bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphological differences of hindlimb levers between wild and farmed American mink (Neovison vison) and implications for reintroduction of mustelids
Authors: Sun Jian , Zhou Xiaoli , Xu Yanchun , Hua Yan , Dahmer Thomas D. , Yang Shuhui
Published: November 2019

Reintroduction is an important strategy to restore or re-establish wild populations of endangered species. Pre-release training is a necessary step to ensure post-reintroduction survival. However, studies reported contradicting outcomes after pre-release training of juveniles and adults. This study used farmed and feral American mink (Neovison vison) to analyze the influence of captive breeding on the morphology, structure and efficiency of the two major hindlimb levers, the femur and tibia pivoted by hip and knee joints that are essential for locomotion. Results showed that captive breeding did not alter the sexual dimorphism of the two levers that are related to survival in the wild. Captive-bred mink showed slightly altered morphology of the femur and fundamental structure of the hindlimb levers that improved efficiency, but this resulted in reduction of performance related to foraging in both terrestrial and aquatic environments, especially for females. These findings suggest that reintroduction of mustelid as exampled by the mink here should focus on juveniles because the skeletal alterations associated with captive rearing were recorded only among adults and are irreversible in adulthood. In contrast, captive-reared juveniles showed no skeletal alterations and would be expected to recovery from any atrophy of the muscular system caused by captive rearing for shorter durations. Our results support the application of pre-release training of juveniles in enriched environments as a method for alleviating structural alteration of appendages and enhancing locomotion to increase survival probability in complex habitats.
Optimization of waterflooding performance by using finite volume-based flow diagnostics simulation
Authors: Boumi Mfoubat Hypp Renaud Niongui , Zaky Esther Itekile
Published: November 2019

From a visual point of view, volumetric information about reservoir portioning and communication such as sweep, flow patterns, and drainage zones are longer better interpreted and pictured when presented by an average volumetric flux calculation. To this hand, finite volume discretization can be used to substitute streamline simulation-based finite difference to assess flow diagnostic information. Herein, we use finite volume-based flow diagnostics to optimize waterflooding. In particular, we discretize in finite volume the flow equation from Darcy’s law single-phase incompressible flow steady state combining with two auxiliary flow equations, time of flight and stationary tracers using the two-point flux approximation to describe fluid particles motion and flow lines. In addition, with the estimation of dynamic heterogeneity, we compute the Lorenz coefficient to highlight the reservoir flow and storage capacity characterization. To optimize waterflooding rates, we first, use an objective function the equalized Lorenz coefficient got through the evaluation of average travel time in cells to increase sweep efficiency and decrease the dynamic heterogeneity coefficient. Second, following the same target, we use the flow diagnostic interactive tools to study the volumetric sweep displacement front and harmonize the flooding breakthrough. In this work, our conceptual approach is to see the reservoir initially filled with oil; then, optimizing the Lorenz coefficient leads us to an oil recovery improvement. To be pragmatic, we apply our waterflooding performance optimization model on two case studies, the ninth SPE comparative solution project, a reexamination of black-oil (synthetic case) and ZHNBA Chinese oilfield (real field dataset).
Vocabulary in learning processes towards conceptual understanding of equivalent fractions—specifying students’ language demands on the basis of lexical trace analyses
Authors: Wessel Lena
Published: November 2019

Although the teaching of vocabulary in mathematics lessons is requested in content- and language-integrated lesson designs, the clarification of the specific lexical language demands is still an open question for many mathematical topics. In a content- and language-integrated lesson design towards understanding the concept of equivalent fractions, the vocabulary (words and phrases) used by 17 students has been analyzed with qualitative means of data analysis. The qualitative in-depth analyses underline the importance of meaning-related vocabulary for making structural relations between the fractions in view explicit. Quantitative analyses of inventoried vocabulary for the four categories “self-initiated by students,” “triggered by teaching material,” “triggered by teacher,” or “triggered by peers” show the relations of collective and autonomous vocabularies from which the students retrieve their lexical means in oral and written language production.
Gender and collaboration patterns in a temporal scientific authorship network
Authors: Bravo-Hermsdorff Gecia , Felso Valkyrie , Ray Emily , Gunderson Lee M. , Helander Mary E. , Maria Joana , Niv Yael
Published: November 2019

One can point to a variety of historical milestones for gender equality in STEM (science, technology, engineering, and mathematics), however, practical effects are incremental and ongoing. It is important to quantify gender differences in subdomains of scientific work in order to detect potential biases and monitor progress. In this work, we study the relevance of gender in scientific collaboration patterns in the Institute for Operations Research and the Management Sciences (INFORMS), a professional society with sixteen peer-reviewed journals. Using their publication data from 1952 to 2016, we constructed a large temporal bipartite network between authors and publications, and augmented the author nodes with gender labels. We characterized differences in several basic statistics of this network over time, highlighting how they have changed with respect to relevant historical events. We find a steady increase in participation by women (e.g., fraction of authorships by women and of new women authors) starting around 1980. However, women still comprise less than 25% of the INFORMS society and an even smaller fraction of authors with many publications. Moreover, we describe a methodology for quantifying the structural role of an authorship with respect to the overall connectivity of the network, using it to measure subtle differences between authorships by women and by men. Specifically, as measures of structural importance of an authorship, we use effective resistance and contraction importance, two measures related to diffusion throughout a network. As a null model, we propose a degree-preserving temporal and geometric network model with emergent communities. Our results suggest the presence of systematic differences between the collaboration patterns of men and women that cannot be explained by only local statistics.
Measuring the appeal of mobility-augmented reality games, based on the innovative models of interaction: a case study
Authors: Shen Kai-Shuan
Published: November 2019

