laramie T. , Lanning Nathan T. , Marsay Chris M. , Buck Clifton S. , Aguilar‐Islas Ana M. , Rember Robert , Landing William M. , Sherrell Robert M. , Fitzsimmons Jessica N.
Published: July 2021

The surface waters of the Arctic Ocean include an important inventory of freshwater from rivers, sea ice melt, and glacial meltwaters. While some freshwaters are mixed directly into the surface ocean, cryospheric reservoirs, such as snow, sea ice, and melt ponds act as incubators for trace metals, as well as potential sources to the surface ocean upon melting. The availability and reactivity of these metals depends on their speciation, which may vary across each pool or undergo transformation upon mixing. We present here baseline measurements of colloidal (∼0.003–0.200 μm) iron (Fe), zinc (Zn), nickel (Ni), copper (Cu), cadmium (Cd), and manganese (Mn) in snow, sea ice, melt ponds, and the underlying seawater. We consider both the total concentration of colloidal metals ([cMe]) in each cryospheric reservoir and the contribution of cMe to the overall dissolved metal phase (%cMe). Notably, snow contained higher (cMe) as well as higher %cMe relative to seawater for metals such as Fe and Zn across most stations. Stations close to the North Pole had relatively high aerosol deposition, imparting high (cFe) and (cZn), as well as high %cFe, %cZn, %cMn, and %cCd (>80%). In contrast, surface seawater concentrations of Cd, Cu, Mn, and Ni were dominated by the soluble phase (<0.003 μm), suggesting little impact of cMe from the melting cryosphere, or rapid aggregation/disaggregation dynamics within surface waters leading to the loss of cMe. This has important implications for how trace metal biogeochemistry speciation and thus fluxes may change in a future ice‐free Arctic Ocean.
Mean Dynamics and Elevation‐Contributing Area Covariance in Landscape Evolution Models
Authors: Hooshyar Milad , Porporato Amilcare
Published: July 2021

The temporal dynamics of the land surface are commonly modeled by so‐called landscape evolution models, consisting of coupled partial differential equations accounting for the balance of sediment and water. An average sediment budget equation for a landscape evolution model in detachment‐limited condition is derived in terms of curvature‐dependent and curvature‐independent components. This highlights the role of plane curvature and spatial distribution of surface divergence/convergence on the average erosion rate. Performing a Reynolds‐type averaging of the original equations leads to a decomposition of the erosion into an unchannelized erosion sink and a channelization sediment flux. The latter is the derivative of a potential (referred to as “channelization sediment potential”) that arises from the negative correlation of elevation and specific drainage area and closely resembles, in both form and behavior, the Reynolds stress in fluid turbulence. The negative elevation‐area covariance emerges as a statistical signature of surface channelization. Building on analogies between landscape channelization and fluid turbulence, these theoretical results may provide a path to estimate model parameters from observations and offer useful benchmarks for numerical simulations in the channelized regime.
Long-term activity of tandem CD19/CD20 CAR therapy in refractory/relapsed B-cell lymphoma: a single-arm, phase 1–2 trial
Authors: Zhang Yajing , Wang Yao , Liu Yang , Tong Chuan , Wang Chunmeng , Guo Yelei , Ti Dongdong , Yang Qingming , Qiao Shen , Wu Zhiqiang , Han Weidong
Published: July 2021

Increasing the remission rate and reducing the recurrence rate can improve the clinical efficacy of chimeric antigen receptor (CAR) T cell therapy in recurrent/refractory non-Hodgkin lymphoma (r/rNHL). In this open-label, single-arm phase I/II trial, 87 patients with r/rNHL, including 58 patients with aggressive diffuse large B-cell lymphoma and 24 with high tumour burden, received an infusion at doses of 0.5 × 106–8 × 106 TanCAR7 T cells per kilogram of body weight after conditioning chemotherapy. The best overall response rate was 78% (95% confidence interval [CI], 68–86); response rates were consistent across prognostic subgroups. The median follow-up was 27.7 months. The median progression-free survival was 27.6 months (95% CI, 11 to not reached). Cytokine release syndrome (CRS) occurred in 61 patients (70%) with 60% of cases being grade 1 or 2 and 10% being grade 3 or greater. Grade 3 CAR T cell-related encephalopathy syndrome (CRES) occurred in 2 patients (2%). Two patients died from treatment-associated severe pulmonary infection, and one died from CRS-related pulmonary injury between 1 and 3 months post infusion. Long-term remissions were observed following the use of TanCAR7 T cells in r/rNHL with a safety profile that included CRS but few cases of CRES.
Tumour heterogeneity and evolutionary dynamics in colorectal cancer
Authors: Chan Dedrick Kok Hong , Buczacki Simon James Alexander
Published: July 2021

