bluuebunny/crossref_metadata_2025 huggingface dataset:
VPOT: A Customizable Variant Prioritization Ordering Tool for Annotated Variants
Authors: Ip Eddie , Chapman Gavin , Winlaw David , Dunwoodie Sally L. , Giannoulatou Eleni
Published: November 2019

Next-generation sequencing (NGS) technologies generate thousands to millions of genetic variants per sample. Identification of potential disease-causal variants is labor intensive as it relies on filtering using various annotation metrics and consideration of multiple pathogenicity prediction scores. We have developed VPOT (variant prioritization ordering tool), a python-based command line tool that allows researchers to create a single fully customizable pathogenicity ranking score from any number of annotation values, each with a user-defined weighting. The use of VPOT can be informative when analyzing entire cohorts, as variants in a cohort can be prioritized. VPOT also provides additional functions to allow variant filtering based on a candidate gene list or by affected status in a family pedigree. VPOT outperforms similar tools in terms of efficacy, flexibility, scalability, and computational performance. VPOT is freely available for public use at GitHub (https://github.com/VCCRI/VPOT/). Documentation for installation along with a user tutorial, a default parameter file, and test data are provided.
Making Global Policy
Authors: Stone Diane
Published: November 2019

Global policy making is taking shape in a wide range of public sector activities managed by transnational policy communities. Public policy scholars have long recognised the impact of globalisation on the industrialised knowledge economies of OECD states, as well as on social and economic policy challenges faced by developing and transition states. But the focus has been on domestic politics and policy. Today, policy studies literature is building new concepts of 'transnational public-private partnership', 'trans-governmentalism' and 'science diplomacy' to account for rapid growth of global policy networks and informal international organisations delivering public goods and services. This Element goes beyond traditional texts which focus on public policy as an activity of states to outline how global policy making has driven many global and regional transformations over the past quarter-century. This title is also available as Open Access on Cambridge Core.
Institutional complementarity, firm behavior, and firm heterogeneity: A cross-national analysis
Authors: Camyar Isa , Ulupinar Bahar
Published: November 2019

How do political economic institutions and different types of institutional complementarity in particular influence firm behavior? Existing studies do not offer much help in answering this question. In this research, we systematically connect institutional complementarity and its two distinct logics (the logic of reinforcement and the logic of compensation) to firm performance. Using a sample of more than fourteen thousand firms from twenty advanced industrial democracies, our empirical analysis finds that institutional complementarity is related to firm performance in a distinct way. That is, the different logics of institutional complementarity apply only to specific segments of the economy. While the logic of reinforcement works for small firms and labor-intensive firms, the logic of compensation favors large firms and capital-intensive firms. The empirical novelty of our research lies in offering a cross-national, firm-level and large-n analysis of institutional complementarity. Theoretically, our finding of firm heterogeneity helps in establishing the boundary conditions of institutional complementarity and hence advances the general understanding of the subject.
Association of maternal prenatal psychological stressors and distress with maternal and early infant faecal bacterial profile
Authors: Naudé Petrus J.W. , Claassen-Weitz Shantelle , Gardner-Lubbe Sugnet , Botha Gerrit , Kaba Mamadou , Zar Heather J. , Nicol Mark P. , Stein Dan J.
Published: November 2019

Objective:

Findings from animal studies indicate that the early gut bacteriome is a potential mechanism linking maternal prenatal stress with health trajectories in offspring. However, clinical studies are scarce and the associations of maternal psychological profiles with the early infant faecal bacteriome are unknown. This study aimed to investigate the associations of prenatal stressors and distress with early infant faecal bacterial profiles in a South African birth cohort study.

Methods:

Associations between prenatal symptoms of depression, distress, intimate partner violence (IPV) and posttraumatic stress disorder (PTSD) and faecal bacterial profiles were evaluated in meconium and subsequent stool specimens from 84 mothers and 101 infants at birth, and longitudinally from a subset of 69 and 36 infants at 4–12 and 20–28 weeks of age, respectively, in a South African birth cohort study.

Results:

Infants born to mothers that were exposed to high levels of IPV had significantly higher proportions ofCitrobacterand three unclassified genera, all of which belonging to the family Enterobacteriaceae detected at birth. Proportions of these Enterobacteriaceae remained significantly increased over time (birth to 20–28 weeks of life) in infants born to mothers with high levels of IPV exposure compared to infants from mothers with no/low IPV exposure. Infants born to mothers exposed to IPV also had higher proportions of the genusWeissellaat 4–12 weeks compared to infants from mothers with no/low IPV exposure. Faecal specimens from mothers exposed to IPV had higher proportions of the family Lactobacillaceae and lower proportions of Peptostreptococcaceae at birth. Maternal psychological distress was associated with decreased proportions of the family Veillonellaceae in infants at 20–28 weeks and a slower decline in Gammaproteobacteria over time. No changes in beta diversity were apparent for maternal or infant faecal bacterial profiles in relation to any of the prenatal measures for psychological adversities.