This study presents the issues why gamers prefer mobility-augmented reality games to other types of game and what specific characteristics cause them to invest a large amount of their time on tireless game-play. Furthermore, the appeal of mobility-augmented reality games was studied to solve the above mentioned issues. Then, how human–computer interaction based on mobility-augmented reality games was promoted to create a new marketing mode was explored. Then, Pokémon GO, as the worldwide major mobility-augmented reality game, was selected as the research target in this study. The researcher interviewed 9 experts, collected 235 Knasei words from 33 articles, and surveyed 335 gamers through a questionnaire to collect the data about users’ preferences. A preference-based study was believed to disclose the motivated reasons for the appeal of mobility-augmented reality games. The researcher analyzed the gathered Kansei concepts and questionnaires using the two-stage procedures, including evaluation grid method (EGM) and Quantification Theory Type I. During the first stage the hierarchy of the relationship among the types of appeal factors, the reasons for users’ preferences, and the explicit design characteristics of Pokémon GO present the semantic structure of appeal and were determined using EGM through the accumulation of the review of articles and the interviews of experts. During the second stage the strongest two original evaluation items of Pokémon GO are determined as “social interaction” and “scenario interaction” based on the statistical analysis of Quantification Theory Type I, and their corresponding “upper-level” and “lower-level” considerations are proved to have influence on them. Finally, the paper found that the popularity of Pokémon GO can be ascribed to the design of the innovative models of game interaction, which targets the psychological preferences of gamers. This means that the interaction model between a customer and an enterprise can be developed outside the box and a new type of marketing can be formed. The study proved that the innovative models of interaction successfully drove gamers’ motivations to play Pokémon GO. Designers and researchers of mobility-augmented reality games can absorb important information through this study. This study enriches the field of mobile communication, online marketing, and human–computer interaction in cyberspace.
Not just a bad metaphor, but a little piece of a big bad metaphor
Authors: Reeke George N.
Published: November 2019

Besides failing for the reasons Brette gives, codes fail to help us understand brain function because codes imply algorithms that compute outputs without reference to the signals' meanings. Algorithms cannot be found in the brain, only manipulations that operate on meaningful signals and that cannot be described as computations, that is, sequences of predefined operations.
Our understanding of neural codes rests on Shannon's foundations
Authors: Gallistel Charles R.
Published: November 2019

Shannon's theory lays the foundation for understanding the flow of information from world into brain: There must be a set of possible messages. Brain structure determines what they are. Many messages convey quantitative facts (distances, directions, durations, etc.). It is impossible to consider how neural tissue processes these numbers without first considering how it encodes them.
From mental representations to neural codes: A multilevel approach
Authors: Gauthier Jon , Loula João , Pollock Eli , Wilson Tyler Brooke , Wong Catherine
Published: November 2019

Representation and computation are the best tools we have for explaining intelligent behavior. In our program, we explore the space of representations present in the mind by constraining them to explain data at multiple levels of analysis, from behavioral patterns to neural activity. We argue that this integrated program assuages Brette's worries about the study of the neural code.
Beyond Neural Coding? Lessons from Perceptual Control Theory
Authors: Arsiwalla Xerxes D. , Bote Ruben Moreno , Verschure Paul
Published: November 2019

Pointing to similarities between challenges encountered in today's neural coding and twentieth-century behaviorism, we draw attention to lessons learned from resolving the latter. In particular, Perceptual Control Theory posits behavior as a closed-loop control process with immediate and teleological causes. With two examples, we illustrate how these ideas may also address challenges facing current neural coding paradigms.
Elected member influence in the United Nations Security Council
Authors: Farrall Jeremy , Loiselle Marie-Eve , Michaelsen Christopher , Prantl Jochen , Whalan Jeni
Published: November 2019

This article reassesses how members of the UN Security Council exercise influence over the Council’s decision-making process, with particular focus on the ten elected members (the E10). A common understanding of Security Council dynamics accords predominance to the five permanent members (the P5), suggesting bleak prospects for the Council as a forum that promotes the voices and representation of the 188 non-permanent members. The assumption is that real power rests with the P5, while the E10 are there to make up the numbers. By articulating a richer account of Council dynamics, this article contests the conventional wisdom that P5 centrality crowds out space for the E10 to influence Council decision-making. It also shows that opportunities for influencing Council decision-making go beyond stints of elected membership. It argues that the assumed centrality of the P5 on the Council thus needs to be qualified and re-evaluated.
NUMERICAL ENTROPY PRODUCTION AS SMOOTHNESS INDICATOR FOR SHALLOW WATER EQUATIONS
Authors: MUNGKASI SUDI , ROBERTS STEPHEN GWYN
Published: November 2019

The numerical entropy production (NEP) for shallow water equations (SWE) is discussed and implemented as a smoothness indicator. We consider SWE in three different dimensions, namely, one-dimensional, one-and-a-half-dimensional, and two-dimensional SWE. An existing numerical entropy scheme is reviewed and an alternative scheme is provided. We prove the properties of these two numerical entropy schemes relating to the entropy steady state and consistency with the entropy equality on smooth regions. Simulation results show that both schemes produce NEP with the same behaviour for detecting discontinuities of solutions and perform similarly as smoothness indicators. An implementation of the NEP for an adaptive numerical method is also demonstrated.
Experimental Investigation of the Dynamics of Trapped Nonwetting Droplets Subjected to Seismic Stimulation in Constricted Tubes
Authors: Zhang Yandong , Zeng Chao , Bai Baojun , Deng Wen
Published: November 2019

