bluuebunny/crossref_metadata_2025_split huggingface dataset:
A temporal shift of the evolutionary principle shaping intratumor heterogeneity in colorectal cancer
Authors: Saito Tomoko , Niida Atsushi , Uchi Ryutaro , Hirata Hidenari , Komatsu Hisateru , Sakimura Shotaro , Hayashi Shuto , Nambara Sho , Kuroda Yosuke , Ito Shuhei , Eguchi Hidetoshi , Masuda Takaaki , Sugimachi Keishi , Tobo Taro , Nishida Haruto , Daa Tsutomu , Chiba Kenichi , Shiraishi Yuichi , Yoshizato Tetsuichi , Kodama Masaaki , Okimoto Tadayoshi , Mizukami Kazuhiro , Ogawa Ryo , Okamoto Kazuhisa , Shuto Mitsutaka , Fukuda Kensuke , Matsui Yusuke , Shimamura Teppei , Hasegawa Takanori , Doki Yuichiro , Nagayama Satoshi , Yamada Kazutaka , Kato Mamoru , Shibata Tatsuhiro , Mori Masaki , Aburatani Hiroyuki , Murakami Kazunari , Suzuki Yutaka , Ogawa Seishi , Miyano Satoru , Mimori Koshi 
Published: July 2018

AbstractAdvanced colorectal cancer harbors extensive intratumor heterogeneity shaped by neutral evolution; however, intratumor heterogeneity in colorectal precancerous lesions has been poorly studied. We perform multiregion whole-exome sequencing on ten early colorectal tumors, which contained adenoma and carcinoma in situ. By comparing with sequencing data from advanced colorectal tumors, we show that the early tumors accumulate a higher proportion of subclonal driver mutations than the advanced tumors, which is highlighted by subclonal mutations in KRAS and APC. We also demonstrate that variant allele frequencies of subclonal mutations tend to be higher in early tumors, suggesting that the subclonal mutations are subject to selective sweep in early tumorigenesis while neutral evolution is dominant in advanced ones. This study establishes that the evolutionary principle underlying intratumor heterogeneity shifts from Darwinian to neutral evolution during colorectal tumor progression.
Tunable flexible artificial synapses: a new path toward a wearable electronic system
Authors: Yang Kunlong , Yuan Sijian , Huan Yuxiang , Wang Jiao , Tu Li , Xu Jiawei , Zou Zhuo , Zhan Yiqiang , Zheng Lirong , Seoane Fernando 
Published: July 2018

AbstractThe flexible electronics has been deemed to be a promising approach to the wearable electronic systems. However, the mismatching between the existing flexible deices and the conventional computing paradigm results an impasse in this field. In this work, a new way to access to this goal is proposed by combining flexible devices and the neuromorphic architecture together. To achieve that, a high-performance flexible artificial synapse is created based on a carefully designed and optimized memristive transistor. The device exhibits high-performance which has near-linear non-volatile resistance change under 10,000 identical pulse signals within the 515% dynamic range, and has the energy consumption as low as 45 fJ per pulse. It also displays multiple synaptic plasticity features, which demonstrates its potential for real-time online learning. Besides, the adaptability by virtue of its three-terminal structure specifically contributes its improved uniformity, repeatability, and reduced power consumption. This work offers a very viable solution for the future wearable computing.
Curcumin alleviates persistence of Acinetobacter baumannii against colistin
Authors: Kaur Amanjot , Sharma Prince , Capalash Neena 
Published: July 2018

AbstractPersisters are phenotypic variants of normal susceptible bacterial populations that survive prolonged exposure to high doses of antibiotics and are responsible for pertinacious infections and post-treatment relapses. Out of the three antibiotics, Acinetobacter baumannii formed the highest percentage of persister cells against rifampicin followed by amikacin and the least against colistin. Colistin-treated cells formed the high levels of reactive oxygen species (ROS) whose quenching with bipyridyl and thiourea led to an increased persister population. Curcumin, a polyphenolic pro-oxidant, significantly decreased persistence against colistin. The quenching of ROS generated by curcumin-colistin combination and the use of resveratrol, an anti-oxidant, with colistin increased the persister population, supporting the significance of ROS in decreased persistence against this combination. The down-regulation of repair genes by this combination in comparison to colistin alone supported the modulation of gene expression in response to ROS and their importance in decreased persistence. Increased membrane permeability by colistin, facilitating the penetration of curcumin into cells and resulting in increased ROS and compromised repair compounded by the decreased efflux of colistin by the inhibition of efflux pumps, may be responsible for enhanced lethality and low persistence. Hence, the curcumin-colistin combination can be another option with anti-persister potential for the control of chronic A. baumannii infections.
Vineyard under-vine floor management alters soil microbial composition, while the fruit microbiome shows no corresponding shifts
Authors: Chou Ming-Yi , Vanden Heuvel Justine , Bell Terrence H. , Panke-Buisse Kevin , Kao-Kniffin Jenny 
Published: July 2018

