bluuebunny/crossref_metadata_2025 huggingface dataset:
Responding through transposition: public Euroskepticism and European policy implementation
Authors: Williams Christopher J.
Published: July 2016

Do public attitudes concerning the European Union affect the speed with which member states transpose European directives? It is posited in this article that member state governments do respond to public attitudes regarding the EU when transposing European directives. Specifically, it is hypothesized that member state governments slow transposition of directives when aggregate public Euroskepticism is greater. This expectation is tested using extended Cox proportional hazard modeling and data derived from the EU’s legislative archives, the official journals of EU member states, and the Eurobarometer survey series. It is found that member state governments do slow transposition in response to higher aggregate public Euroskepticism. These findings have important implications for the study of European policy implementation, as well as for our understanding of political responsiveness in the EU.
Adaptive thermostability of light-harvesting complexes in marine picocyanobacteria
Authors: Pittera Justine , Partensky Frédéric , Six Christophe
Published: July 2016

Marine Synechococcus play a key role in global oceanic primary productivity. Their wide latitudinal distribution has been attributed to the occurrence of lineages adapted to distinct thermal niches, but the physiological and molecular bases of this ecotypic differentiation remain largely unknown. By comparing six strains isolated from different latitudes, we showed that the thermostability of their light-harvesting complexes, called phycobilisomes (PBS), varied according to the average sea surface temperature at strain isolation site. Comparative analyses of thermal unfolding curves of the three phycobiliproteins (PBP) constituting PBS rods suggested that the differences in thermostability observed on whole PBSs relied on the distinct molecular flexibility and stability of their individual components. Phycocyanin was the least thermostable of all rod PBP, constituting a fragility point of the PBS under heat stress. Amino-acid composition analyses and structural homology modeling notably revealed the occurrence of two amino-acid substitutions, which might have a role in the observed differential thermotolerance of this phycobiliprotein among temperature ecotypes. We hypothesize that marine Synechococcus ancestors occurred first in warm niches and that during the colonization of cold, high latitude thermal niches, their descendants have increased the molecular flexibility of PBP to maintain optimal light absorption capacities, this phenomenon likely resulting in a decreased stability of these proteins. This apparent thermoadaptability of marine Synechococcus has most probably contributed to the remarkable ubiquity of these picocyanobacteria in the ocean.
Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability
Authors:   UK10K, Riazuddin S , Hussain M , Razzaq A , Iqbal Z , Shahzad M , Polla D L , Song Y , van Beusekom E , Khan A A , Tomas-Roca L , Rashid M , Zahoor M Y , Wissink-Lindhout W M , Basra M A R , Ansar M , Agha Z , van Heeswijk K , Rasheed F , Van de Vorst M , Veltman J A , Gilissen C , Akram J , Kleefstra T , Assir M Z , Grozeva D , Carss K , Raymond F L , O'Connor T D , Riazuddin S A , Khan S N , Ahmed Z M , de Brouwer A P M , van Bokhoven H , Riazuddin S
Published: July 2016

Intellectual disability (ID) is a clinically and genetically heterogeneous disorder, affecting 1–3% of the general population. Although research into the genetic causes of ID has recently gained momentum, identification of pathogenic mutations that cause autosomal recessive ID (ARID) has lagged behind, predominantly due to non-availability of sizeable families. Here we present the results of exome sequencing in 121 large consanguineous Pakistani ID families. In 60 families, we identified homozygous or compound heterozygous DNA variants in a single gene, 30 affecting reported ID genes and 30 affecting novel candidate ID genes. Potential pathogenicity of these alleles was supported by co-segregation with the phenotype, low frequency in control populations and the application of stringent bioinformatics analyses. In another eight families segregation of multiple pathogenic variants was observed, affecting 19 genes that were either known or are novel candidates for ID. Transcriptome profiles of normal human brain tissues showed that the novel candidate ID genes formed a network significantly enriched for transcriptional co-expression (P<0.0001) in the frontal cortex during fetal development and in the temporal–parietal and sub-cortex during infancy through adulthood. In addition, proteins encoded by 12 novel ID genes directly interact with previously reported ID proteins in six known pathways essential for cognitive function (P<0.0001). These results suggest that disruptions of temporal parietal and sub-cortical neurogenesis during infancy are critical to the pathophysiology of ID. These findings further expand the existing repertoire of genes involved in ARID, and provide new insights into the molecular mechanisms and the transcriptome map of ID.
Two functionally distinct kinetochore pools of BubR1 ensure accurate chromosome segregation
Authors: Zhang Gang , Mendez Blanca Lopez , Sedgwick Garry G. , Nilsson Jakob
Published: July 2016

The BubR1/Bub3 complex is an important regulator of chromosome segregation as it facilitates proper kinetochore–microtubule interactions and is also an essential component of the spindle assembly checkpoint (SAC). Whether BubR1/Bub3 localization to kinetochores in human cells stimulates SAC signalling or only contributes to kinetochore–microtubule interactions is debated. Here we show that two distinct pools of BubR1/Bub3 exist at kinetochores and we uncouple these with defined BubR1/Bub3 mutants to address their function. The major kinetochore pool of BubR1/Bub3 is dependent on direct Bub1/Bub3 binding and is required for chromosome alignment but not for the SAC. A distinct pool of BubR1/Bub3 localizes by directly binding to phosphorylated MELT repeats on the outer kinetochore protein KNL1. When we prevent the direct binding of BubR1/Bub3 to KNL1 the checkpoint is weakened because BubR1/Bub3 is not incorporated into checkpoint complexes efficiently. In conclusion, kinetochore localization supports both known functions of BubR1/Bub3.
Raman spectroscopic signature of fractionalized excitations in the harmonic-honeycomb iridates β- and γ-Li2IrO3
Authors: Glamazda A. , Lemmens P. , Do S. -H. , Choi Y. S. , Choi K. -Y.
Published: July 2016