Multiphase fluid flow in porous media can be affected by the dynamic stressing caused by earthquakes or human‐made blasts. Changes in the permeability of porous media can be induced by the mobilization of trapped colloids, immiscible droplets, or bubbles due to such dynamic stressing. In order to analyze the mechanism of this seismic‐induced mobilization, a theoretical fluid dynamics conceptual model had been developed to describe this phenomenon in constricted tubes. In the research presented in this paper, we made an experimental effort to obtain reliable data to study the dynamics of nonwetting droplets and validate the previous theoretical fluid dynamics conceptual model in constricted tubes. In our experiments, we considered not only the frequencies and acceleration amplitudes of the seismic stimulation but also different initial positions of the nonwetting droplets, aspect ratios of the constricted tubes, and viscosities of nonwetting phases. We used a high‐speed camera to capture video of the mobilization process of droplets inside capillary tubes, and then manually tracked the displacement of the droplets. Our experimental observation revealed a strong dependence on the critical acceleration amplitude for mobilization on the initial position of a droplet's front menisci. Finally, the reliability of the theoretical model was validated against the experimental data on amplitude amplifications in oscillation experiments and critical amplitudes in mobilization experiments, as dependent on the frequency.
Uplift of Trail Ridge, Florida, by Karst Dissolution, Glacial Isostatic Adjustment, and Dynamic Topography
Authors: Creveling Jessica R. , Austermann Jacqueline , Dutton Andrea
Published: November 2019

The present elevation of Trail Ridge, a purported Pleistocene paleoshoreline (2.21 ± 0.38 Ma) up to ~70 m high, is attributed to isostatic uplift from karst‐induced mass loss of the underlying Florida Platform. However, glacial isostatic adjustment, dynamic topography (DT), and elastic flexure also contribute to the observed topography. We investigated the combined contribution of these geophysical processes to the elevation of Trail Ridge by adapting a numerical model of karst‐induced Airy isostatic uplift that is driven by sea level change since ~3 Ma with a gravitationally self‐consistent glacial isostatic adjustment model. We treat DT as a free parameter and explore a spectrum of scenarios, from dynamic subsidence (−25 m/Myr) to dynamic uplift (+25 m/Myr), with values consistent with mantle convection simulations for the region. We demonstrate a trade‐off between the age of Trail Ridge, karstification efficiency, and DT rate that necessitates robust estimates of two of these variables when solving for the third. For example, adopting spring‐efflux‐derived estimates of subsurface carbonate dissolution (1 m/38,000 yr) and a 10 m/Myr dynamic topographic uplift for the northern Florida Platform predicts an age of ~2.1 Ma for a model 70 m elevation marker, consistent with the bounds of the electron spin resonance optical dating geochronology. In contrast, by assuming a more rapid carbonate dissolution efficiency (1 m/11,000 yr) and dynamic subsidence of −15 m/Myr predicts a similar age. A refined karst‐induced isostatic uplift model age for Trail Ridge requires both improved rates of regional karst dissolution, dynamic topographic change, and elastic flexure.
Lightning and Associated Convection Features in the Presence of Absorbing Aerosols Over Northern Alabama
Authors: Ren Tong , Rapp Anita D. , Mecikalski John R. , Apke Jason
Published: November 2019

Many of the previous aerosol‐convection/lightning enhancement studies are based on convective storms that occur in the presence of absorbing aerosols; such aerosols may impact deep convection through their microphysical and radiative effects. In this study, lightning flash rates (FRs) are analyzed together with aerosol optical depth (AOD) retrievals from the Moderate Resolution Imaging Spectroradiometer for summer storms during 2002–2015. Aerosol index retrievals from the Ozone Monitoring Instrument are used to separate nonabsorbing and absorbing aerosol cases. Statistical analyses are performed to test for significant sample differences and linear relationships between the AOD of case studies and the FRs, convective available potential energy, planetary boundary layer height, and low‐level vertical wind shear to identify if evidence of regulation of storms by absorbing aerosols exists. Overall, AOD and FR do not show any significant linear relationship. When just observing absorbing aerosols, however, AOD and FR show a stronger (but still very weak) positive correlation. The weak correlation may be related to the absorbing aerosols' impact on convective available potential energy, which has a moderate linear correlation to AOD particularly when the instability is low, which implies some kind of convection or convective environment modification by absorbing aerosols. Although the planetary boundary layer height tends to decrease with increasing amount of absorbing aerosols, it is found that low‐level vertical wind shear does not correlate with AOD for either absorbing or nonabsorbing aerosols. This result suggests little influence of the interaction between absorbing aerosols and turbulent mixing on storms.
Coupled Snow and Frozen Ground Physics Improves Cold Region Hydrological Simulations: An Evaluation at the upper Yangtze River Basin (Tibetan Plateau)
Authors: Qi Jia , Wang Lei , Zhou Jing , Song Lei , Li Xiuping , Zeng Tian
Published: November 2019

