bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbon Isotopic Fractionation of Alkenones and Gephyrocapsa Coccoliths Over the Late Quaternary (Marine Isotope Stages 12–9) Glacial‐Interglacial Cycles at the Western Tropical Atlantic
Authors: González‐Lanchas A. , Hernández‐Alméida I. , Flores J.‐A. , Sierro F. J. , Guitian J. , Stoll H. M.
Published: July 2021

The sensitivity of coccolithophores to changing CO2 and its role modulating cellular photosynthetic carbon isotopic fractionation (εp) is crucial to understand the future adaptation of these organisms to higher CO2 world and to assess the reliability of εp for past CO2 estimation. Here, we present εp measured on natural fossil samples across the glacial‐interglacial (G‐I) CO2 variations of marine isotope stages 12 to 9 interval (454–334 ka) at the western tropical Atlantic Ocean Drilling Program Site 925 together with a set of organic and inorganic geochemical, micropaleontological and morphometrical data from Gephyrocapsa coccoliths in the same samples. The ∼2‰ variation in εp is significantly correlated with the CO2[aq] concentrations calculated from assumption of air‐sea equilibrium with measured ice core pCO2 concentrations. The sensitivity of εp to CO2[aq] is similar to that derived from a multiple regression model of culture observations and is not well simulated with the classical purely diffusive model of algal CO2 acquisition. The measured range of Gephyrocapsa cell sizes is insufficient to explain the non‐CO2 effects on εp at this location, via either direct size effect or growth rate correlated to cell size. Primary productivity, potentially triggered by shifting growth rates and light levels, may also affect εp. Proposed productivity proxies % Florisphaera profunda and the ratio between the C37 to C38.et alkenone (C37/C38.et ratio) both correlates modestly with the non‐CO2 effects on εp. When the observed G‐I εp to CO2 sensitivity at this site is used to estimate pCO2 from εp since the Miocene, the inferred pCO2 declines are larger in amplitude compared to that calculated from a theoretical εp diffusive model. We find that oxygen and carbon stable isotope vital effects in the near monogeneric‐separated Gephyrocapsa coccoliths (respectively Δδ18OGephyrocapsa–Trilobatus sacculifer and εcoccolith) are coupled through the time series, but the origins of these vital effects are not readily explained by existing models.
Impact of Cosolvents on the Interphase Mass Transfer of NAPLs in Porous Media
Authors: Yaksi Korcan , Demiray Zeynep , Copty Nadim K.
Published: July 2021

Cosolvent flushing has evolved as a viable technology for the remediation of groundwater resources contaminated with non‐aqueous phase liquids (NAPLs). This study investigates the effect of cosolvents on the interphase mass transfer of NAPLs into the flushing solutions, a key process that controls the effectiveness of the enhanced dissolution technology. A series of laboratory‐scale flow cell experiments were conducted to test the effect of cosolvent content, mean grain diameter and flushing velocity on the interphase mass transfer of NAPLs present in saturated porous media pooled form. The cosolvent and NAPL selected for this purpose are ethanol and 1,2‐dichlorobenzene, respectively. The experimental results are interpreted using a two‐dimensional numerical model and validated with a one‐dimensional analytical solution. The best fit mass transfer coefficients estimated from the model are used to develop Sherwood correlations expressed in terms of the Peclet and Schmidt numbers and the porous media main grain diameter. It is observed that the presence of the cosolvent can have an important impact on the interphase mass transfer coefficient. Specifically, the Sherwood correlation is found to be inversely proportional to the Schmidt number, expressed as a function of the viscosity and density of the cosolvent flushing solution. The developed Sherwood correlations can potentially be used in modeling studies and field applications involving the enhanced dissolution of entrapped NAPLs.
A River Network‐Based Hierarchical Model for Deriving Flood Frequency Distributions and Its Application to the Upper Yangtze Basin
Authors: Jiang Cong , Xiong Lihua , Xu Chong‐Yu , Yan Lei
Published: July 2021

In flood frequency analysis, expanding the additional information with hydrological reasoning beyond local at‐site flood samples can be very useful for improving the accuracy of flood frequency distribution (FFD) estimation as well as reflecting a better understanding of flood characteristics. In this study, a river network‐based hierarchical model is developed to estimate the FFDs in the Upper Yangtze basin by making full use of the hydrological reasoning information of both the flood dependence within the river network and reservoir regulation. Under this hierarchical model, a covariate analysis based on the generalized additive model for location, scale and shape is performed to obtain the conditional distribution of the interested flood variable given both its upstream flood variables and the reservoir index quantifying reservoir regulation; and then, the FFD of the interested flood variable is derived by combining its conditional distribution with the probability distribution of the upstream flood variables. The application to the Upper Yangtze basin indicates that the proposed hierarchical model suggests a satisfactory performance in FFD estimation. It is also found that the reservoir regulation, especially that of the Three Gorges Reservoir, is of great significance in reducing the flood magnitude in the basin. Compared to the conventional FFD estimation method that directly fits the assumed theoretical probability distributions to the at‐site flood samples, the hierarchical model incorporating the flood dependence within the river network exhibits an advantage in capturing the effect of reservoir regulation on the floods as well as in reducing the uncertainty in flood quantile estimation.
Composition of Coronal Hole Boundary Layers at Low Heliographic Latitudes
Authors: Delano K. , Elliott H. A. , Lepri S. T. , Fuselier S. A.
Published: July 2021

