bluuebunny/crossref_metadata_2025 huggingface dataset:
Venusian Habitable Climate Scenarios: Modeling Venus Through Time and Applications to Slowly Rotating Venus‐Like Exoplanets
Authors: Way M. J. , Del Genio Anthony D.
Published: April 2020

One popular view of Venus' climate history describes a world that has spent much of its life with surface liquid water, plate tectonics, and a stable temperate climate. Part of the basis for this optimistic scenario is the high deuterium to hydrogen ratio from the Pioneer Venus mission that was interpreted to imply Venus had a shallow ocean's worth of water throughout much of its history. Another view is that Venus had a long‐lived (∼100 million years) primordial magma ocean with a CO2and steam atmosphere. Venus' long‐lived steam atmosphere would sufficient time to dissociate most of the water vapor, allow significant hydrogen escape, and oxidize the magma ocean. A third scenario is that Venus had surface water and habitable conditions early in its history for a short period of time (<1 Gyr), but that a moist/runaway greenhouse took effect because of a gradually warming Sun, leaving the planet desiccated ever since. Using a general circulation model, we demonstrate the viability of the first scenario using the few observational constraints available. We further speculate that large igneous provinces and the global resurfacing hundreds of millions of years ago played key roles in ending the clement period in its history and presenting the Venus we see today. The results have implications for what astronomers term “the habitable zone,” and if Venus‐like exoplanets exist with clement conditions akin to modern Earth, we propose to place them in what we term the “optimistic Venus zone.”
Synchronization and Delay Between Circulation Patterns and High Streamflow Events in Germany
Authors: Conticello Federico Rosario , Cioffi Francesco , Lall Upmanu , Merz Bruno
Published: April 2020

River floods cause extensive losses to economy, ecology, and society throughout the world. They are driven by the space‐time structure of catchment rainfall, which is determined by large‐scale, or even global‐scale, atmospheric processes. The identification of coherent, large‐scale atmospheric circulation structures that determine the moisture transport and convergence associated with rainfall‐induced flooding can help improve its predictability and phenomenology. In this paper, we extend a methodology, used for the analysis of extreme rainfall events, to high streamflow events (HSEs). The approach combines multiple machine learning methods to link HSEs to atmospheric circulation patterns. An application to the German streamflow network using reanalysis data for the period 1960 to 2012 is presented. Daily streamflow from 166 gauges, homogeneously distributed across Germany, are used. Geopotential height fields and integrated vapor transport (IVT) are derived from reanalysis data. An unsupervised neural network, Self Organizing Maps, is applied to geopotential height to identify a finite number of circulation patterns (CPs). Event synchronization between CPs and HSEs is used to establish if they are linked or not. If they are linked, the Event Synchronization method computes the delay between the occurrence of a CP and a HSE. Finally, local logistic regression is used to estimate the probability of occurrence of a HSE, as function of CP and IVT. We demonstrate that our approach is very effective to evaluate HSE probability occurrence across Germany.
Publisher Correction: A square-root topological insulator with non-quantized indices realized with photonic Aharonov–Bohm cages
Authors: Kremer Mark , Petrides Ioannis , Meyer Eric , Heinrich Matthias , Zilberberg Oded , Szameit Alexander
Published: April 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Spatiotemporal refinement of signal flow through association cortex during learning
Authors: Gilad Ariel , Helmchen Fritjof
Published: April 2020

Association areas in neocortex encode novel stimulus-outcome relationships, but the principles of their engagement during task learning remain elusive. Using chronic wide-field calcium imaging, we reveal two phases of spatiotemporal refinement of layer 2/3 cortical activity in mice learning whisker-based texture discrimination in the dark. Even before mice reach learning threshold, association cortex—including rostro-lateral (RL), posteromedial (PM), and retrosplenial dorsal (RD) areas—is generally suppressed early during trials (between auditory start cue and whisker-texture touch). As learning proceeds, a spatiotemporal activation sequence builds up, spreading from auditory areas to RL immediately before texture touch (whereas PM and RD remain suppressed) and continuing into barrel cortex, which eventually efficiently discriminates between textures. Additional correlation analysis substantiates this diverging learning-related refinement within association cortex. Our results indicate that a pre-learning phase of general suppression in association cortex precedes a learning-related phase of task-specific signal flow enhancement.
Cysteine synthases CYSL-1 and CYSL-2 mediate C. elegans heritable adaptation to P. vranovensis infection
Authors: Burton Nicholas O. , Riccio Cristian , Dallaire Alexandra , Price Jonathan , Jenkins Benjamin , Koulman Albert , Miska Eric A.
Published: April 2020

Parental exposure to pathogens can prime offspring immunity in diverse organisms. The mechanisms by which this heritable priming occurs are largely unknown. Here we report that the soil bacteria Pseudomonas vranovensis is a natural pathogen of the nematode Caenorhabditis elegans and that parental exposure of animals to P. vranovensis promotes offspring resistance to infection. Furthermore, we demonstrate a multigenerational enhancement of progeny survival when three consecutive generations of animals are exposed to P. vranovensis. By investigating the mechanisms by which animals heritably adapt to P. vranovensis infection, we found that parental infection by P. vranovensis results in increased expression of the cysteine synthases cysl-1 and cysl-2 and the regulator of hypoxia inducible factor rhy-1 in progeny, and that these three genes are required for adaptation to P. vranovensis. These observations establish a CYSL-1, CYSL-2, and RHY-1 dependent mechanism by which animals heritably adapt to infection.
High-throughput discovery of high Curie point two-dimensional ferromagnetic materials
Authors: Kabiraj Arnab , Kumar Mayank , Mahapatra Santanu
Published: April 2020