The fractionalization of elementary excitations in quantum spin systems is a central theme in current condensed matter physics. The Kitaev honeycomb spin model provides a prominent example of exotic fractionalized quasiparticles, composed of itinerant Majorana fermions and gapped gauge fluxes. However, identification of the Majorana fermions in a three-dimensional honeycomb lattice remains elusive. Here we report spectroscopic signatures of fractional excitations in the harmonic-honeycomb iridates β- and γ-Li2IrO3. Using polarization-resolved Raman spectroscopy, we find that the dynamical Raman response of β- and γ-Li2IrO3 features a broad scattering continuum with distinct polarization and composition dependence. The temperature dependence of the Raman spectral weight is dominated by the thermal damping of fermionic excitations. These results suggest the emergence of Majorana fermions from spin fractionalization in a three-dimensional Kitaev–Heisenberg system.
Negative capacitance transistors with monolayer black phosphorus
Authors: Liu Fei , Zhou Yan , Wang Yijiao , Liu Xiaoyan , Wang Jian , Guo Hong
Published: July 2016

Quantum transport properties of negative capacitance transistors (NC-FETs) with monolayer black phosphorus (ML-BP) are theoretically studied. Our calculations show that atomistic thin ML-BP can enhance the amplification effect of the ferroelectric layer, and subthreshold swing is effectively reduced to 27 mV per decade in ML-BP NC-FETs. Device performance can be further improved by increasing the thickness of ferroelectric layer and using thinner or high-k insulate layer. Due to the temperature dependence of ferroelectric layer ML-BP NC-FETs have higher on-state current at low temperature, which is different from that of MOSFETs. By considering the metal–ferroelectric interface layer, our calculations show that the device performance is degraded by the interface. Compared with the International Technology Roadmap (ITRS) 2013 requirements, ML-BP NC-FETs can fulfil the ITRS requirements for high-performance logic with a reduced supply voltage. The new device can achieve very low power delay product per device width at VD=0.3 V, which is just 44% of that in ML-BP FETs.
Antibacterial effect of copper-bearing titanium alloy (Ti-Cu) against Streptococcus mutans and Porphyromonas gingivalis
Authors: Liu Rui , Memarzadeh Kaveh , Chang Bei , Zhang Yumei , Ma Zheng , Allaker Robert P. , Ren Ling , Yang Ke
Published: July 2016

Formation of bacterial biofilms on dental implant material surfaces (titanium) may lead to the development of peri-implant diseases influencing the long term success of dental implants. In this study, a novel Cu-bearing titanium alloy (Ti-Cu) was designed and fabricated in order to efficiently kill bacteria and discourage formation of biofilms and then inhibit bacterial infection and prevent implant failure, in comparison with pure Ti. Results from biofilm based gene expression studies, biofilm growth observation, bacterial viability measurements and morphological examination of bacteria, revealed antimicrobial/antibiofilm activities of Ti-Cu alloy against the oral specific bacterial species, Streptococcus mutans and Porphyromonas gingivalis. Proliferation and adhesion assays with mesenchymal stem cells and measurement of the mean daily amount of Cu ion release demonstrated Ti-Cu alloy to be biocompatible. In conclusion, Ti-Cu alloy is a promising dental implant material with antimicrobial/antibiofilm activities and acceptable biocompatibility.
Collective Influence Algorithm to find influencers via optimal percolation in massively large social media
Authors: Morone Flaviano , Min Byungjoon , Bo Lin , Mari Romain , Makse Hernán A.
Published: July 2016

We elaborate on a linear-time implementation of Collective-Influence (CI) algorithm introduced by Morone, Makse, Nature 524, 65 (2015) to find the minimal set of influencers in networks via optimal percolation. The computational complexity of CI is O(N log N) when removing nodes one-by-one, made possible through an appropriate data structure to process CI. We introduce two Belief-Propagation (BP) variants of CI that consider global optimization via message-passing: CI propagation (CIP) and Collective-Immunization-Belief-Propagation algorithm (CIBP) based on optimal immunization. Both identify a slightly smaller fraction of influencers than CI and, remarkably, reproduce the exact analytical optimal percolation threshold obtained in Random Struct. Alg. 21, 397 (2002) for cubic random regular graphs, leaving little room for improvement for random graphs. However, the small augmented performance comes at the expense of increasing running time to O(N2), rendering BP prohibitive for modern-day big-data. For instance, for big-data social networks of 200 million users (e.g., Twitter users sending 500 million tweets/day), CI finds influencers in 2.5 hours on a single CPU, while all BP algorithms (CIP, CIBP and BDP) would take more than 3,000 years to accomplish the same task.
Standardized Chinese Formula Xin-Ke-Shu inhibits the myocardium Ca2+ overloading and metabolic alternations in isoproterenol-induced myocardial infarction rats
Authors: Liu Yue-Tao , Zhou Chao , Jia Hong-Mei , Chang Xing , Zou Zhong-Mei
Published: July 2016