Conclusion:

Maternal lifetime IPV and antenatal psychological distress are associated with altered bacterial profiles in infant and maternal faecal bacteria. These findings may provide insights in the involvement of the gut bacteria linking maternal psychological adversity and the maturing infant brain.
LEARNING FORMULAIC SEQUENCES THROUGH VIEWING L2 TELEVISION AND FACTORS THAT AFFECT LEARNING
Authors: Puimège Eva , Peters Elke
Published: November 2019

The present study explores the incidental learning of formulaic sequences (FS) from audio-visual input and factors affecting the learning of FS. A pretest-posttest, within-participant design was adopted. English-as-a-foreign-language learners (L1 = Dutch; n = 42) watched a one-hour English-language documentary without subtitles. Learning gains were measured at the level of form recall and meaning recall. Significant learning gains were found in both the form recall and meaning recall tests, indicating that several knowledge aspects of FS can be learned incidentally from audio-visual input. The findings also revealed a positive relationship between learners’ prior vocabulary knowledge and the learning gains. Further, several item-related factors affected the learning gains (e.g., collocate-node relationship, frequency). Finally, the findings showed the incremental nature of learning FS, as preknowledge of the meaning of the FS prior to the TV viewing was the strongest predictor of learning the form of FS.
Beresford Hope, the Church of England, and the Elementary Education Act of 1870
Authors: Turner Michael J.
Published: November 2019

Historians have used a number of political, social, and other factors to explain the controversy surrounding elementary education in Victorian Britain. This article underscores the importance of religious motivations. The Act of 1870 – a significant extension of state responsibility – did not end debates about the purpose of education and the pros and cons of government involvement and religious instruction. Prominent among voluntaryists and anti-secularists was A. J. Beresford Hope, whose position offers useful insights into the educational agencies of the Church and the manner in which churchmen responded to new circumstances. This article explains Hope’s attitude and uses it to explore some of the causes and consequences of the Act of 1870. What type of schooling best suited the British people? Should it have a basis in something other than religion? How could the Church and its supporters meet the challenges posed by education reform?
A wideband dielectric resonator antenna with switchable diversity patterns
Authors: Abdalrazik Ahmad , Abdel-Rahman Adel B. , Allam Ahmed , Abo-Zahhad Mohammed
Published: November 2019

In this paper, a reduced-size dielectric resonator antenna with switchable diversity patterns is proposed. Ring- and linear-shaped slots are etched in the ground plane of the antenna so as to generate two modes $TE_{\delta 11}^x$ and $TE_{\delta 12}^x$ at a center frequency of 19 GHz. Moreover, two groups of PIN diodes are integrated into these slots to short one group of slots, and let the other group generates the required mode. Thus, the antenna is able to generate two switchable patterns with an envelope correlation coefficient of 0.4. Furthermore, the antenna size is reduced to half of its original size by placing a copper sheet over certain plane of the antenna structure. The antenna achieves wide bandwidths of 17.6–20.9 GHz (17.1$\percnt $) and 18.3–21.6 GHz (13.8$\percnt $) in cases of exciting $TE_{\delta 11}^x$ and $TE_{\delta 12}^x$ modes, respectively. The antenna also attainsa high gain of 7.1 and 3.2 dB at the center frequency.
DNA methylation at LRP1 gene locus mediates the association between maternal total cholesterol changes in pregnancy and cord blood leptin levels
Authors: Guay Simon-Pierre , Houde Andrée-Anne , Breton Edith , Baillargeon Jean-Patrice , Perron Patrice , Gaudet Daniel , Hivert Marie-France , Brisson Diane , Bouchard Luigi
Published: November 2019

Placental lipids transfer is essential for optimal fetal development, and alterations of these mechanisms could lead to a higher risk of adverse birth outcomes. Low-density lipoprotein receptor (LDLR), LDL receptor-related protein 1 (LRP1), and scavenger receptor class B type 1 (SCARB1) genes are encoding lipoprotein receptors expressed in the placenta where they participate in cholesterol exchange from maternal to fetal circulation. The aim of this study was thus to investigate the association between maternal lipid changes occurring in pregnancy, placental DNA methylation (DNAm) variations at LDLR, LRP1, and SCARB1 gene loci, and newborn’s anthropometric profile at birth. Sixty-nine normoglycemic women were followed from the first trimester of pregnancy until delivery. Placental DNAm was quantified at 43 Cytosine-phosphate-Guanines (CpGs) at LDLR, LRP1, and SCARB1 gene loci using pyrosequencing: 4 CpGs were retained for further analysis. Maternal clinical data were collected at each trimester of pregnancy. Newborns’ data were collected from medical records. Statistical models included minimally newborn sex and gestational and maternal age. Maternal total cholesterol changes during pregnancy (ΔT3-T1) were correlated with DNAm variations at LDLR (r = −0.32, p = 0.01) and LRP1 (r = 0.34, p = 0.007). DNAm at these loci was also correlated with newborns’ cord blood triglyceride and leptin levels. Mediation analysis supports a causal relationship between maternal cholesterol changes, DNAm levels at LRP1 locus, and cord blood leptin concentration (pmediation = 0.02). These results suggest that LRP1 DNAm link maternal blood cholesterol changes in pregnancy and offspring adiposity at birth, which provide support for a better follow-up of blood lipids in pregnancy.
A Scaling for Wave Dispersion Relationships in Ice‐Covered Waters
Authors: Yu Jie , Rogers W. Erick , Wang David W.
Published: November 2019

We consider the scaling of dispersion relationships for wave propagation on ice‐covered waters, aiming to identify a set of parameters that are physically meaningful and can be used in various continuum‐based theories. These parameters characterize the relative importance of the effects of ice inertia, effective viscosity, and elasticity, hence can be used to guide the dynamic similarity between different scales. Application to laboratory and field measurements shows scale collapse of data sets toward a general trend. From the dimensionless parameters of the theoretical prediction, the effective ice properties can be estimated more consistently.
Assessment of CMIP5 GCM Simulation Performance for Temperature Projection in the Tibetan Plateau
Authors: Jia Kun , Ruan Yunfeng , Yang Yanzhao , You Zhen
Published: November 2019