Colorectal cancer (CRC) has a global burden of disease. Our current understanding of CRC has progressed from initial discoveries which focused on the stepwise accumulation of key driver mutations, as encapsulated in the Vogelstein model, to one in which marked heterogeneity leads to a complex interplay between clonal populations. Current evidence suggests that an initial explosion, or “Big Bang”, of genetic diversity is followed by a period of neutral dynamics. A thorough understanding of this interplay between clonal populations during neutral evolution gives insights into the roles in which driver genes may participate in the progress from normal colonic epithelium to adenoma and carcinoma. Recent advances have focused not only on genetics, transcriptomics, and proteomics but have also investigated the ecological and evolutionary processes which transform normal cells into cancer. This review first describes the role which driver mutations play in the Vogelstein model and subsequently demonstrates the evidence which supports a more complex model. This article also aims to underscore the significance of tumour heterogeneity and diverse clonal populations in cancer progression.
Cytokinin drives assembly of the phyllosphere microbiome and promotes disease resistance through structural and chemical cues
Authors: Gupta Rupali , Elkabetz Dorin , Leibman-Markus Meirav , Sayas Tali , Schneider Anat , Jami Elie , Kleiman Maya , Bar Maya
Published: July 2021

The plant hormone cytokinin (CK) is an important developmental regulator, promoting morphogenesis and delaying differentiation and senescence. From developmental processes, to growth, to stress tolerance, CKs are central in plant life. CKs are also known to mediate plant immunity and disease resistance, and several classes of microbes can also produce CKs, affecting the interaction with their plant hosts. While host species and genotype can be a driving force in shaping the plant microbiome, how plant developmental hormones such as CK can shape the microbiome is largely uninvestigated. Here, we examined the relationship between CK and the phyllosphere microbiome, finding that CK acts as a selective force in microbiome assembly, increasing richness, and promoting the presence of Firmicutes. CK-mediated immunity was found to partially depend on the microbial community, and bacilli isolated from previously described CK-rich plant genotypes, which overexpress a CK biosynthesis gene or have increased CK sensitivity, induced plant immunity, and promoted disease resistance. Using a biomimetic system, we investigated the relationship between the leaf microstructure, which is differentially patterned upon changes in CK content or signaling, and the growth of different phyllosphere microbes. We found that leaf structures derived from CK-rich plant genotypes support bacilli in the biomimetic system. CK was able to promote the growth, swarming, and biofilm formation of immunity inducing bacillus isolates in vitro. Overall, our results indicate that host genotype and hormonal profiles can act as a strong selective force in microbiome assembly, underlying differential immunity profiles, and pathogen resistance as a result.
PLEKHO2 inhibits TNFα-induced cell death by suppressing RIPK1 activation
Authors: Zhou Chenchen , Zhang Xueli , Yang Cuiping , He Yuan , Zhang Luo
Published: July 2021

Receptor interaction protein kinase 1 (RIPK1) plays a diverse role in tumor necrosis factor α (TNFα) signalings. The ubiquitination of RIPK1 is essential for NF-κB activation, whereas its kinase activity promotes apoptosis and necroptosis. However, the mechanisms underlying have not been fully illuminated. Here we report that PH domain-containing family O member 2 (PLEKHO2) inhibits RIPK1-dependent cell death and is necessary for NF-κB activation in response to TNFα. Cells of PLKEHO2 deficiency are more susceptible to TNF-α induced apoptosis and necroptosis with increased RIPK1 activation, which is consistent with the observation that the susceptibility of PLEKHO2−/− cells is effectively prevented by treatment of RIPK1 kinase inhibitor. Moreover, PLEKHO2 deficient cells exhibit compromised RIPK1 ubiquitination and NF-κB activation in response to TNFα. Ultimately, PLEKHO2-deficient mice display greatly increased hepatotoxicity and lethality after TNFα-induced hepatitis. In summary, our study revealed that PLEKHO2 is a novel inhibitor of apoptosis and necroptosis, which plays a key role in regulating RIPK1 ubiquitination and activation
Melatonin inhibits triple-negative breast cancer progression through the Lnc049808-FUNDC1 pathway
Authors: Yang Anli , Peng Fu , Zhu Lewei , Li Xing , Ou Shunling , Huang Zhongying , Wu Song , Peng Cheng , Liu Peng , Kong Yanan
Published: July 2021