Xin-Ke-Shu (XKS) is a traditional Chinese patent medicine used for treatment of coronary heart diseases in China. However, its mechanism of action is still unclear. In this paper, the mediation of XKS on the isoproterenol (ISO)-induced myocardial infarction (MI) rat were evaluated based on a tissue-targeted metabonomics in vitro/vivo. The result indicated that twelve metabolic pathways were involved in the therapeutic effect of XKS in vivo, where seven pathways were associated with the Ca2+ overloading mechanism. In agreement with regulation on metabolic variations, XKS markedly reversed the over-expressions of three involved proteins including phospholipase A2 IIA (PLA2 IIA), calcium/calmodulin-dependent protein kinase II (CaMK II) and Pro-Caspase-3. The metabolic regulations of XKS on H9c2 cell also partially confirmed its metabolic effect. These metabolic characteristics in vitro/vivo and western blotting analysis suggested that XKS protected from MI metabolic perturbation major via inhibition of Ca2+ overloading mechanism. Furthermore, 11 active ingredients of XKS exerted steady affinity with the three proteins through the molecular docking study. Our findings indicate that the metabonomics in vitro/vivo combined with western blotting analysis offers the opportunity to gain insight into the comprehensive efficacy of TCMs on the whole metabolic network.
Quantum information tapping using a fiber optical parametric amplifier with noise figure improved by correlated inputs
Authors: Guo Xueshi , Li Xiaoying , Liu Nannan , Ou Z. Y.
Published: July 2016

One of the important functions in a communication network is the distribution of information. It is not a problem to accomplish this in a classical system since classical information can be copied at will. However, challenges arise in quantum system because extra quantum noise is often added when the information content of a quantum state is distributed to various users. Here, we experimentally demonstrate a quantum information tap by using a fiber optical parametric amplifier (FOPA) with correlated inputs, whose noise is reduced by the destructive quantum interference through quantum entanglement between the signal and the idler input fields. By measuring the noise figure of the FOPA and comparing with a regular FOPA, we observe an improvement of 0.7 ± 0.1 dB and 0.84 ± 0.09 dB from the signal and idler outputs, respectively. When the low noise FOPA functions as an information splitter, the device has a total information transfer coefficient of Ts+Ti = 1.5 ± 0.2, which is greater than the classical limit of 1. Moreover, this fiber based device works at the 1550 nm telecom band, so it is compatible with the current fiber-optical network for quantum information distribution.
Vitamin D Deficiency Promotes Liver Tumor Growth in Transforming Growth Factor-β/Smad3-Deficient Mice Through Wnt and Toll-like Receptor 7 Pathway Modulation
Authors: Chen Jian , Katz Lior H. , Muñoz Nina M. , Gu Shoujun , Shin Ji-hyun , Jogunoori Wilma S. , Lee Mi-Hye , Belkin Mitchell D. , Kim Sang-Bae , White Jon C. , Andricovich Jaclyn , Tzatsos Alexandros , Li Shulin , Kim Sang Soo , Shetty Kirti , Mishra Bibhuti , Rashid Asif , Lee Ju-Seog , Mishra Lopa
Published: July 2016

Disruption of the TGF-β pathway is associated with liver fibrosis and suppression of liver tumorigenesis, conditions associated with low Vitamin D (VD) levels. However, potential contributions of VD to liver tumor progression in the context of TGF-β signaling remain unexplored. Our analyses of VD deprivation (VDD) in in vivo models of liver tumor formation revealed striking three-fold increases in tumor burden in Smad3+/− mice, with a three-fold increase in TLR7 expression compared to controls. ChIP and transcriptional assays confirm Smad3 binding at two TLR7 promoter SBE sites. Molecular interactions between TGF-β pathway and VDD were validated clinically, where an absence of VD supplementation was associated with low TGF-β pathway member expression levels and β-catenin activation in fibrotic/cirrhotic human liver tissues. Subsequent supplementing VD led to restoration of TGF-β member expression with lower β-catenin levels. Bioinformatics analysis provides positive supportive correlation between somatic mutations for VD-related genes and the TGF-β pathway. We conclude that VDD promotes tumor growth in the context of Smad3 disruption, potentially through regulation of TLR7 expression and β-catenin activation. VD could therefore be a strong candidate for liver cancer prevention in the context of aberrant Smad3 signaling.
Gibberellin-Regulation and Genetic Variations in Leaf Elongation for Tall Fescue in Association with Differential Gene Expression Controlling Cell Expansion
Authors: Xu Qian , Krishnan Sanalkumar , Merewitz Emily , Xu Jichen , Huang Bingru
Published: July 2016

Leaf elongation rate (LER) is an important factor controlling plant growth and productivity. The objective of this study was to determine whether genetic variation in LER for a fast-growing (‘K-31’), and a dwarf cultivar (‘Bonsai’) of tall fescue (Festuca arundinacea) and gibberellic acid (GA) regulation of LER were associated with differential expression of cell-expansion genes. Plants were treated with GA3, trinexapac-ethyl (TE) (GA inhibitor), or water (untreated control) in a hydroponic system. LER of ‘K-31’ was 63% greater than that of ‘Bonsai’, which corresponded with 32% higher endogenous GA4content in leaf and greater cell elongation and production rates under the untreated control condition. Exogenous application of GA3significantly enhanced LER while TE treatment inhibited leaf elongation due to GA3-stimulation or TE-inhibition of cell elongation and production rate in leaves for both cultivars. Real-time quantitative polymerase chain reaction analysis revealed that three α-expansins, one β-expansin, and three xyloglucan endotransglycosylase (XET) genes were associated with GA-stimulation of leaf elongation, of which, the differential expression ofEXPA4andEXPA7was related to the genotypic variation in LER of two cultivars. Those differentially-expressed expansin and XET genes could play major roles in genetic variation and GA-regulated leaf elongation in tall fescue.
Electrophysiological fingerprints of OFF bipolar cells in rat retina
Authors: Vielma Alex H. , Schmachtenberg Oliver
Published: July 2016

