bluuebunny/crossref_metadata_2025 huggingface dataset:
Raw milk producers with high levels of hygiene and safety
Authors: Berge A. C. , Baars T.
Published: January 2020

There is world-wide increasing interest in the consumption of unprocessed, natural food commodities including fresh (unpasteurised) milk and milk products. Consumers are actively seeking out raw milk, partly due to health reasons, but also for taste, freshness, closeness to the producer and to support local agriculture. The need for high levels of hygiene and safety in farms producing raw milk for direct consumption has long been recognised and has led to federal and industry-initiated systems for safe raw milk production. Raw milk producers in North America and Europe have demonstrated that raw milk, intended for direct consumption, can be produced safe and hygienic. The aim of this paper is to describe practices that have been developed for safe raw milk production. The German Vorzugsmilch is a federally regulated programme for legal raw milk production that was established already in the 1930s to provide raw milk with high hygienic standards controlled for zoonotic diseases to consumers. The Raw Milk Institute is a non-profit organisation established in California that has developed a voluntary safe raw milk programme in North America. RAWMI has developed a risk analysis and management system for raw milk dairy farmers to assist farmers in making individually tailored solutions for various production systems. In British Colombia, Canada, small herd share farms have employed good manufacturing practices, a risk management approach and performed monthly samples for pathogens and indicator bacteria to demonstrate safety and consistency. The major components of the raw milk systems applied, and the results of regular milk microbial indicator bacteria are presented. For the German system, the results from standard monthly pathogen tests are compared to zoonotic pathogen tests from other milk sources. The overall results indicate that raw milk can be produced with a high level of hygiene and safety in various systems.
Final Thoughts on Beiläufigkeit
Authors: Pollock Susan , Bernbeck Reinhard , Schreiber Stefan , Appel Lena , Loy Anna K.
Published: January 2020

The essays in this theme section demonstrate clearly the diversity and complexity of a topic that seems negligible in practice but emerges as important upon further reflection—the incidentalness of things. In this brief afterword, we highlight three of the themes addressed by all or most of the contributions, which we suggest are of particular relevance when considering the place of the incidental in our archaeological engagements.
The Changing Legal Landscape
Authors: Hale Brenda
Published: January 2020

The Willi Steiner Memorial Lecture 2019 was delivered at the British and Irish Association of Law Librarians’ Annual Conference by Brenda Hale, Baroness Hale of Richmond, DBE,1 the President of the Supreme Court of the United Kingdom. Lady Hale reflected upon some of the major changes in the law and access to justice since she was an undergraduate at the University of Cambridge and Willi Steiner was Law Librarian at the Squire Law Library. Her lecture coincided with BIALL's fiftieth anniversary year and focused on five significant developments: the explosion of judicial review of administrative action, the arrival of EU law, the growth of international human rights law, the recognition of gender and other equality, and devolution and the evolution of a new constitutional role for the courts.
Geochemistry and Microtextures of Vein Calcites Pervading the Izu‐Bonin Forearc and Rear Arc Crust: New Insights From IODP Expeditions 352 and 351
Authors: Quandt D. , Micheuz P. , Kurz W. , Bernasconi S. M. , Hippler D. , Krenn K. , Hauzenberger C. A.
Published: January 2020

International Ocean Discovery Program Expeditions 352 and 351 drilled into the Western Pacific Izu‐Bonin forearc and rear arc. The drill cores revealed that the forearc is composed of forearc basalts (FAB) and boninites and the rear arc consists of FAB‐like rocks. These rocks are pervaded by calcite veins. Blocky vein microtextures enclosing host rock fragments dominate in all locations and suggest hydrofracturing and advective fluid flow. Significant diffusion‐fed and crystallization pressure‐driven antitaxial veining is restricted to the rear arc. The lack of faults and presence of an Eocene sedimentary cover in the rear arc facilitated antitaxial veining. Rare earth element and isotopic (δ18O, δ13C, 87Sr/86Sr, and Δ47) tracers indicate varying parental fluid compositions ranging from pristine to variably modified seawater. The most pristine seawater signatures are recorded by FAB‐hosted low‐T (<30 °C) vein calcites. Their 87Sr/86Sr ratios intersect the 87Sr/86Sr seawater curve at ~35–33 and ~22 Ma. These intersections are interpreted as precipitation ages, which concur with Pacific slab rollback. Boninite‐hosted low‐T (<30 °C) vein calcites precipitated from seawater that was modified by fluid‐rock interactions. Mixing calculations yield a mixture of >95% seawater and <5% basaltic 87Sr/86Sr. In the rear arc, low‐T rock alteration lowered the circulating seawater in δ18O and 87Sr/86Sr. Thus, vein calcites precipitated from modified seawater with up to 20–30% basaltic 87Sr/86Sr at temperatures up to 74 ± 12 °C. These results show how the local geology and vein growth dynamics affect microtextures and geochemical compositions of vein precipitates.
Modeling the Relationship of Groundwater Salinity to Neonatal and Infant Mortality From the Bangladesh Demographic Health Survey 2000 to 2014
Authors: Naser Abu Mohd , Wang Qiao , Shamsudduha Mohammad , Chellaraj Gnanaraj , Joseph George
Published: January 2020

