bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medical relevance of protein-truncating variants across 337,205 individuals in the UK Biobank study
Authors: DeBoever Christopher , Tanigawa Yosuke , Lindholm Malene E. , McInnes Greg , Lavertu Adam , Ingelsson Erik , Chang Chris , Ashley Euan A. , Bustamante Carlos D. , Daly Mark J. , Rivas Manuel A. 
Published: April 2018

AbstractProtein-truncating variants can have profound effects on gene function and are critical for clinical genome interpretation and generating therapeutic hypotheses, but their relevance to medical phenotypes has not been systematically assessed. Here, we characterize the effect of 18,228 protein-truncating variants across 135 phenotypes from the UK Biobank and find 27 associations between medical phenotypes and protein-truncating variants in genes outside the major histocompatibility complex. We perform phenome-wide analyses and directly measure the effect in homozygous carriers, commonly referred to as “human knockouts,” across medical phenotypes for genes implicated as being protective against disease or associated with at least one phenotype in our study. We find several genes with strong pleiotropic or non-additive effects. Our results illustrate the importance of protein-truncating variants in a variety of diseases.
Epigenetic landscape influences the liver cancer genome architecture
Authors: Hama Natsuko , Totoki Yasushi , Miura Fumihito , Tatsuno Kenji , Saito-Adachi Mihoko , Nakamura Hiromi , Arai Yasuhito , Hosoda Fumie , Urushidate Tomoko , Ohashi Shoko , Mukai Wakako , Hiraoka Nobuyoshi , Aburatani Hiroyuki , Ito Takashi , Shibata Tatsuhiro 
Published: April 2018

AbstractThe accumulations of different types of genetic alterations such as nucleotide substitutions, structural rearrangements and viral genome integrations and epigenetic alterations contribute to carcinogenesis. Here, we report correlation between the occurrence of epigenetic features and genetic aberrations by whole-genome bisulfite, whole-genome shotgun, long-read, and virus capture sequencing of 373 liver cancers. Somatic substitutions and rearrangement breakpoints are enriched in tumor-specific hypo-methylated regions with inactive chromatin marks and actively transcribed highly methylated regions in the cancer genome. Individual mutation signatures depend on chromatin status, especially, signatures with a higher transcriptional strand bias occur within active chromatic areas. Hepatitis B virus (HBV) integration sites are frequently detected within inactive chromatin regions in cancer cells, as a consequence of negative selection for integrations in active chromatin regions. Ultra-high structural instability and preserved unmethylation of integrated HBV genomes are observed. We conclude that both precancerous and somatic epigenetic features contribute to the cancer genome architecture.
Warm summers during the Younger Dryas cold reversal
Authors: Schenk Frederik , Väliranta Minna , Muschitiello Francesco , Tarasov Lev , Heikkilä Maija , Björck Svante , Brandefelt Jenny , Johansson Arne V. , Näslund Jens-Ove , Wohlfarth Barbara 
Published: April 2018

AbstractThe Younger Dryas (YD) cold reversal interrupts the warming climate of the deglaciation with global climatic impacts. The sudden cooling is typically linked to an abrupt slowdown of the Atlantic Meridional Overturning Circulation (AMOC) in response to meltwater discharges from ice sheets. However, inconsistencies regarding the YD-response of European summer temperatures have cast doubt whether the concept provides a sufficient explanation. Here we present results from a high-resolution global climate simulation together with a new July temperature compilation based on plant indicator species and show that European summers remain warm during the YD. Our climate simulation provides robust physical evidence that atmospheric blocking of cold westerly winds over Fennoscandia is a key mechanism counteracting the cooling impact of an AMOC-slowdown during summer. Despite the persistence of short warm summers, the YD is dominated by a shift to a continental climate with extreme winter to spring cooling and short growing seasons.
Feed-forward alpha particle radiotherapy ablates androgen receptor-addicted prostate cancer
Authors: McDevitt Michael R. , Thorek Daniel L. J. , Hashimoto Takeshi , Gondo Tatsuo , Veach Darren R. , Sharma Sai Kiran , Kalidindi Teja Muralidhar , Abou Diane S. , Watson Philip A. , Beattie Bradley J. , Timmermand Oskar Vilhemsson , Strand Sven-Erik , Lewis Jason S. , Scardino Peter T. , Scher Howard I. , Lilja Hans , Larson Steven M. , Ulmert David 
Published: April 2018