Melatonin has been reported to have tumor-suppressive effects via comprehensive molecular mechanisms, and long non-coding RNAs (lncRNAs) may participate in this process. However, the mechanism by which melatonin affects the function of lncRNAs in triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, is still unknown. Therefore, we aimed to investigate the differentially expressed mRNAs and lncRNAs in melatonin-treated TNBC cells and the interaction mechanisms. Microarray analyses were performed to identify differentially expressed mRNAs and lncRNAs in TNBC cell lines after melatonin treatment. To explore the functions and underlying mechanisms of the mRNAs and lncRNAs candidates, a series of in vitro experiments were conducted, including CCK-8, Transwell, colony formation, luciferase reporter gene, and RNA immunoprecipitation (RIP) assays, and mouse xenograft models were established. We found that after melatonin treatment, FUNDC1 and lnc049808 downregulated in TNBC cell lines. Knockdown of FUNDC1 and lnc049808 inhibited TNBC cell proliferation, invasion, and metastasis. Moreover, lnc049808 and FUNDC1 acted as competing endogenous RNAs (ceRNAs) for binding to miR-101. These findings indicated that melatonin inhibited TNBC progression through the lnc049808-FUNDC1 pathway and melatonin could be used as a potential therapeutic agent for TNBC.
Recent advances in organic luminescent materials with narrowband emission
Authors: Ha Jung Min , Hur Seon Hyoung , Pathak Ambika , Jeong Ji-Eun , Woo Han Young
Published: July 2021

The International Telecommunication Union announced a new color gamut standard of broadcast service television (BT 2020) for ultra-high-definition TV in 2012. To satisfy the wide-color gamut standard of BT 2020, monochromatic red (R), green (G), and blue (B) emissions require a small full width at half-maximum, which is an important property for improving color purity. Although organic light-emitting diode (OLED) displays are currently one of the main types of display technologies, their broad emission via strong vibronic coupling between ground and excited states is a major hurdle to overcome in the development of next-generation wide-color gamut displays. Thus, the development of OLED emitters with narrowband R–G–B emissions is of great significance. In this review, the recent progress in the development of OLED materials with narrowband emission is summarized by grouping them into fluorescent, phosphorescent, and thermally activated delayed fluorescent emitters to reveal the correlation between molecular structures, optical properties, and device characteristics. We discuss rational molecular design strategies to achieve narrow photoluminescence and electroluminescence and the underlying mechanisms for controlling the emission bandwidth. Finally, the challenges in the realization of wide-color gamut OLED displays and the future prospects of such devices are discussed.
SARS-CoV-2 infection induces the dedifferentiation of multiciliated cells and impairs mucociliary clearance
Authors: Robinot Rémy , Hubert Mathieu , de Melo Guilherme Dias , Lazarini Françoise , Bruel Timothée , Smith Nikaïa , Levallois Sylvain , Larrous Florence , Fernandes Julien , Gellenoncourt Stacy , Rigaud Stéphane , Gorgette Olivier , Thouvenot Catherine , Trébeau Céline , Mallet Adeline , Duménil Guillaume , Gobaa Samy , Etournay Raphaël , Lledo Pierre-Marie , Lecuit Marc , Bourhy Hervé , Duffy Darragh , Michel Vincent , Schwartz Olivier , Chakrabarti Lisa A.
Published: July 2021

Understanding how SARS-CoV-2 spreads within the respiratory tract is important to define the parameters controlling the severity of COVID-19. Here we examine the functional and structural consequences of SARS-CoV-2 infection in a reconstructed human bronchial epithelium model. SARS-CoV-2 replication causes a transient decrease in epithelial barrier function and disruption of tight junctions, though viral particle crossing remains limited. Rather, SARS-CoV-2 replication leads to a rapid loss of the ciliary layer, characterized at the ultrastructural level by axoneme loss and misorientation of remaining basal bodies. Downregulation of the master regulator of ciliogenesis Foxj1 occurs prior to extensive cilia loss, implicating this transcription factor in the dedifferentiation of ciliated cells. Motile cilia function is compromised by SARS-CoV-2 infection, as measured in a mucociliary clearance assay. Epithelial defense mechanisms, including basal cell mobilization and interferon-lambda induction, ramp up only after the initiation of cilia damage. Analysis of SARS-CoV-2 infection in Syrian hamsters further demonstrates the loss of motile cilia in vivo. This study identifies cilia damage as a pathogenic mechanism that could facilitate SARS-CoV-2 spread to the deeper lung parenchyma.
Glucocorticoid receptor triggers a reversible drug-tolerant dormancy state with acquired therapeutic vulnerabilities in lung cancer
Authors: Prekovic Stefan , Schuurman Karianne , Mayayo-Peralta Isabel , Manjón Anna G. , Buijs Mark , Yavuz Selçuk , Wellenstein Max D. , Barrera Alejandro , Monkhorst Kim , Huber Anne , Morris Ben , Lieftink Cor , Chalkiadakis Theofilos , Alkan Ferhat , Silva Joana , Győrffy Balázs , Hoekman Liesbeth , van den Broek Bram , Teunissen Hans , Debets Donna O. , Severson Tesa , Jonkers Jos , Reddy Timothy , de Visser Karin E. , Faller William , Beijersbergen Roderick , Altelaar Maarten , de Wit Elzo , Medema Rene , Zwart Wilbert
Published: July 2021