In some polar coronal holes, previous studies have identified a coronal hole boundary layer (CHBL), which is different in composition from the coronal hole core region. However, compositionally distinct CHBL structure at low heliographic latitudes remains underexplored. Using solar wind composition measurements from the Advanced Composition Explorer (ACE), we study two particular low‐latitude coronal holes of 2003: a large polar hole extension with outward magnetic polarity and a smaller equatorial hole with inward magnetic polarity. For both of these coronal holes, we examine the distribution of two composition parameters, the O7+ to O6+ charge state density ratio (n(O7+)/n(O6+)) and the Fe to O abundance ratio (n(Fe)/n(O)), and find that each hole has an identifiable CHBL based on an anticorrelation of solar wind speed and n(O7+)/n(O6+). We also examine the FIP (first ionization potential) effect in the CHBL using n(Fe)/n(O), and find that there is no significant change from the CHBL to the core region for one of the coronal holes we study, while the other coronal hole has a noticeable decrease in n(Fe)/n(O) values in its core. Finally, we discuss our results in the context of previous work studying CHBL structure.
Inferring Jovian Electron Densities Using Plasma Wave Spectra Obtained by the Juno/Waves Instrument
Authors: Sulaiman A. H. , Elliott S. S. , Kurth W. S. , Faden J. B. , Hospodarsky G. B. , Menietti J. D.
Published: July 2021

The Waves instrument onboard the Juno spacecraft has plasma wave‐measuring capabilities using a single electric dipole antenna and a uniaxial magnetic search coil. Together, these simultaneously measure electric and magnetic field spectral densities in the frequency range 50 Hz–20 kHz, above which only electric field spectral densities are measured up to 41 MHz. A major objective of the Juno mission is to explore Jupiter's high‐latitude magnetosphere and ionosphere. One of the key contributions of the Waves instrument is the determination of electron densities from plasma wave spectra. Given the very high magnetic field strengths near Juno's perijove passes, established techniques cannot be utilized to infer electron densities since such highly magnetized space plasma conditions have not previously been met in planetary missions. By revisiting theoretical treatments of plasma waves, we describe a novel method to determine electron densities from plasma wave spectra that is unique to the near‐Jupiter region. In the absence of the commonly observed upper hybrid resonance frequency in high‐density space plasmas (e.g., the vicinities of Io, Ganymede, Enceladus, and the near‐Earth environment), we achieve this by identifying emission cutoffs at the lower hybrid frequency and electron plasma frequency. Further, we discuss the development of the process and tools for identifying and digitizing appropriate resonance and cutoff frequencies.
Lifestyles, genetics, and future perspectives on gastric cancer in east Asian populations
Authors: Katoh Hiroto , Ishikawa Shumpei
Published: July 2021

The prevalence of gastric cancer (GC) differs among regions worldwide, with the highest occurrence in east Asia. Thus, its etiology, with respect to ethnic background, environmental factors, and lifestyles, is also thought to differ essentially. In addition, etiology of GC is speculated to be changing due to the recent decrease in the Helicobacter pylori (H. pylori) infection in Japan. State-of-the-art somatic/germline cancer genomics has clarified the etiologies of gastric carcinogenesis. In this review article, we summarize past and present milestones in our understanding of GC achieved through genomic approaches, including a recent report that revealed higher-than-expected frequencies of GCs attributed to east Asian-specific germline variants in ALDH2 or CDH1 in combination with lifestyles. Based on this updated knowledge, we also discuss the possible impact of and high-risk approaches for GCs in the upcoming “H. pylori-negative era.”
Pharmacological inhibitors of anaplastic lymphoma kinase (ALK) induce immunogenic cell death through on-target effects
Authors: Petrazzuolo Adriana , Perez-Lanzon Maria , Martins Isabelle , Liu Peng , Kepp Oliver , Minard-Colin Véronique , Maiuri Maria Chiara , Kroemer Guido
Published: July 2021

Immunogenic cell death (ICD) is clinically relevant because cytotoxicants that kill malignant cells via ICD elicit anticancer immune responses that prolong the effects of chemotherapies beyond treatment discontinuation. ICD is characterized by a series of stereotyped changes that increase the immunogenicity of dying cells: exposure of calreticulin on the cell surface, release of ATP and high mobility group box 1 protein, as well as a type I interferon response. Here, we examined the possibility that inhibition of an oncogenic kinase, anaplastic lymphoma kinase (ALK), might trigger ICD in anaplastic large cell lymphoma (ALCL) in which ALK is activated due to a chromosomal translocation. Multiple lines of evidence plead in favor of specific ICD-inducing effects of crizotinib and ceritinib in ALK-dependent ALCL: (i) they induce ICD stigmata at pharmacologically relevant, low concentrations; (ii) can be mimicked in their ICD-inducing effects by ALK knockdown; (iii) lose their effects in the context of resistance-conferring ALK mutants; (iv) ICD-inducing effects are mimicked by inhibition of the signal transduction pathways operating downstream of ALK. When ceritinib-treated murine ALK-expressing ALCL cells were inoculated into the left flank of immunocompetent syngeneic mice, they induced an immune response that slowed down the growth of live ALCL cells implanted in the right flank. Although ceritinib induced a transient shrinkage of tumors in lymphoma-bearing mice, irrespective of their immunocompetence, relapses occurred more frequently in the context of immunodeficiency, reducing the effects of ceritinib on survival by approximately 50%. Complete cure only occurred in immunocompetent mice and conferred protection to rechallenge with the same ALK-expressing lymphoma but not with another unrelated lymphoma. Moreover, immunotherapy with PD-1 blockade tended to increase cure rates. Altogether, these results support the contention that specific ALK inhibition stimulates the immune system by inducing ICD in ALK-positive ALCL.
Renewable fatty acid ester production in Clostridium
Authors: Feng Jun , Zhang Jie , Ma Yuechao , Feng Yiming , Wang Shangjun , Guo Na , Wang Haijiao , Wang Pixiang , Jiménez-Bonilla Pablo , Gu Yanyan , Zhou Junping , Zhang Zhong-Tian , Cao Mingfeng , Jiang Di , Wang Shuning , Liu Xian-Wei , Shao Zengyi , Borovok Ilya , Huang Haibo , Wang Yi
Published: July 2021