We evaluated the relationship of drinking water salinity to neonatal and infant mortality using Bangladesh Demographic Health Surveys of 2000, 2004, 2007, 2011, and 2014. Point data of groundwater electrical conductivity (EC)— a measure of salinity—were collated from the Bangladesh Water Development Board and digitizing salinity contour map. Data for groundwater dissolved elements (sodium, calcium, magnesium, and potassium) data came from a national hydrochemistry survey in Bangladesh. Point EC and dissolved minerals data were then interpolated over entire Bangladesh and extracted to each cluster location, the primary sampling unit of Bangladesh Demographic Health Surveys. We used restricted cubic splines and survey design‐specific logistic regression models to determine the relationship of water salinity to neonatal and infant mortality. A U‐shaped association between drinking water salinity and neonatal and infant mortality was found, suggesting higher mortality when salinity was very low and high. Compared to mildly saline (EC ≥0.7 and < 2 mS/cm) water drinkers, freshwater (EC < 0.7 mS/cm) drinkers had 1.37 (95% CI: 1.01, 1.84) times higher neonatal mortality and 1.43 (95% CI: 1.08, 1.89) times higher infant mortality. Compared to mildly saline water drinkers, severe‐saline (EC ≥10 mS/cm) water drinkers had 1.77 (95% CI: 1.17, 2.68) times higher neonatal mortality and 1.93 (95% CI: 1.35, 2.76) times higher infant mortality. We found that mild‐salinity water had a high concentration of calcium and magnesium, whereas severe‐salinity water had a high concentration of sodium. Freshwater had the least concentrations of salubrious calcium and magnesium.
Improved ENSO Prediction Skill Resulting From Reduced Climate Drift in IAP‐DecPreS: A Comparison of Full‐Field and Anomaly Initializations
Authors: Hu Shuai , Zhou Tianjun , Wu Bo
Published: January 2020

When initiated from observational conditions, coupled climate models used in seasonal predictions generally experience climate drifts. How climate drift affects El Niño–Southern Oscillation (ENSO) prediction is important but not clearly understood. Here, we investigate this issue by comparing seasonal hindcasts using two distinct initialization approaches, namely, anomaly and full‐field initializations, based on a climate prediction system named IAP‐DecPreS. The differences between the two approaches are mainly evident in the drift behavior. We find that the hindcasts based on anomaly initialization (Hindcast‐A) have higher ENSO prediction skill compared to those based on full‐field initialization (Hindcast‐F). The climate drifts are largely reduced in the Hindcast‐A as expected. In contrast, the Hindcast‐F features a growing warming of the equatorial central eastern Pacific with increasing lead times. To investigate the impact of drift on the prediction, the 1997/1998 and 2015/2016 El Niño cases are analyzed. At a 7‐month lead, the Hindcast‐A reasonably predicts the two events, while the Hindcast‐F shows large errors in both evolution and amplitude. Budget analyses show that the underestimation of warming tendency in the Hindcast‐F is caused by cooling effects of excessive anomalous surface shortwave radiative flux and anomalous temperature advection by mean horizontal currents, both of which are associated with the climate drift. Our results imply that the use of the AI scheme can improve ENSO predictions through a reduction in climate drift in IAP‐DecPreS. The drifts can dynamically influence ENSO predictions, and their impact cannot be thoroughly removed via the empirical bias correction. Thus, reducing drift impacts is necessary.
SPEAR: The Next Generation GFDL Modeling System for Seasonal to Multidecadal Prediction and Projection
Authors: Delworth Thomas L. , Cooke William F. , Adcroft Alistair , Bushuk Mitchell , Chen Jan‐Huey , Dunne Krista A. , Ginoux Paul , Gudgel Richard , Hallberg Robert W. , Harris Lucas , Harrison Matthew J. , Johnson Nathaniel , Kapnick Sarah B. , Lin Shian‐Jian , Lu Feiyu , Malyshev Sergey , Milly Paul C. , Murakami Hiroyuki , Naik Vaishali , Pascale Salvatore , Paynter David , Rosati Anthony , Schwarzkopf M.D. , Shevliakova Elena , Underwood Seth , Wittenberg Andrew T. , Xiang Baoqiang , Yang Xiaosong , Zeng Fanrong , Zhang Honghai , Zhang Liping , Zhao Ming
Published: January 2020

We document the development and simulation characteristics of the next generation modeling system for seasonal to decadal prediction and projection at the Geophysical Fluid Dynamics Laboratory (GFDL). SPEAR (Seamless System for Prediction and EArth System Research) is built from component models recently developed at GFDL—the AM4 atmosphere model, MOM6 ocean code, LM4 land model, and SIS2 sea ice model. The SPEAR models are specifically designed with attributes needed for a prediction model for seasonal to decadal time scales, including the ability to run large ensembles of simulations with available computational resources. For computational speed SPEAR uses a coarse ocean resolution of approximately 1.0° (with tropical refinement). SPEAR can use differing atmospheric horizontal resolutions ranging from 1° to 0.25°. The higher atmospheric resolution facilitates improved simulation of regional climate and extremes. SPEAR is built from the same components as the GFDL CM4 and ESM4 models but with design choices geared toward seasonal to multidecadal physical climate prediction and projection. We document simulation characteristics for the time mean climate, aspects of internal variability, and the response to both idealized and realistic radiative forcing change. We describe in greater detail one focus of the model development process that was motivated by the importance of the Southern Ocean to the global climate system. We present sensitivity tests that document the influence of the Antarctic surface heat budget on Southern Ocean ventilation and deep global ocean circulation. These findings were also useful in the development processes for the GFDL CM4 and ESM4 models.
Quantifying Geochemical Processes of Arsenic Mobility in Groundwater From an Inland Basin Using a Reactive Transport Model
Authors: Gao Z.P. , Jia Y.F. , Guo H.M. , Zhang D. , Zhao B.
Published: January 2020