Retinal bipolar cells (BCs) divide photoreceptor output into different channels for the parallel extraction of temporal and chromatic stimulus properties. In rodents, five types of OFF BCs have been differentiated, based on morphological and functional criteria, but their electrophysiological characterization remains incomplete. This study analyzed OFF BCs with the patch clamp technique in acute slices of rat retina. Their specific voltage-dependent currents and glutamate responses are shown to represent individual fingerprints which define the signal processing and filtering properties of each cell type and allow their unequivocal identification. Two additions to the rat BC repertoire are presented: OFF BC-2′, a variation of BC-2 with wider axonal arbours and prominent Na+currents, is described for the first time in rodents and OFF BC-3b, previously identified in mouse, is electrophysiologically characterized in rat. Moreover, the glutamate responses of rat OFF BCs are shown to be differentially sensitive to AMPA- and kainate-receptor blockers and to modulation by nitric oxide (NO) through a cGMP-dependent mechanism. These results contribute to our understanding of the diversity and function of bipolar cells in mammals.
Ligand binding to an Allergenic Lipid Transfer Protein Enhances Conformational Flexibility resulting in an Increase in Susceptibility to Gastroduodenal Proteolysis
Authors: Abdullah Syed Umer , Alexeev Yuri , Johnson Philip E. , Rigby Neil M. , Mackie Alan R. , Dhaliwal Balvinder , Mills E. N. Clare
Published: July 2016

Non-specific lipid transfer proteins (LTPs) are a family of lipid-binding molecules that are widely distributed across flowering plant species, many of which have been identified as allergens. They are highly resistant to simulated gastroduodenal proteolysis, a property that may play a role in determining their allergenicity and it has been suggested that lipid binding may further increase stability to proteolysis. It is demonstrated that LTPs from wheat and peach bind a range of lipids in a variety of conditions, including those found in the gastroduodenal tract. Both LTPs are initially cleaved during gastroduodenal proteolysis at three major sites between residues 39–40, 56–57 and 79–80, with wheat LTP being more resistant to cleavage than its peach ortholog. The susceptibility of wheat LTP to proteolyic cleavage increases significantly upon lipid binding. This enhanced digestibility is likely to be due to the displacement of Tyr79 and surrounding residues from the internal hydrophobic cavity upon ligand binding to the solvent exposed exterior of the LTP, facilitating proteolysis. Such knowledge contributes to our understanding as to how resistance to digestion can be used in allergenicity risk assessment of novel food proteins, including GMOs.
Self-assembly Controls Self-cleavage of HHR from ASBVd (−): a Combined SANS and Modeling Study
Authors: Leclerc Fabrice , Zaccai Giuseppe , Vergne Jacques , Řìhovà Martina , Martel Anne , Maurel Marie-Christine
Published: July 2016

In the Avocado Sunblotch Viroid (ASBVd: 249-nt) from the Avsunviroidae family, a symmetric rolling-circle replication operates through an autocatalytic mechanism mediated by hammerhead ribozymes (HHR) embedded in both polarity strands. The concatenated multimeric ASBVd (+) and ASBVd (−) RNAs thus generated are processed by cleavage to unit-length where ASBVd (−) self-cleaves with more efficiency. Absolute scale small angle neutron scattering (SANS) revealed a temperature-dependent dimer association in both ASBVd (−) and its derived 79-nt HHR (−). A joint thermodynamic analysis of SANS and catalytic data indicates the rate-determining step corresponds to the dimer/monomer transition. 2D and 3D models of monomeric and dimeric HHR (−) suggest that the inter-molecular contacts stabilizing the dimer (between HI and HII domains) compete with the intra-molecular ones stabilizing the active conformation of the full-length HHR required for an efficient self-cleavage. Similar competing intra- and inter-molecular contacts are proposed in ASBVd (−) though with a remoter region from an extension of the HI domain.
Quantum phase estimation using path-symmetric entangled states
Authors: Lee Su-Yong , Lee Chang-Woo , Lee Jaehak , Nha Hyunchul
Published: July 2016

We study the sensitivity of phase estimation using a generic class of path-symmetric entangled states |φ〉|0〉 + |0〉|φ〉, where an arbitrary state |φ〉 occupies one of two modes in quantum superposition. With this generalization, we identify the fundamental limit of phase estimation under energy constraint that is characterized by the photon statistics of the component state |φ〉. We show that quantum Cramer-Rao bound (QCRB) can be indefinitely lowered with super-Poissonianity of the state |φ〉. For possible measurement schemes, we demonstrate that a full photon-counting employing the path-symmetric entangled states achieves the QCRB over the entire range [0, 2π] of unknown phase shift ϕ whereas a parity measurement does so in a certain confined range of ϕ. By introducing a component state of the form "Equation missing", we particularly show that an arbitrarily small QCRB can be achieved even with a finite energy in an ideal situation. This component state also provides the most robust resource against photon loss among considered entangled states over the range of the average input energy Nav > 1. Finally we propose experimental schemes to generate these path-symmetric entangled states for phase estimation.
Cortisol coregulation in fish
Authors: Fürtbauer Ines , Heistermann Michael
Published: July 2016