Bioproduction of renewable chemicals is considered as an urgent solution for fossil energy crisis. However, despite tremendous efforts, it is still challenging to generate microbial strains that can produce target biochemical to high levels. Here, we report an example of biosynthesis of high-value and easy-recoverable derivatives built upon natural microbial pathways, leading to improvement in bioproduction efficiency. By leveraging pathways in solventogenic clostridia for co-producing acyl-CoAs, acids and alcohols as precursors, through rational screening for host strains and enzymes, systematic metabolic engineering-including elimination of putative prophages, we develop strains that can produce 20.3 g/L butyl acetate and 1.6 g/L butyl butyrate. Techno-economic analysis results suggest the economic competitiveness of our developed bioprocess. Our principles of selecting the most appropriate host for specific bioproduction and engineering microbial chassis to produce high-value and easy-separable end products may be applicable to other bioprocesses.
Associations between dimensions of behaviour, personality traits, and mental-health during the COVID-19 pandemic in the United Kingdom
Authors: Hampshire Adam , Hellyer Peter J. , Soreq Eyal , Mehta Mitul A. , Ioannidis Konstantinos , Trender William , Grant Jon E. , Chamberlain Samuel R.
Published: July 2021

The COVID-19 pandemic (including lockdown) is likely to have had profound but diverse implications for mental health and well-being, yet little is known about individual experiences of the pandemic (positive and negative) and how this relates to mental health and well-being, as well as other important contextual variables. Here, we analyse data sampled in a large-scale manner from 379,875 people in the United Kingdom (UK) during 2020 to identify population variables associated with mood and mental health during the COVID-19 pandemic, and to investigate self-perceived pandemic impact in relation to those variables. We report that while there are relatively small population-level differences in mood assessment scores pre- to peak-UK lockdown, the size of the differences is larger for people from specific groups, e.g. older adults and people with lower incomes. Multiple dimensions underlie peoples’ perceptions, both positive and negative, of the pandemic’s impact on daily life. These dimensions explain variance in mental health and can be statistically predicted from age, demographics, home and work circumstances, pre-existing conditions, maladaptive technology use and personality traits (e.g., compulsivity). We conclude that a holistic view, incorporating the broad range of relevant population factors, can better characterise people whose mental health is most at risk during the COVID-19 pandemic.
Discovery and prioritization of variants and genes for kidney function in >1.2 million individuals
Authors: Stanzick Kira J. , Li Yong , Schlosser Pascal , Gorski Mathias , Wuttke Matthias , Thomas Laurent F. , Rasheed Humaira , Rowan Bryce X. , Graham Sarah E. , Vanderweff Brett R. , Patil Snehal B. ,   VA Million Veteran Program, Robinson-Cohen Cassiane , Gaziano John M. , O’Donnell Christopher J. , Willer Cristen J. , Hallan Stein , Åsvold Bjørn Olav , Gessner Andre , Hung Adriana M. , Pattaro Cristian , Köttgen Anna , Stark Klaus J. , Heid Iris M. , Winkler Thomas W.
Published: July 2021

Genes underneath signals from genome-wide association studies (GWAS) for kidney function are promising targets for functional studies, but prioritizing variants and genes is challenging. By GWAS meta-analysis for creatinine-based estimated glomerular filtration rate (eGFR) from the Chronic Kidney Disease Genetics Consortium and UK Biobank (n = 1,201,909), we expand the number of eGFRcrea loci (424 loci, 201 novel; 9.8% eGFRcrea variance explained by 634 independent signal variants). Our increased sample size in fine-mapping (n = 1,004,040, European) more than doubles the number of signals with resolved fine-mapping (99% credible sets down to 1 variant for 44 signals, ≤5 variants for 138 signals). Cystatin-based eGFR and/or blood urea nitrogen association support 348 loci (n = 460,826 and 852,678, respectively). Our customizable tool for Gene PrioritiSation reveals 23 compelling genes including mechanistic insights and enables navigation through genes and variants likely relevant for kidney function in human to help select targets for experimental follow-up.
Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase
Authors: Garvie Colin W. , Wu Xiaoyun , Papanastasiou Malvina , Lee Sooncheol , Fuller James , Schnitzler Gavin R. , Horner Steven W. , Baker Andrew , Zhang Terry , Mullahoo James P. , Westlake Lindsay , Hoyt Stephanie H. , Toetzl Marcus , Ranaghan Matthew J. , de Waal Luc , McGaunn Joseph , Kaplan Bethany , Piccioni Federica , Yang Xiaoping , Lange Martin , Tersteegen Adrian , Raymond Donald , Lewis Timothy A. , Carr Steven A. , Cherniack Andrew D. , Lemke Christopher T. , Meyerson Matthew , Greulich Heidi
Published: July 2021

DNMDP and related compounds, or velcrins, induce complex formation between the phosphodiesterase PDE3A and the SLFN12 protein, leading to a cytotoxic response in cancer cells that express elevated levels of both proteins. The mechanisms by which velcrins induce complex formation, and how the PDE3A-SLFN12 complex causes cancer cell death, are not fully understood. Here, we show that PDE3A and SLFN12 form a heterotetramer stabilized by binding of DNMDP. Interactions between the C-terminal alpha helix of SLFN12 and residues near the active site of PDE3A are required for complex formation, and are further stabilized by interactions between SLFN12 and DNMDP. Moreover, we demonstrate that SLFN12 is an RNase, that PDE3A binding increases SLFN12 RNase activity, and that SLFN12 RNase activity is required for DNMDP response. This new mechanistic understanding will facilitate development of velcrin compounds into new cancer therapies.
Complete loss of H3K9 methylation dissolves mouse heterochromatin organization
Authors: Montavon Thomas , Shukeir Nicholas , Erikson Galina , Engist Bettina , Onishi-Seebacher Megumi , Ryan Devon , Musa Yaarub , Mittler Gerhard , Meyer Alexandra Graff , Genoud Christel , Jenuwein Thomas
Published: July 2021