High arsenic (As) groundwater is frequently found in inland basins, yet the contributions of different processes to aqueous As distributions remain unresolved. In the Hetao Basin, a typical inland basin, groundwater As concentrations generally increased from the alluvial fan through the transition area to the flat plain. A geochemical process‐based reactive transport model was established to evaluate and quantify the processes of As mobilization in the northwestern Hetao Basin. Thirty‐six groundwater samples and eight sediment samples were collected from the alluvial fan to the flat plain to investigate the geochemical characteristics of the groundwater system. Along the approximate flow path, groundwater evolved from oxic‐suboxic conditions to anoxic conditions, with increasing concentrations of As, Fe (II), and NH4+, and decreasing Eh and SO42−/Cl−. Modeling results indicated that the observed concentrations of Fe (II) were caused by reductive dissolution of Fe (III) oxides and subsequent precipitation of mackinawite and siderite. Reductive dissolution of Fe (III) oxides was primarily driven by organic matter degradation (>75%), followed by H2S oxidation (<25%). More As was sequestered by mackinawite precipitation and adsorption than that released via abiotic reduction of Fe (III) oxides by H2S. Reductive dissolution of Fe (III) oxides was the dominant mechanism for liberating As in both the transition area and the flat plain (>70%), and As desorption under elevated pH and competitive adsorption by HCO3− and PO43− made an important contribution to As enrichment (up to 30%). Overall, this study provides an insight into the relative contributions of different geochemical processes to As enrichment in inland basins.
Electronic parameters in cobalt-based perovskite-type oxides as descriptors for chemocatalytic reactions
Authors: Simböck Johannes , Ghiasi M. , Schönebaum Simon , Simon Ulrich , de Groot Frank M. F. , Palkovits Regina
Published: January 2020

Perovskite-type transition metal (TM) oxides are effective catalysts in oxidation and decomposition reactions. Yet, the effect of compositional variation on catalytic efficacy is not well understood. The present analysis of electronic characteristics of B-site substituted LaCoO3 derivatives via in situ X-ray absorption spectroscopy (XAS) establishes correlations of electronic parameters with reaction rates: TM t2g and eg orbital occupancy yield volcano-type or non-linear correlations with NO oxidation, CO oxidation and N2O decomposition rates. Covalent O 2p-TM 3d interaction, in ultra-high vacuum, is a linear descriptor for reaction rates in NO oxidation and CO oxidation, and for N2O decomposition rates in O2 presence. Covalency crucially determines the ability of the catalytically active sites to interact with surface species during the kinetically relevant step of the reaction. The nature of the kinetically relevant step and of surface species involved lead to the vast effect of XAS measurement conditions on the validity of correlations.
A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism
Authors: Pradas-Juni Marta , Hansmeier Nils R. , Link Jenny C. , Schmidt Elena , Larsen Bjørk Ditlev , Klemm Paul , Meola Nicola , Topel Hande , Loureiro Rute , Dhaouadi Ines , Kiefer Christoph A. , Schwarzer Robin , Khani Sajjad , Oliverio Matteo , Awazawa Motoharu , Frommolt Peter , Heeren Joerg , Scheja Ludger , Heine Markus , Dieterich Christoph , Büning Hildegard , Yang Ling , Cao Haiming , Jesus Dario F. De , Kulkarni Rohit N. , Zevnik Branko , Tröder Simon E. , Knippschild Uwe , Edwards Peter A. , Lee Richard G. , Yamamoto Masayuki , Ulitsky Igor , Fernandez-Rebollo Eduardo , Vallim Thomas Q. de Aguiar , Kornfeld Jan-Wilhelm
Published: January 2020

Obesity and type 2 diabetes mellitus are global emergencies and long noncoding RNAs (lncRNAs) are regulatory transcripts with elusive functions in metabolism. Here we show that a high fraction of lncRNAs, but not protein-coding mRNAs, are repressed during diet-induced obesity (DIO) and refeeding, whilst nutrient deprivation induced lncRNAs in mouse liver. Similarly, lncRNAs are lost in diabetic humans. LncRNA promoter analyses, global cistrome and gain-of-function analyses confirm that increased MAFG signaling during DIO curbs lncRNA expression. Silencing Mafg in mouse hepatocytes and obese mice elicits a fasting-like gene expression profile, improves glucose metabolism, de-represses lncRNAs and impairs mammalian target of rapamycin (mTOR) activation. We find that obesity-repressed LincIRS2 is controlled by MAFG and observe that genetic and RNAi-mediated LincIRS2 loss causes elevated blood glucose, insulin resistance and aberrant glucose output in lean mice. Taken together, we identify a MAFG-lncRNA axis controlling hepatic glucose metabolism in health and metabolic disease.
Long-range exciton transport and slow annihilation in two-dimensional hybrid perovskites
Authors: Deng Shibin , Shi Enzheng , Yuan Long , Jin Linrui , Dou Letian , Huang Libai
Published: January 2020

Two-dimensional hybrid organic-inorganic perovskites with strongly bound excitons and tunable structures are desirable for optoelectronic applications. Exciton transport and annihilation are two key processes in determining device efficiencies; however, a thorough understanding of these processes is hindered by that annihilation rates are often convoluted with exciton diffusion constants. Here we employ transient absorption microscopy to disentangle quantum-well-thickness-dependent exciton diffusion and annihilation in two-dimensional perovskites, unraveling the key role of electron-hole interactions and dielectric screening. The exciton diffusion constant is found to increase with quantum-well thickness, ranging from 0.06 ± 0.03 to 0.34 ± 0.03 cm2 s−1, which leads to long-range exciton diffusion over hundreds of nanometers. The exciton annihilation rates are more than one order of magnitude lower than those found in the monolayers of transition metal dichalcogenides. The combination of long-range exciton transport and slow annihilation highlights the unique attributes of two-dimensional perovskites as an exciting class of optoelectronic materials.
Ultracompact 3D microfluidics for time-resolved structural biology
Authors: Knoška Juraj , Adriano Luigi , Awel Salah , Beyerlein Kenneth R. , Yefanov Oleksandr , Oberthuer Dominik , Peña Murillo Gisel E. , Roth Nils , Sarrou Iosifina , Villanueva-Perez Pablo , Wiedorn Max O. , Wilde Fabian , Bajt Saša , Chapman Henry N. , Heymann Michael
Published: January 2020