AbstractHuman kallikrein peptidase 2 (hK2) is a prostate specific enzyme whose expression is governed by the androgen receptor (AR). AR is the central oncogenic driver of prostate cancer (PCa) and is also a key regulator of DNA repair in cancer. We report an innovative therapeutic strategy that exploits the hormone-DNA repair circuit to enable molecularly-specific alpha particle irradiation of PCa. Alpha-particle irradiation of PCa is prompted by molecularly specific-targeting and internalization of the humanized monoclonal antibody hu11B6 targeting hK2 and further accelerated by inherent DNA-repair that up-regulate hK2 (KLK2) expression in vivo. hu11B6 demonstrates exquisite targeting specificity for KLK2. A single administration of actinium-225 labeled hu11B6 eradicates disease and significantly prolongs survival in animal models. DNA damage arising from alpha particle irradiation induces AR and subsequently KLK2, generating a unique feed-forward mechanism, which increases binding of hu11B6. Imaging data in nonhuman primates support the possibility of utilizing hu11B6 in man.
Policy review of the means of implementation targets and indicators for the sustainable development goal for water and sanitation
Authors: Bartram Jamie , Brocklehurst Clarissa , Bradley David , Muller Mike , Evans Barbara 
Published: April 2018

AbstractThe Sustainable Development Goals, adopted by the Member States of the United Nations in September 2016, contain both ‘Outcome’ and ‘Means of Implementation’ targets. However, there is generally weak evidence linking the Means of Implementation to outcomes, they are imperfectly conceptualised and inconsistently formulated, and tracking their largely qualitative indicators will be difficult. In this paper, we analyse and critique the Means of Implementation targets of the Sustainable Development Goal on water and sanitation (SDG6). Improvements are recommended that would reflect: the considerable investment needed to attain SDG6; the important role of the state, including government leadership and planning; the utility of disaggregating financial and capacity-building assistance; and the need for people to realise their rights to information, voice and remedy. Recommendations are also made for relevant indicators, including indicators that are applicable to governments in both aid-providing and aid-receiving countries.
Human mesenchymal stem cell basal membrane bending on gratings is dependent on both grating width and curvature
Authors: Zeng Yukai , Wong Sum Thai , Teo Soo Kng , Leong Kam W. , Chiam Keng-Hwee , Yim Evelyn K. F. 
Published: April 2018

AbstractThe topography of the extracellular substrate provides physical cues to elicit specific downstream biophysical and biochemical effects in cells. An example of such a topographical substrate is periodic gratings, where the dimensions of the periodic gratings influence cell morphology and directs cell differentiation. We first develop a novel sample preparation technique using Spurr’s resin to allow for cross-sectional transmission electron microscopy imaging of cells on grating grooves, and observed that the plasma membrane on the basal surface of these cells can deform and bend into grooves between the gratings. We postulate that such membrane bending is an important first step in eliciting downstream effects. Thus, we use a combination of image analysis and mathematical modeling to explain the extent of bending of basal membrane into grooves. We show that the extent to which the basal membrane bends into grooves depends on both groove width and angle of the grating ridge. Our model predicts that the basal membrane will bend into grooves when they are wider than 1.9 µm in width. The existence of such a threshold may provide an explanation for how the width of periodic gratings may bring about cellular downstream effects, such as cell proliferation or differentiation.
Erythromycin leads to differential protein expression through differences in electrostatic and dispersion interactions with nascent proteins
Authors: Nguyen Hoang Linh , Pham Dang Lan , O’Brien Edward P. , Li Mai Suan 
Published: April 2018

AbstractThe antibiotic activity of erythromycin, which reversibly binds to a site within the bacterial ribosome exit tunnel, against many gram positive microorganisms indicates that it effectively inhibits the production of proteins. Similar to other macrolides, the activity of erythromycin is far from universal, as some peptides can bypass the macrolide-obstructed exit tunnel and become partially or fully synthesized. It is unclear why, at the molecular level, some proteins can be synthesized while others cannot. Here, we use steered molecular dynamics simulations to examine how erythromycin inhibits synthesis of the peptide ErmCL but not the peptide H-NS. By pulling these peptides through the exit tunnel of the E.coli ribosome with and without erythromycin present, we find that erythromycin directly interacts with both nascent peptides, but the force required for ErmCL to bypass erythromycin is greater than that of H-NS. The largest forces arise three to six residues from their N-terminus as they start to bypass Erythromycin. Decomposing the interaction energies between erythromycin and the peptides at this point, we find that there are stronger electrostatic and dispersion interactions with the more C-terminal residues of ErmCL than with H-NS. These results suggest that erythromycin slows or stalls synthesis of ErmCL compared to H-NS due to stronger interactions with particular residue positions along the nascent protein.
RNA-Seq analysis of interferon inducible p204-mediated network in anti-tumor immunity
Authors: Jian Jinlong , Wei Wei , Yin Guowei , Hettinghouse Aubryanna , Liu Chuanju , Shi Yongxiang 
Published: April 2018