Histone H3 lysine 9 (H3K9) methylation is a central epigenetic modification that defines heterochromatin from unicellular to multicellular organisms. In mammalian cells, H3K9 methylation can be catalyzed by at least six distinct SET domain enzymes: Suv39h1/Suv39h2, Eset1/Eset2 and G9a/Glp. We used mouse embryonic fibroblasts (MEFs) with a conditional mutation for Eset1 and introduced progressive deletions for the other SET domain genes by CRISPR/Cas9 technology. Compound mutant MEFs for all six SET domain lysine methyltransferase (KMT) genes lack all H3K9 methylation states, derepress nearly all families of repeat elements and display genomic instabilities. Strikingly, the 6KO H3K9 KMT MEF cells no longer maintain heterochromatin organization and have lost electron-dense heterochromatin. This is a compelling analysis of H3K9 methylation-deficient mammalian chromatin and reveals a definitive function for H3K9 methylation in protecting heterochromatin organization and genome integrity.
Parallel processing of working memory and temporal information by distinct types of cortical projection neurons
Authors: Bae Jung Won , Jeong Huijeong , Yoon Young Ju , Bae Chan Mee , Lee Hyeonsu , Paik Se-Bum , Jung Min Whan
Published: July 2021

It is unclear how different types of cortical projection neurons work together to support diverse cortical functions. We examined the discharge characteristics and inactivation effects of intratelencephalic (IT) and pyramidal tract (PT) neurons—two major types of cortical excitatory neurons that project to cortical and subcortical structures, respectively—in the deep layer of the medial prefrontal cortex in mice performing a delayed response task. We found stronger target-dependent firing of IT than PT neurons during the delay period. We also found the inactivation of IT neurons, but not PT neurons, impairs behavioral performance. In contrast, PT neurons carry more temporal information than IT neurons during the delay period. Our results indicate a division of labor between IT and PT projection neurons in the prefrontal cortex for the maintenance of working memory and for tracking the passage of time, respectively.
Innate-like self-reactive B cells infiltrate human renal allografts during transplant rejection
Authors: Asano Yuta , Daccache Joe , Jain Dharmendra , Ko Kichul , Kinloch Andrew , Veselits Margaret , Wolfgeher Donald , Chang Anthony , Josephson Michelle , Cunningham Patrick , Tambur Anat , Khan Aly A. , Pillai Shiv , Chong Anita S. , Clark Marcus R.
Published: July 2021

Intrarenal B cells in human renal allografts indicate transplant recipients with a poor prognosis, but how these cells contribute to rejection is unclear. Here we show using single-cell RNA sequencing that intrarenal class-switched B cells have an innate cell transcriptional state resembling mouse peritoneal B1 or B-innate (Bin) cells. Antibodies generated by Bin cells do not bind donor-specific antigens nor are they enriched for reactivity to ubiquitously expressed self-antigens. Rather, Bin cells frequently express antibodies reactive with either renal-specific or inflammation-associated antigens. Furthermore, local antigens can drive Bin cell proliferation and differentiation into plasma cells expressing self-reactive antibodies. These data show a mechanism of human inflammation in which a breach in organ-restricted tolerance by infiltrating innate-like B cells drives local tissue destruction.
The molecular basis of regulation of bacterial capsule assembly by Wzc
Authors: Yang Yun , Liu Jiwei , Clarke Bradley R. , Seidel Laura , Bolla Jani R. , Ward Philip N. , Zhang Peijun , Robinson Carol V. , Whitfield Chris , Naismith James H.
Published: July 2021

Bacterial extracellular polysaccharides (EPSs) play critical roles in virulence. Many bacteria assemble EPSs via a multi-protein “Wzx-Wzy” system, involving glycan polymerization at the outer face of the cytoplasmic/inner membrane. Gram-negative species couple polymerization with translocation across the periplasm and outer membrane and the master regulator of the system is the tyrosine autokinase, Wzc. This near atomic cryo-EM structure of dephosphorylated Wzc from E. coli shows an octameric assembly with a large central cavity formed by transmembrane helices. The tyrosine autokinase domain forms the cytoplasm region, while the periplasmic region contains small folded motifs and helical bundles. The helical bundles are essential for function, most likely through interaction with the outer membrane translocon, Wza. Autophosphorylation of the tyrosine-rich C-terminus of Wzc results in disassembly of the octamer into multiply phosphorylated monomers. We propose that the cycling between phosphorylated monomer and dephosphorylated octamer regulates glycan polymerization and translocation.
Designing polymer nanocomposites with high energy density using machine learning
Authors: Shen Zhong-Hui , Bao Zhi-Wei , Cheng Xiao-Xing , Li Bao-Wen , Liu Han-Xing , Shen Yang , Chen Long-Qing , Li Xiao-Guang , Nan Ce-Wen
Published: July 2021