To advance microfluidic integration, we present the use of two-photon additive manufacturing to fold 2D channel layouts into compact free-form 3D fluidic circuits with nanometer precision. We demonstrate this technique by tailoring microfluidic nozzles and mixers for time-resolved structural biology at X-ray free-electron lasers (XFELs). We achieve submicron jets with speeds exceeding 160 m s−1, which allows for the use of megahertz XFEL repetition rates. By integrating an additional orifice, we implement a low consumption flow-focusing nozzle, which is validated by solving a hemoglobin structure. Also, aberration-free in operando X-ray microtomography is introduced to study efficient equivolumetric millisecond mixing in channels with 3D features integrated into the nozzle. Such devices can be printed in minutes by locally adjusting print resolution during fabrication. This technology has the potential to permit ultracompact devices and performance improvements through 3D flow optimization in all fields of microfluidic engineering.
Ultraflexible and transparent electroluminescent skin for real-time and super-resolution imaging of pressure distribution
Authors: Lee Byeongmoon , Oh Ji-Young , Cho Hyeon , Joo Chul Woong , Yoon Hyungsoo , Jeong Sujin , Oh Eunho , Byun Junghwan , Kim Hanul , Lee Seunghwan , Seo Jiseok , Park Chan Woo , Choi Sukyung , Park Nae-Man , Kang Seung-Youl , Hwang Chi-Sun , Ahn Seong-Deok , Lee Jeong-Ik , Hong Yongtaek
Published: January 2020

The ability to image pressure distribution over complex three-dimensional surfaces would significantly augment the potential applications of electronic skin. However, existing methods show poor spatial and temporal fidelity due to their limited pixel density, low sensitivity, or low conformability. Here, we report an ultraflexible and transparent electroluminescent skin that autonomously displays super-resolution images of pressure distribution in real time. The device comprises a transparent pressure-sensing film with a solution-processable cellulose/nanowire nanohybrid network featuring ultrahigh sensor sensitivity (>5000 kPa−1) and a fast response time (<1 ms), and a quantum dot-based electroluminescent film. The two ultrathin films conform to each contact object and transduce spatial pressure into conductivity distribution in a continuous domain, resulting in super-resolution (>1000 dpi) pressure imaging without the need for pixel structures. Our approach provides a new framework for visualizing accurate stimulus distribution with potential applications in skin prosthesis, robotics, and advanced human-machine interfaces.
Charge transfer from the carotenoid can quench chlorophyll excitation in antenna complexes of plants
Authors: Cupellini Lorenzo , Calvani Dario , Jacquemin Denis , Mennucci Benedetta
Published: January 2020

The photosynthetic apparatus of higher plants can dissipate excess excitation energy during high light exposure, by deactivating excited chlorophylls through a mechanism called nonphotochemical quenching (NPQ). However, the precise molecular details of quenching and the mechanism regulating the quenching level are still not completely understood. Focusing on the major light-harvesting complex LHCII of Photosystem II, we show that a charge transfer state involving Lutein can efficiently quench chlorophyll excitation, and reduce the excitation lifetime of LHCII to the levels measured in the deeply quenched LHCII aggregates. Through a combination of molecular dynamics simulations, multiscale quantum chemical calculations, and kinetic modeling, we demonstrate that the quenching level can be finely tuned by the protein, by regulating the energy of the charge transfer state. Our results suggest that a limited conformational rearrangement of the protein scaffold could act as a molecular switch to activate or deactivate the quenching mechanism.
Metabolism of multiple glycosaminoglycans by Bacteroides thetaiotaomicron is orchestrated by a versatile core genetic locus
Authors: Ndeh Didier , Baslé Arnaud , Strahl Henrik , Yates Edwin A. , McClurgg Urszula L. , Henrissat Bernard , Terrapon Nicolas , Cartmell Alan
Published: January 2020

The human gut microbiota (HGM), which is critical to human health, utilises complex glycans as its major carbon source. Glycosaminoglycans represent an important, high priority, nutrient source for the HGM. Pathways for the metabolism of various glycosaminoglycan substrates remain ill-defined. Here we perform a biochemical, genetic and structural dissection of the genetic loci that orchestrates glycosaminoglycan metabolism in the organism Bacteroides thetaiotaomicron. Here, we report: the discovery of two previously unknown surface glycan binding proteins which facilitate glycosaminoglycan import into the periplasm; distinct kinetic and genetic specificities of various periplasmic lyases which dictate glycosaminoglycan metabolic pathways; understanding of endo sulfatase activity questioning the paradigm of how the ‘sulfation problem’ is handled by the HGM; and 3D crystal structures of the polysaccharide utilisation loci encoded sulfatases. Together with comparative genomic studies, our study fills major gaps in our knowledge of glycosaminoglycan metabolism by the HGM.
miR-548x and miR-4698 controlled cell proliferation by affecting the PI3K/AKT signaling pathway in Glioblastoma cell lines
Authors: kalhori Mohammad Reza , Arefian Ehsan , Fallah Atanaki Fereshteh , Kavousi Kaveh , Soleimani Masoud
Published: January 2020