The performance of 33 Coupled Model Intercomparison Project 5 (CMIP5) general circulation models (GCMs) in temperature simulations in the Tibetan Plateau (TP) was comprehensively assessed by an improved score‐based and multiple‐criteria method using data collected from 1961 to 2005. Future temperatures were also simulated based on a multimodel ensemble coupled with the Delta downscaling method for near‐term (2006–2050) and long‐term (2051–2095) projections under Representative Concentration Pathways (RCP, scenarios RCP4.5 and RCP8.5). Our results demonstrated that all the GCMs evaluated in our study could capture the seasonal temperature patterns. However, most GCMs tended to underestimate temperatures by an average of −2.0°C. All the GCMs could effectively simulate temporal distribution, with a mean correlation coefficient of 0.997. However, they did not perform well in reproducing spatial distribution. Different assessment criteria lead to inconsistent results; however, the improved rank score method with multiple criteria provided a robust assessment of GCMs performance. MPI‐ESM‐LR, CMCC‐CMS, and GFDL‐ESM 2M showed a better temperature simulation performance compared to the other GCMs that we have assessed. Topographic correction could effectively enhance spatial distribution simulation; however, this increased temperature underestimation. Future temperatures were projected to increase by 1.4°C and 1.6°C in near‐term, and by 2.4°C and 4.0°C in long‐term under RCP4.5 and RCP8.5 scenarios, respectively. High temperatures mainly occurring in the southeastern end of the Himalayas, as well as the northern and southeastern margins of the TP. The results are expected to provide valuable information on climate change and its impact on hydrology, ecology, and socioeconomics of the TP.
Will Earth’s Grandest Canyon Keep Getting Grander?
Authors: Morton Mary
Published: November 2019

Living in Geologic Time: Rafting through the past, present, and future of the Colorado River and the Grand Canyon.
Podcast: A Nuclear Legacy Buried in Ice
Authors: Bompey Nanci
Published: November 2019

The radioactive remains of nuclear testing during the Cold War and from nuclear disasters like Chernobyl are still with us and can be found in some of the remotest glaciers on Earth.
Computers Tease Out Secrets of Jupiter’s Aurorae
Authors: Redd Nola
Published: November 2019

Aurorae once classified by human eyes are now being sorted by machines. The change may help astronomers understand how the mysterious features are powered.
Age of the Canada Basin, Arctic Ocean: Indications From High‐Resolution Magnetic Data
Authors: Zhang T. , Dyment J. , Gao J.Y.
Published: November 2019

The origin and history of the Amerasia basin are long‐running debates, which hinder our knowledge of the Mesozoic tectonic configurations and geodynamic processes in the Arctic. This lack of knowledge is due in part to the paucity of accurate magnetic data in the ice‐covered basin. Here, we identify the crustal age of the Canada Basin, a major part of the Amerasia Basin, through high‐resolution deep‐tow and sea‐surface magnetic data. The best fit of the four pairs of magnetic lineations revealed by the high‐resolution magnetic data is 139.5–128.6 Ma (or 142.4–132.8 Ma, depending on the geomagnetic polarity timescale). The crustal age provides crucial constraints on the evolution of the circum‐Arctic tectonic features and generally supports the hypothesis that the opening of the Amerasia Basin is related to the subductions during the closure of the South Anyui Ocean.
Reconstruction of Local Magnetic Structures by a Modified Radial Basis Function Method
Authors: Chen Wenming , Wang Xiaogang , Tsyganenko N. A. , Andreeva V. A. , Semenov V. S.
Published: November 2019

Local magnetic structures in space environments, in particular, those in the diffusion region such as magnetic nulls or separators, are very difficult to identify by satellite measurements but important for understanding of magnetic reconnection. Multi‐spacecraft missions such as Cluster or MMS, however, provide an opportunity to reconstruct the fine structures using vector data of space magnetometers. In this paper, we introduce a method for such a local reconstruction, based on the modified radial basis functions (Andreeva & Tsyganenko, 2016, https://doi.org/10.1002/2016JA023217), used previously for the global magnetic field modeling. A principal advantage of this method is its freedom from a priori assumptions on the magnetic field topology. The method has been tested on 21/2 and 3D reconnection geometries and provided a good agreement with preset models. The relative errors of null positions, γ‐line directions, and ∑‐surface normal directions are found to be below 6% even with 20% random errors added to the target magnetic field vectors in reconstruction of 3D separator model geometry. Applications of the method to the field reconstruction based on Cluster measurements are also presented and discussed.
Seismicity, Fault Slip Rates, and Fault Interactions in a Fault System
Authors: Gao Yajing , Luo Gang , Sun Yunqiang
Published: November 2019