Cortisol coregulation, which is the up- or down-regulation of partners’ physiological stress responses, has been described for individuals with strong attachment bonds, e.g. parents and their children and romantic relationship partners. Research into moderating effects on cortisol coregulation suggests stronger covariation among distressed partners. Whether cortisol coregulation is unique to humans or can also be found in other species that share universal features of the vertebrate stress response remains unexplored. Using a repeated measures approach and non-invasive waterborne hormone analysis, we test the hypothesis that dyads of three-spined stickleback fish (Gasterosteus aculeatus) coregulate their cortisol levels in shared environments. Dyadic cortisol levels were unrelated when cohabiting (home tank), but significantly covaried when sharing a more stressful (as indicated by higher cortisol levels) environment (open field). Time-lag analysis further revealed that open field cortisol levels were predicted by partner’s cortisol levels prior to the shared experience. To our knowledge, this study provides the first evidence for coregulatory processes on cortisol responses in a non-human animal that lacks strong bonds and social attachment relationships, suggesting a shared evolutionary origin of cortisol coregulation in vertebrates. From an adaptive perspective, cortisol coregulation may serve to reduce risk in challenging, potentially threatening situations.
Metabolic pathways regulated by γ-aminobutyric acid (GABA) contributing to heat tolerance in creeping bentgrass (Agrostis stolonifera)
Authors: Li Zhou , Yu Jingjin , Peng Yan , Huang Bingru
Published: July 2016

γ-Aminobutyric acid is a non-protein amino acid involved in various metabolic processes. The objectives of this study were to examine whether increased GABA could improve heat tolerance in cool-season creeping bentgrass through physiological analysis and to determine major metabolic pathways regulated by GABA through metabolic profiling. Plants were pretreated with 0.5 mM GABA or water before exposed to non-stressed condition (21/19 °C) or heat stress (35/30 °C) in controlled growth chambers for 35 d. The growth and physiological analysis demonstrated that exogenous GABA application significantly improved heat tolerance of creeping bentgrass. Metabolic profiling found that exogenous application of GABA led to increases in accumulations of amino acids (glutamic acid, aspartic acid, alanine, threonine, serine and valine), organic acids (aconitic acid, malic acid, succinic acid, oxalic acid and threonic acid), sugars (sucrose, fructose, glucose, galactose and maltose) and sugar alcohols (mannitol and myo-inositol). These findings suggest that GABA-induced heat tolerance in creeping bentgrass could involve the enhancement of photosynthesis and ascorbate-glutathione cycle, the maintenance of osmotic adjustment and the increase in GABA shunt. The increased GABA shunt could be the supply of intermediates to feed the tricarboxylic acid cycle of respiration metabolism during a long-term heat stress, thereby maintaining metabolic homeostasis.
Visualization of heterogeneity and regional grading of gliomas by multiple features using magnetic resonance-based clustered images
Authors: Inano Rika , Oishi Naoya , Kunieda Takeharu , Arakawa Yoshiki , Kikuchi Takayuki , Fukuyama Hidenao , Miyamoto Susumu
Published: July 2016

Preoperative glioma grading is important for therapeutic strategies and influences prognosis. Intratumoral heterogeneity can cause an underestimation of grading because of the sampling error in biopsies. We developed a voxel-based unsupervised clustering method with multiple magnetic resonance imaging (MRI)-derived features using a self-organizing map followed by K-means. This method produced novel magnetic resonance-based clustered images (MRcIs) that enabled the visualization of glioma grades in 36 patients. The 12-class MRcIs revealed the highest classification performance for the prediction of glioma grading (area under the receiver operating characteristic curve = 0.928; 95% confidential interval = 0.920–0.936). Furthermore, we also created 12-class MRcIs in four new patients using the previous data from the 36 patients as training data and obtained tissue sections of the classes 11 and 12, which were significantly higher in high-grade gliomas (HGGs) and those of classes 4, 5 and 9, which were not significantly different between HGGs and low-grade gliomas (LGGs), according to a MRcI-based navigational system. The tissues of classes 11 and 12 showed features of malignant glioma, whereas those of classes 4, 5 and 9 showed LGGs without anaplastic features. These results suggest that the proposed voxel-based clustering method provides new insights into preoperative regional glioma grading.
Genetic associations of the thyroid stimulating hormone receptor gene with Graves diseases and Graves ophthalmopathy: A meta-analysis
Authors: Xiong Haibo , Wu Mingxing , Yi Hong , Wang Xiuqing , Wang Qian , Nadirshina Sophia , Zhou Xiyuan , Liu Xueqin
Published: July 2016

Graves’ disease (GD) is a common thyroid disease, and Graves ophthalmopathy(GO) is the most common extra-thyroidal manifestation of GD. Genetic associations of the thyroid stimulating hormone receptor (TSHR) gene with GD and GO have been studied in different population groups for a long time. We aimed to obtain a more precise estimation of the effects of TSHR single nucleotide polymorphisms (SNPs) on GD/GO using a meta-analysis. Publications were searched on Pub Med and EMBASE up to December 30, 2015. Eight studies involving three SNPs (rs179247, rs12101255, and rs2268458), which included 4790 cases and 5350 controls, met the selection criteria. The pooled odds ratios (OR) and the 95% confidence intervals (CI) were estimated. SNPs rs179247 (dominant model [GG + GA vs. AA]: OR = 0.66, 95%CI: 0.61–0.73, P = 0.000, I2 = 0%) and rs12101255 (dominant model [TT + TC vs. CC]: OR = 1.67, 95%CI: 1.53–1.83, P = 0.000, I2 = 0%) were significantly associated with GD in all of the genetic models. TSHR rs12101255 and rs2268458 polymorphisms had no association between GO and GD (GD without GO). The results indicate that rs179247 and rs12101255 are likely to be genetic biomarkers for GD. Further studies with different population groups and larger sample sizes are needed to confirm the genetic associations of the TSHR gene with GD/GO.
Environment-Wide Association Study of Blood Pressure in the National Health and Nutrition Examination Survey (1999–2012)
Authors: McGinnis Denise P. , Brownstein John S. , Patel Chirag J.
Published: July 2016