Databases for two-dimensional materials host numerous ferromagnetic materials without the vital information of Curie temperature since its calculation involves a manually intensive complex process. In this work, we develop a fully automated, hardware-accelerated, dynamic-translation based computer code, which performs first principles-based computations followed by Heisenberg model-based Monte Carlo simulations to estimate the Curie temperature from the crystal structure. We employ this code to conduct a high-throughput scan of 786 materials from a database to discover 26 materials with a Curie point beyond 400 K. For rapid data mining, we further use these results to develop an end-to-end machine learning model with generalized chemical features through an exhaustive search of the model space as well as the hyperparameters. We discover a few more high Curie point materials from different sources using this data-driven model. Such material informatics, which agrees well with recent experiments, is expected to foster practical applications of two-dimensional magnetism.
ATP7B variant c.1934T > G p.Met645Arg causes Wilson disease by promoting exon 6 skipping
Authors: Merico Daniele , Spickett Carl , O’Hara Matthew , Kakaradov Boyko , Deshwar Amit G. , Fradkin Phil , Gandhi Shreshth , Gao Jiexin , Grant Solomon , Kron Ken , Schmitges Frank W. , Shalev Zvi , Sun Mark , Verby Marta , Cahill Matthew , Dowling James J. , Fransson Johan , Wienholds Erno , Frey Brendan J.
Published: April 2020

Wilson disease is a recessive genetic disorder caused by pathogenic loss-of-function variants in the ATP7B gene. It is characterized by disrupted copper homeostasis resulting in liver disease and/or neurological abnormalities. The variant NM_000053.3:c.1934T > G (Met645Arg) has been reported as compound heterozygous, and is highly prevalent among Wilson disease patients of Spanish descent. Accordingly, it is classified as pathogenic by leading molecular diagnostic centers. However, functional studies suggest that the amino acid change does not alter protein function, leading one ClinVar submitter to question its pathogenicity. Here, we used a minigene system and gene-edited HepG2 cells to demonstrate that c.1934T > G causes ~70% skipping of exon 6. Exon 6 skipping results in frameshift and stop-gain, leading to loss of ATP7B function. The elucidation of the mechanistic effect for this variant resolves any doubt about its pathogenicity and enables the development of genetic medicines for restoring correct splicing.
Using syndrome mining with the Health and Retirement Study to identify the deadliest and least deadly frailty syndromes
Authors: Chao Yi-Sheng , Wu Chao-Jung , Wu Hsing-Chien , Hsu Hui-Ting , Tsao Lien-Cheng , Cheng Yen-Po , Lai Yi-Chun , Chen Wei-Chih
Published: April 2020

Syndromes are defined with signs or symptoms that occur together and represent conditions. We use a data-driven approach to identify the deadliest and most death-averse frailty syndromes based on frailty symptoms. A list of 72 frailty symptoms was retrieved based on three frailty indices. We used data from the Health and Retirement Study (HRS), a longitudinal study following Americans aged 50 years and over. Principal component (PC)-based syndromes were derived based on a principal component analysis of the symptoms. Equal-weight 4-item syndromes were the sum of any four symptoms. Discrete-time survival analysis was conducted to compare the predictive power of derived syndromes on mortality. Deadly syndromes were those that significantly predicted mortality with positive regression coefficients and death-averse ones with negative coefficients. There were 2,797 of 5,041 PC-based and 964,774 of 971,635 equal-weight 4-item syndromes significantly associated with mortality. The input symptoms with the largest regression coefficients could be summed with three other input variables with small regression coefficients to constitute the leading deadliest and the most death-averse 4-item equal-weight syndromes. In addition to chance alone, input symptoms’ variances and the regression coefficients or p values regarding mortality prediction are associated with the identification of significant syndromes.
Mutually exclusive locales for N-linked glycans and disorder in human glycoproteins
Authors: Goutham Shyamili , Kumari Indu , Pally Dharma , Singh Alvina , Ghosh Sujasha , Akhter Yusuf , Bhat Ramray
Published: April 2020

Several post-translational protein modifications lie predominantly within regions of disorder: the biased localization has been proposed to expand the binding versatility of disordered regions. However, investigating a representative dataset of 500 human N-glycoproteins, we observed the sites of N-linked glycosylations or N-glycosites, to be predominantly present in the regions of predicted order. When compared with disordered stretches, ordered regions were not found to be enriched for asparagines, serines and threonines, residues that constitute the sequon signature for conjugation of N-glycans. We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures. When compared with control disordered residue stretches without any N-glycosites, N-glycosite neighborhoods were depleted of charged, polar, hydrophobic and flexible residues and enriched for aromatic, accessible and order-promoting residues with a tendency to be part of coiled and β structures. N-glycosite neighborhoods also showed greater phylogenetic conservation among amniotes, compared with control ordered regions, which in turn were more conserved than disordered control regions. Our results lead us to propose that unique primary structural compositions and differential propensities for evolvability allowed for the mutual spatial exclusion of N-glycosite neighborhoods and disordered stretches.
Stable isotopes reveal the importance of seabirds and marine foods in the diet of St Kilda field mice
Authors: Bicknell Anthony W. J. , Walker Benjamin W. , Black Tom , Newton Jason , Pemberton Josephine M. , Luxmoore Richard , Inger Richard , Votier Stephen C.
Published: April 2020