Glioblastoma multiforme (GBM) is the most aggressive and prevalent form of brain tumor cancers that originate from glial cells. This study proposed to investigate the effect of miR-548x and miR-4698 on the proliferation and the PI3K/AKT signaling pathway in glioblastoma cell lines. The molecular features of glioblastoma were studied using KEGG and TCGA sites. Next, by using miRwalk 2.0 and TargetScan version 7.1, the microRNAs that target critical genes in the PI3k/AKT pathway were selected according to score. The pre-miR-548x and pre-miR-4698 were cloned in a pCDH plasmid to produced lentiviral vector. The expression levels of miR-548x, miR-4698 and target genes were detected by qRT-PCR. The MTT, cell cycle, annexin and colony formation assay was used to detect the cell proliferation. MiR-548x and miR-4698 predicted target genes (Rheb, AKT1, mTOR, PDK1) were also evaluated by luciferase assay. The expression of AKT was detected by western blotting. Our results described that overexpression of miR-548x and miR-4698 could inhibit proliferation of A-172 and U251 cells. Also, miR-548x promoted the cell cycle arrest of GBM cell lines. The luciferase reporter assay results showed the 3′ UTR of PDK1, RHEB, and mTOR are direct targets of the miR-548x and miR-4698. Too, the western blot analysis revealed that miR-548x and miR-4698 could downregulate the AKT1 protein expression. Overall, our findings suggest that miR-548x and miR-4698 could function as tumor suppressor genes in glioblastoma by controlling the PI3K/AKT signaling pathway and may act as gene therapy for clinical treatment of glioblastoma multiforme.
Author Correction: Transcriptome and digital gene expression analysis unravels the novel mechanism of early flowering in Angelica sinensis
Authors: Yu Guang , Zhou Yuan , Yu Juanjuan , Hu Xueqin , Tang Ye , Yan Hui , Duan Jinao
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
From LaH10 to room–temperature superconductors
Authors: Kostrzewa M. , Szczęśniak K. M. , Durajski A. P. , Szczęśniak R.
Published: January 2020

Thermodynamic parameters of the LaH10 superconductor were an object of our interest. LaH10 is characterised by the highest experimentally observed value of the critical temperature: $${{\boldsymbol{T}}}_{{\boldsymbol{C}}}^{{\boldsymbol{a}}}={\bf{215}}$$TCa=215 K (pa = 150 GPa) and $${{\boldsymbol{T}}}_{{\boldsymbol{C}}}^{b}={\bf{260}}$$TCb=260 K (pb = 190 GPa). It belongs to the group of superconductors with a strong electron-phonon coupling (λa ~ 2.2 and λb ~ 2.8). We calculated the thermodynamic parameters of this superconductor and found that the values of the order parameter, the thermodynamic critical field, and the specific heat differ significantly from the values predicted by the conventional BCS theory. Due to the specific structure of the Eliashberg function for the hydrogenated compounds, the qualitative analysis suggests that the superconductors of the LaδX1−δH10-type (LaXH-type) structure, where X ∈ {Sc, Y}, would exhibit significantly higher critical temperature than TC obtained for LaH10. In the case of LaScH we came to the following assessments: $${{\boldsymbol{T}}}_{{\boldsymbol{C}}}^{{\boldsymbol{a}}}\in \left\langle {\bf{220}},{\bf{267}}\right\rangle $$TCa∈220,267 K and $${{\boldsymbol{T}}}_{{\boldsymbol{C}}}^{{\boldsymbol{b}}}\in \left\langle {\bf{263}},{\bf{294}}\right\rangle $$TCb∈263,294 K, while the results for LaYH were: $${{\boldsymbol{T}}}_{{\boldsymbol{C}}}^{{\boldsymbol{a}}}\in \left\langle {\bf{218}},{\bf{247}}\right\rangle $$TCa∈218,247 K and $${{\boldsymbol{T}}}_{{\boldsymbol{C}}}^{{\boldsymbol{b}}}\in \left\langle {\bf{261}},{\bf{274}}\right\rangle $$TCb∈261,274 K.
Model Predictive Control for Finite Input Systems using the D-Wave Quantum Annealer
Authors: Inoue Daisuke , Yoshida Hiroaki
Published: January 2020

The D-Wave quantum annealer has emerged as a novel computational architecture that is attracting significant interest, but there have been only a few practical algorithms exploiting the power of quantum annealers. Here we present a model predictive control (MPC) algorithm using a quantum annealer for a system allowing a finite number of input values. Such an MPC problem is classified as a non-deterministic polynomial-time-hard combinatorial problem, and thus real-time sequential optimization is difficult to obtain with conventional computational systems. We circumvent this difficulty by converting the original MPC problem into a quadratic unconstrained binary optimization problem, which is then solved by the D-Wave quantum annealer. Two practical applications, namely stabilization of a spring-mass-damper system and dynamic audio quantization, are demonstrated. For both, the D-Wave method exhibits better performance than the classical simulated annealing method. Our results suggest new applications of quantum annealers in the direction of dynamic control problems.
Downregulation of testosterone production through luteinizing hormone receptor regulation in male rats exposed to 17α-ethynylestradiol
Authors: Lin Po-Han , Kuo Tsung-Hsien , Chen Chih-Chieh , Jian Cai-Yun , Chen Chien-Wei , Wang Kai-Lee , Kuo Yuh-Chen , Shen Heng-Yi , Hsia Shih-Min , Wang Paulus S. , Lieu Fu-Kong , Wang Shyi-Wu
Published: January 2020