Identifying environmental exposures associated with blood pressure is a priority. Recently, we proposed the environment-wide association study to search for and replicate environmental factors associated with phenotypes. We conducted the environment-wide association study (EWAS) using the National Health and Nutrition Examination Surveys (1999–2012) which evaluated a total of 71,916 participants to prioritize environmental factors associated with systolic and diastolic blood pressure. We searched for factors on participants from survey years 1999–2006 and tentatively replicated findings in participants from years 2007–2012. Finally, we estimated the overall association and performed a second meta-analysis using all survey years (1999–2012). For systolic blood pressure, self-reported alcohol consumption emerged as our top finding (a 0.04 increase in mmHg of systolic blood pressure for 1 standard deviation increase in self-reported alcohol), though the effect size is small. For diastolic blood pressure, urinary cesium was tentatively replicated; however, this factor demonstrated high heterogeneity between populations (I2 = 51%). The lack of associations across this wide of an analysis raises the call for a broader search for environmental factors in blood pressure.
Exploring metal detoxification and accumulation potential during vermicomposting of Tea factory coal ash: sequential extraction and fluorescence probe analysis
Authors: Goswami Linee , Pratihar Sanjay , Dasgupta Suman , Bhattacharyya Pradip , Mudoi Pronab , Bora Jayanta , Bhattacharya Satya Sundar , Kim Ki Hyun
Published: July 2016

Metal contamination from coal ashes (CAs) is widely recognized as a significant environmental concern. To learn more about metal detoxification and accumulation potential of earthworm species, metal-rich tea factory coal ashes (TFCA) were fed to Eisenia fetida and Lampito mauritii by employing a fluorescent tag detection method. Fascinatingly, on feeding fluorescence probed Zn and Cd along with cow dung to Eisenia fetida, the detection of the gut-proteins with a molecular mass higher than 100 kDa was a distinct evidence of metal binding. Significant increases were observed in the content of humified organic C [humic acid (HAC) and fulvic acid C (FAC)] and degree of humification during vermicomposting. Concurrently, considerably large amount of toxic metals (Cr, Cd, Pb, and Zn) was transformed from exchangeable to recalcitrant (organic matter and mineral bound) fractions. Moreover, total metal concentrations were reduced with high removal efficiency upon vermicomposting.
Highly efficient metallic optical incouplers for quantum well infrared photodetectors
Authors: Liu Long , Chen Yu , Huang Zhong , Du Wei , Zhan Peng , Wang Zhenlin
Published: July 2016

Herein, we propose a highly efficient metallic optical incoupler for a quantum well infrared photodetector (QWIP) operating in the spectrum range of 14~16 μm, which consists of an array of metal micropatches and a periodically corrugated metallic back plate sandwiching a semiconductor active layer. By exploiting the excitations of microcavity modes and hybrid spoof surface plasmons (SSPs) modes, this optical incoupler can convert infrared radiation efficiently into the quantum wells (QWs) layer of semiconductor region with large electrical field component (Ez) normal to the plane of QWs. Our further numerical simulations for optimization indicate that by tuning microcavity mode to overlap with hybrid SSPs mode in spectrum, a coupled mode is formed, which leads to 33-fold enhanced light absorption for QWs centered at wavelength of 14.5 μm compared with isotropic absorption of QWs without any metallic microstructures, as well as a large value of coupling efficiency (η) of |Ez|2 ~ 6. This coupled mode shows a slight dispersion over ~40° and weak polarization dependence, which is quite beneficial to the high performance infrared photodetectors.
Is ragweed pollen allergenicity governed by environmental conditions during plant growth and flowering?
Authors: Ghiani Alessandra , Ciappetta Silvia , Gentili Rodolfo , Asero Riccardo , Citterio Sandra
Published: July 2016

Pollen allergenicity is one of the main factors influencing the prevalence and/or severity of allergic diseases. However, how genotype and environment contribute to ragweed pollen allergenicity has still to be established. To throw some light on the factors governing allergenicity, in this work 180 ragweed plants from three Regions (Canada, France, Italy) were grown in both controlled (constant) and standard environmental conditions (seasonal changes in temperature, relative humidity and light). Pollen from single plants was characterized for its allergenic potency and for the underlying regulation mechanisms by studying the qualitative and quantitative variations of the main isoforms of the major ragweed allergen Amb a 1. Results showed a statistically higher variability in allergenicity of pollen from standard conditions than from controlled conditions growing plants. This variability was due to differences among single plants, regardless of their origin and was not ascribed to differences in the expression and IgE reactivity of individual Amb a 1 isoforms but rather to quantitative differences involving all the studied isoforms. It suggests that the allergenic potency of ragweed pollen and thus the severity of ragweed pollinosis mainly depends on environmental conditions during plant growth and flowering, which regulate the total Amb a 1 content.
The phylogeny of C/S1 bZIP transcription factors reveals a shared algal ancestry and the pre-angiosperm translational regulation of S1 transcripts
Authors: Peviani Alessia , Lastdrager Jeroen , Hanson Johannes , Snel Berend
Published: July 2016