Introduced mammals have devastated island nesting seabird populations worldwide. Declines in breeding seabirds on St Kilda, UK, have been linked to climate change and predation from great skuasStercorarius skuas, but the introduced St Kilda field mouseApodemus sylvaticus hirtensismay also play a role by feeding on adults, chicks or eggs. Here, we use stable isotopes in St Kilda mouse blood and potential dietary items to investigate their foraging ecology, specifically focussing on the importance of seabirds and marine foods in their diet. Mice were seasonally sampled at three sites on Hirta, St Kilda over three consecutive years (2010–2012). The δ13C and δ15N ratios were used in analyses, including isotope niche and dietary source mixing models, to examine foraging behaviour among locations and between seabird breeding seasons. Mice sampled in Carn Mor – where the majority of the island’s seabirds nest - had consistently higher δ13C than other locations throughout the year, with δ15N also being significantly higher for all but one comparison. The isotopic niche width (SEAs) of Carn Mor mice in each season were distinct from the other locations, and became smaller during the seabird breeding season. Dietary mixing models revealed that seabirds made up a large proportion of the diet for mice from Carn Mor, particularly during the seabird breeding season. In conclusion, our work reveals that seabird-derived foods are likely to form a significant part of the diet of St Kilda mice populations located in and around breeding colonies. It is unclear however, whether this is from scavenging or predation of seabirds, or through their discarded food items. Given that mice have had significant effects on seabird populations elsewhere, it is important to carry out further work to determine whether mice are a significant cause of seabird mortality in this island ecosystem.
Acclimation of bacterial cell state for high-throughput enzyme engineering using a DmpR-dependent transcriptional activation system
Authors: Kwon Kil Koang , Yeom Soo-Jin , Choi Su-Lim , Rha Eugene , Lee Hyewon , Kim Haseong , Lee Dae-Hee , Lee Seung-Goo
Published: April 2020

Genetic circuit-based biosensors have emerged as an effective analytical tool in synthetic biology; these biosensors can be applied to high-throughput screening of new biocatalysts and metabolic pathways. Sigma 54 (σ54)-dependent transcription factor (TF) can be a valuable component of these biosensors owing to its intrinsic silent property compared to most of the housekeeping sigma 70 (σ70) TFs. Here, we show that these unique characteristics of σ54-dependent TFs can be used to control the host cell state to be more appropriate for high-throughput screening. The acclimation of cell state was achieved by using guanosine (penta)tetraphosphate ((p)ppGpp)-related genes (relA, spoT) and nutrient conditions, to link the σ54 TF-based reporter expression with the target enzyme activity. By controlling stringent programmed responses and optimizing assay conditions, catalytically improved tyrosine phenol lyase (TPL) enzymes were successfully obtained using a σ54-dependent DmpR as the TF component, demonstrating the practical feasibility of this biosensor. This combinatorial strategy of biosensors using σ factor-dependent TFs will allow for more effective high-throughput enzyme engineering with broad applicability.
Long-term voluntary running prevents the onset of symptomatic Friedreich’s ataxia in mice
Authors: Zhao Henan , Lewellen Bevan M. , Wilson Rebecca J. , Cui Di , Drake Joshua C. , Zhang Mei , Yan Zhen
Published: April 2020

The common clinical symptoms of Friedreich’s ataxia (FRDA) include ataxia, muscle weakness, type 2 diabetes and heart failure, which are caused by impaired mitochondrial function due to the loss of frataxin (FXN) expression. Endurance exercise is the most powerful intervention for promoting mitochondrial function; however, its impact on FRDA has not been studied. Here we found that mice with genetic knockout and knock-in of the Fxn gene (KIKO mice) developed exercise intolerance, glucose intolerance and moderate cardiac dysfunction at 6 months of age. These abnormalities were associated with impaired mitochondrial respiratory function concurrent with reduced iron regulatory protein 1 (Irp1) expression as well as increased oxidative stress, which were not due to loss of mitochondrial content and antioxidant enzyme expression. Importantly, long-term (4 months) voluntary running in KIKO mice starting at a young age (2 months) completely prevented the functional abnormalities along with restored Irp1 expression, improved mitochondrial function and reduced oxidative stress in skeletal muscle without restoring Fxn expression. We conclude that endurance exercise training prevents symptomatic onset of FRDA in mice associated with improved mitochondrial function and reduced oxidative stress. These preclinical findings may pave the way for clinical studies of the impact of endurance exercise in FRDA patients.
Digital Image Analysis of Heterogeneous Tuberculosis Pulmonary Pathology in Non-Clinical Animal Models using Deep Convolutional Neural Networks
Authors: Asay Bryce C. , Edwards Blake Blue , Andrews Jenna , Ramey Michelle E. , Richard Jameson D. , Podell Brendan K. , Gutiérrez Juan F. Muñoz , Frank Chad B. , Magunda Forgivemore , Robertson Gregory T. , Lyons Michael , Ben-Hur Asa , Lenaerts Anne J.
Published: April 2020