Abstractp204, a murine member of the interferon-inducible p200 protein family, and its human analogue, IFI16, have been shown to function as tumor suppressors in vitro, but the molecular events involved, in particular in vivo, remain unclear. Herein we induced the Lewis Lung carcinoma (LLC) murine model of human lung cancer in p204 null mice (KO) and their control littermates (WT). We compared the transcriptome in spleen from WT and p204 KO mice using a high-throughput RNA-sequencing array. A total 30.02 Gb of clean data were obtained, and overall Q30% was greater than 90.54%. More than 75% of clean data from 12 transcriptome samples were mapped to exons. The results showed that only 11 genes exhibited altered expression in untreated p204 KO mice relative to untreated WT mice, while 393 altered genes were identified in tumor-bearing p204 KO mice when compared with tumor-bearing WT mice. Further differentially expressed gene cluster and gene ontology consortium classification revealed that numerous cytokines and their receptors, chemoattractant molecules, and adhesion molecules were significantly induced in p204 KO mice. This study provides novel insights to the p204 network in anti-tumor immune response and also presents a foundation for future work concerning p204-mediated gene expressions and pathways.
Quantitative shadow compensated optical coherence tomography of choroidal vasculature
Authors: Vupparaboina Kiran Kumar , Dansingani Kunal K. , Goud Abhilash , Rasheed Mohammed Abdul , Jawed Fayez , Jana Soumya , Richhariya Ashutosh , Freund K. Bailey , Chhablani Jay 
Published: April 2018

AbstractConventionally rendered optical coherence tomography (OCT) images of the posterior segment contain shadows which influence the visualization of deep structures such as the choroid. The purpose of this study was to determine whether OCT shadow compensation (SC) alters the appearance of the choroid and the apparent choroidal vascularity index (CVI), an OCT-derived estimated ratio of luminal to total choroidal volume. All scans were shadow compensated using a previously published algorithm, binarized using a novel validated algorithm and extracted binarized choroid to estimate CVI. On 27 raw swept-source OCT volume-scans of healthy subjects, the effect of SC on CVI was established both qualitatively and quantitatively. In shadow compensated scans, the choroid was visualized with greater brightness than the neurosensory retina and the masking of deep tissues by retinal blood vessels was greatly reduced. Among study subjects, significant mean difference in CVI of −0.13 was observed between raw and shadow compensated scans. Conventionally acquired OCT underestimates both choroidal reflectivity and calculated CVI. Quantitative analysis based on subjective grading demonstrated that SC increased the contrast between stromal and luminal regions and are in agreement with true tissue regions. This study is warranted to determine the effects of SC on CVI in diseased eyes.
PEDOT:PSS/graphene quantum dots films with enhanced thermoelectric properties via strong interfacial interaction and phase separation
Authors: Du Fei-Peng , Cao Nan-Nan , Zhang Yun-Fei , Fu Ping , Wu Yan-Guang , Lin Zhi-Dong , Shi Run , Amini Abbas , Cheng Chun 
Published: April 2018

AbstractThe typical conductive polymer of PEDOT:PSS has recently attracted intensive attention in thermoelectric conversion because of its low cost and low thermal conductivity as well as high electrical conductivity. However, compared to inorganic counterparts, the relatively poor thermoelectric performance of PEDOT:PSS has greatly limited its development and high-tech applications. Here, we report a dramatic enhancement in the thermoelectric performance of PEDOT:PSS by constructing unique composite films with graphene quantum dots (GQDs). At room temperature, the electrical conductivity and Seebeck coefficient of PEDOT:PSS/GQDs reached to 7172 S/m and 14.6 μV/K, respectively, which are 30.99% and 113.2% higher than those of pristine PEDOT:PSS. As a result, the power factor of the optimized PEDOT:PSS/GQDs composite is 550% higher than that of pristine PEDOT:PSS. These significant improvements are attributed to the ordered alignment of PEDOT chains on the surface of GQDs, originated from the strong interfacial interaction between PEDOT:PSS and GQDs and the separation of PEDOT and PSS phases. This study evidently provides a promising route for PEDOT:PSS applied in high-efficiency thermoelectric conversion.
Assessing the Nature of the Distribution of Localised States in Bulk GaAsBi
Authors: Wilson Tom , Hylton Nicholas P. , Harada Yukihiro , Pearce Phoebe , Alonso-Álvarez Diego , Mellor Alex , Richards Robert D. , David John P. R. , Ekins-Daukes Nicholas J. 
Published: April 2018