The pharmaceutical 17α-ethynylestradiol (EE2) is considered as an endocrine-disrupting chemical that interferes with male reproduction and hormonal activation. In this study, we investigated the molecular mechanism underlying EE2-regulatory testosterone release in vitro and in vivo. The results show that EE2 treatment decreased testosterone release from rat Leydig cells. Treatment of rats with EE2 reduced plasma testosterone levels and decreased the sensitivity of human chorionic gonadotropin (hCG). EE2 reduced luteinizing hormone receptor (LHR) expression associated with decreased cAMP generation by downregulation of adenylyl cyclase activity and decreased intracellular calcium-mediated pathways. The expression levels of StAR and P450scc were decreased in Leydig cells by treatment of rats with EE2 for 7 days. The sperm motility in the vas deferens and epididymis was reduced, but the histopathological features of the testis and the total sperm number of the vas deferens were not affected. Moreover, the serum dihydrotestosterone (DHT) level was decreased by treatment with EE2. The prostate gland and seminal vesicle atrophied significantly, and their expression level of 5α-reductase type II was reduced after EE2 exposure. Taken together, these results demonstrate an underlying mechanism of EE2 to downregulate testosterone production in Leydig cells, explaining the damaging effects of EE2 on male reproduction.
Brain regions associated with periodic leg movements during sleep in restless legs syndrome
Authors: Kim Tae-Joon , Cha Kwang Su , Lee Sanghun , Yang Tae-Won , Kim Keun Tae , Park Byeong-Su , Jun Jin-Sun , Lim Jung-Ah , Byun Jung-Ick , Sunwoo Jun-Sang , Shin Jung-Won , Kim Kyung Hwan , Lee Sang Kun , Jung Ki-Young
Published: January 2020

The neural substrates related to periodic leg movements during sleep (PLMS) remain uncertain, and the specific brain regions involved in PLMS have not been evaluated. We investigated the brain regions associated with PLMS and their severity using the electroencephalographic (EEG) source localization method. Polysomnographic data, including electromyographic, electrocardiographic, and 19-channel EEG signals, of 15 patients with restless legs syndrome were analyzed. We first identified the source locations of delta-band (2–4 Hz) spectral power prior to the onset of PLMS using a standardized low-resolution brain electromagnetic tomography method. Next, correlation analysis was conducted between current densities and PLMS index. Delta power initially and most prominently increased before leg movement (LM) onset in the PLMS series. Sources of delta power at −4~−3 seconds were located in the right pericentral, bilateral dorsolateral prefrontal, and cingulate regions. PLMS index was correlated with current densities at the right inferior parietal, temporoparietal junction, and middle frontal regions. In conclusion, our results suggest that the brain regions activated before periodic LM onset or associated with their severity are the large-scale motor network and provide insight into the cortical contribution of PLMS pathomechanism.
Evaluation of macular thickness and volume tested by optical coherence tomography as biomarkers for Alzheimer’s disease in a memory clinic
Authors: Sánchez Domingo , Castilla-Marti Miguel , Marquié Marta , Valero Sergi , Moreno-Grau Sonia , Rodríguez-Gómez Octavio , Piferrer Albert , Martínez Gabriel , Martínez Joan , Rojas Itziar De , Hernández Isabel , Abdelnour Carla , Rosende-Roca Maitée , Vargas Liliana , Mauleón Ana , Gil Silvia , Alegret Montserrat , Ortega Gemma , Espinosa Ana , Pérez-Cordón Alba , Sanabria Ángela , Roberto Natalia , Ciudin Andreea , Simó Rafael , Hernández Cristina , Tárraga Lluís , Boada Mercè , Ruiz Agustín
Published: January 2020

Building on previous studies that report thinning of the macula in Alzheimer’s disease (AD) and mild cognitive impairment (MCI) patients, the use of optical coherence tomography (OCT) has been proposed as a potential biomarker for AD. However, other studies contradict these results. A total of 930 participants (414 cognitively healthy people, 192 with probable amnestic MCI, and 324 probable AD patients) from a memory clinic were consecutively included in this study and underwent a spectral domain OCT scan (Maestro, Topcon) to assess total macular volume and thickness. Macular width measurements were also taken in several subregions (central, inner, and outer rings) and in layers such as the retinal nerve fiber (RNFL) and ganglion cell (CGL). The study employed a design of high ecological validity, with adjustment by age, education, sex, and OCT image quality. AD, MCI, and control groups did not significantly vary with regard to volume and retinal thickness in different layers. When these groups were compared, multivariate-adjusted analysis disclosed no significant differences in total (p = 0.564), CGL (p = 0.267), RNFL (p = 0.574), and macular thickness and volume (p = 0.380). The only macular regions showing significant differences were the superior (p = 0.040) and nasal (p = 0.040) sectors of the inner macular ring. However, adjustment for multiple comparisons nullified this significance. These results are not supporting existing claims for the usefulness of macular thickness as a biomarker of cognitive impairment in a memory unit. OCT biomarkers for AD should be subject to further longitudinal testing.
Dietary supplemental plant oils reduce methanogenesis from anaerobic microbial fermentation in the rumen
Authors: Vargas Julio Ernesto , Andrés Sonia , López-Ferreras Lorena , Snelling Timothy J. , Yáñez-Ruíz David R. , García-Estrada Carlos , López Secundino
Published: January 2020