The glucocorticoid receptor (GR) regulates gene expression, governing aspects of homeostasis, but is also involved in cancer. Pharmacological GR activation is frequently used to alleviate therapy-related side-effects. While prior studies have shown GR activation might also have anti-proliferative action on tumours, the underpinnings of glucocorticoid action and its direct effectors in non-lymphoid solid cancers remain elusive. Here, we study the mechanisms of glucocorticoid response, focusing on lung cancer. We show that GR activation induces reversible cancer cell dormancy characterised by anticancer drug tolerance, and activation of growth factor survival signalling accompanied by vulnerability to inhibitors. GR-induced dormancy is dependent on a single GR-target gene,CDKN1C, regulated through chromatin looping of a GR-occupied upstream distal enhancer in a SWI/SNF-dependent fashion. These insights illustrate the importance of GR signalling in non-lymphoid solid cancer biology, particularly in lung cancer, and warrant caution for use of glucocorticoids in treatment of anticancer therapy related side-effects.
A small molecule that induces translational readthrough of CFTR nonsense mutations by eRF1 depletion
Authors: Sharma Jyoti , Du Ming , Wong Eric , Mutyam Venkateshwar , Li Yao , Chen Jianguo , Wangen Jamie , Thrasher Kari , Fu Lianwu , Peng Ning , Tang Liping , Liu Kaimao , Mathew Bini , Bostwick Robert J. , Augelli-Szafran Corinne E. , Bihler Hermann , Liang Feng , Mahiou Jerome , Saltz Josef , Rab Andras , Hong Jeong , Sorscher Eric J. , Mendenhall Eric M. , Coppola Candice J. , Keeling Kim M. , Green Rachel , Mense Martin , Suto Mark J. , Rowe Steven M. , Bedwell David M.
Published: July 2021

Premature termination codons (PTCs) prevent translation of a full-length protein and trigger nonsense-mediated mRNA decay (NMD). Nonsense suppression (also termed readthrough) therapy restores protein function by selectively suppressing translation termination at PTCs. Poor efficacy of current readthrough agents prompted us to search for better compounds. An NMD-sensitive NanoLuc readthrough reporter was used to screen 771,345 compounds. Among the 180 compounds identified with readthrough activity, SRI-37240 and its more potent derivative SRI-41315, induce a prolonged pause at stop codons and suppress PTCs associated with cystic fibrosis in immortalized and primary human bronchial epithelial cells, restoring CFTR expression and function. SRI-41315 suppresses PTCs by reducing the abundance of the termination factor eRF1. SRI-41315 also potentiates aminoglycoside-mediated readthrough, leading to synergistic increases in CFTR activity. Combining readthrough agents that target distinct components of the translation machinery is a promising treatment strategy for diseases caused by PTCs.
Near-field thermophotovoltaics for efficient heat to electricity conversion at high power density
Authors: Mittapally Rohith , Lee Byungjun , Zhu Linxiao , Reihani Amin , Lim Ju Won , Fan Dejiu , Forrest Stephen R. , Reddy Pramod , Meyhofer Edgar
Published: July 2021

Thermophotovoltaic approaches that take advantage of near-field evanescent modes are being actively explored due to their potential for high-power density and high-efficiency energy conversion. However, progress towards functional near-field thermophotovoltaic devices has been limited by challenges in creating thermally robust planar emitters and photovoltaic cells designed for near-field thermal radiation. Here, we demonstrate record power densities of ~5 kW/m2 at an efficiency of 6.8%, where the efficiency of the system is defined as the ratio of the electrical power output of the PV cell to the radiative heat transfer from the emitter to the PV cell. This was accomplished by developing novel emitter devices that can sustain temperatures as high as 1270 K and positioning them into the near-field (<100 nm) of custom-fabricated InGaAs-based thin film photovoltaic cells. In addition to demonstrating efficient heat-to-electricity conversion at high power density, we report the performance of thermophotovoltaic devices across a range of emitter temperatures (~800 K–1270 K) and gap sizes (70 nm–7 µm). The methods and insights achieved in this work represent a critical step towards understanding the fundamental principles of harvesting thermal energy in the near-field.
Diffusion controls the ventilation of a Pacific Shadow Zone above abyssal overturning
Authors: Holzer Mark , DeVries Tim , de Lavergne Casimir
Published: July 2021