Seismicity and the partitioning of slip rates in interacting and mechanically coupled fault systems are poorly understood. We developed and used three‐dimensional viscoelastoplastic finite element models to simulate earthquakes, earthquake cycles, and synthetic seismicity in single and bifurcated fault systems and investigate seismicity, fault slip rates, and interactions and mechanical coupling between faults in fault systems. The modeled interseismic velocities and coseismic displacements are consistent with those from analytical and quasi‐analytical solutions. We found that the modeled frequency‐magnitude relation satisfies the Gutenberg‐Richter relation and the b value is inversely related to differential stress. We observed that the seismicity on two parallel faults is often interdependent and complementary: high seismic moment release rates on a fault are usually accompanied by low ones on the other fault and vice versa; the two faults collectively accommodate far‐field tectonic loading and crustal relative motion. Model results showed that when two parallel faults have the same or similar strength, they have similar seismicity and long‐term slip rates, but when one of the two faults has lower strength, it has more active seismicity and a faster slip rate than the other; the sum of their slip rates equals the far‐field crustal relative motion in both cases. The results in this study provide scientific insights into the spatiotemporal migration of seismicity and partitioning of fault slip rates in an interacting and mechanically coupled fault system and help to qualify b values and to evaluate the earthquake hazard and risk on each of the faults in such a system.
Total Variation Regularization of Geodetically Constrained Block Models in Southwest Taiwan
Authors: Huang Mong‐Han , Evans Eileen L.
Published: November 2019

Rapid convergence between the Eurasian plate and the Philippine Sea Plate makes Taiwan one of the most active tectonic regions in the world, and this strain is accommodated on a complex network of thrust and strike‐slip faulting. Here, we use ascending and descending Interferometric Synthetic Aperture Radar (InSAR) data integrated with continuous GPS measurements to monitor interseismic deformation in southwest Taiwan. Geodetic observations show rapid (20–40 mm/year) southwestward motion in the Pingtung plain in south Taiwan and more than 10 mm/year uplift in the southern part of the Western Foothills. We use combined InSAR and CGPS measurements from 2004 to 2010 to constrain a block model of horizontal interseismic crustal deformation. Total variation regularization (TVR) serves as a tool for block model selection to algorithmically assess the block model geometry based on geodetic observations, simultaneously estimating block rotations and fault slip rates on block‐bounding faults. The block model results suggest that the margins of the Western Foothills accommodate most of the interseismic deformation in southwestern Taiwan. Thirty‐five independent blocks are required to explain interseismic crustal deformation with a mean residual velocity of 3.6 mm/year. Based on this horizontal model, we then forward predict vertical displacement and find good consistency between the predicted uplift and the geodetic observations. Our approach shows an efficient and objective way to estimate fault activities and seismic hazards in the interseismic period based on dense geodetic measurements and their uncertainties.
Effect of Water on the Thermal Properties of Olivine With Implications for Lunar Internal Temperature
Authors: Zhang Baohua , Ge Jianhua , Xiong Zili , Zhai Shuangmeng
Published: November 2019

How water could affect thermal transport properties is a key question that needs to be quantified experimentally when it is incorporated as structurally bound hydroxyl groups in the lattice of mantle minerals. In this study, thermal diffusivity (D) and thermal conductivity (κ) of San Carlos olivine aggregates with various water contents (up to 0.2 wt.% H2O) were measured simultaneously using transient plane‐source method up to 873 K and 3 GPa. Experimental results demonstrate that water content can significantly reduce the thermal diffusivity (D) and thermal conductivity (κ) of olivine aggregate. With the increase of H2O content from 0.08 to 0.2 wt.%, the absolute values of D and κ for olivine samples decrease by 5–13% and 17–33% and by 3–8% and 14–21%, respectively. D and κ of olivine aggregate decrease with temperature but increase with pressure. Heat capacity is influenced by pressure negatively. Combining the present data with surface heat flow of the Moon as well as heat production, the calculated temperature profiles provide new constraints on the lunar geotherm and possible H2O content in the lunar interior.
Heteroepitaxial vertical perovskite hot-electron transistors down to the monolayer limit
Authors: Kim Brian S. Y. , Hikita Yasuyuki , Yajima Takeaki , Hwang Harold Y.
Published: November 2019

Two-dimensional heterostructures combined with vertical geometries are candidates to probe and utilize the physical properties of atomically-thin materials. The vertical configuration enables a unique form of hot-carrier spectroscopy as well as atomic-scale devices. Here, we present the room-temperature evolution of heteroepitaxial perovskite hot-electron transistors using a SrRuO3 base down to the monolayer limit (∼4 Å). As a fundamental electronic probe, we observe an abrupt transition in the hot-electron mean free path as a function of base thickness, coinciding with the thickness-dependent resistive transition. As a path towards devices, we demonstrate the integrated synthesis of perovskite one-dimensional electrical edge contacts using water-soluble and growth-compatible Sr3Al2O6 hard masks. Edge-contacted monolayer-base transistors exhibit on/off ratios reaching ∼108, complete electrostatic screening by the base manifesting pure hot-electron injection, and excellent scaling of the output current density with device dimensions. These results open new avenues for incorporating emergent phenomena at oxide interfaces and in heterostructures.
Freezing of Gait can persist after an acute levodopa challenge in Parkinson’s disease
Authors: Lucas McKay J. , Goldstein Felicia C. , Sommerfeld Barbara , Bernhard Douglas , Perez Parra Sahyli , Factor Stewart A.
Published: November 2019