Ruminants contribute to the emissions of greenhouse gases, in particular methane, due to the microbial anaerobic fermentation of feed in the rumen. The rumen simulation technique was used to investigate the effects of the addition of different supplemental plant oils to a high concentrate diet on ruminal fermentation and microbial community composition. The control (CTR) diet was a high-concentrate total mixed ration with no supplemental oil. The other experimental diets were supplemented with olive (OLV), sunflower (SFL) or linseed (LNS) oils at 6%. Rumen digesta was used to inoculate the fermenters, and four fermentation units were used per treatment. Fermentation end-products, extent of feed degradation and composition of the microbial community (qPCR) in digesta were determined. Compared with the CTR diet, the addition of plant oils had no significant (P > 0.05) effect on ruminal pH, substrate degradation, total volatile fatty acids or microbial protein synthesis. Gas production from the fermentation of starch or cellulose were decreased by oil supplementation. Methane production was reduced by 21–28% (P < 0.001), propionate production was increased (P < 0.01), and butyrate and ammonia outputs and the acetate to propionate ratio were decreased (P < 0.001) with oil-supplemented diets. Addition of 6% OLV and LNS reduced (P < 0.05) copy numbers of total bacteria relative to the control. In conclusion, the supplementation of ruminant diets with plant oils, in particular from sunflower or linseed, causes some favorable effects on the fermentation processes. The addition of vegetable oils to ruminant mixed rations will reduce methane production increasing the formation of propionic acid without affecting the digestion of feed in the rumen. Adding vegetable fats to ruminant diets seems to be a suitable approach to decrease methane emissions, a relevant cleaner effect that may contribute to alleviate the environmental impact of ruminant production.
Effects of sea ice on growth rates of an endangered population of gray whales
Authors: Gailey G. , Sychenko O. , Tyurneva O. , Yakovlev Y. , Vertyankin V. , van der Wolf P. , Drozdov K. , Zhmaev I.
Published: January 2020

The western gray whale population is endangered with approximately 175 individuals and 33 known reproductive females. Photo-identification studies were conducted from 2002–2017 during the gray whale foraging season off northeastern Sakhalin Island, Russia. Despite abundant prey resources, significant variation in whales’ body condition, inter-birth intervals and calf survival have been documented with limited understanding of factors that account for the observed variability. We examine sea ice concentrations at their known foraging grounds to define the maximum duration of a “foraging season”. We explore the relationship between foraging season length during a female’s pregnancy and post-weaning calf survival and reproduction. Approximately 77% of the variation in calf survival, which ranged annually from 10–80%, was associated with the duration of the feeding season while the mother was pregnant. Poor body conditions and prolonged inter-birth intervals of western gray whales have also been documented to coincide with shorter duration in feeding seasons found in this study. These results imply that shorter foraging seasons are associated with reduced energy intake by physically limiting the number of days gray whales can forage, and thus sea ice conditions may be one limiting factor affecting growth rates of this endangered population of baleen whales.
An RNAi supplemented diet as a reverse genetics tool to control bluegreen aphid, a major pest of legumes
Authors: Jacques Silke , Reidy-Crofts Jenny , Sperschneider Jana , Kamphuis Lars G. , Gao Ling-Ling , Edwards Owain R. , Singh Karam B.
Published: January 2020

Aphids are important agricultural pests causing major yield losses worldwide. Since aphids can rapidly develop resistance to chemical insecticides there is an urgent need to find alternative aphid pest management strategies. Despite the economic importance of bluegreen aphid (Acyrthosiphon kondoi), very few genetic resources are available to expand our current understanding and help find viable control solutions. An artificial diet is a desirable non-invasive tool to enable the functional characterisation of genes in bluegreen aphid and discover candidate target genes for future use in RNA interference (RNAi) mediated crop protection against aphids. To date no artificial diet has been developed for bluegreen aphid, so we set out to develop a suitable diet by testing and optimising existing diets. Here, we describe an artificial diet for rearing bluegreen aphid and also provide a proof of concept for the supplementation of the diet with RNAi molecules targeting the salivary gland transcript C002 and gap gene hunchback, resulting in bluegreen aphid mortality which has not yet been documented in this species. Managing this pest, for example via RNAi delivery through artificial feeding will be a major improvement to test bluegreen aphid candidate target genes for future pest control and gain significant insights into bluegreen aphid gene function.
Hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors induce autophagy and have a protective effect in an in-vitro ischaemia model
Authors: Singh Ayesha , Wilson James W. , Schofield Christopher J. , Chen Ruoli
Published: January 2020

This study compared effects of five hypoxia-inducible factor (HIF) prolyl hydroxylases (PHD) inhibitors on PC12 cells and primary rat neurons following oxygen-glucose deprivation (OGD). At 100 µM, the PHD inhibitors did not cause cytotoxicity and apoptosis. MTT activity was only significantly reduced by FG4592 or Bayer 85–3934 in PC12 cells. The PHD inhibitors at 100 µM significantly increased the LC3-II/LC3-I expression ratio and downregulated p62 in PC12 cells, so did FG4592 (30 µM) and DMOG (100 µM) in neurons. HIF-1α was stabilised in PC12 cells by all the PHD inhibitors at 100 µM except for DMOG, which stabilised HIF-1α at 1 and 2 mM. In primary neurons, HIF-1α was stabilised by FG4592 (30 µM) and DMOG (100 µM). Pretreatment with the PHD inhibitors 24 hours followed by 24 hour reoxygenation prior to 6 hours OGD (0.3% O2) significantly reduced LDH release and increased MTT activity compared to vehicle (1% DMSO) pretreatment. In conclusion, the PHD inhibitors stabilise HIF-1α in normoxia, induce autophagy, and protect cells from a subsequent OGD insult. The new class of PHD inhibitors (FG4592, FG2216, GSK1278863, Bay85-3934) have the higher potency than DMOG. The interplay between autophagy, HIF stabilisation and neuroprotection in ischaemic stroke merits further investigation.
Electro-Haptic Enhancement of Spatial Hearing in Cochlear Implant Users
Authors: Fletcher Mark D. , Cunningham Robyn O. , Mills Sean R.
Published: January 2020