Mid-depth North Pacific waters are rich in nutrients and respired carbon accumulated over centuries. The rates and pathways with which these waters exchange with the surface ocean are uncertain, with divergent paradigms of the Pacific overturning: one envisions bottom waters upwelling to 1.5 km depth; the other confines overturning beneath a mid-depth Pacific shadow zone (PSZ) shielded from mean advection. Here global inverse modelling reveals a PSZ where mean ages exceed 1400 years with overturning beneath. The PSZ is supplied primarily by Antarctic and North-Atlantic ventilated waters diffusing from below and from the south. Half of PSZ waters re-surface in the Southern Ocean, a quarter in the subarctic Pacific. The abyssal North Pacific, despite strong overturning, has mean re-surfacing times also exceeding 1400 years because of diffusion into the overlying PSZ. These results imply that diffusive transports – distinct from overturning transports – are a leading control on Pacific nutrient and carbon storage.
Interplay and cooperation between SREBF1 and master transcription factors regulate lipid metabolism and tumor-promoting pathways in squamous cancer
Authors: Li Li-Yan , Yang Qian , Jiang Yan-Yi , Yang Wei , Jiang Yuan , Li Xiang , Hazawa Masaharu , Zhou Bo , Huang Guo-Wei , Xu Xiu-E , Gery Sigal , Zhang Ying , Ding Ling-Wen , Ho Allen S. , Zumsteg Zachary S. , Wang Ming-Rong , Fullwood Melissa J. , Freedland Stephen J. , Meltzer Stephen J. , Xu Li-Yan , Li En-Min , Koeffler H. Phillip , Lin De-Chen
Published: July 2021

Squamous cell carcinomas (SCCs) comprise one of the most common histologic types of human cancer. Transcriptional dysregulation of SCC cells is orchestrated by tumor protein p63 (TP63), a master transcription factor (TF) and a well-researched SCC-specific oncogene. In the present study, both Gene Set Enrichment Analysis (GSEA) of SCC patient samples and in vitro loss-of-function assays establish fatty-acid metabolism as a key pathway downstream of TP63. Further studies identify sterol regulatory element binding transcription factor 1 (SREBF1) as a central mediator linking TP63 with fatty-acid metabolism, which regulates the biosynthesis of fatty-acids, sphingolipids (SL), and glycerophospholipids (GPL), as revealed by liquid chromatography tandem mass spectrometry (LC-MS/MS)-based lipidomics. Moreover, a feedback co-regulatory loop consisting of SREBF1/TP63/Kruppel like factor 5 (KLF5) is identified, which promotes overexpression of all three TFs in SCCs. Downstream of SREBF1, a non-canonical, SCC-specific function is elucidated: SREBF1 cooperates with TP63/KLF5 to regulate hundreds of cis-regulatory elements across the SCC epigenome, which converge on activating cancer-promoting pathways. Indeed, SREBF1 is essential for SCC viability and migration, and its overexpression is associated with poor survival in SCC patients. Taken together, these data shed light on mechanisms of transcriptional dysregulation in cancer, identify specific epigenetic regulators of lipid metabolism, and uncover SREBF1 as a potential therapeutic target and prognostic marker in SCC.
Si-C is a method for inferring super-resolution intact genome structure from single-cell Hi-C data
Authors: Meng Luming , Wang Chenxi , Shi Yi , Luo Qiong
Published: July 2021

There is a strong demand for methods that can efficiently reconstruct valid super-resolution intact genome 3D structures from sparse and noise single-cell Hi-C data. Here, we develop Single-Cell Chromosome Conformation Calculator (Si-C) within the Bayesian theory framework and apply this approach to reconstruct intact genome 3D structures from single-cell Hi-C data of eight G1-phase haploid mouse ES cells. The inferred 100-kb and 10-kb structures consistently reproduce the known conserved features of chromatin organization revealed by independent imaging experiments. The analysis of the 10-kb resolution 3D structures reveals cell-to-cell varying domain structures in individual cells and hyperfine structures in domains, such as loops. An average of 0.2 contact reads per divided bin is sufficient for Si-C to obtain reliable structures. The valid super-resolution structures constructed by Si-C demonstrate the potential for visualizing and investigating interactions between all chromatin loci at the genome scale in individual cells.
Abraxas suppresses DNA end resection and limits break-induced replication by controlling SLX4/MUS81 chromatin loading in response to TOP1 inhibitor-induced DNA damage
Authors: Wu Xiao , Wang Bin
Published: July 2021

Although homologous recombination (HR) is indicated as a high-fidelity repair mechanism, break-induced replication (BIR), a subtype of HR, is a mutagenic mechanism that leads to chromosome rearrangements. It remains poorly understood how cells suppress mutagenic BIR. Trapping of Topoisomerase 1 by camptothecin (CPT) in a cleavage complex on the DNA can be transformed into single-ended double-strand breaks (seDSBs) upon DNA replication or colliding with transcriptional machinery. Here, we demonstrate a role of Abraxas in limiting seDSBs undergoing BIR-dependent mitotic DNA synthesis. Through counteracting K63-linked ubiquitin modification, Abraxas restricts SLX4/Mus81 recruitment to CPT damage sites for cleavage and subsequent resection processed by MRE11 endonuclease, CtIP, and DNA2/BLM. Uncontrolled SLX4/MUS81 loading and excessive end resection due to Abraxas-deficiency leads to increased mitotic DNA synthesis via RAD52- and POLD3- dependent, RAD51-independent BIR and extensive chromosome aberrations. Our work implicates Abraxas/BRCA1-A complex as a critical regulator that restrains BIR for protection of genome stability.
GazeBase, a large-scale, multi-stimulus, longitudinal eye movement dataset
Authors: Griffith Henry , Lohr Dillon , Abdulin Evgeny , Komogortsev Oleg
Published: July 2021