Study objectives included testing whether presumed levodopa-unresponsive freezing of gait (FOG) in Parkinson’s disease (PD) actually persists in the presence of adequate dopaminergic dosing and to investigate whether the presence of other parkinsonian features and their responsiveness to therapy varies across patients without FOG (NO-FOG), with levodopa-responsive FOG (OFF-FOG), and with levodopa-unresponsive FOG (ONOFF-FOG). Fifty-five PD patients completed levodopa challenges after >12-h OFF with supratherapeutic doses of dopaminergic medications. Observed responses in FOG, measured with MDS-UPDRS-III during the patient reported full “ON”, were used to classify them as NO-FOG, OFF-FOG, or ONOFF-FOG. Serum levodopa levels were measured. Only those with ≥20% improvement in MDS-UPDRS-III score were included in analyses. Levodopa challenge was sufficient to bring about a full “ON” state with ≥20% improvement in 45 patients. Levodopa-equivalent-dose utilized was 142 ± 56% of patients’ typical morning doses. Overall, 19/45 patients exhibited FOG in the full “ON” state (ONOFF-FOG), 11 were classified as OFF-FOG, and 15 NO-FOG. Linear mixed models revealed a highly significant association between serum levodopa level and total MDS-UPDRS-III score that was similar across groups. The ONOFF-FOG group exhibited significantly higher New-FOG-questionnaire and MDS-UPDRS-II scores compared to the OFF-FOG group. Among MDS-UPDRS-III subdomains significant effects of group (highest in ONOFF-FOG) were identified for other axial parkinsonian features. We found that FOG can persist in the full “ON” state brought about by ample dopaminergic dosing in PD. Other axial measures can also be levodopa-unresponsive among those with ONOFF-FOG only. These data provide evidence that ONOFF-FOG is distinct from responsive freezing.
Molecular Characterization of Auxin Efflux Carrier- ABCB1 in hexaploid wheat
Authors: Mohan Amita , Dhaliwal Amandeep K. , Nagarajan Ragupathi , Gill Kulvinder S.
Published: November 2019

Auxin is an important phytohormone that regulates response, differentiation, and development of plant cell, tissue, and organs. Along with its local production, long-distance transport coordinated by the efflux/influx membrane transporters is instrumental in plant development and architecture. In the present study, we cloned and characterized a wheat (Triticum aestivum) auxin efflux carrier ABCB1. The TaABCB1 was physically localized to the proximal 15% of the short arm of wheat homoeologous group 7 chromosomes. Size of the Chinese spring (CS) homoeologs genomic copies ranged from 5.3–6.2 kb with the7Acopy being the largest due to novel insertions in its third intron. The three homoeologous copies share 95–97% sequence similarity at the nucleotide, 98–99% amino acid, and overall Q-score of 0.98 at 3-D structure level. Though detected in all analyzed tissues,TaABCB1predominantly expressed in the meristematic tissues likely due to the presence of meristem-specific activation regulatory element identified in the promoter region. RNAi plants ofTaABCB1gene resulted in reduced plant height and increased seed width. Promoter analysis revealed several responsive elements detected in the promoter region including that for different hormones as auxin, gibberellic acid, jasmonic acid and abscisic acid, light, and circadian regulated elements.
Elevated glucose acts directly on osteocytes to increase sclerostin expression in diabetes
Authors: Pacicca Donna M. , Brown Tammy , Watkins Dara , Kover Karen , Yan Yun , Prideaux Matthew , Bonewald Lynda
Published: November 2019

Bone quality in diabetic patients is compromised, leading to weaker bones and increased fracture risk. However, the mechanism by which this occurs in diabetic bone remains to be fully elucidated. We hypothesized that elevated glucose and glucose variation would affect the function of osteocytes, essential regulators of bone homeostasis and quality. To first test this hypothesis, we used the IDG-SW3 osteocyte-like cell line to examine the effects of glucose levels on osteocyte function and viability in vitro. We confirmed our in vitro findings using the in vivo streptozotocin-induced (STZ) diabetic rat model and ex-vivo cultured osteocytes from these rats. IDG-SW3 cells cultured under high glucose conditions displayed significantly increased Sost mRNA(100-fold) and sclerostin protein, a negative regulator of bone formation(5000-fold), compared to cells in control media. mRNA expression of osteoblast markers such as Osx, Ocn and Col1a1 was unaffected by glucose. Factors associated with osteoclast activation were affected by glucose, with Rankl being upregulated by low glucose. Opg was also transiently upregulated by high glucose in mature IDG-SW3 cells. Induction of diabetes in Sprague-Dawley rats via a single dose of STZ (70 mg/kg) resulted in elevated maximum glucose and increased variability compared to control animals (670/796 vs. 102/142 mg/dL). This was accompanied by increased Sost/sclerostin expression in the osteocytes of these animals. These results show that glucose levels directly regulate osteocyte function through sclerostin expression and suggest a potential mechanism for the negative impact of diabetes on bone quality.
Ontology-based prediction of cancer driver genes
Authors: Althubaiti Sara , Karwath Andreas , Dallol Ashraf , Noor Adeeb , Alkhayyat Shadi Salem , Alwassia Rolina , Mineta Katsuhiko , Gojobori Takashi , Beggs Andrew D. , Schofield Paul N. , Gkoutos Georgios V. , Hoehndorf Robert
Published: November 2019

Identifying and distinguishing cancer driver genes among thousands of candidate mutations remains a major challenge. Accurate identification of driver genes and driver mutations is critical for advancing cancer research and personalizing treatment based on accurate stratification of patients. Due to inter-tumor genetic heterogeneity many driver mutations within a gene occur at low frequencies, which make it challenging to distinguish them from non-driver mutations. We have developed a novel method for identifying cancer driver genes. Our approach utilizes multiple complementary types of information, specifically cellular phenotypes, cellular locations, functions, and whole body physiological phenotypes as features. We demonstrate that our method can accurately identify known cancer driver genes and distinguish between their role in different types of cancer. In addition to confirming known driver genes, we identify several novel candidate driver genes. We demonstrate the utility of our method by validating its predictions in nasopharyngeal cancer and colorectal cancer using whole exome and whole genome sequencing.
Southeastern China Boreal Winter Precipitation Anomalies are Dependent on Intensity of El Niño
Authors: Ke Zongjian , Jiang Xingwen , Wang Zunya
Published: November 2019