Cryosphere plays an important role in cold‐region (e.g., Tibetan Plateau) hydrological processes under climate change, and thus cryosphere physics should be carefully represented in the hydrological modeling. In this study, based on the Water and Energy Budget‐based Distributed Hydrological Model (WEB‐DHM), we have further improved the cold‐region hydrological processes, by incorporating the enthalpy‐based coupled snow and frozen ground physics (hereinafter WEB‐DHM‐SF), and comprehensively evaluated at the upper Yangtze River Basin under widespread snow cover and frozen ground. The model was calibrated and validated at the basin scale using observed discharge at Zhimenda station during 1981–2016 and simulated discharge with high accuracies. The model also successfully reproduced the basin‐wide daytime and nighttime land surface temperature (LST) as well as snow depth in basin‐averaged time series and spatial distributions. At the point scale, the model successfully reproduced soil moisture and temperature profiles at Tuotuohe based on available yearlong observations. Furthermore, experiments were designed to investigate model improvements and indicated that the incorporation of the three‐layer snow scheme with correct consideration of incident solar radiation attenuation among snow layers resulted in lowered snow melting and reduced discharges. Additionally, the incorporation of frozen ground physics with a correct description of soil water phase changes rendered the modeled soil moistures and temperatures more accurate in the cold season. Through rigorous evaluations of model performance, the incorporation of coupled snow and frozen ground physics demonstrates significant promise for improving cryosphere hydrological simulations in river basins on the TP.
Exploring the Temperature Dependence of Clumped Isotopes in Modern Porites Corals
Authors: Guo Yangrui , Deng Wenfeng , Wei Gangjian , Chen Xuefei , Liu Xi , Wang Xijie , Lo Li , Cai Guanqiang , Zeng Ti
Published: November 2019

Porites corals are valuable geological archives for reconstructing past sea surface temperature (SST) in tropical oceans. Their clumped isotope compositions (indicated by Δ47 values) provide a potential proxy for SST. The Δ47 value in Porites coral usually departs from thermodynamic equilibrium due to vital effects. To explore the temperature dependence of Δ47 values in corals, we determined δ13C, δ18O, and Δ47 values in two modern Porites corals from the South China Sea. Our results indicate no intercolony or intracolony biases in Δ47 values on annual timescales. However, on seasonal timescales, Δ47 enrichment associated with δ13C depletion is observed at an intracolony level. This cannot be explained by incomplete hydration and/or hydroxylation of metabolic CO2; instead, we interpret this new pattern of isotopic anomalies as a peculiar evidence of vital effects on Δ47 and δ13C fractionation. Although complicated by vital effects, the Δ47 signature in Porites corals still preserved a robust SST dependence, similar to those of recently published Δ47‐T calibrations. The observed Δ47 offset relative to inorganic carbonate due to the vital effects is consistent, and relative variations in seasonal SST can be obtained. This study refines the Δ47 thermometer in Porites corals and strengthens its capacity to be used to reconstruct past SST.
Graft immaturity and safety concerns in transplanted human kidney organoids
Authors: Nam Sun Ah , Seo Eunjeong , Kim Jin Won , Kim Hyung Wook , Kim Hong Lim , Kim Kyuryung , Kim Tae-Min , Ju Ji Hyeon , Gomez Ivan G. , Uchimura Kohei , Humphreys Benjamin D. , Yang Chul Woo , Lee Jae Yeon , Kim Jin , Cho Dong Woo , Freedman Benjamin S. , Kim Yong Kyun
Published: November 2019

For chronic kidney disease, regeneration of lost nephrons with human kidney organoids derived from induced pluripotent stem (iPS) cells is proposed to be an attractive potential therapeutic option. It remains unclear, however, whether organoids transplanted into kidneys in vivo would be safe or functional. Here, we purified kidney organoids and transplanted them beneath the kidney capsules of immunodeficient mice to test their safety and maturity. Kidney organoid grafts survived for months after transplantation and became vascularized from host mouse endothelial cells. Nephron-like structures in grafts appeared more mature than kidney organoids in vitro, but remained immature compared with the neighboring mouse kidney tissue. Ultrastructural analysis revealed filtration barrier-like structures, capillary lumens, and tubules with brush border in the transplanted kidney organoids, which were more mature than those of the kidney organoids in vitro but not as organized as adult mammalian kidneys. Immaturity was a common feature of three separate differentiation protocols by immunofluorescence analysis and single cell RNA sequencing. Stroma of transplanted kidney organoid grafts were filled with vimentin-positive mesenchymal cells, and chondrogenesis, cystogenesis, and stromal expansion were observed in the long term. Transcription profiles showed that long-term maintenance after kidney organoid transplantation induced transcriptomic reprogramming with prominent suppression of cell-cycle-related genes and upregulation of extracellular matrix organization. Our data suggest that kidney organoids derived from iPS cells may be transplantable but strategies to improve nephron differentiation and purity are required before they can be applied in humans as a therapeutic option.
Inflammation induced by incomplete radiofrequency ablation accelerates tumor progression and hinders PD-1 immunotherapy
Authors: Shi Liangrong , Wang Junjun , Ding Nianhua , Zhang Yi , Zhu Yibei , Dong Shunli , Wang Xiaohui , Peng Changli , Zhou Chunhui , Zhou Ledu , Li Xiaodong , Shi Hongbing , Wu Wei , Long Xueyin , Wu Changping , Liao Weihua
Published: November 2019