This manuscript presents GazeBase, a large-scale longitudinal dataset containing 12,334 monocular eye-movement recordings captured from 322 college-aged participants. Participants completed a battery of seven tasks in two contiguous sessions during each round of recording, including a – (1) fixation task, (2) horizontal saccade task, (3) random oblique saccade task, (4) reading task, (5/6) free viewing of cinematic video task, and (7) gaze-driven gaming task. Nine rounds of recording were conducted over a 37 month period, with participants in each subsequent round recruited exclusively from prior rounds. All data was collected using an EyeLink 1000 eye tracker at a 1,000 Hz sampling rate, with a calibration and validation protocol performed before each task to ensure data quality. Due to its large number of participants and longitudinal nature, GazeBase is well suited for exploring research hypotheses in eye movement biometrics, along with other applications applying machine learning to eye movement signal analysis. Classification labels produced by the instrument’s real-time parser are provided for a subset of GazeBase, along with pupil area.
A database of submarine landslides offshore West and Southwest Iberia
Authors: Gamboa Davide , Omira Rachid , Terrinha Pedro
Published: July 2021

Submarine landslides are major geohazards occurring on distinct seabed domains ranging from shallow coastal areas to the deeper points of the ocean. The nature and relief of the seabed are key factors influencing the location and size of submarine landslides. Efforts have recently been made to compile databases of submarine landslide distribution and morphometry, a crucial task to assess submarine geohazards. The MAGICLAND (Marine Geo-hazards Induced by underwater Landslides in the SW Iberian Margin) database here presented contributed to that assessment offshore Portugal. Based on EMODnet bathymetric DEMs and GIS analysis, the morphometric properties of 1552 submarine landslides were analysed and wealth of 40 parameters was obtained. This dataset is now made available for the free use and benefit of the international marine community. Further contributions or analysis based on, and complementing the MAGICLAND database will be welcome.
Clinical characteristics of optic neuritis phenotypes in a 3-year follow-up Chinese cohort
Authors: Feng Chaoyi , Chen Qian , Zhao Guixian , Li Zhenxin , Chen Weimin , Sha Yan , Sun Xinghuai , Wang Min , Tian Guohong
Published: July 2021

To evaluate the clinical characteristics of optic neuritis (ON) with different phenotypes. This prospective study recruited patients with new-onset ON between January 2015 and March 2017 who were followed-up for 3 years. They were divided into the myelin oligodendrocyte glycoprotein-seropositive (MOG-ON), aquaporin-4-seropositive (AQP4-ON), and double-seronegative (seronegative-ON) groups, and their clinical characteristics and imaging findings were evaluated and compared. Two-hundred-eighty patients (405 eyes) were included (MOG-ON: n = 57, 20.4%; AQP4-ON: n = 98, 35.0%; seronegative-ON: n = 125, 44.6%). The proportion of eyes with best-corrected visual acuity > 20/25 at the 3-year follow-up was similar between the MOG-ON and seronegative-ON groups; the proportion in both groups was higher than that in the AQP4-ON group (p < 0.001). Relapse rates were higher in the MOG-ON and AQP4-ON groups than in the seronegative-ON group (p < 0.001). Average retinal nerve fiber layer (RNFL) thickness at 3 years was similar between the MOG-ON and AQP4-ON groups (63.41 ± 13.39 and 59.40 ± 11.46 μm, p = 0.476) but both were thinner than the seronegative-ON group (74.06 ± 11.14 μm, p < 0.001). Macular ganglion cell-inner plexiform layer (GCIPL) revealed the same pattern. Despite RNFL and GCIPL thinning, the MOG-ON group’s outcome was as favorable as that of the seronegative-ON group, whereas the AQP4-ON group showed unsatisfactory results.
Direct treatment of interaction between laser-field and electrons for simulating laser processing of metals
Authors: Miyamoto Yoshiyuki
Published: July 2021