Addressing microstructure-property relations of polymer nanocomposites is vital for designing advanced dielectrics for electrostatic energy storage. Here, we develop an integrated phase-field model to simulate the dielectric response, charge transport, and breakdown process of polymer nanocomposites. Subsequently, based on 6615 high-throughput calculation results, a machine learning strategy is schemed to evaluate the capability of energy storage. We find that parallel perovskite nanosheets prefer to block and then drive charges to migrate along with the interfaces in x-y plane, which could significantly improve the breakdown strength of polymer nanocomposites. To verify our predictions, we fabricate a polymer nanocomposite P(VDF-HFP)/Ca2Nb3O10, whose highest discharged energy density almost doubles to 35.9 J cm−3 compared with the pristine polymer, mainly benefit from the improved breakdown strength of 853 MV m−1. This work opens a horizon to exploit the great potential of 2D perovskite nanosheets for a wide range of applications of flexible dielectrics with the requirement of high voltage endurance.
A Bayesian analysis of classical shadows
Authors: Lukens Joseph M. , Law Kody J. H. , Bennink Ryan S.
Published: July 2021

The method of classical shadows proposed by Huang, Kueng, and Preskill heralds remarkable opportunities for quantum estimation with limited measurements. Yet its relationship to established quantum tomographic approaches, particularly those based on likelihood models, remains unclear. In this article, we investigate classical shadows through the lens of Bayesian mean estimation (BME). In direct tests on numerical data, BME is found to attain significantly lower error on average, but classical shadows prove remarkably more accurate in specific situations—such as high-fidelity ground truth states—which are improbable in a fully uniform Hilbert space. We then introduce an observable-oriented pseudo-likelihood that successfully emulates the dimension-independence and state-specific optimality of classical shadows, but within a Bayesian framework that ensures only physical states. Our research reveals how classical shadows effect important departures from conventional thinking in quantum state estimation, as well as the utility of Bayesian methods for uncovering and formalizing statistical assumptions.
A DICOM dataset for evaluation of medical image de-identification
Authors: Rutherford Michael , Mun Seong K. , Levine Betty , Bennett William , Smith Kirk , Farmer Phil , Jarosz Quasar , Wagner Ulrike , Freyman John , Blake Geri , Tarbox Lawrence , Farahani Keyvan , Prior Fred
Published: July 2021

We developed a DICOM dataset that can be used to evaluate the performance of de-identification algorithms. DICOM objects (a total of 1,693 CT, MRI, PET, and digital X-ray images) were selected from datasets published in the Cancer Imaging Archive (TCIA). Synthetic Protected Health Information (PHI) was generated and inserted into selected DICOM Attributes to mimic typical clinical imaging exams. The DICOM Standard and TCIA curation audit logs guided the insertion of synthetic PHI into standard and non-standard DICOM data elements. A TCIA curation team tested the utility of the evaluation dataset. With this publication, the evaluation dataset (containing synthetic PHI) and de-identified evaluation dataset (the result of TCIA curation) are released on TCIA in advance of a competition, sponsored by the National Cancer Institute (NCI), for algorithmic de-identification of medical image datasets. The competition will use a much larger evaluation dataset constructed in the same manner. This paper describes the creation of the evaluation datasets and guidelines for their use.
3D printed microfluidic lab-on-a-chip device for fiber-based dual beam optical manipulation
Authors: Wang Haoran , Enders Anton , Preuss John-Alexander , Bahnemann Janina , Heisterkamp Alexander , Torres-Mapa Maria Leilani
Published: July 2021

3D printing of microfluidic lab-on-a-chip devices enables rapid prototyping of robust and complex structures. In this work, we designed and fabricated a 3D printed lab-on-a-chip device for fiber-based dual beam optical manipulation. The final 3D printed chip offers three key features, such as (1) an optimized fiber channel design for precise alignment of optical fibers, (2) an optically clear window to visualize the trapping region, and (3) a sample channel which facilitates hydrodynamic focusing of samples. A square zig–zag structure incorporated in the sample channel increases the number of particles at the trapping site and focuses the cells and particles during experiments when operating the chip at low Reynolds number. To evaluate the performance of the device for optical manipulation, we implemented on-chip, fiber-based optical trapping of different-sized microscopic particles and performed trap stiffness measurements. In addition, optical stretching of MCF-7 cells was successfully accomplished for the purpose of studying the effects of a cytochalasin metabolite, pyrichalasin H, on cell elasticity. We observed distinct changes in the deformability of single cells treated with pyrichalasin H compared to untreated cells. These results demonstrate that 3D printed microfluidic lab-on-a-chip devices offer a cost-effective and customizable platform for applications in optical manipulation.
Pattern interaction effect
Authors: Floryan J. M. , Inasawa A.
Published: July 2021

Unexpected responses of physical systems to external stimuli can be observed when the stimuli are organized into spatial patterns and, especially, when stimuli of different physical origins are involved, leading to the pattern interaction problem. Combinations of weak stimuli—individually only capable of producing marginal local responses—can produce a global response without involving any bifurcations. Its existence is demonstrated by the interaction of properly tuned topography and temperature patterns. When these patterns overlap in a symmetry preserving manner, the resulting convection has the form of local rolls. When these patterns are misaligned, the resulting convection involves global horizontal particle movement with direction depending on the type of misalignment.
Physical collection and viability of airborne bacteria collected under electrostatic field with different sampling media and protocols towards rapid detection
Authors: Hong Seongkyeol , Kim Myeong-Woo , Jang Jaesung
Published: July 2021