Previous studies reported that boreal winter precipitation in southeastern China (SEC) tends to increase during El Niño. In this study, however, we find that most weak El Niño events are accompanied by below-normal precipitation in SEC, although strong El Niño events are accompanied by above-normal precipitation in SEC for both eastern Pacific El Niño and central Pacific El Niño. Both the cold SST anomalies in the western North Pacific (WNP) and the warm SST anomalies in the central tropical Pacific are important for the formation of anomalous anticyclone over the WNP, which favors above-normal precipitation over SEC by transporting more water vapor to SEC. The cold SST anomalies in the WNP only excite a weak anomalous anticyclone locally when the weak warm SST anomalies in the central tropical Pacific are accompanied by weak enhanced convection anomalies. In such condition, El Niño does not affect precipitation in SEC apparently.
Membrane-bound Gaussia luciferase as a tool to track shedding of membrane proteins from the surface of extracellular vesicles
Authors: Zaborowski Mikołaj Piotr , Cheah Pike See , Zhang Xuan , Bushko Isabella , Lee Kyungheon , Sammarco Alessandro , Zappulli Valentina , Maas Sybren Lein Nikola , Allen Ryan M. , Rumde Purva , György Bence , Aufiero Massimo , Schweiger Markus W. , Lai Charles Pin- Kuang , Weissleder Ralph , Lee Hakho , Vickers Kasey C. , Tannous Bakhos A. , Breakefield Xandra O.
Published: November 2019

Extracellular vesicles (EVs) released by cells play a role in intercellular communication. Reporter and targeting proteins can be modified and exposed on the surface of EVs to investigate their half-life and biodistribution. A characterization of membrane-bound Gaussia luciferase (mbGluc) revealed that its signal was detected also in a form smaller than common EVs (<70 nm). We demonstrated that mbGluc initially exposed on the surface of EVs, likely undergoes proteolytic cleavage and processed fragments of the protein are released into the extracellular space in active form. Based on this observation, we developed a new assay to quantitatively track shedding of membrane proteins from the surface of EVs. We used this assay to show that ectodomain shedding in EVs is continuous and is mediated by specific proteases, e.g. metalloproteinases. Here, we present a novel tool to study membrane protein cleavage and release using both in vitro and in vivo models.
Recent Increase in Winter Hazy Days over Central India and the Arabian Sea
Authors: Thomas Abin , Sarangi Chandan , Kanawade Vijay P.
Published: November 2019

Indian subcontinent is greatly vulnerable to air pollution, especially during the winter season. Here, we use 15 years (2003–2017) of satellite and model reanalysis datasets over India and adjoining Seas to estimate the trend in hazy days (i.e. days with high aerosol loading) during the dry winter season (November to February). The number of hazy days is increasing at the rate of ~2.6 days per year over Central India. Interestingly, this is higher than over the Indo-Gangetic Plain (~1.7 days/year), a well known global hotspot of particulate pollution. Consistent increasing trends in absorbing aerosols are also visible in the recent years. As a result, the estimated atmospheric warming trends over Central India are two-fold higher than that over Indo-Gangetic Plain. This anomalous increment in hazy days over Central India is associated with the relatively higher increase in biomass burning over the region. Moreover, the trend in aerosol loading over the Arabian Sea, which is located downwind to Central India, is also higher than that over the Bay of Bengal during the dry winter season. Our findings not only draw attention to the rapid deteriorating air quality over Central India, but also underline the significance of increasing biomass burning under the recent climate change.
Risk of Venous Thromboembolism after New Onset Heart Failure
Authors: Smilowitz Nathaniel R. , Zhao Qi , Wang Li , Shrestha Sulena , Baser Onur , Berger Jeffrey S.
Published: November 2019

New-onset heart failure (HF) is associated with cardiovascular morbidity and mortality. It is uncertain to what extent HF confers an increased risk of venous thromboembolism (VTE). Adults ≥65 years old hospitalized with a new diagnosis of HF were identified from Medicare claims from 2007–2013. We identified the incidence, predictors and outcomes of VTE in HF. We compared VTE incidence during follow-up after HF hospitalization with a corresponding period 1-year prior to the HF diagnosis. Among 207,535 patients with a new HF diagnosis, the cumulative incidence of VTE was 1.4%, 2.5%, and 10.5% at 30 days, 1 year, and 5 years, respectively. The odds of VTE were greatest immediately after new-onset HF and steadily declined over time (OR 2.2 [95% CI 2.0–2.3], OR 1.5 [1.4–1.7], and OR 1.2 [1.2–1.3] at 0–30 days, 4–6 months, and 7–9 months, respectively). Over 26-month follow-up, patients with HF were at two-fold higher risk of VTE than patients without HF (adjusted HR 2.31 [2.18–2.45]). VTE during follow-up was associated with long-term mortality (adjusted HR 1.60, 95% CI 1.56–1.64). In conclusion, patients with HF are at increased risk of VTE early after a new HF diagnosis. VTE in patients with HF is associated with long-term mortality.
Engineering dual-glycan responsive expression systems for tunable production of heterologous proteins in Bacteroides thetaiotaomicron
Authors: Jones Darryl R. , Smith Marshall B. , McLean Richard , Grondin Julie M. , Amundsen Carolyn R. , Inglis G. Douglas , Selinger Brent , Abbott D. Wade
Published: November 2019