Radiofrequency ablation (RFA) promotes tumor antigen-specific T cell responses and enhances the effect of immunotherapy in preclinical settings. Here we report that the existence of remnant tumor masses due to incomplete RFA (iRFA) is associated with earlier new metastases and poor survival in patients with colorectal cancer liver metastases (CRCLM). Using mouse models, we demonstrate that iRFA promotes tumor progression and hinders the efficacy of anti-PD-1 therapy. Immune analysis reveals that iRFA induces sustained local inflammation with predominant myeloid suppressor cells, which inhibit T cell function in tumors. Mechanistically, tumor cell-derived CCL2 is critical for the accumulation of monocytes and tumor-associated macrophages (TAMs). The crosstalk between TAMs and tumor cells enhances the CCL2 production by tumor cells. Furthermore, we find that administration of a CCR2 antagonist or the loss of CCL2 expression in tumor cells enhances the antitumor activity of PD-1 blockade, providing a salvage alternative for residual tumors after iRFA.
Accurate, scalable and integrative haplotype estimation
Authors: Delaneau Olivier , Zagury Jean-François , Robinson Matthew R. , Marchini Jonathan L. , Dermitzakis Emmanouil T.
Published: November 2019

The number of human genomes being genotyped or sequenced increases exponentially and efficient haplotype estimation methods able to handle this amount of data are now required. Here we present a method, SHAPEIT4, which substantially improves upon other methods to process large genotype and high coverage sequencing datasets. It notably exhibits sub-linear running times with sample size, provides highly accurate haplotypes and allows integrating external phasing information such as large reference panels of haplotypes, collections of pre-phased variants and long sequencing reads. We provide SHAPEIT4 in an open source format and demonstrate its performance in terms of accuracy and running times on two gold standard datasets: the UK Biobank data and the Genome In A Bottle.
Postglacial change of the floristic diversity gradient in Europe
Authors: Giesecke Thomas , Wolters Steffen , van Leeuwen Jacqueline F. N. , van der Knaap Pim W. O. , Leydet Michelle , Brewer Simon
Published: November 2019

Climate warming is expected to cause a poleward spread of species, resulting in increased richness at mid to high latitudes and weakening the latitudinal diversity gradient. We used pollen data to test if such a change in the latitudinal diversity gradient occurred during the last major poleward shift of plant species in Europe following the end of the last glacial period. In contrast to expectations, the slope of the gradient strengthened during the Holocene. The increase in temperatures around 10 ka ago reduced diversity at mid to high latitude sites due to the gradual closure of forests. Deforestation and the introduction of agriculture during the last 5 ky had a greater impact on richness in central Europe than the earlier climate warming. These results do not support the current view that global warming alone will lead to a loss in biodiversity, and demonstrate that non-climatic human impacts on the latitudinal diversity gradient is of a greater magnitude than climate change.
Core architecture of a bacterial type II secretion system
Authors: Chernyatina Anastasia A. , Low Harry H.
Published: November 2019

Bacterial type II secretion systems (T2SSs) translocate virulence factors, toxins and enzymes across the cell outer membrane. Here we use negative stain and cryo-electron microscopy to reveal the core architecture of an assembled T2SS from the pathogen Klebsiella pneumoniae. We show that 7 proteins form a ~2.4 MDa complex that spans the cell envelope. The outer membrane complex includes the secretin PulD, with all domains modelled, and the pilotin PulS. The inner membrane assembly platform components PulC, PulE, PulL, PulM and PulN have a relative stoichiometric ratio of 2:1:1:1:1. The PulE ATPase, PulL and PulM combine to form a flexible hexameric hub. Symmetry mismatch between the outer membrane complex and assembly platform is overcome by PulC linkers spanning the periplasm, with PulC HR domains binding independently at the secretin base. Our results show that the T2SS has a highly dynamic modular architecture, with implication for pseudo-pilus assembly and substrate loading.
Nanocomposite electrodes for high current density over 3 A cm−2 in solid oxide electrolysis cells
Authors: Shimada Hiroyuki , Yamaguchi Toshiaki , Kishimoto Haruo , Sumi Hirofumi , Yamaguchi Yuki , Nomura Katsuhiro , Fujishiro Yoshinobu
Published: November 2019

Solid oxide electrolysis cells can theoretically achieve high energy-conversion efficiency, but current density must be further increased to improve the hydrogen production rate, which is essential to realize widespread application. Here, we report a structure technology for solid oxide electrolysis cells to achieve a current density higher than 3 A cm−2, which exceeds that of state-of-the-art electrolyzers. Bimodal-structured nanocomposite oxygen electrodes are developed where nanometer-scale Sm0.5Sr0.5CoO3−δ and Ce0.8Sm0.2O1.9 are highly dispersed and where submicrometer-scale particles form conductive networks with broad pore channels. Such structure is realized by fabricating the electrode structure from the raw powder material stage using spray pyrolysis. The solid oxide electrolysis cells with the nanocomposite electrodes exhibit high current density in steam electrolysis operation (e.g., at 1.3 V), reaching 3.13 A cm−2 at 750 °C and 4.08 A cm−2 at 800 °C, corresponding to a hydrogen production rate of 1.31 and 1.71 L h−1 cm−2 respectively.
Pharmacokinetics of Micafungin in Critically Ill Patients
Authors: Gastine Silke , Lanckohr Christian , Blessou Magalie , Horn Dagmar , Fobker Manfred , Bause Daniela , Hempel Georg , Ellger Björn
Published: November 2019