Basic leucine zippers (bZIPs) form a large plant transcription factor family. C and S1 bZIP groups can heterodimerize, fulfilling crucial roles in seed development and stress response. S1 sequences also harbor a unique regulatory mechanism, termed Sucrose-Induced Repression of Translation (SIRT). The conservation of both C/S1 bZIP interactions and SIRT remains poorly characterized in non-model species, leaving their evolutionary origin uncertain and limiting crop research. In this work, we explored recently published plant sequencing data to establish a detailed phylogeny of C and S1 bZIPs, investigating their intertwined role in plant evolution, and the origin of SIRT. Our analyses clarified C and S1 bZIP orthology relationships in angiosperms, and identified S1 sequences in gymnosperms. We experimentally showed that the gymnosperm orthologs are regulated by SIRT, tracing back the origin of this unique regulatory mechanism to the ancestor of seed plants. Additionally, we discovered an earlier S ortholog in the charophyte algae Klebsormidium flaccidum, together with a C ortholog. This suggests that C and S groups originated by duplication from a single algal proto-C/S ancestor. Based on our observations, we propose a model wherein the C/S1 bZIP dimer network evolved in seed plants from pre-existing C/S bZIP interactions.
Synthesis and Characterization of Hexagonal Boron Nitride as a Gate Dielectric
Authors: Jang Sung Kyu , Youn Jiyoun , Song Young Jae , Lee Sungjoo
Published: July 2016

Two different growth modes of large-area hexagonal boron nitride (h-BN) film, a conventional chemical vapor deposition (CVD) growth mode and a high-pressure CVD growth mode, were compared as a function of the precursor partial pressure. Conventional self-limited CVD growth was obtained below a critical partial pressure of the borazine precursor, whereas a thick h-BN layer (thicker than a critical thickness of 10 nm) was grown beyond a critical partial pressure. An interesting coincidence of a critical thickness of 10 nm was identified in both the CVD growth behavior and in the breakdown electric field strength and leakage current mechanism, indicating that the electrical properties of the CVD h-BN film depended significantly on the film growth mode and the resultant film quality.
Effects of Lead and Mercury on Sulfate-Reducing Bacterial Activity in a Biological Process for Flue Gas Desulfurization Wastewater Treatment
Authors: Zhang Liang , Lin Xiaojuan , Wang Jinting , Jiang Feng , Wei Li , Chen Guanghao , Hao Xiaodi
Published: July 2016

Biological sulfate-reducing bacteria (SRB) may be effective in removing toxic lead and mercury ions (Pb(II) and Hg(II)) from wet flue gas desulfurization (FGD) wastewater through anaerobic sulfite reduction. To confirm this hypothesis, a sulfite-reducing up-flow anaerobic sludge blanket reactor was set up to treat FGD wastewater at metal loading rates of 9.2 g/m3-d Pb(II) and 2.6 g/m3-d Hg(II) for 50 days. The reactor removed 72.5 ± 7% of sulfite and greater than 99.5% of both Hg(II) and Pb(II). Most of the removed lead and mercury were deposited in the sludge as HgS and PbS. The contribution of cell adsorption and organic binding to Pb(II) and Hg(II) removal was 20.0 ± 0.1% and 1.8 ± 1.0%, respectively. The different bioavailable concentration levels of lead and mercury resulted in different levels of lethal toxicity. Cell viability analysis revealed that Hg(II) was less toxic than Pb(II) to the sludge microorganisms. In the batch tests, increasing the Hg(II) feeding concentration increased sulfite reduction rates. In conclusion, a sulfite-reducing reactor can efficiently remove sulfite, Pb(II) and Hg(II) from FGD wastewater.
Deleterious coding variants in multi-case families with non-syndromic cleft lip and/or palate phenotypes
Authors: Pengelly Reuben J. , Arias Liliana , Martínez Julio , Upstill-Goddard Rosanna , Seaby Eleanor G. , Gibson Jane , Ennis Sarah , Collins Andrew , Briceño Ignacio
Published: July 2016

Nonsyndromic Cleft Lip and/or Palate (NSCLP) is regarded as a multifactorial condition in which clefting is an isolated phenotype, distinguished from the largely monogenic, syndromic forms which include clefts among a spectrum of phenotypes. Nonsyndromic clefting has been shown to arise through complex interactions between genetic and environmental factors. However, there is increasing evidence that the broad NSCLP classification may include a proportion of cases showing familial patterns of inheritance and contain highly penetrant deleterious variation in specific genes. Through exome sequencing of multi-case families ascertained in Bogota, Colombia, we identify 28 non-synonymous single nucleotide variants that are considered damaging by at least one predictive score. We discuss the functional impact of candidate variants identified. In one family we find a coding variant in the MSX1 gene which is predicted damaging by multiple scores. This variant is in exon 2, a highly conserved region of the gene. Previous sequencing has suggested that mutations in MSX1 may account for ~2% of NSCLP. Our analysis further supports evidence that a proportion of NSCLP cases arise through monogenic coding mutations, though further work is required to unravel the complex interplay of genetics and environment involved in facial clefting.
A paper/polymer hybrid microfluidic microplate for rapid quantitative detection of multiple disease biomarkers
Authors: Sanjay Sharma T. , Dou Maowei , Sun Jianjun , Li XiuJun
Published: July 2016