Efforts to develop effective and safe drugs for treatment of tuberculosis require preclinical evaluation in animal models. Alongside efficacy testing of novel therapies, effects on pulmonary pathology and disease progression are monitored by using histopathology images from these infected animals. To compare the severity of disease across treatment cohorts, pathologists have historically assigned a semi-quantitative histopathology score that may be subjective in terms of their training, experience, and personal bias. Manual histopathology therefore has limitations regarding reproducibility between studies and pathologists, potentially masking successful treatments. This report describes a pathologist-assistive software tool that reduces these user limitations, while providing a rapid, quantitative scoring system for digital histopathology image analysis. The software, called ‘Lesion Image Recognition and Analysis’ (LIRA), employs convolutional neural networks to classify seven different pathology features, including three different lesion types from pulmonary tissues of the C3HeB/FeJ tuberculosis mouse model. LIRA was developed to improve the efficiency of histopathology analysis for mouse tuberculosis infection models, this approach has also broader applications to other disease models and tissues. The full source code and documentation is available from https://Github.com/TB-imaging/LIRA.
Ospemifene displays broad-spectrum synergistic interactions with itraconazole through potent interference with fungal efflux activities
Authors: Eldesouky Hassan E. , Salama Ehab A. , Hazbun Tony R. , Mayhoub Abdelrahman S. , Seleem Mohamed N.
Published: April 2020

Azole antifungals are vital therapeutic options for treating invasive mycotic infections. However, the emergence of azole-resistant isolates combined with limited therapeutic options presents a growing challenge in medical mycology. To address this issue, we utilized microdilution checkerboard assays to evaluate nine stilbene compounds for their ability to interact synergistically with azole drugs, particularly against azole-resistant fungal isolates. Ospemifene displayed the most potent azole chemosensitizing activity, and its combination with itraconazole displayed broad-spectrum synergistic interactions against Candida albicans, Candida auris, Cryptococcus neoformans, and Aspergillus fumigatus (ΣFICI = 0.05–0.50). Additionally, in a Caenorhabditis elegans infection model, the ospemifene-itraconazole combination significantly reduced fungal CFU burdens in infected nematodes by ~75–96%. Nile Red efflux assays and RT-qPCR analysis suggest ospemifene interferes directly with fungal efflux systems, thus permitting entry of azole drugs into fungal cells. This study identifies ospemifene as a novel antifungal adjuvant that augments the antifungal activity of itraconazole against a broad range of fungal pathogens.
Polyfunctional HIV-1 specific response by CD8+ T lymphocytes expressing high levels of CD300a
Authors: Vitallé Joana , Terrén Iñigo , Gamboa-Urquijo Leire , Orrantia Ane , Tarancón-Díez Laura , Genebat Miguel , Leal Manuel , Ruiz-Mateos Ezequiel , Borrego Francisco , Zenarruzabeitia Olatz
Published: April 2020

CD300a receptor is found on different CD8+ T cell subsets and its expression has been associated to a more cytotoxic molecular signature. CD300a has an important role in some viral infections and its expression levels are known to be modulated by human immunodeficiency virus (HIV)−1 infection on several cell types. The main objective of this work was to investigate CD300a expression and its regulation during HIV-1 specific CD8+ T cell responses. CD300a receptor expression was analysed by multiparametric flow cytometry on CD8+ T lymphocytes from HIV negative donors, naive HIV-1+ individuals and HIV-1+ subjects under suppressive combined antiretroviral therapy (cART). HIV-1 specific CD8+ T cell response was studied by stimulating cells with HIV-1 derived peptides or with a Gag HIV-1 peptide. Our results showed that HIV-1 specific CD8+ T cells expressing higher levels of CD300a were more polyfunctional showing an increased degranulation and cytokine production. Moreover, we observed an up-regulation of CD300a expression after Gag HIV-1 peptide stimulation. Finally, our results demonstrated an inverse correlation between CD300a expression on CD8+ T lymphocytes and HIV disease progression markers. In conclusion, CD300a expression is associated to a better and more polyfunctional HIV-1 specific CD8+ T cell response.
A novel mechanical chest compressor with rapid deployment in all population cardiopulmonary resuscitation
Authors: Sung Chih-Wei , Wang Hung-Chih , Shieh Jiann-Shing , Jaw Fu-Shan
Published: April 2020

Cardiopulmonary resuscitation (CPR) resuscitates patients suffering from cardiac arrest. Mechanical chest compression CPR highlights the need for high CPR quality to facilitate survival and neurological recovery. However, current CPR devices cannot be used on pregnant women or infants. These devices’ long re-setup times interrupt CPR and can cause cerebral ischemia. This study designed a novel device with a crank-sliding mechanism. The polar coordinate system (r, θ, z) shortened the setup time and enabled adjustment without moving the patient. We compared our device with commercial products (e.g., LUCAS-2) by quantifying the compression pressure. Control groups for manual CPR of trained physicians and untrained citizens were recruited. We used Resusci Anne products as models. Our results indicated that our design exhibited performance similar to that of LUCAS-2 in adults (557.8 vs. 623.6 mmHg, p = 0.217) and met the current CPR standard guidelines. Notably, our device is applicable to pregnant women [565 vs. 564.5 (adults) mmHg, p = 0.987] and infants [570.8 vs. 564.5 (adults) mmHg, p = 0.801] without lowering the compression quality. The overall compression quality and stability of mechanical chest compression CPR were favorable to those of manual CPR. Our device provides an innovative prototype for the next generation of CPR facilities.
Reduced microbial diversity induces larger volatile organic compound emissions from soils
Authors: Abis Letizia , Loubet Benjamin , Ciuraru Raluca , Lafouge Florence , Houot Sabine , Nowak Virginie , Tripied Julie , Dequiedt Samuel , Maron Pierre Alain , Sadet-Bourgeteau Sophie
Published: April 2020