Electrostatic samplers have been increasingly studied for sampling of viral and bacterial aerosols, and bioaerosol samplers are required to provide concentrated liquid samples with high physical collection and biological recovery, which would be critical for rapid detection. Here, the effects of sampling media and protocols on the physical collection and biological recovery of two airborne bacteria (Pseudomonas fluorescens and Micrococcus luteus) under electrostatic field were investigated using a personal electrostatic particle concentrator (EPC). Deionized (DI) water with/without sodium dodecyl sulfate (SDS) and phosphate buffered saline were tested as sampling media. A polystyrene container was mounted onto the collection electrode of the EPC for stable storage and vortexing after capture. Many bacterial cells were found to be deposited on the bottom surface of the container submerged in the media via electrophoresis, and among the tested sampling protocols, wet sampling with a container and subsequent vortexing offered the most bacteria in the collection suspension. Experiments with several sampling media showed that 0.001–0.01% SDS-DI water demonstrated the highest recovery rate in the EPC. These findings would be valuable in the field of sampling and subsequent rapid detection of bioaerosols.
Metastability relationship between two- and three-dimensional crystal structures: a case study of the Cu-based compounds
Authors: Ono Shota
Published: July 2021

Some of the three-dimensional (3D) crystal structures are constructed by stacking two-dimensional (2D) layers. To study whether this geometric concept, i.e., using 2D layers as building blocks for 3D structures, can be applied to computational materials design, we theoretically investigate the dynamical stability of copper-based compounds CuX (a metallic element X) in the B$$_h$$

h

and L1$$_1$$

1

structures constructed from the buckled honeycomb (BHC) structure and in the B2 and L1$$_0$$

0

structures constructed from the buckled square (BSQ) structure. We demonstrate that (i) if CuX in the BHC structure is dynamically stable, those in the B$$_h$$

h

and L1$$_1$$

1

structures are also stable. Using molecular dynamics simulations, we particularly show that CuAu in the B$$_h$$

h

and L1$$_1$$

1

structures withstand temperatures as high as 1000 K. Although the interrelationship of the metastability between the BSQ and the 3D structures (B2 and L1$$_0$$

0

) is not clear, we find that (ii) if CuX in the B2 (L1$$_0$$

0

) structure is dynamically stable, that in the L1$$_0$$

0

(B2) is unstable. This is rationalized by the tetragonal Bain path calculations.
Patient characteristics and outcomes associated with adherence to the low PEEP/FIO2 table for acute respiratory distress syndrome
Authors: See Kay Choong , Sahagun Juliet , Taculod Juvel
Published: July 2021

It remains uncertain how best to set positive end-expiratory pressure (PEEP) for mechanically ventilated patients with the acute respiratory distress syndrome (ARDS). Among patients on low tidal volume ventilation (LTVV), we investigated if further adherence to the low PEEP/FIO2 (inspired oxygen fraction) table would be associated with better survival compared to nonadherence. Patients with ARDS, admitted directly from the Emergency Department to our 20-bed Medical Intensive Care Unit (ICU) from August 2016 to July 2017, were retrospectively studied. To determine adherence to the low PEEP/FIO2 table, PEEP and FIO2 12 h after ICU admission were used, to reflect ventilator adjustments by ICU clinicians after initial stabilization. Logistic regression was used to analyze hospital mortality as an outcome with adherence to the low PEEP/FIO2 as the key independent variable, adjusted for age, APACHE II score, initial P/F ratio and initial systolic blood pressure. 138 patients with ARDS were analysed. Overall adherence to the low PEEP/FIO2 table was 75.4%. Among patients on LTVV, nonadherence to the low PEEP/FIO2 table was associated with increased mortality compared to adherence (adjusted odds ratio 4.10, 95% confidence interval 1.68–9.99, P = 0.002). Patient characteristics at baseline were not associated with adherence to the low PEEP/FIO2 table.
Mechanisms and consequences of casein kinase II and ankyrin-3 regulation of the epithelial Na+ channel
Authors: Abd El-Aziz Tarek Mohamed , Soares Antonio G. , Mironova Elena , Boiko Nina , Kaur Amanpreet , Archer Crystal R. , Stockand James D. , Berman Jonathan M.
Published: July 2021

Activity of the Epithelial Na+ Channel (ENaC) in the distal nephron fine-tunes renal sodium excretion. Appropriate sodium excretion is a key factor in the regulation of blood pressure. Consequently, abnormalities in ENaC function can cause hypertension. Casein Kinase II (CKII) phosphorylates ENaC. The CKII phosphorylation site in ENaC resides within a canonical “anchor” ankyrin binding motif. CKII-dependent phosphorylation of ENaC is necessary and sufficient to increase channel activity and is thought to influence channel trafficking in a manner that increases activity. We test here the hypothesis that phosphorylation of ENaC by CKII within an anchor motif is necessary for ankyrin-3 (Ank-3) regulation of the channel, which is required for normal channel locale and function, and the proper regulation of renal sodium excretion. This was addressed using a fluorescence imaging strategy combining total internal reflection fluorescence (TIRF) microscopy with fluorescence recovery after photobleaching (FRAP) to quantify ENaC expression in the plasma membrane in living cells; and electrophysiology to quantify ENaC activity in split-open collecting ducts from principal cell-specific Ank-3 knockout mice. Sodium excretion studies also were performed in parallel in this knockout mouse. In addition, we substituted a key serine residue in the consensus CKII site in β-ENaC with alanine to abrogate phosphorylation and disrupt the anchor motif. Findings show that disrupting CKII signaling decreases ENaC activity by decreasing expression in the plasma membrane. In the principal cell-specific Ank-3 KO mouse, ENaC activity and sodium excretion were significantly decreased and increased, respectively. These results are consistent with CKII phosphorylation of ENaC functioning as a “switch” that favors Ank-3 binding to increase channel activity.
Multiple slips impact in the MHD hybrid nanofluid flow with Cattaneo–Christov heat flux and autocatalytic chemical reaction
Authors: Gul Hina , Ramzan Muhammad , Chung Jae Dong , Chu Yu-Ming , Kadry Seifedine
Published: July 2021