AbstractA comprehensive assessment of the nature of the distribution of sub band-gap energy states in bulk GaAsBi is presented using power and temperature dependent photoluminescence spectroscopy. The observation of a characteristic red-blue-red shift in the peak luminescence energy indicates the presence of short-range alloy disorder in the material. A decrease in the carrier localisation energy demonstrates the strong excitation power dependence of localised state behaviour and is attributed to the filling of energy states furthest from the valence band edge. Analysis of the photoluminescence lineshape at low temperature presents strong evidence for a Gaussian distribution of localised states that extends from the valence band edge. Furthermore, a rate model is employed to understand the non-uniform thermal quenching of the photoluminescence and indicates the presence of two Gaussian-like distributions making up the density of localised states. These components are attributed to the presence of microscopic fluctuations in Bi content, due to short-range alloy disorder across the GaAsBi layer, and the formation of Bi related point defects, resulting from low temperature growth.
Morphological parameters and anatomical locations associated with rupture status of small intracranial aneurysms
Authors: Duan Zhihui , Li Yuanhui , Guan Sheng , Ma Congmin , Han Yuezhen , Ren Xiangyang , Wei Liping , Li Wenbo , Lou Jiyu , Yang Zhiyuan 
Published: April 2018

AbstractCharacterization of the rupture risk factors for small intracranial aneurysms (SIAs, ≤5 mm) is clinically valuable. The present study aims to identify image-based morphological parameters and anatomical locations associated with the rupture status of SIAs. Two hundred and sixty-three patients with single SIAs (128 ruptured, 135 unruptured) were included, and six morphological parameters, including size, aspect ratio (AR), size ratio (SR), height–width ratio (H/W), flow angle (FA) and aneurysm width–parent artery diameter ratio, and the aneurysm locations were evaluated using three-dimensional geometry, and were used to identify a correlation with aneurysm rupture. Statistically significant differences were observed between ruptured and unruptured groups for AR, SR, H/W, FA, and aneurysm locations, from univariate analyses. Logistic regression analysis further revealed that AR (p = 0.034), SR (p = 0.004), H/W (p = 0.003), and FA (p < 0.001) had the strongest independent correlation with ruptured SIAs after adjustment for age, gender and other clinical risk factors. A future study on a larger SIA cohort need to establish to what extent the AR, SR, H/W and FA increase the risk of rupture in patients with unruptured SIAs in terms of absolute risks.
Graded pitch profile for the helicoidal broadband reflector and left-handed circularly polarizing cuticle of the scarab beetle Chrysina chrysargyrea
Authors: Mendoza-Galván A. , del Río L. Fernández , Järrendahl K. , Arwin H. 
Published: April 2018

AbstractThe cuticle of the beetle Chrysina chrysargyrea reflects left-handed polarized light in the broad spectral range from 340 to 1000 nm. Interference oscillations in the experimental Mueller-matrix spectroscopic ellipsometry data reveal that transparent materials comprise the cuticle. A spectral analysis of the interference oscillations makes evident that the pitch profile across the cuticle is graded. The graded pitch and effective refractive indices are determined through non-linear regression analysis of the experimental Mueller matrix by using a cuticle model based on twisted biaxial dielectric slices. Non-uniformity in cuticle thickness as well as in pitch profile near the cuticle surface account for depolarizance of the Mueller matrix. Transmission electron microscopy supports the reliability of the results.
Transcriptomic analysis of the liver of cholesterol-fed rabbits reveals altered hepatic lipid metabolism and inflammatory response
Authors: Wang Weirong , Chen Yulong , Bai Liang , Zhao Sihai , Wang Rong , Liu Baoning , Zhang Yali , Fan Jianglin , Liu Enqi 
Published: April 2018