Microorganisms in soil are known to be a source and a sink of volatile organic compounds (VOCs). The role of the microbial VOCs on soil ecosystem regulation has been increasingly demonstrated in the recent years. Nevertheless, little is known about the influence of the microbial soil community structure and diversity on VOC emissions. This novel study analyzed the effect of reduced microbial diversity in soil on VOC emissions. We found that reduced levels of microbial diversity in soil increased VOC emissions from soils, while the number of different VOCs emitted decreased. Furthermore, we found that Proteobacteria, Bacteroidetes and fungi phyla were positively correlated to VOC emissions, and other prokaryotic phyla were either negatively correlated or very slightly positively correlated to VOCs emissions. Our interpretation is that Proteobacteria, Bacteroidetes and fungi were VOC producers while the other prokaryotic phyla were consumers. Finally, we discussed the possible role of VOCs as mediators of microbial interactions in soil.
Author Correction: Hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors induce autophagy and have a protective effect in an in-vitro ischaemia model
Authors: Singh Ayesha , Wilson James W. , Schofield Christopher J. , Chen Ruoli
Published: April 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Fine mapping and candidate gene analysis of the white flower gene Brwf in Chinese cabbage (Brassica rapa L.)
Authors: Zhang Ning , Chen Lin , Ma Shuai , Wang Ruofan , He Qiong , Tian Min , Zhang Lugang
Published: April 2020

Flower color can be applied to landscaping and identification of the purity of seeds in hybrid production. However, the molecular basis of white flower trait remains largely unknown inBrassica rapa. In this study, an F2population was constructed from the cross between 15S1040 (white flower) and 92S105 (yellow flower) for fine mapping of white flower genes inB.rapa. Genetic analysis indicated that white flower trait is controlled by two recessive loci,Brwf1andBrwf2. Using InDel and SNP markers,Brwf1was mapped to a 49.6-kb region on chromosome A01 containing 9 annotated genes, and among them,Bra013602encodes a plastid-lipid associated protein (PAP);Brwf2was located in a 59.3-kb interval on chromosome A09 harboring 12 annotated genes, in whichBra031539was annotated as acarotenoid isomerasegene (CRTISO). The amino acid sequences of BrPAP and BrCRTISO were compared between two yellow-flowered and three white-flowered lines and critical amino acid mutations of BrPAP and BrCRTISO were identified between yellow-flowered and white-flowered lines. Therefore,Bra013602andBra031539were predicted as potential candidates for white flower trait. Our results provide a foundation for further identification ofBrwfand increase understanding of the molecular mechanisms underlying white flower formation in Chinese cabbage.
A comparative study of extracellular vesicle-associated and cell-free DNA and RNA for HPV detection in oropharyngeal squamous cell carcinoma
Authors: Nguyen Bella , Meehan Katie , Pereira Michelle R. , Mirzai Bob , Lim Si Hong , Leslie Connull , Clark Michael , Sader Chady , Friedland Peter , Lindsay Andrew , Tang Colin , Millward Michael , Gray Elin S. , Lim Annette M.
Published: April 2020

Purpose: This study compares the detection sensitivity of two separate liquid biopsy sources, cell-free (cf) DNA/RNA and extracellular vesicle (EV)-associated DNA/RNA (EV-DNA/RNA), to identify circulating Human Papilloma Virus (HPV) DNA/RNA in plasma obtained from patients with oropharyngeal squamous cell carcinoma (OPCSCC). We also report on the longitudinal changes observed in HPV-DNA levels in response to treatment. Experimental design: A prospective study was conducted that included 22 patients with locally advanced disease and six patients with metastatic OPCSCC. Twenty-three patients had HPV-related OPCSCC defined by p16 immunohistochemistry. Levels of circulating HPV-DNA and HPV-RNA from plasma-derived cf-DNA/RNA and EV-DNA/RNA were quantified using digital droplet PCR. Results: Circulating HPV-DNA was detected with higher sensitivity in cf-DNA compared to EV-DNA at 91% vs. 42% (p = <0.001). Similarly, circulating tumoral HPV-RNA was detected at a higher sensitivity in cf-RNA compared to EV-RNA, at 83% vs. 50% (p = 0.0019). In the locally advanced cohort, 100% (n = 16) of HPV-OPCSCC patients demonstrated a reduction in circulating HPV-DNA levels in cf-DNA following curative treatment, with 81% of patients demonstrating complete clearance to undetectable levels. However, in metastatic HPV-OPCSCC patients (n = 4), HPV-DNA levels did not correlate with treatment response. Conclusion: Our study demonstrates that although HPV-DNA/RNA can be detected in EV associated DNA/RNA, cf-DNA/RNA is the more sensitive liquid biopsy medium. As circulating HPV-DNA levels were found to only correlate with treatment response in the locally advanced but not metastatic setting in our small cohort of patients, the use of HPV-DNA as a dynamic biomarker to monitor treatment response requires further evaluation.
Separation and identification of an impurity from the istradefylline intermediate
Authors: Xu Haojie , Wang Yiyun , Wang Hongyi , Zheng Zhonghui , Meng Zihui , Xue Min , Xu Zhibin
Published: April 2020

An impurity has been separated by preparative HPLC and characterized by IR, MS, NMR and XRD analyses as (E)-N-ethyl-2-cyano-3-ethylamino-2-butenamide, which is a by-product of the intermediate A1 obtained from the istradefylline.
Aerobic oxidative synthesis of quinazolinones and benzothiazoles in the presence of laccase/DDQ as a bioinspired cooperative catalytic system under mild conditions
Authors: Ghorashi Nadia , Shokri Zahra , Moradi Reza , Abdelrasoul Amira , Rostami Amin
Published: April 2020