We investigated covariates of pharmacokinetics of micafungin in critically ill patients. After application of micafungin, plasma samples were collected. Non-linear mixed effects modelling (NONMEM 7.3) was used to develop the pharmacokinetic model. Using this model, the adequacy of a fixed 100 mg dosing regimen was evaluated in the study cohort. A two-compartment model with linear elimination was found to describe the obtained data. SOFA score was identified as a significant covariate on both clearance and central volume of distribution, respectively. Patients in highly critical condition, represented by a SOFA above 10 showed a 30.8% lower central volume of distribution than the less critically ill patients. For patients with bilirubin levels above 4 mg/dl, clearance was decreased by 21.1%. Renal replacement therapy (RRT) did not influence micafungin clearance or the volumes of distribution. In a posthoc evaluation of the modeled population, 100 mg micafungin was suitable when assessing the PKPD targets (AUC/MIC) for C. albicans and C. glabrata, with insufficient target attainment for C. parapsilosis. Micafungin pharmacokinetics appear not to be influenced by the status of RRT. A dose of 100 mg micafungin is suitable for infections with C. albicans and C. glabrata in critically ill patients.
Wild specimens of sand fly phlebotomine Lutzomyia evansi, vector of leishmaniasis, show high abundance of Methylobacterium and natural carriage of Wolbachia and Cardinium types in the midgut microbiome
Authors: Vivero Rafael J. , Villegas-Plazas Marcela , Cadavid-Restrepo Gloria E. , Herrera Claudia Ximena Moreno , Uribe Sandra I. , Junca Howard
Published: November 2019

Phlebotomine sand flies are remarkable vectors of several etiologic agents (virus, bacterial, trypanosomatidLeishmania), posing a heavy health burden for human populations mainly located at developing countries. Their intestinal microbiota is involved in a wide range of biological and physiological processes, and could exclude or facilitate such transmission of pathogens. In this study, we investigated the Eubacterial microbiome from digestive tracts ofLu. evansiadults structure using 16S rRNA gene sequence amplicon high throughput sequencing (Illumina MiSeq) obtained from digestive tracts ofLu. evansiadults. The samples were collected at two locations with high incidence of the disease in humans: peri-urban and forest ecosystems from the department of Sucre, Colombia. 289,068 quality-filtered reads of V4 region of 16S rRNA gene were obtained and clustered into 1,762 operational taxonomic units (OTUs) with 97% similarity. Regarding eubacterial diversity, 14 bacterial phyla and 2 new candidate phyla were found to be consistently associated with the gut microbiome content. Proteobacteria, Firmicutes, and Bacteroidetes were the most abundant phyla in all the samples and the core microbiome was particularly dominated byMethylobacteriumgenus.Methylobacteriumspecies, are known to have mutualistic relationships with some plants and are involved in shaping the microbial community in the phyllosphere. As a remarkable feature, OTUs classified asWolbachiaspp. were found abundant on peri-urban ecosystem samples, in adult male (OTUs n = 776) and unfed female (OTUs n = 324). Furthermore, our results provide evidence of OTUs classified asCardiniumendosymbiont in relative abundance, notably higher with respect toWolbachia. The variation in insect gut microbiota may be determined by the environment as also for the type of feeding. Our findings increase the richness of the microbiota associated withLu. evansi. In this study, OTUs ofMethylobacteriumfound inLu. evansiwas higher in engorged females, suggesting that there are interactions between microbes from plant sources, blood nutrients and the parasites they transmit during the blood intake.
Long-term dispersion of river gravel in a canyon in the Atacama Desert, Central Andes, deduced from their 10Be concentrations
Authors: Carretier Sébastien , Regard Vincent , Leanni Laëtitia , Farías Marcelo
Published: November 2019

Intense storms or earthquakes in mountains can supply large amounts of gravel to rivers. Gravel clasts then travel at different rates, with periods of storage and periods of displacement leading to their downstream dispersion over millennia. The rate of this dispersion controls the long-term downcutting rate in mountainous rivers as well as the grain-size signature of climate and tectonic variations in sedimentary basins. Yet, the millennial dispersion rates of gravel are poorly known. Here, we use 10Be concentrations measured in individual pebbles from a localized source along a 56 km-long canyon in the Central Andes to document the distribution of long-term gravel transit rates. We show that an inverse grain-size velocity relationship previously established from short-term tracer gravel in different rivers worldwide can be extrapolated to the long-term transit rates in the Aroma River, suggesting some universality of this relationship. Gravel are also dispersed by large differences in the mean transport rates independent of gravel size, highlighting that some gravel rest at the river surface over tens of thousands of years. These different transport rates imply a strong spreading of the gravel plumes, providing direct proof for the long-term river buffering of sediment signals between mountainous sources and sedimentary basins. The inferred distribution of residence times suggests the first evidence of anomalous diffusion in gravel transport over long timespans.
Specificity and Efficiency of the Uracil DNA Glycosylase-Mediated Strand Cleavage Surveyed on Large Sequence Libraries
Authors: Hölz Kathrin , Pavlic Angelina , Lietard Jory , Somoza Mark M.
Published: November 2019