Cochlear implants (CIs) have enabled hundreds of thousands of profoundly hearing-impaired people to perceive sounds by electrically stimulating the auditory nerve. However, CI users are often very poor at locating sounds, which leads to impaired sound segregation and threat detection. We provided missing spatial hearing cues through haptic stimulation to augment the electrical CI signal. We found that this “electro-haptic” stimulation dramatically improved sound localisation. Furthermore, participants were able to effectively integrate spatial information transmitted through these two senses, performing better with combined audio and haptic stimulation than with either alone. Our haptic signal was presented to the wrists and could readily be delivered by a low-cost wearable device. This approach could provide a non-invasive means of improving outcomes for the vast majority of CI users who have only one implant, without the expense and risk of a second implantation.
Fibrous configuration of the fascia iliaca compartment: An epoxy sheet plastination and confocal microscopy study
Authors: Xu Zhaoyang , Mei Bin , Liu Ming , Tu Lili , Zhang Han , Zhang Ming
Published: January 2020

Background and Objectives: The underlying anatomical mechanism of the ultrasound-guided fascia iliaca compartment (FIC) block for anaesthesia and analgesia in the lower limb has not been illuminated and numerous variations were attempted to achieve an optimal needle placement. This study aimed to define the fibrous configuration of the FIC. Methods: A total of 46 adult cadavers were studied using dissection, latex injection, epoxy sheet plastination and confocal microscopy. Results: (1) The fascia iliaca originated from the peripheral fascicular aponeurotic sheet of the iliopsoas. (2) The FIC was a funnel-shaped adipose space between the fascia iliaca and the epimysium of the iliopsoas, had a superior and an inferior opening and contained the femoral and lateral femoral cutaneous nerves but not obturator nerve. (3) The estimated volume of the FIC in the cadavers was about 23 mls, of which about one third was below the level of the anterior superior iliac spine. Conclusions: This study revealed that the fascia iliaca was aponeurotic and may be less permeable for the local anesthetics. Conclusions: The FIC contained only the femoral and lateral femoral cutaneous nerves and communicated with the extraperitoneal space and femoral triangle adipose space via its superior and inferior opening, respectively.
Parathyroid hormone receptor 1 (PTHR1) is a prognostic indicator in canine osteosarcoma
Authors: Al-Khan Awf A. , Nimmo Judith S. , Tayebi Mourad , Ryan Stewart D. , Simcock James O. , Tarzi Raboola , Kuntz Charles A. , Saad Eman S. , Day Michael J. , Richardson Samantha J. , Danks Janine A.
Published: January 2020

Osteosarcoma (OS) is the most common malignant primary bone tumour in humans and dogs. Several studies have established the vital role of parathyroid hormone-related protein (PTHrP) and its receptor (PTHR1) in bone formation and remodeling. In addition, these molecules play a role in the progression and metastasis of many human tumour types. This study investigated the expression of PTHR1 and PTHrP in canine OS tissues and assessed their prognostic value. Formalin-fixed, paraffin-embedded tissue samples from 50 dogs diagnosed with primary OS were immunolabeled with antibodies specific for PTHR1 and PTHrP. The immunostaining intensity of tumours from patients with OS was correlated with survival time. Both PTHR1 and PTHrP were detected in all OS samples (n = 50). Dogs with OS tumours showing high immunostaining intensity for PTHR1 (n = 36) had significantly shorter survival times (p = 0.028, Log Rank; p = 0.04, Cox regression) when compared with OS that had low immunostaining intensity for PTHR1 (n = 14).PTHrP immunostaining intensity did not correlate with survival time (p > 0.05). The results of this study indicate that increased expression of PTHR1 antigen in canine OS is associated with poor prognosis. This suggests that PTHR1 may be useful as a prognostic indicator in canine OS.
Performance comparison of next generation sequencing analysis pipelines for HIV-1 drug resistance testing
Authors: Lee Emma R. , Parkin Neil , Jennings Cheryl , Brumme Chanson J. , Enns Eric , Casadellà Maria , Howison Mark , Coetzer Mia , Avila-Rios Santiago , Capina Rupert , Marinier Eric , Van Domselaar Gary , Noguera-Julian Marc , Kirkby Don , Knaggs Jeff , Harrigan Richard , Quiñones-Mateu Miguel , Paredes Roger , Kantor Rami , Sandstrom Paul , Ji Hezhao
Published: January 2020

Next generation sequencing (NGS) is a trending new standard for genotypic HIV-1 drug resistance (HIVDR) testing. Many NGS HIVDR data analysis pipelines have been independently developed, each with variable outputs and data management protocols. Standardization of such analytical methods and comparison of available pipelines are lacking, yet may impact subsequent HIVDR interpretation and other downstream applications. Here we compared the performance of five NGS HIVDR pipelines using proficiency panel samples from NIAID Virology Quality Assurance (VQA) program. Ten VQA panel specimens were genotyped by each of six international laboratories using their own in-house NGS assays. Raw NGS data were then processed using each of the five different pipelines including HyDRA, MiCall, PASeq, Hivmmer and DEEPGEN. All pipelines detected amino acid variants (AAVs) at full range of frequencies (1~100%) and demonstrated good linearity as compared to the reference frequency values. While the sensitivity in detecting low abundance AAVs, with frequencies between 1~20%, is less a concern for all pipelines, their specificity dramatically decreased at AAV frequencies <2%, suggesting that 2% threshold may be a more reliable reporting threshold for ensured specificity in AAV calling and reporting. More variations were observed among the pipelines when low abundance AAVs are concerned, likely due to differences in their NGS read quality control strategies. Findings from this study highlight the need for standardized strategies for NGS HIVDR data analysis, especially for the detection of minority HIVDR variants.