In this paper laccase/DDQ as a bioinspired cooperative catalytic system was applied for the synthesis of quinazolinones and benzothiazoles using air or O2 as ideal oxidant in aqueous media under mild conditions.
Synthesis of graphene aerogels using cyclohexane and n-butanol as soft templates
Authors: Zhang Xin , Su Jie , Wang Xueyuan , Tong Xiaolei , Yao Fanglian , Yuan Caideng
Published: April 2020

Graphene aerogels (GAs) were synthesized via a one-step hydrothermal method.
Fixed-point “blasting” triggered by second near-infrared window light for augmented interventional photothermal therapy
Authors: Cao Yongbin , Ouyang Boshu , Yang Xiaowei , Jiang Qin , Yu Lin , Shen Shun , Ding Jiandong , Yang Wuli
Published: April 2020

Tumors were effectively destroyed by a mild photothermal effect and the subsequent gas mechanical damage triggered by NIR-II light.
Exchange interactions in photoinduced magnetostructural states of copper(ii)–nitroxide spin dyads
Authors: Tumanov Sergey V. , Veber Sergey L. , Tolstikov Svyatoslav E. , Artiukhova Natalia A. , Ovcharenko Victor I. , Fedin Matvey V.
Published: April 2020

We investigate intra- and intercluster exchange couplings in photoinduced states of copper(ii)–nitroxide based molecular magnets (“breathing crystals”) using variable-temperature EPR spectroscopy.
Design and synthesis of photoluminescent active interpenetrating metal–organic frameworks usingN-2-aryl-1,2,3-triazole ligands
Authors: Li Jingyang , He Ying , Wang Li , Pan Qinhe , Song Zhiguang , Shi Xiaodong
Published: April 2020

N-2-aryl-1,2,3-triazole derivatives were synthesized as new ligand systems for the construction of photoluminescent active metal–organic frameworks (MOFs).
Bulky 1,1′-bisphosphanoferrocenes and their coordination behaviour towards Cu(i)
Authors: Dey Subhayan , Buzsáki Daniel , Bruhn Clemens , Kelemen Zsolt , Pietschnig Rudolf
Published: April 2020

Bulky dppf analogues have been reported for which donor properties and coordination behavior have been explored and tested in a catalytic model reaction.
Alkali-metal- and halide-free dinuclear mixed-valent samarium and europium complexes
Authors: Mukthar Nishya F. M. , Schley Nathan D. , Ung Gaël
Published: April 2020

The synthesis of alkali metal- and halide-free mixed valent dilanthanide complexes supported by a calix[4]pyrrole ligand is described. Bond activation using both a base and one-electron reductant is showcased.
Efficacy of chitosan/double-stranded RNA polyplex nanoparticles for gene silencing under variable environmental conditions
Authors: Lichtenberg Stuart S. , Nuti Kanthi , DeRouchey Jason , Tsyusko Olga V. , Unrine Jason M.
Published: April 2020

Chitosan/dsRNA polyplex nanoparticles have shown great potential as insect biocontrol agents. Here, we show that polyplex nanoparticles have their gene silencing capacity altered by environmental variables.
A lupine (Lupinus angustifolious L.) peptide prevents non-alcoholic fatty liver disease in high-fat-diet-induced obese mice
Authors: Lemus-Conejo Ana , Grao-Cruces Elena , Toscano Rocio , Varela Lourdes M. , Claro Carmen , Pedroche Justo , Millan Francisco , Millan-Linares Maria C. , Montserrat-de la Paz Sergio
Published: April 2020

A lupine (Lupinus angustifolious L.) peptide prevents non-alcoholic fatty liver disease in high-fat-diet-induced obese mice.
3D architectures of single-crystalline complex oxides
Authors: Kim Shin-Ik , Choi Hyung-Jin , Lee Gwangyeob , Roh Chang Jae , Jung Inki , Jung Soo Young , Ning Ruiguang , Won Sung Ok , Chang Hye Jung , Lee Jong Seok , Kim Seong Keun , Kim Jin-Sang , Kang Chong-Yun , Choi Ji-Won , Baek Seung-Hyub
Published: April 2020

We proposed 3D architectures of complex oxides as a way to derive novel properties: various 3D shapes were formed by self-shaped free-standing membranes, and curvature-induced polarization in an otherwise nonpolar material was observed.
Modular synthesis of oligoacetylacetones via site-selective silylation of acetylacetone derivatives
Authors: Sarkar Parantap , Inaba Yuya , Shirakura Hayato , Yoneda Tomoki , Inokuma Yasuhide
Published: April 2020

Aliphatic oligoketones with tailored carbonyl and substituent sequences were modularly synthesized utilizing site-selective formation of enol silyl ethers. Their unique conformational preferences in solid-state were revealed by X-ray crystallography.
Near-IR absorption and photocurrent generation using a first-of-its-kind boron difluoride formazanate non-fullerene acceptor
Authors: Koenig Josh D. B. , Farahat Mahmoud E. , Dhindsa Jasveer S. , Gilroy Joe B. , Welch Gregory C.
Published: April 2020