Laser ablation is often simulated by the two-temperature model in which electrons are assumed to be thermalized by laser irradiation, while an explicit representation of interaction between laser-field and electrons is challenging but beneficial as being free from any adjustable parameters. Here, an ab initio method based on the time-dependent density functional theory (TDDFT) in which electron-ion dynamics under a laser field are numerically simulated is examined as a tool for simulating femtosecond laser processing of metals. Laser-induced volume expansion in surface normal directions of Cu(111) and Ni(111) surfaces are simulated by using repeating slab models. The amount of simulated volume expansion is compared between Cu(111) and Ni(111) slabs for the same laser pulse conditions, and the Ni slab is found to expand more than the Cu slab despite the smaller thermal expansion coefficient of Ni compared with Cu. The analyzed electronic excitation and lattice motion were compared to those in the two-temperature model. The threshold fluence to release surface Cu atom deduced from current TDDFT approach is found to be comparable to those of Cu ablation reported experimentally.
Multidisciplinary assessment of the Abbott BinaxNOW SARS-CoV-2 point-of-care antigen test in the context of emerging viral variants and self-administration
Authors: Frediani Jennifer K. , Levy Joshua M. , Rao Anuradha , Bassit Leda , Figueroa Janet , Vos Miriam B. , Wood Anna , Jerris Robert , Van Leung-Pineda  , Gonzalez Mark D. , Rogers Beverly B. , Mavigner Maud , Schinazi Raymond F. , Schoof Nils , Waggoner Jesse J. , Kempker Russell R. , Rebolledo Paulina A. , O’Neal Jared W. , Stone Cheryl , Chahroudi Ann , Morris Claudia R. , Suessmith Allie , Sullivan Julie , Farmer Sarah , Foster Amanda , Roback John D. , Ramachandra Thanuja , Washington CaDeidre , Le Kristie , Cordero Maria C. , Esper Annette , Nehl Eric J. , Wang Yun F. , Tyburski Erika A. , Martin Greg S. , Lam Wilbur A.
Published: July 2021

While there has been significant progress in the development of rapid COVID-19 diagnostics, as the pandemic unfolds, new challenges have emerged, including whether these technologies can reliably detect the more infectious variants of concern and be viably deployed in non-clinical settings as “self-tests”. Multidisciplinary evaluation of the Abbott BinaxNOW COVID-19 Ag Card (BinaxNOW, a widely used rapid antigen test, included limit of detection, variant detection, test performance across different age-groups, and usability with self/caregiver-administration. While BinaxNOW detected the highly infectious variants, B.1.1.7 (Alpha) first identified in the UK, B.1.351 (Beta) first identified in South Africa, P.1 (Gamma) first identified in Brazil, B.1.617.2 (Delta) first identified in India and B.1.2, a non-VOC, test sensitivity decreased with decreasing viral loads. Moreover, BinaxNOW sensitivity trended lower when devices were performed by patients/caregivers themselves compared to trained clinical staff, despite universally high usability assessments following self/caregiver-administration among different age groups. Overall, these data indicate that while BinaxNOW accurately detects the new viral variants, as rapid COVID-19 tests enter the home, their already lower sensitivities compared to RT-PCR may decrease even more due to user error.
Origin of light instability in amorphous IGZO thin-film transistors and its suppression
Authors: Mativenga Mallory , Haque Farjana , Billah Mohammad Masum , Um Jae Gwang
Published: July 2021

Radiating amorphous In–Ga–Zn–O (a-IGZO) thin-film transistors (TFTs) with deep ultraviolet light (λ = 175 nm) is found to induce rigid negative threshold-voltage shift, as well as a subthreshold hump and an increase in subthreshold-voltage slope. These changes are attributed to the photo creation and ionization of oxygen vacancy states (VO), which are confined mainly to the top surface of the a-IGZO film (backchannel). Photoionization of these states generates free electrons and the transition from the neutral to the ionized VO is accompanied by lattice relaxation, which raises the energy of the ionized VO. This and the possibility of atomic exchange with weakly bonded hydrogen leads to metastability of the ionized VO, consistent with the rigid threshold-voltage shift and increase in subthreshold-voltage slope. The hump is thus a manifestation of the highly conductive backchannel and its formation can be suppressed by reduction of the a-IGZO film thickness or application of a back bias after radiation. These results support photo creation and ionization of VO as the main cause of light instability in a-IGZO TFTs and provide some insights on how to minimize the effect.
Circulating tumor cell copy-number heterogeneity in ALK-rearranged non-small-cell lung cancer resistant to ALK inhibitors
Authors: Oulhen Marianne , Pawlikowska Patrycja , Tayoun Tala , Garonzi Marianna , Buson Genny , Forcato Claudio , Manaresi Nicolò , Aberlenc Agathe , Mezquita Laura , Lecluse Yann , Lavaud Pernelle , Naltet Charles , Planchard David , Besse Benjamin , Farace Françoise
Published: July 2021