AbstractThe microbiome of a vineyard may play a critical role in fruit development, and consequently, may impact quality properties of grape and wine. Vineyard management approaches that have directly manipulated the microbiome of grape clusters have been studied, but little is known about how vineyard management practices that impact the soil microbial pool can influence this dynamic. We examined three under-vine soil management practices: 1) herbicide application, 2) soil cultivation (vegetation removal), and 3) natural vegetation (no vegetation removal) in a Riesling vineyard in New York over a three-year period. The microbiomes associated with soil and grapes were profiled using high-throughput sequencing of the bacterial 16 S rRNA gene and fungal ITS regions. Our results showed that soil bacterial composition under natural vegetation differs from that seen in glyphosate-maintained bare soil. Soil fungal composition under the natural vegetation treatment was distinct from other treatments. Although our study revealed soil microbiome shifts based on under-vine management, there were no corresponding changes in fruit-associated microbial composition. These results suggested that other vineyard management practices or environmental factors are more influential in shaping the grape-associated microbiome.
High Serum Iron level is Associated with Increased Mortality in Patients with Sepsis
Authors: Lan Peng , Pan Kong-han , Wang Shuo-jia , Shi Qiu-cheng , Yu Yun-xian , Fu Ying , Chen Yan , Jiang Yan , Hua Xiao-ting , Zhou Jian-cang , Yu Yun-song 
Published: July 2018

AbstractIron is an essential nutrient for bacterial survival and thus higher iron levels may precipitate bacterial infections. We investigated the association between the serum iron level and prognosis in patients with sepsis by using the single-centre Medical Information Mart for Intensive Care III (MIMIC-III) database. Sepsis patients with iron parameters measured on ICU admission were included and stratified according to quartiles of serum iron levels. A total of 1,891 patients diagnosed with sepsis according to the Sepsis-3 criteria were included in this study, 324 of whom were septic shock. After adjusting for confounding variables, higher iron quartile was associated with an increase in 90-day mortality in the Cox regression analysis. Moreover, a stepwise increase in the risk of 90-day mortality was observed as the quartiles of serum iron levels increased in the patients with sepsis. In conclusion, higher serum iron levels were independently associated with increased 90-day mortality in this large cohort of patients with sepsis.
Response Modality vs. Target Modality: Sensory Transformations and Comparisons in Cross-modal Slant Matching Tasks
Authors: Liu Juan , Ando Hiroshi 
Published: July 2018

AbstractHumans constantly combine multi-sensory spatial information to successfully interact with objects in peripersonal space. Previous studies suggest that sensory inputs of different modalities are encoded in different reference frames. In cross-modal tasks where the target and response modalities are different, it is unclear which reference frame these multiple sensory signals are transformed to for comparison. The current study used a slant perception and parallelity paradigm to explore this issue. Participants perceived (either visually or haptically) the slant of a reference board and were asked to either adjust an invisible test board by hand manipulation or to adjust a visible test board through verbal instructions to be physically parallel to the reference board. We examined the patterns of constant error and variability of unimodal and cross-modal tasks with various reference slant angles at different reference/test locations. The results revealed that rather than a mixture of the patterns of unimodal conditions, the pattern in cross-modal conditions depended almost entirely on the response modality and was not substantially affected by the target modality. Deviations in haptic response conditions could be predicted by the locations of the reference and test board, whereas the reference slant angle was an important predictor in visual response conditions.
Discovery of glycocholic acid and taurochenodeoxycholic acid as phenotypic biomarkers in cholangiocarcinoma
Authors: Song Won-Suk , Park Hae-Min , Ha Jung Min , Shin Sung Gyu , Park Han-Gyu , Kim Joonwon , Zhang Tianzi , Ahn Da-Hee , Kim Sung-Min , Yang Yung-Hun , Jeong Jae Hyun , Theberge Ashleigh B. , Kim Byung-Gee , Lee Jong Kyun , Kim Yun-Gon 
Published: July 2018