We report the synthesis and characterization of the first non-fullerene acceptor containing a boron difluoride formazanate core end-capped with N-annulated perylene diimides.
High-efficiency adsorption and regeneration of methylene blue and aniline onto activated carbon from waste edible fungus residue and its possible mechanism
Authors: Li Hongyan , Liu Lianxin , Cui Jianguo , Cui Jiali , Wang Fang , Zhang Feng
Published: April 2020

Edible fungus residue as an efficient and low-cost precursor was used to produce Edible Fungus residue Activated Carbon (EFAC) using the zinc chloride activation method at a 1 : 2 impregnation ratio and 600 °C activation for 3 hours.
SERS using two-photon polymerized nanostructures for mycotoxin detection
Authors: Liu Qing , Vanmol Koen , Lycke Sylvia , Van Erps Jürgen , Vandenabeele Peter , Thienpont Hugo , Ottevaere Heidi
Published: April 2020

Nano-pillar arrays are presented ranging from 200 nm to 600 nm as SERS substrates for mycotoxin detection, fabricated by two-photon polymerization. This versatile approach gives new opportunities for material characterization in chemical and biological applications.
Controllable synthesis of a chemically stable molecular sieving nanofilm for highly efficient organic solvent nanofiltration
Authors: Li Yi , Li Sha , Zhu Junyong , Volodine Alexander , Van der Bruggen Bart
Published: April 2020

A chemically stable molecular sieving nanofilm with Janus pore structure was synthesized with high permeability in both polar and non-polar solvent.
Combinational modulations of NiSe2 nanodendrites by phase engineering and iron-doping towards an efficient oxygen evolution reaction
Authors: Zhou Jun , Yuan Liwei , Wang Jingwen , Song Lingling , You Yu , Zhou Ru , Zhang Junjun , Xu Jun
Published: April 2020

Combinational modulations of phase engineering and heteroatom doping are realized to prepare Fe-doped marcasite NiSe2 nanodendrites, which serve as a superior OER electrocatalyst with improved conductivity and excellent catalytic activity.
Hydrogenated dual-shell sodium titanate cubes for sodium-ion batteries with optimized ion transportation
Authors: Xie Fangxi , Zhang Lei , Jiao Yan , Vasileff Anthony , Chao Dongliang , Qiao Shi-Zhang
Published: April 2020

Dual-shell structured sodium titanate cubes with oxygen vacancies are rationally designed and synthesized. Various state-of-the-art approaches offer understandings of its enhanced ion kinetics as an anode for sodium-ion battery..
Effect of molecular weight and polymer composition on gallol-functionalized underwater adhesive
Authors: Yu Jinhong , Cheng Bohan , Ejima Hirotaka
Published: April 2020

A gallol-functionalized polymer showed strong adhesion ability underwater. The effect of molecular weight and gallol content have been optimized resulting in the underwater adhesion strength as high as 4 MPa.
Dual-triggered nanoaggregates of cucurbit[7]uril and gold nanoparticles for multi-spectroscopic quantification of creatinine in urinalysis
Authors: Chio Weng-I Katherine , Moorthy Suresh , Perumal Jayakumar , U. S. Dinish , Parkin Ivan P. , Olivo Malini , Lee Tung-Chun
Published: April 2020

A novel nanosensing platform was developed for the quantitative detection of creatinine of clinically relevant concentrationsviaUV-Vis spectroscopy and surface-enhanced Raman spectroscopy.
Clock-in, clock-out: circadian timekeeping between tissues
Authors: Smith Jacob G. , Sassone-Corsi Paolo
Published: April 2020

Life evolved in the presence of alternating periods of light and dark that accompany the daily rotation of the Earth on its axis. This offered an advantage for organisms able to regulate their physiology to anticipate these daily cycles. In each light-sensitive organism studied, spanning single-celled bacteria to complex mammals, there exist timekeeping mechanisms able to control physiology over the course of 24 hours. Endowed with internal timekeeping, organisms can put their previously stored energy to the most efficient use, selectively ramping up biological processes at specific times of day or night according to when they will be needed. Humans have evolved to be more active during the day (diurnal), likely due to the increased opportunities for foraging or hunting in our evolutionary past, and this daily activity is accompanied by an up-regulation of genes involved in metabolism to increase the energy available for such behaviours. Remarkably, this happens without conscious thought—due to a complex organism-wide signalling apparatus known as the circadian clock network, which conveys time information between cells and tissues.
Phosphorylation of vaccinia-related kinase 1 at threonine 386 transduces glucose stress signal in human liver cells
Authors: Yokobori Kosuke , Miyauchi Yuu , Williams Jason G. , Negishi Masahiko
Published: April 2020

Vaccinia-related kinase 1 (VRK1) is a chromatin-associated Ser-Thr kinase that regulates numerous downstream factors including DNA repair as well as stress factors c-Jun and p53. Both c-Jun and p53 are phosphorylated at Ser63 and Thr18, respectively, in response to low glucose (40 mg/dl of medium) but not high glucose (140 mg/dl of medium) in human hepatoma-derived Huh-7 cells. Here, we have determined the molecular mechanism by which VRK1 phosphorylates these residues in response to glucose in Huh-7 cells. Human VRK1 auto-phosphorylates Ser376 and Thr386 in in vitro kinase assays. In Huh-7 cells, this auto-phosphorylation activity is regulated by glucose signaling; Thr386 is auto-phosphorylated only in low glucose medium, while Ser376 is not phosphorylated in either medium. A correlation of this low glucose response phosphorylation of Thr386 with the phosphorylation of c-Jun and p53 suggests that VRK1 phosphorylated at Thr386 catalyzes this phosphorylation. In fact, VRK1 knockdown by siRNA decreases and over-expression of VRK1 T386D increases phosphorylated c-Jun and p53 in Huh-7 cells. Phosphorylation by VRK1 of c-Jun but not p53 is regulated by cadherin Plakophilin-2 (PKP2). The PKP2 is purified from whole extracts of Huh-7 cells cultured in low glucose medium and is characterized to bind a C-terminal peptide of the VRK1 molecules to regulate its substrate specificity toward c-Jun. siRNA knockdowns show that PKP2 transduces low glucose signaling to VRK1 only to phosphorylate c-Jun, establishing the low glucose-PKP2-VRK1-c-Jun pathway as a glucose stress signaling pathway.
Solid accretion onto planetary cores in radiative disks
Authors: Zormpas Apostolos , Picogna Giovanni , Ercolano Barbara , Kley Wilhelm
Published: April 2020