Enzyme linked immunosorbent assay (ELISA) is one of the most widely used laboratory disease diagnosis methods. However, performing ELISA in low-resource settings is limited by long incubation time, large volumes of precious reagents and well-equipped laboratories. Herein, we developed a simple, miniaturized paper/PMMA (poly(methyl methacrylate)) hybrid microfluidic microplate for low-cost, high throughput and point-of-care (POC) infectious disease diagnosis. The novel use of porous paper in flow-through microwells facilitates rapid antibody/antigen immobilization and efficient washing, avoiding complicated surface modifications. The top reagent delivery channels can simply transfer reagents to multiple microwells thus avoiding repeated manual pipetting and costly robots. Results of colorimetric ELISA can be observed within an hour by the naked eye. Quantitative analysis was achieved by calculating the brightness of images scanned by an office scanner. Immunoglobulin G (IgG) and Hepatitis B surface Antigen (HBsAg) were quantitatively analyzed with good reliability in human serum samples. Without using any specialized equipment, the limits of detection of 1.6 ng/mL for IgG and 1.3 ng/mL for HBsAg were achieved, which were comparable to commercial ELISA kits using specialized equipment. We envisage that this simple POC hybrid microplate can have broad applications in various bioassays, especially in resource-limited settings.
Electroretinographic effects of retinal dragging and retinal folds in eyes with familial exudative vitreoretinopathy
Authors: Yaguchi Yukari , Katagiri Satoshi , Fukushima Yoko , Yokoi Tadashi , Nishina Sachiko , Kondo Mineo , Azuma Noriyuki
Published: July 2016

We evaluated the retinal function of retinal dragging (Rdrag) and radial retinal folds (Rfolds) in eyes with familial exudative vitreoretinopathy (FEVR) using full-field electroretinography (ERG). Seventeen eyes of nine patients with FEVR who had Rdrag or Rfolds were retrospectively studied. Eyes were classified into four groups according to the severity of the retinal alterations: Group 1, without Rdrag or Rfolds (5 eyes); Group 2, with Rdrag (4 eyes); Group 3, with Rfolds (6 eyes); and Group 4, with Rfolds in which all major retinal vessels were involved (2 eyes). The amplitudes of all ERG components and the implicit times of the photopic a- and b-waves and 30-Hz flicker responses were decreased or prolonged as the severity of the retinal alterations increased (P < 0.01). The photopic negative response was most severely affected and nearly undetectable in all eyes in Groups 3 and 4, although the other ERG components were detectable in all eyes in Group 3 and one eye in Group 4. These results suggest the decrease of retinal functions was correlated with the degree of severity of Rdrag and Rfolds in eyes with FEVR. In addition, the function of the retinal ganglion cells appears to be more severely affected compared with the others.
Viperin inhibits rabies virus replication via reduced cholesterol and sphingomyelin and is regulated upstream by TLR4
Authors: Tang Hai-Bo , Lu Zhuan-Ling , Wei Xian-Kai , Zhong Tao-Zhen , Zhong Yi-Zhi , Ouyang Ling-Xuan , Luo Yang , Xing Xing-Wei , Liao Fang , Peng Ke-Ke , Deng Chao-Qian , Minamoto Nobuyuki , Luo Ting Rong
Published: July 2016

Viperin (virus inhibitory protein, endoplasmic reticulum-associated, IFN-inducible) is an interferon-inducible protein that mediates antiviral activity. Generally, rabies virus (RABV) multiplies extremely well in susceptible cells, leading to high virus titres. In this study, we found that viperin was significantly up-regulated in macrophage RAW264.7 cells but not in NA, BHK-21 or BSR cells. Transient viperin overexpression in BSR cells and stable expression in BHK-21 cells could inhibit RABV replication, including both attenuated and street RABV. Furthermore, the inhibitory function of viperin was related to reduce cholesterol/sphingomyelin on the membranes of RAW264.7 cells. We explored the up-stream regulation pathway of viperin in macrophage RAW264.7 cells in the context of RABV infection. An experiment confirmed that a specific Toll-like receptor 4 (TLR4) inhibitor, TAK-242, could inhibit viperin expression in RABV-infected RAW264.7 cells. These results support a regulatory role for TLR4. Geldanamycin, a specific inhibitor of interferon regulatory factor 3 (IRF3) (by inhibiting heat-shock protein 90 (Hsp90) of the IRF3 phosphorylation chaperone), significantly delayed and reduced viperin expression, indicating that IRF3 is involved in viperin induction in RAW264.7 cells. Taken together, our data support the therapeutic potential for viperin to inhibit RABV replication, which appears to involve upstream regulation by TLR4.
Efficient organic photomemory with photography-ready programming speed
Authors: Kim Mincheol , Seong Hyejeong , Lee Seungwon , Kwon Hyukyun , Im Sung Gap , Moon Hanul , Yoo Seunghyup
Published: July 2016

We propose a device architecture for a transistor-type organic photomemory that can be programmed fast enough for use in electrical photography. Following the strategies used in a flash memory where an isolated charge storage node or floating gate is employed, the proposed organic photomemory adopts an isolated photo-absorption zone that is embedded between upper and lower insulator layers without directly interfacing with a semiconductor channel layer. This isolated photo-absorption zone then allows the device to operate in electrically ‘on’ state, in which the high electric-field region can have a maximal spatial overlap with the illuminated area for efficient and facile light-programming. With the proposed approach, a significant threshold voltage shift is attained even with the exposure time as short as 5 ms. High quality dielectric layers prepared by initiated chemical vapor deposition ensure erasing to occur only with electrical signal in a controlled manner. Retention time up to 700 s is demonstrated.