The present study deliberates the nanofluid flow containing multi and single-walled carbon nanotubes submerged into Ethylene glycol in a Darcy–Forchheimer permeable media over a stretching cylinder with multiple slips. The innovation of the envisaged mathematical model is enriched by considering the impacts of non-uniform source/sink and modified Fourier law in the energy equation and autocatalytic chemical reaction in the concentration equation. Entropy optimization analysis of the mathematical model is also performed in the present problem. Pertinent transformations procedure is implemented for the conversion of the non-linear system to the ordinary differential equations. The succor of the Shooting technique combined with the bvp4c MATLAB software is utilized for the solution of a highly nonlinear system of equations. The impacts of the leading parameters versus engaged fields are inspected through graphical sketches. The outcomes show that a strong magnetic field strengthens the temperature profile and decays the velocity profile. Also, the fluid velocity is lessened for growing estimates of the parameter of slip. Additionally, it is detected that entropy number augmented for higher thermal relaxation parameter and Reynolds number. To substantiate the existing mathematical model, a comparison table is also added. An excellent correlation is achieved here.
Mutation in FBXO32 causes dilated cardiomyopathy through up-regulation of ER-stress mediated apoptosis
Authors: Al-Yacoub Nadya , Colak Dilek , Mahmoud Salma Awad , Hammonds Maya , Muhammed Kunhi , Al-Harazi Olfat , Assiri Abdullah M. , Al-Buraiki Jehad , Al-Habeeb Waleed , Poizat Coralie
Published: July 2021

Endoplasmic reticulum (ER) stress induction of cell death is implicated in cardiovascular diseases. Sustained activation of ER-stress induces the unfolded protein response (UPR) pathways, which in turn activate three major effector proteins. We previously reported a missense homozygous mutation in FBXO32 (MAFbx, Atrogin-1) causing advanced heart failure by impairing autophagy. In the present study, we performed transcriptional profiling and biochemical assays, which unexpectedly revealed a reduced activation of UPR effectors in patient mutant hearts, while a strong up-regulation of the CHOP transcription factor and of its target genes are observed. Expression of mutant FBXO32 in cells is sufficient to induce CHOP-associated apoptosis, to increase the ATF2 transcription factor and to impair ATF2 ubiquitination. ATF2 protein interacts with FBXO32 in the human heart and its expression is especially high in FBXO32 mutant hearts. These findings provide a new underlying mechanism for FBXO32-mediated cardiomyopathy, implicating abnormal activation of CHOP. These results suggest alternative non-canonical pathways of CHOP activation that could be considered to develop new therapeutic targets for the treatment of FBXO32-associated DCM.
A diffusion anisotropy descriptor links morphology effects of H-ZSM-5 zeolites to their catalytic cracking performance
Authors: Liu Xiaoliang , Shi Jing , Yang Guang , Zhou Jian , Wang Chuanming , Teng Jiawei , Wang Yangdong , Xie Zaiku
Published: July 2021

Zeolite morphology is crucial in determining their catalytic activity, selectivity and stability, but quantitative descriptors of such a morphology effect are challenging to define. Here we introduce a descriptor that accounts for the morphology effect in the catalytic performances of H-ZSM-5 zeolite for C4 olefin catalytic cracking. A series of H-ZSM-5 zeolites with similar sheet-like morphology but different c-axis lengths were synthesized. We found that the catalytic activity and stability is improved in samples with longer c-axis. Combining time-resolved in-situ FT-IR spectroscopy with molecular dynamics simulations, we show that the difference in catalytic performance can be attributed to the anisotropy of the intracrystalline diffusive propensity of the olefins in different channels. Our descriptor offers mechanistic insight for the design of highly effective zeolite catalysts for olefin cracking.
Chemoenzymatic synthesis of 3-ethyl-2,5-dimethylpyrazine by L-threonine 3-dehydrogenase and 2-amino-3-ketobutyrate CoA ligase/L-threonine aldolase
Authors: Motoyama Tomoharu , Nakano Shogo , Hasebe Fumihito , Miyata Ryo , Kumazawa Shigenori , Miyoshi Noriyuki , Ito Sohei
Published: July 2021

Pyrazines are typically formed from amino acids and sugars in chemical reactions such as the Maillard reaction. In this study, we demonstrate that 3-ethyl-2,5-dimethylpyrazine can be produced from L-Thr by a simple bacterial operon. We conclude that EDMP is synthesized chemoenzymatically from L-Thr via the condensation reaction of two molecules of aminoacetone and one molecule of acetaldehyde. Aminoacetone is supplied by L-threonine 3-dehydrogenase using L-Thr as a substrate via 2-amino-3-ketobutyrate. Acetaldehyde is supplied by 2-amino-3-ketobutyrate CoA ligase bearing threonine aldolase activity from L-Thr when CoA was at low concentrations. Considering the rate of EDMP production, the reaction intermediate is stable for a certain time, and moderate reaction temperature is important for the synthesis of EDMP. When the precursor was supplied from L-Thr by these enzymes, the yield of EDMP was increased up to 20.2%. Furthermore, we demonstrate that this reaction is useful for synthesizing various alkylpyrazines.
Supramolecular copolymer modified statin-loaded discoidal rHDLs for atherosclerotic anti-inflammatory therapy by cholesterol efflux and M2 macrophage polarization
Authors: Zhang Qiqi , He Jianhua , Xu Fengfei , Huang Xinya , Wang Yanyan , Zhang Wenli , Liu Jianping
Published: July 2021

The construction of supramolecular copolymer modified AT-d-rHDL and the atherosclerotic anti-inflammatory therapy on foam cells by synergistic M2 polarization of responsive cholesterol efflux and drug delivery.
A computational study of the electrochemical cyanide reduction for ambient ammonia production on a nickel cathode
Authors: Brennan Kevin , Watson Graeme W. , García-Melchor Max
Published: July 2021