The solid accretion rate, which is necessary to grow gas giant planetary cores within the disk lifetime, has been a major constraint for theories of planet formation. We tested the solid accretion rate efficiency on planetary cores of different masses embedded in their birth disk by means of 3D radiation-hydrodynamics, where we followed the evolution of a swarm of embedded solids of different sizes. We found that by using a realistic equation of state and radiative cooling, the disk at 5 au is able to efficiently cool and reduce its aspect ratio. As a result, the pebble isolation mass is reached before the core grows to 10 M⊕, thus fully stopping the pebble flux and creating a transition disk. Moreover, the reduced isolation mass halts the solid accretion before the core reaches the critical mass, leading to a barrier to giant planet formation, and this explains the large abundance of super-Earth planets in the observed population.
Angular differential kernel phases
Authors: Laugier Romain , Martinache Frantz , Cvetojevic Nick , Mary David , Ceau Alban , N’Diaye Mamadou , Kammerer Jens , Lozi Julien , Guyon Olivier , Lopez Coline
Published: April 2020

Context. To reach its optimal performance, Fizeau interferometry requires that we work to resolve instrumental biases through calibration. One common technique used in high contrast imaging is angular differential imaging, which calibrates the point spread function and flux leakage using a rotation in the focal plane.

Aims. Our aim is to experimentally demonstrate and validate the efficacy of an angular differential kernel-phase approach, a new method for self-calibrating interferometric observables that operates similarly to angular differential imaging, while retaining their statistical properties.

Methods. We used linear algebra to construct new observables that evolve outside of the subspace spanned by static biases. On-sky observations of a binary star with the SCExAO instrument at the Subaru telescope were used to demonstrate the practicality of this technique. We used a classical approach on the same data to compare the effectiveness of this method.

Results. The proposed method shows smaller and more Gaussian residuals compared to classical calibration methods, while retaining compatibility with the statistical tools available. We also provide a measurement of the stability of the SCExAO instrument that is relevant to the application of the technique.

Conclusions. Angular differential kernel phases provide a reliable method for calibrating biased observables. Although the sensitivity at small separations is reduced for small field rotations, the calibration is effectively improved and the number of subjective choices is reduced.
Revised mass-radius relationships for water-rich rocky planets more irradiated than the runaway greenhouse limit
Authors: Turbet Martin , Bolmont Emeline , Ehrenreich David , Gratier Pierre , Leconte Jérémy , Selsis Franck , Hara Nathan , Lovis Christophe
Published: April 2020

Mass-radius relationships for water-rich rocky planets are usually calculated assuming most water is present in condensed (either liquid or solid) form. Planet density estimates are then compared to these mass-radius relationships, even when these planets are more irradiated than the runaway greenhouse irradiation limit (around 1.1 times the insolation at Earth for planets orbiting a Sun-like star), for which water has been shown to be unstable in condensed form and would instead form a thick H2O-dominated atmosphere. Here we use a 1-D radiative-convective inverse version of the LMD generic numerical climate model to derive new theoretical mass-radius relationships appropriate for water-rich rocky planets that are more irradiated than the runaway greenhouse irradiation limit, meaning planets endowed with a steam, water-dominated atmosphere. As a result of the runaway greenhouse radius inflation effect introduced in previous work, these new mass-radius relationships significantly differ from those traditionally used in the literature. For a given water-to-rock mass ratio, these new mass-radius relationships lead to planet bulk densities much lower than calculated when water is assumed to be in condensed form. In other words, using traditional mass-radius relationships for planets that are more irradiated than the runaway greenhouse irradiation limit tends to dramatically overestimate -possibly by several orders of magnitude- their bulk water content. In particular, this result applies to TRAPPIST-1 b, c, and d, which can accommodate a water mass fraction of at most 2, 0.3 and 0.08%, respectively, assuming planetary core with a terrestrial composition. In addition, we show that significant changes of mass-radius relationships (between planets less and more irradiated than the runaway greenhouse limit) can be used to remove bulk composition degeneracies in multiplanetary systems such as TRAPPIST-1. Broadly speaking, our results demonstrate that non-H2/He-dominated atmospheres can have a first-order effect on the mass-radius relationships, even for rocky planets receiving moderate irradiation. Finally, we provide an empirical formula for the H2O steam atmosphere thickness as a function of planet core gravity and radius, water content, and irradiation. This formula can easily be used to construct mass-radius relationships for any water-rich, rocky planet (i.e., with any kind of interior composition ranging from pure iron to pure silicate) more irradiated than the runaway greenhouse irradiation threshold.