Uracil-DNA glycosylase (UDG) is a critical DNA repair enzyme that is well conserved and ubiquitous in nearly all life forms. UDG protects genomic information integrity by catalyzing the excision from DNA of uracil nucleobases resulting from misincorporation or spontaneous cytosine deamination. UDG-mediated strand cleavage is also an important tool in molecular biotechnology, allowing for controlled and location-specific cleavage of single- and double DNA chemically or enzymatically synthesized with single or multiple incorporations of deoxyuridine. Although the cleavage mechanism is well-understood, detailed knowledge of efficiency and sequence specificity, in both single and double-stranded DNA contexts, has so far remained incomplete. Here we use an experimental approach based on the large-scale photolithographic synthesis of uracil-containing DNA oligonucleotides to comprehensively probe the context-dependent uracil excision efficiency of UDG.
Targeted enhancement of flotillin-dependent endocytosis augments cellular uptake and impact of cytotoxic drugs
Authors: Fekri Farnaz , Abousawan John , Bautista Stephen , Orofiamma Laura , Dayam Roya M. , Antonescu Costin N. , Karshafian Raffi
Published: November 2019

Cellular uptake is limiting for the efficacy of many cytotoxic drugs used to treat cancer. Identifying endocytic mechanisms that can be modulated with targeted, clinically-relevant interventions is important to enhance the efficacy of various cancer drugs. We identify that flotillin-dependent endocytosis can be targeted and upregulated by ultrasound and microbubble (USMB) treatments to enhance uptake and efficacy of cancer drugs such as cisplatin. USMB involves targeted ultrasound following administration of encapsulated microbubbles, used clinically for enhanced ultrasound image contrast. USMB treatments robustly enhanced internalization of the molecular scaffold protein flotillin, as well as flotillin-dependent fluid-phase internalization, a phenomenon dependent on the protein palmitoyltransferase DHHC5 and the Src-family kinase Fyn. USMB treatment enhanced DNA damage and cell killing elicited by the cytotoxic agent cisplatin in a flotillin-dependent manner. Thus, flotillin-dependent endocytosis can be modulated by clinically-relevant USMB treatments to enhance drug uptake and efficacy, revealing an important new strategy for targeted drug delivery for cancer treatment.
Mechanical properties of the shoulder and pectoralis major in breast cancer patients undergoing breast-conserving surgery with axillary surgery and radiotherapy
Authors: Lipps David B. , Leonardis Joshua M. , Dess Robert T. , McGinnis Gwendolyn J. , Marsh Robin B. , Strauss Jonathan B. , Hayman James A. , Pierce Lori J. , Jagsi Reshma
Published: November 2019

Breast-conserving surgery (BCS) and radiotherapy reduce breast cancer recurrence but can cause functional deficits in breast cancer survivors. A cross-sectional study quantified the long-term pathophysiological impact of these treatments on biomechanical measures of shoulder stiffness and ultrasound shear wave elastography measures of the shear elastic modulus of the pectoralis major (PM). Nine node-positive patients treated with radiotherapy to the breast and regional nodes after BCS and axillary lymph node dissection (Group 1) were compared to nine node-negative patients treated with radiotherapy to the breast alone after BCS and sentinel node biopsy (Group 2) and nine healthy age-matched controls. The mean follow-up for Group 1 and Group 2 patients was 988 days and 754 days, respectively. Shoulder stiffness did not differ between the treatment groups and healthy controls (p = 0.23). The PM shear elastic modulus differed between groups (p = 0.002), with Group 1 patients exhibiting a stiffer PM than Group 2 patients (p < 0.001) and healthy controls (p = 0.027). The mean prescribed radiotherapy dose to the PM was significantly correlated with passive shear elastic modulus (p = 0.018). Breast cancer patients undergoing more extensive axillary surgery and nodal radiotherapy did not experience long-term functional deficits to shoulder integrity but did experience long-term mechanical changes of the PM.
Entropic nonclassicality and quantum non-Gaussianity tests via beam splitting
Authors: Park Jiyong , Lee Jaehak , Nha Hyunchul
Published: November 2019

We propose entropic nonclassicality criteria for quantum states of light that can be readily tested using homodyne detection with beam splitting operation. Our method draws on the fact that the entropy of quadrature distributions for a classical state is non-increasing under an arbitrary loss channel. We show that our test is strictly stronger than the variance-based squeezing condition and that it can also be extended to detect quantum non-Gaussianity in conjunction with phase randomization. Furthermore, we address how our criteria can be used to identify single-mode resource states to generate two-mode states demonstrating EPR paradox, i.e., quantum steering, via beam-splitter setting.
Germline and somatic mutations of homologous recombination-associated genes in Japanese ovarian cancer patients
Authors: Sugino Kentaro , Tamura Ryo , Nakaoka Hirofumi , Yachida Nozomi , Yamaguchi Manako , Mori Yutaro , Yamawaki Kaoru , Suda Kazuaki , Ishiguro Tatsuya , Adachi Sosuke , Isobe Masanori , Yamaguchi Masayuki , Kashima Katsunori , Motoyama Teiichi , Inoue Ituro , Yoshihara Kosuke , Enomoto Takayuki
Published: November 2019