Electroreduction of cyanide can proceed through one of two pathways. The first one results in the generation and desorption of methylamine as major product, whereas the second path the formation of this species, yielding methane and ammonia.
Neuroprotective mechanisms of red clover and soy isoflavones in Parkinson's disease models
Authors: de Rus Jacquet Aurélie , Ambaw Abeje , Tambe Mitali Arun , Ma Sin Ying , Timmers Michael , Grace Mary H. , Wu Qing-Li , Simon James E. , McCabe George P. , Lila Mary Ann , Shi Riyi , Rochet Jean-Christophe
Published: July 2021

The isoflavone-rich extracts red clover and soy and the individual isoflavones daidzein and equol protect neuronal cultures against triggers of Parkinson's disease, and rescue motor deficits in rats exposed to the neurotoxin 6-OHDA.
Distribution and patterns of use of food additives in foods and beverages available in Brazilian supermarkets
Authors: Montera Vanessa dos Santos Pereira , Martins Ana Paula Bortoletto , Borges Camila Aparecida , Canella Daniela Silva
Published: July 2021

This cross-sectional study reported the frequency and pattern of use of additives in 9856 food items sold in Brazil and the association of these patterns with ultra-processed foods and beverages.
A drastic improvement in photocatalytic H2 production by TiO2 nanosheets grown directly on Ta2O5 substrates
Authors: Osuagwu Benedict , Raza Waseem , Tesler Alexander B. , Schmuki Patrik
Published: July 2021

Herein we demonstrate that anatase TiO2 nanosheets (NS) can be grown on a Ta2O5 substrate. A Ta2O5 back contact exhibit a 170-fold increase in photocatalytic H2 production rate than that obtained by TiO2 NSs grown normally on FTO substrate.
Recent advances in bone-targeting nanoparticles for biomedical applications
Authors: Zhou Xue , Cornel Erik Jan , He Shisheng , Du Jianzhong
Published: July 2021

This review summarizes the progress in bone-targeting ligands, bone-targeting nanoparticles and their potential biomedical applications.
Coumarin as a green inhibitor of chloride-induced aluminum corrosion: theoretical calculation and experimental exploration
Authors: Tang Huajie , Sun Jianlin , Su Daoxin , Huang Ying , Wu Ping
Published: July 2021

The corrosion inhibition mechanism of coumarin in a chloride-containing environment.
A new solvate of clonixin and a comparison of the two clonixin solvates
Authors: Zhoujin Yunping , Zhang Mingtao , Parkin Sean , Li Tonglei , Yu Faquan , Long Sihui
Published: July 2021

A new solvate of clonixin (CLX), a dimethylacetamide (DMA) solvate, has been obtained by crystal growth in DMA.
Development of a cyan blue-emitting Ba3La2(BO3)4:Ce3+,Tb3+ phosphor for use in dental glazing materials: color tunable emission and energy transfer
Authors: Jeong Gyu Jin , Kang Tae Wook , Park Young Ji , Park Ye Jin , Lee Younki , Bae Byungseo , Kim Sun Woog
Published: July 2021

Herein, we demonstrated the possibility of using Ba3La2(BO3)4:Ce3+,Tb3+ phosphors in dental glazing paste.
Red to orange thermally activated delayed fluorescence polymers based on 2-(4-(diphenylamino)-phenyl)-9H-thioxanthen-9-one-10,10-dioxide for efficient solution-processed OLEDs
Authors: Khammultri Praetip , Chasing Pongsakorn , Chitpakdee Chirawat , Namuangruk Supawadee , Sudyoadsuk Taweesak , Promarak Vinich
Published: July 2021

TADF conjugated polymers having 2-(4-(diphenylamino)-phenyl)-9H-thioxanthen-9-one-10,10-dioxide as a TADF unit showed red/orange color emissions and enabled OLED devices with a maximum external quantum efficiency of 10.44% and a maximum current efficiency of 14.97 cd A−1
Expanding the reactivity of inorganic clusters towards proteins: the interplay between the redox and hydrolytic activity of Ce(iv)-substituted polyoxometalates as artificial proteases
Authors: Abdelhameed Shorok A. M. , Ly Hong Giang T. , Moons Jens , de Azambuja Francisco , Proost Paul , Parac-Vogt Tatjana N.
Published: July 2021

The redox chemistry of CeIV-polyoxometalates towards proteins is linked to the redox-active residues on protein surface. It can be tuned by adjusting reaction parameters, directly impacting its efficiency and selectivity as an artificial protease.
Correction: Mechanistic details of the cobalt-mediated dehydrogenative dimerization of aminoquinoline-directed benzamides
Authors: Xu Li-Ping , Liu Elaine E. L.-N. , Bacsa John , Ajitha Manjaly J. , MacBeth Cora E. , Musaev Djamaladdin G.
Published: July 2021

Correction for ‘Mechanistic details of the cobalt-mediated dehydrogenative dimerization of aminoquinoline-directed benzamides’ by Li-Ping Xu et al., Chem. Sci., 2020, 11, 6085–6096, DOI: 10.1039/D0SC02066D.
Making THE vaccine
Authors: Dewi Joe Carina Citra , Ritchie Adam John
Published: July 2021

The COVID-19 pandemic has caused millions of deaths and devastated communities across the globe. Vaccines will play a key role in bringing the pandemic under control, with successful clinical trials, authorizations and roll-out having now occurred in several countries. However, large-scale manufacturing of such vaccines remains a bottleneck to delivering doses to billions of people at risk of infection, as well as producing new versions of the vaccines that target variants. Here we discuss the current status of manufacturing, focusing on the adenovirus-vectored vaccine developed by the University of Oxford and how the process for manufacturing it was developed.