Gatekeeper mutations are identified in only 50% of the cases at resistance to Anaplastic Lymphoma Kinase (ALK)-tyrosine kinase inhibitors (TKIs). Circulating tumor cells (CTCs) are relevant tools to identify additional resistance mechanisms and can be sequenced at the single-cell level. Here, we provide in-depth investigation of copy number alteration (CNA) heterogeneity in phenotypically characterized CTCs at resistance to ALK-TKIs in ALK-positive non-small cell lung cancer. Single CTC isolation and phenotyping were performed by DEPArray or fluorescence-activated cell sorting following enrichment and immunofluorescence staining (ALK/cytokeratins/CD45/Hoechst). CNA heterogeneity was evaluated in six ALK-rearranged patients harboring ≥ 10 CTCs/20 mL blood at resistance to 1st and 3rd ALK-TKIs and one presented gatekeeper mutations. Out of 82 CTCs isolated by FACS, 30 (37%) were ALK+/cytokeratins-, 46 (56%) ALK-/cytokeratins+ and 4 (5%) ALK+/cytokeratins+. Sequencing of 43 CTCs showed highly altered CNA profiles and high levels of chromosomal instability (CIN). Half of CTCs displayed a ploidy >2n and 32% experienced whole-genome doubling. Hierarchical clustering showed significant intra-patient and wide inter-patient CTC diversity. Classification of 121 oncogenic drivers revealed the predominant activation of cell cycle and DNA repair pathways and of RTK/RAS and PI3K to a lower frequency. CTCs showed wide CNA heterogeneity and elevated CIN at resistance to ALK-TKIs. The emergence of epithelial ALK-negative CTCs may drive resistance through activation of bypass signaling pathways, while ALK-rearranged CTCs showed epithelial-to-mesenchymal transition characteristics potentially contributing to ALK-TKI resistance. Comprehensive analysis of CTCs could be of great help to clinicians for precision medicine and resistance to ALK-targeted therapies.
Comprehensive functional evaluation of variants of fibroblast growth factor receptor genes in cancer
Authors: Nakamura Ikuko Takeda , Kohsaka Shinji , Ikegami Masachika , Ikeuchi Hiroshi , Ueno Toshihide , Li Kunhua , Beyett Tyler S. , Koyama Takafumi , Shimizu Toshio , Yamamoto Noboru , Takahashi Fumiyuki , Takahashi Kazuhisa , Eck Michael J. , Mano Hiroyuki
Published: July 2021

Various genetic alterations of the fibroblast growth factor receptor (FGFR) family have been detected across a wide range of cancers. However, inhibition of FGFR signaling by kinase inhibitors demonstrated limited clinical effectiveness. Herein, we evaluated the transforming activity and sensitivity of 160 nonsynonymousFGFRmutations and ten fusion genes to seven FGFR tyrosine kinase inhibitors (TKI) using the mixed-all-nominated-in-one (MANO) method, a high-throughput functional assay. The oncogenicity of 71 mutants was newly discovered in this study. The FGFR TKIs showed anti-proliferative activities against the wild-type FGFRs and their fusions, while several hotspot mutants were relatively resistant to those TKIs. The drug sensitivities assessed with the MANO method were well concordant with those evaluated using in vitro and in vivo assays. Comprehensive analysis of published FGFR structures revealed a possible mechanism through which oncogenicFGFRmutations reduce sensitivity to TKIs. It was further revealed that recurrent compound mutations within FGFRs affect the transforming potential and TKI-sensitivity of corresponding kinases. In conclusion, our study suggests the importance of selecting suitable inhibitors against individualFGFRvariants. Moreover, it reveals the necessity to develop next-generation FGFR inhibitors, which are effective against all oncogenicFGFRvariants.
Cuticular modified air sacs underlie white coloration in the olive fruit fly, Bactrocera oleae
Authors: Rebora Manuela , Salerno Gianandrea , Piersanti Silvana , Kovalev Alexander , Gorb Stanislav
Published: July 2021

Here, the ultrastructure and development of the white patches on thorax and head of Bactrocera oleae are analysed using scanning electron microscopy, transmission electron microscopy, and fluorescence microscopy. Based on these analyses and measurements of patch reflectance spectra, we infer that white patches are due to modified air sacs under transparent cuticle. These air sacs show internal arborisations with beads in an empty space, constituting a three-dimensional photonic solid responsible for light scattering. The white patches also show UV-induced blue autofluorescence due to the air sac resilin content. To the best of our knowledge, this research describes a specialized function for air sacs and the first observation of structural color produced by tracheal structures located under transparent cuticles in insects. Sexual dimorphism in the spectral emission also lays a structural basis for further investigations on the biological role of white patches in B. oleae.
Thermal and mechanical activation of dynamically stable ionic interaction toward self-healing strengthening elastomers
Authors: Peng Yan , Hou Yujia , Wu Qi , Ran Qichao , Huang Guangsu , Wu Jinrong
Published: July 2021

By integrating the intrinsic thermodynamic instability of ionomers and the engineered kinetic stability of ionic interaction with large steric hindrance, a self-healing strengthening material is fabricated for the first time.
Bifunctional citrate-Ni0.9Co0.1(OH)x layer coated fluorine-doped hematite for simultaneous hole extraction and injection towards efficient photoelectrochemical water oxidation
Authors: Wang Peng , Li Feng , Long Xuefeng , Wang Tong , Chai Huan , Yang Honglei , Li Shuwen , Ma Jiantai , Jin Jun
Published: July 2021

Here, the hole extraction of Ni sites and the hole injection of Co sites in the bifunctional Cit-Ni0.9Co0.1(OH)x overlayer contribute to a continuous hole migration pathway from the bulk of the photoanode to the electrolyte.