Genetically engineering intestinal bacteria, such as Bacteroides thetaiotaomicron (B. theta), holds potential for creating new classes of biological devices, such as diagnostics or therapeutic delivery systems. Here, we have developed a series of B. theta strains that produce functional transgenic enzymes in response to dextran and arabinogalactan, two chemically distinct glycans. Expression systems for single glycan induction, and a novel “dual-glycan” expression system, requiring the presence of both dextran and arabinogalactan, have been developed. In addition, we have created two different chromosomal integration systems and one episomal vector system, compatible with engineered recipient strains, to improve the throughput and flexibility of gene cloning, integration, and expression in B. theta. To monitor activity, we have demonstrated the functionality of two different transgenic enzymes: NanoLuc, a luciferase, and BuGH16C, an agarase from the human intestinal bacterium, Bacteroides uniforms NP1. Together this expression platform provides a new collection of glycan-responsive tools to improve the strength and fidelity of transgene expression in B. theta and provides proof-of-concept for engineering more complex multi-glycan expression systems.
Microvolt T-wave alternans at the end of surgery is associated with postoperative mortality in cardiac surgery patients
Authors: Koo Chang-Hoon , Lee Hyung-Chul , Kim Tae Kyong , Cho Youn Joung , Nam Karam , Choi Eue-Keun , Choi Sheung-Nyoung , Yoon Sehee , Jeon Yunseok
Published: November 2019

Microvolt T-wave alternans (MTWA), which reflects electrical dispersion of repolarization, is known to be associated with arrhythmia or sudden cardiac death in high risk patients. In this study we investigated the relationship between MTWA and postoperative mortality in 330 cardiac surgery patients. Electrocardiogram, official national data and electric chart were analysed to provide in-hospital and mid-term outcome. MTWA at the end of surgery was significantly associated with in-hospital mortality in both univariate analysis (OR = 27.378, 95% CI 5.616–133.466, p < 0.001) and multivariate analysis (OR = 59.225, 95% CI 6.061–578.748, p < 0.001). Cox proportional hazards model revealed MTWA at the end of surgery was independently associated with mid-term mortality (HR = 4.337, 95% CI 1.594–11.795). The area under the curve of the model evaluating MTWA at the end of surgery was 0.764 (95% CI, 0.715–0.809) and it increased to 0.929 (95% CI, 0.896–0.954) when combined with the EuroSCORE II. MTWA positive at the end of surgery had a 60-fold increase in in-hospital mortality and a 4-fold increase in mid-term mortality. Moreover, MTWA at the end of surgery could predict in-hospital mortality and this predictability is more robust when combined with the EuroSCORE II.
Preoperative CT texture features predict prognosis after curative resection in pancreatic cancer
Authors: Kim Hyung Sun , Kim Young Jae , Kim Kwang Gi , Park Joon Seong
Published: November 2019

Pancreatic cancer is a lethal disease, and resistance to chemotherapy is a critical factor influencing the postoperative prognosis. Tumour heterogeneity is an important indicator of chemoresistance. Therefore, we analysed tumour heterogeneity in preoperative computed tomography scans by performing texture analysis using the grey-level run-length matrix and analysed the correlation of survival with the value obtained in these analyses. We analysed 116 consecutive patients who underwent curative resection and had preoperative contrast-enhanced computed tomography data available for analysis. A region of interest was drawn on all slices with a visible tumour and normal pancreas on the arterial phase computed tomography scans; the correlation of pathological characteristics with grey-level run-length matrix features was analysed. We then performed Kaplan–Meier survival curve analysis among pancreatic cancer patients. The grey-level non-uniformity values in grey-level run-length matrix features for tumours were higher than those for normal pancreas. High grey-level non-uniformity values represent a non-uniform texture, i.e., heterogeneity. Grey-level run-length matrix features showed that recurrence-free survival was shorter in the group with high grey-level non-uniformity 135 values (p = 0.025). Our analyses of the correlation between pathological outcomes and grey-level run-length matrix features in pancreatic cancer patients showed that grey-level non-uniformity values were powerful prognostic indicators.
A new model isolates glioblastoma clonal interactions and reveals unexpected modes for regulating motility, proliferation, and drug resistance
Authors: Davis Justin B , Krishna Sreshta S , Abi Jomaa Ryan , Duong Cindy T. , Espina Virginia , Liotta Lance A , Mueller Claudius
Published: November 2019

Tumor clonal heterogeneity drives treatment resistance. But robust models are lacking that permit eavesdropping on the basic interaction network of tumor clones. We developed an in vitro, functional model of clonal cooperation using U87MG glioblastoma cells, which isolates fundamental clonal interactions. In this model pre-labeled clones are co-cultured to track changes in their individual motility, growth, and drug resistance behavior while mixed. This highly reproducible system allowed us to address a new class of fundamental questions about clonal interactions. We demonstrate that (i) a single clone can switch off the motility of the entire multiclonal U87MG cell line in 3D culture, (ii) maintenance of clonal heterogeneity is an intrinsic and influential cancer cell property, where clones coordinate growth rates to protect slow growing clones, and (iii) two drug sensitive clones can develop resistance de novo when cooperating. Furthermore, clonal communication for these specific types of interaction did not require diffusible factors, but appears to depend on cell-cell contact. This model constitutes a straightforward but highly reliable tool for isolating the complex clonal interactions that make up the fundamental “hive mind” of the tumor. It uniquely exposes clonal interactions for future pharmacological and biochemical studies.
Low-frequency oscillations in coupled phase oscillators with inertia
Authors: Song Huihui , Zhang Xuewei , Wu Jinjie , Qu Yanbin
Published: November 2019