We explored the frequency of germline and somatic mutations in homologous recombination (HR)-associated genes in major histological types of ovarian cancer. We performed targeted sequencing to assess germline and somatic mutations of 16 HR-associated genes and 4 mismatch repair (MMR) genes among 207 ovarian cancer patients (50 high-grade serous carcinomas (HGSC), 99 clear cell carcinomas (CCC), 39 endometrioid carcinomas (EC), 13 mucinous carcinomas (MC), and 6 low-grade serous carcinomas (LGSC)). Germline or somatic mutations of HR-associated genes were detected in 44% of HGSC, 28% of CCC, 23% of EC, 16% of MC, and 17% of LGSC patients. The profile of HR-associated gene mutations was remarkably different among each histological type. Germline BRCA1/2 mutations were frequently detected in HGSC and were rarely observed in CCC, EC, and MC patients. ATM somatic mutation was more frequently detected in CCC (9%) and EC patients (18%) than in HGSC patients (4%). There was a positive correlation between MMR gene mutations and HR-associated gene mutations (p = 0.0072). Our findings might be useful in selection of ovarian cancer patients that should be treated with PARP inhibitors.
Alpha-PET for Prostate Cancer: Preclinical investigation using 149Tb-PSMA-617
Authors: Umbricht Christoph A. , Köster Ulli , Bernhardt Peter , Gracheva Nadezda , Johnston Karl , Schibli Roger , van der Meulen Nicholas P. , Müller Cristina
Published: November 2019

In this study, it was aimed to investigate 149Tb-PSMA-617 for targeted α-therapy (TAT) using a mouse model of prostate-specific membrane antigen (PSMA)-expressing prostate cancer. 149Tb-PSMA-617 was prepared with >98% radiochemical purity (6 MBq/nmol) for the treatment of mice with PSMA-positive PC-3 PIP tumors. 149Tb-PSMA-617 was applied at 1 × 6 MBq (Day 0) or 2 × 3 MBq (Day 0 & Day 1 or Day 0 & Day 3) and the mice were monitored over time until they had reached a pre-defined endpoint which required euthanasia. The tumor growth was significantly delayed in mice of the treated groups as compared to untreated controls (p < 0.05). TAT was most effective in mice injected with 2 × 3 MBq (Day 0 & 1) resulting in a median lifetime of 36 days, whereas in untreated mice, the median lifetime was only 20 days. Due to the β+-emission of 149Tb, tumor localization was feasible using PET/CT after injection of 149Tb-PSMA-617 (5 MBq). The PET images confirmed the selective accumulation of 149Tb-PSMA-617 in PC-3 PIP tumor xenografts. The unique characteristics of 149Tb for TAT make this radionuclide of particular interest for future clinical translation, thereby, potentially enabling PET-based imaging to monitor the radioligand’s tissue distribution.
Apple B-box factors regulate light-responsive anthocyanin biosynthesis genes
Authors: Plunkett Blue J. , Henry-Kirk Rebecca , Friend Adam , Diack Robert , Helbig Susanne , Mouhu Katriina , Tomes Sumathi , Dare Andrew P. , Espley Richard V. , Putterill Joanna , Allan Andrew C.
Published: November 2019

Environmentally-responsive genes can affect fruit red colour via the activation of MYB transcription factors. The apple B-box (BBX) gene, BBX33/CONSTANS-like 11 (COL11) has been reported to influence apple red-skin colour in a light- and temperature-dependent manner. To further understand the role of apple BBX genes, other members of the BBX family were examined for effects on colour regulation. Expression of 23 BBX genes in apple skin was analysed during fruit development. We investigated the diurnal rhythm of expression of the BBX genes, the anthocyanin biosynthetic genes and a MYB activator, MYB10. Transactivation assays on the MYB10 promoter, showed that BBX proteins 1, 17, 15, 35, 51, and 54 were able to directly function as activators. Using truncated versions of the MYB10 promoter, a key region was identified for activation by BBX1. BBX1 enhanced the activation of MYB10 and MdbHLH3 on the promoter of the anthocyanin biosynthetic gene DFR. In transformed apple lines, over-expression of BBX1 reduced internal ethylene content and altered both cyanidin concentration and associated gene expression. We propose that, along with environmental signals, the control of MYB10 expression by BBXs in ‘Royal Gala’ fruit involves the integration of the expression of multiple BBXs to regulate fruit colour.
Boron-doped Nanodiamond as an Electrode Material for Aqueous
Electric Double-layer Capacitors
Authors: Miyashita Kenjo , Kondo Takeshi , Sugai Seiya , Tei Takahiro , Nishikawa Masahiro , Tojo Toshifumi , Yuasa Makoto
Published: November 2019

Herein, a conductive boron-doped nanodiamond (BDND) particle is
prepared as an electrode material for an aqueous electric double-layer capacitor
with high power and energy densities. The BDND is obtained by depositing a
boron-doped diamond (BDD) on a nanodiamond particle substrate with a primary
particle size of 4.7 nm via microwave plasma-assisted chemical vapor deposition,
followed by heat treatment in air. The BDND comprises BDD and
sp2 carbon components, and exhibits a conductivity
above 1 S cm−1 and a specific surface area of
650 m2 g−1.
Cyclic voltammetry measurements recorded in 1 M
H2SO4 at a BDND electrode in a
two-electrode system shows a capacitance of 15.1 F g−1
and a wide potential window (cell voltage) of 1.8 V, which is much larger than that
obtained at an activated carbon electrode, i.e., 0.8 V. Furthermore, the cell
voltage of the BDND electrode reaches 2.8 V when using saturated
NaClO4 as electrolyte. The energy and power densities per
unit weight of the BDND for charging–discharging in 1 M
H2SO4 at the BDND electrode cell are
10 Wh kg−1 and
104 W kg−1, respectively,
and the energy and power densities per unit volume of the BDND layer are 3–4 mWh
cm−3 and 10 W cm−3,
respectively. Therefore, the BDND is a promising candidate for the development of a
compact aqueous EDLC device with high energy and power densities.