AbstractAlthough several biomarkers can be used to distinguish cholangiocarcinoma (CCA) from healthy controls, differentiating the disease from benign biliary disease (BBD) or pancreatic cancer (PC) is a challenge. CCA biomarkers are associated with low specificity or have not been validated in relation to the biological effects of CCA. In this study, we quantitatively analyzed 15 biliary bile acids in CCA (n = 30), BBD (n = 57) and PC (n = 17) patients and discovered glycocholic acid (GCA) and taurochenodeoxycholic acid (TCDCA) as specific CCA biomarkers. Firstly, we showed that the average concentration of total biliary bile acids in CCA patients was quantitatively less than in other patient groups. In addition, the average composition ratio of primary bile acids and conjugated bile acids in CCA patients was the highest in all patient groups. The average composition ratio of GCA (35.6%) in CCA patients was significantly higher than in other patient groups. Conversely, the average composition ratio of TCDCA (13.8%) in CCA patients was significantly lower in all patient groups. To verify the biological effects of GCA and TCDCA, we analyzed the gene expression of bile acid receptors associated with the development of CCA in a CCA cell line. The gene expression of transmembrane G protein coupled receptor (TGR5) and sphingosine 1-phosphate receptor 2 (S1PR2) in CCA cells treated with GCA was 8.6-fold and 3.4-fold higher compared with control (untreated with bile acids), respectively. Gene expression of TGR5 and S1PR2 in TCDCA-treated cells was not significantly different from the control. Taken together, our study identified GCA and TCDCA as phenotype-specific biomarkers for CCA.
Limitations of the IAU2000 nutation model accuracy due to the lack of Oppolzer terms of planetary origin
Authors: Ferrándiz José M. , Navarro Juan F. , Martínez-Belda M. C. , Escapa Alberto , Getino Juan 
Published: July 2018

Context. The current IAU2000 nutation model performed different approximations, one of them being that the Oppolzer terms associated to the planetary perturbations of the nutations were assumed to be smaller than 5 μas and thus were neglected. At present, the uncertainties of the amplitudes of individual components of the observed nutations are better, and the conventional nutation model does not fit the accuracy requirements pursued by the International Astronomical Union (IAU) and the International Association of Geodesy (IAG).
Aims. The objective of this work is to estimate the magnitude of the lacking Oppolzer terms of the planetary nutations and find out whether they are still negligible or not.
Methods. The Oppolzer terms resulting from the direct and indirect planetary perturbations of the Earth’s rotation have been computed for a two-layer Earth model following the Hamiltonian theory of the non-rigid-Earth.
Results. The planetary Oppolzer terms for the non-rigid Earth are not really negligible as believed, and some of them have amplitudes larger than 10 μas, therefore significantly above the current level of uncertainty of individual harmonic constituents.
Conclusions. In the short term, the IAU2000 nutation model must be supplemented with suitable corrections accounting for those missing components; its planetary component must be thoroughly revised in the medium term.
Spatial likelihood analysis for MAGIC telescope data
Authors: Vovk I. , Strzys M. , Fruck C. 
Published: July 2018

Context. The increase in sensitivity of Imaging Atmospheric Cherenkov Telescopes (IACTs) has lead to numerous detections of extended γ-ray sources at TeV energies, sometimes of sizes comparable to the instrument’s field of view. This creates a demand for advanced and flexible data analysis methods that are able to extract source information using the photon counts in the entire field of view.
Aims. We present a new software package, “SkyPrism”, aimed at performing 2D (3D if energy is considered) fits of IACT data that possibly contain multiple and extended sources. The fits are based on sky images binned in energy. Although the development of this package was focused on the analysis of data collected with the MAGIC telescopes, it can further be adapted to other instruments, such as the future Cherenkov Telescope Array.
Methods. We have developed a set of tools that in addition to sky images (count maps) compute the instrument response functions of MAGIC (effective exposure throughout the field of view, point spread function, energy resolution, and background shape) based on the input data, Monte Carlo simulations, and the pointing track of the telescopes. With this information, the package can perform a simultaneous maximum likelihood fit of source models of arbitrary morphology to the sky images providing energy spectra, detection significances, and upper limits.
Results. We demonstrate that the SkyPrism tool accurately reconstructs the MAGIC point spread function, on- and off-axis performance as well as the underlying background. We further show that for a point source analysis with the MAGIC default observational settings, SkyPrism gives results compatible with those of the standard tools while being more flexible and widely applicable.
The ALMA-PILS survey: first detection of methyl isocyanide (CH3NC) in a solar-type protostar
Authors: Calcutt H. , Fiechter M. R. , Willis E. R. , Müller H. S. P. , Garrod R. T. , Jørgensen J. K. , Wampfler S. F. , Bourke T. L. , Coutens A. , Drozdovskaya M. N. , Ligterink N. F. W. , Kristensen L. E. 
Published: July 2018