This work considers a second-order Kuramoto oscillator network periodically driven at one node to model low-frequency forced oscillations in power grids. The phase fluctuation magnitude at each node and the disturbance propagation in the network are numerically analyzed. The coupling strengths in this work are sufficiently large to ensure the stability of equilibria in the unforced system. It is found that the phase fluctuation is primarily determined by the network structural properties and forcing parameters, not the parameters specific to individual nodes such as power and damping. A new “resonance” phenomenon is observed in which the phase fluctuation magnitudes peak at certain critical coupling strength in the forced system. In the cases of long chain and ring-shaped networks, the Kuramoto model yields an important but somehow counter-intuitive result that the fluctuation magnitude distribution does not necessarily follow a simple attenuating trend along the propagation path and the fluctuation at nodes far from the disturbance source could be stronger than that at the source. These findings are relevant to low-frequency forced oscillations in power grids and will help advance the understanding of their dynamics and mechanisms and improve the detection and mitigation techniques.
When and where mortality occurs throughout the annual cycle changes with age in a migratory bird: individual vs population implications
Authors: Sergio Fabrizio , Tavecchia Giacomo , Tanferna Alessandro , Blas Julio , Blanco Guillermo , Hiraldo Fernando
Published: November 2019

The annual cycle of most animals is structured into discrete stages, such as breeding, migration and dispersal. While there is growing appreciation of the importance of different stages of an organism’s annual cycle for its fitness and population dynamics, almost nothing is known about if and how such seasonal effects can change through a species lifespan. Here, we take advantage of the opportunity offered by a long-term satellite/GPS-tracking study and a reliable method of remote death-detection to show that certain stages of both the annual and life cycle of a migratory long-lived raptor, the Black kite Milvus migrans, may represent sensitive bottlenecks for survival. In particular, migratory journeys caused bursts of concentrated-mortality throughout life, but the relative importance of stage-specific survival changed with age. On the other hand, the balance between short-stages of high mortality and long-stages of low mortality made population-growth similarly dependent on all portions of the annual cycle. Our results illustrate how the population dynamics of migratory organisms can be inextricably linked to ecological pressures balanced over multiple stages of the annual cycle and thus multiple areas of the globe, suggesting the frequent need for challenging conservation strategies targeting all portions of a species year-round range.
Author Correction: Entropy is a Simple Measure of the Antibody Profile and is an Indicator of Health Status: A Proof of Concept
Authors: Wang Lu , Whittemore Kurt , Johnston Stephen Albert , Stafford Phillip
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Doxorubicin intercalated copper diethyldithiocarbamate functionalized layered double hydroxide hybrid nanoparticles for targeted therapy of hepatocellular carcinoma
Authors: Xu Ying , Kong Yihan , Xu Jiawen , Li Xiaowen , Gou Jingxin , Yin Tian , He Haibing , Zhang Yu , Tang Xing
Published: November 2019

Hepatocellular carcinoma (HCC) is one of the deadliest cancers due to its long incubation period and low cure rate.
A high-efficiency and stable cupric oxide photocathode coupled with Al surface plasmon resonance and Al2O3 self-passivation
Authors: Xing Haiyang , E Lei , Zhao Dan , Li Xifei , Ruan Mengnan , Liu Zhifeng
Published: November 2019

A high-efficiency and stable CuO/Al/Al2O3 photocathode for photoelectrochemical water splitting has been successfully synthesized by a facile magnetron sputtering combined with spontaneous oxidation method.
Regioselective SNAr reaction of the phenoxathiin-based thiacalixarene as a route to a novel macrocyclic skeleton
Authors: Landovský Tomáš , Eigner Václav , Babor Martin , Tichotová Markéta , Dvořáková Hana , Lhoták Pavel
Published: November 2019

The formation of a novel type of macrocyclic skeleton possessing meta- and para-bridging units can be achieved by SNAr cleavage of an easily accessible phenoxathiin-based thiacalix[4]arene.
A stapled chromogranin A-derived peptide is a potent dual ligand for integrins αvβ6 and αvβ8
Authors: Nardelli Francesca , Ghitti Michela , Quilici Giacomo , Gori Alessandro , Luo Qingqiong , Berardi Andrea , Sacchi Angelina , Monieri Matteo , Bergamaschi Greta , Bermel Wolfgang , Chen Fuxiang , Corti Angelo , Curnis Flavio , Musco Giovanna
Published: November 2019

Combining 2D STD-NMR, computation, biochemical assays and click-chemistry, we have identified a chromogranin-A derived compound (5) that has high affinity and bi-selectivity for αvβ6 and αvβ8 integrins and is stable in microsomal preparations.
The elusive photocatalytic water splitting reaction using sunlight on suspended nanoparticles: is there a way forward?
Authors: Idriss Hicham
Published: November 2019

For many decades hydrogen production from water by photocatalytic methods has been pursued over a variety of semiconductor powder catalysts featuring many structures and compositions. The stoichiometric formation of molecular hydrogen and oxygen has stayed largely elusive.