AbstractRabbits are a suitable animal model for atherosclerosis due to their sensitivity to dietary cholesterol. Moreover, rabbits have lipoprotein profiles that are more similar to humans than those of other laboratory animals. However, little is known about the transcriptomic information related to atherosclerosis in rabbits. We aimed to determine the changes in the livers of rabbits fed a normal chow diet (control) or high cholesterol diet (HCD) by histological examinations and RNA sequencing analysis. Compared with the control group, the lipid levels and small LDL subfractions in plasma were increased, and aortic atherosclerotic plaques were formed in the HCD group. Most importantly, HCD resulted in lipid accumulation and inflammation in the livers. Transcriptomic analysis of the liver showed that HCD induces 1183 differentially expressed genes (DEGs) that mainly participate in the regulation of inflammation and lipid metabolism. Furthermore, the signaling pathways involved in inflammation and lipid metabolism were enriched by KEGG pathway analysis. In addition, hepatic DEGs of the HCD group were further validated by real-time PCR. These results suggest that HCD causes liver lipid accumulation and inflammatory response. Although the relationships between these hepatic changes and atherogenesis need further investigation, these findings provide a fundamental framework for future research on human atherosclerosis using rabbit models.
Adsorption Properties of Granular Activated Carbon-Supported Titanium Dioxide Particles for Dyes and Copper Ions
Authors: Zheng Xin , Yu Nannan , Wang Xiaopeng , Wang Yuhong , Wang Linshan , Li Xiaowu , Hu Xiaomin 
Published: April 2018

AbstractIn the present paper, granular activated carbon (GAC) supported titanium dioxide (TiO2@GAC) particles were prepared by sol-gel process. Their performance in simultaneous adsorption of dye and Cu2+ from wastewater was studied. X-ray diffraction (XRD) indicated that TiO2 of the TiO2@GAC microsphere is anatase type, and Fourier transform infrared spectroscopy (FT-IR) showed that the samples have obvious characteristic peaks in 400–800 cm−1, which indicated that there are Ti-O-Ti bonds. The experimental results showed that the adsorption of TiO2@GAC for Methylene blue (MB) and Cu2+ were favorable under acidity condition, the adsorption of Methyl orange (MO) was favorable under alkalecent condition. The reaction kinetics of TiO2@GAC for MO, MB and Cu2+ were well described as pseudo-second-order kinetic model; The reaction isotherms for MO, MB and Cu2+ were well fitted by Langmuir model. The maximum adsorption capacity of TiO2@GAC for MO, MB and Cu2+ in the single systems were 32.36 mg/g, 25.32 mg/g and 23.42 mg/g, respectively. As for adsorption, Cu2+ had a suppression effect on MB, and a promotion effect on MO, however, the impact of MO and MB on Cu2+ were negligible.
Low Bilirubin Levels Indicate a High Risk of Cerebral Deep White Matter Lesions in Apparently Healthy Subjects
Authors: Higuchi Satoshi , Kabeya Yusuke , Uchida Junko , Kato Kiyoe , Tsukada Nobuhiro 
Published: April 2018

AbstractRecent studies have reported that deep white matter lesions (DWMLs) on magnetic resonance imaging scans are related to the risk of developing impaired cognitive function in future. Bilirubin exhibits a potent antioxidant effect and an inverse relationship has been reported between bilirubin levels and the risk of several atherosclerotic diseases; however, there is limited evidence with regard to the effect of bilirubin levels on cerebrovascular diseases including DWMLs. This cross-sectional study included 1121 apparently healthy Japanese adults. The subjects were divided into three groups according to their bilirubin levels (low, <0.5 mg/dl; intermediate, ≥0.5 mg/dl and <1.0 mg/dl; and high, ≥1.0 mg/dl). The severity of DWMLs was evaluated according to Fazekas scale and their relation to bilirubin levels was examined. The association between bilirubin levels and the presence of severe DWMLs was assessed using multivariate logistic regression analysis. The analysis revealed that the low- and intermediate bilirubin groups indicated 2.36- and 1.33-fold increase in the prevalence of severe DWMLs compared with the high-bilirubin group, respectively (95% confidence interval (CI): 1.12–4.97 (the low-bilirubin group), 95% CI: 0.85–2.07 (the intermediate-bilirubin group). In conclusion, low total bilirubin levels could be associated with a high prevalence of severe DWMLs in apparent healthy subjects.