Context. Methyl isocyanide (CH3NC) is the isocyanide with the largest number of atoms confirmed in the interstellar medium (ISM), but it is not an abundant molecule, having only been detected towards a handful of objects. Conversely, its isomer, methyl cyanide (CH3CN), is one of the most abundant complex organic molecules detected in the ISM, with detections in a variety of low- and high-mass sources.
Aims. The aims of this work are to determine the abundances of methyl isocyanide in the solar-type protostellar binary IRAS 16293–2422 and to understand the stark abundance differences observed between methyl isocyanide and methyl cyanide in the ISM.
Methods. We use Atacama Large Millimeter/submillimeter Array (ALMA) observations from the Protostellar Interferometric Line Survey (PILS) to search for methyl isocyanide and compare its abundance with that of its isomer methyl cyanide. We use a new line catalogue from the Cologne Database for Molecular Spectroscopy (CDMS) to identify methyl isocyanide lines. We also model the chemistry with an updated version of the three-phase chemical kinetics model MAGICKAL, presenting the first chemical modelling of methyl isocyanide to date.
Results. We detect methyl isocyanide for the first time in a solar-type protostar, IRAS 16293–2422 B, and present upper limits for its companion protostar, IRAS 16293–2422 A. Methyl isocyanide is found to be at least 20 times more abundant in source B compared to source A, with a CH3CN/CH3NC abundance ratio of 200 in IRAS 16293–2422 B and >5517 in IRAS 16293–2422 A. We also present the results of a chemical model of methyl isocyanide chemistry in both sources, and discuss the implications for methyl isocyanide formation mechanisms and the relative evolutionary stages of both sources. The chemical modelling is unable to match the observed CH3CN/CH3NC abundance ratio towards the B source at densities representative of that source. The modelling, however, is consistent with the upper limits for the A source. There are many uncertainties in the formation and destruction pathways of methyl isocyanide, and it is therefore not surprising that the initial modelling attempts do not reproduce observations. In particular, it is clear that some destruction mechanism of methyl isocyanide that does not destroy methyl cyanide is needed. Furthermore, these initial model results suggest that the final density plays a key role in setting the abundance ratio. The next steps are therefore to obtain further detections of methyl isocyanide in more objects, as well as undertaking more detailed physico-chemical modelling of sources such as IRAS16293.
Democratizing Strategies for Industry-Funded Medical Research: A Cautionary Tale
Authors: Fernández Pinto Manuela 
Published: July 2018

AbstractThe article examines the process of niche standardization in medical research as an example of democratizing strategies implemented in industry-funded science. I argue that niche standardization can lead to undesirable epistemic and ethical consequences, if the various goals of research are not properly aligned. I examine two examples: the case of Sarafem, approved for the treatment of premenstrual dysphoric disorder in women, and the case of BiDil, approved for exclusive use in African Americans for the treatment of congestive heart failure. I conclude by cautioning against the unqualified support of democratizing strategies in industry-funded research.
A comparative analysis of cell-type adjustment methods for epigenome-wide association studies based on simulated and real data sets
Authors: Brägelmann Johannes , Lorenzo Bermejo Justo 
Published: July 2018

Abstract
Technological advances and reduced costs of high-density methylation arrays have led to an increasing number of association studies on the possible relationship between human disease and epigenetic variability. DNA samples from peripheral blood or other tissue types are analyzed in epigenome-wide association studies (EWAS) to detect methylation differences related to a particular phenotype. Since information on the cell-type composition of the sample is generally not available and methylation profiles are cell-type specific, statistical methods have been developed for adjustment of cell-type heterogeneity in EWAS.
In this study we systematically compared five popular adjustment methods: the factored spectrally transformed linear mixed model (FaST-LMM-EWASher), the sparse principal component analysis algorithm ReFACTor, surrogate variable analysis (SVA), independent SVA (ISVA) and an optimized version of SVA (SmartSVA). We used real data and applied a multilayered simulation framework to assess the type I error rate, the statistical power and the quality of estimated methylation differences according to major study characteristics.
While all five adjustment methods improved false-positive rates compared with unadjusted analyses, FaST-LMM-EWASher resulted in the lowest type I error rate at the expense of low statistical power. SVA efficiently corrected for cell-type heterogeneity in EWAS up to 200 cases and 200 controls, but did not control type I error rates in larger studies. Results based on real data sets confirmed simulation findings with the strongest control of type I error rates by FaST-LMM-EWASher and SmartSVA. Overall, ReFACTor, ISVA and SmartSVA showed the best comparable statistical power, quality of estimated methylation differences and runtime.
The Humour of Noël Du Fail in the
Propos rustiques
Authors: Braybrook Jean 
Published: July 2018

Abstract

In this article, some modern theories of humour are applied to the Breton lawyer and writer of prose, Noël Du Fail, who produces in French linguistically rather difficult texts containing tales that he presents as being told about the countryside and its colourful, talkative inhabitants. In the
Propos rustiques
(1547), the first and most accessible of these works, he reveals himself as a self-conscious humorist. Although he does write (within a complex framework) about discord and fights, employing oppositional humour, he includes in the central chapter (Chapter 7) a narration by the character Pasquier, three major elements of which (the evocation of a character called Thenot, a description of a child’s playthings, and a short poem praising the rustic life) can be seen as contributing to a mirroring or
mise en abyme
of Du Fail’s predominantly gentle comic art. Finally, underpinning the chapter and indeed his work as a whole are figurative expressions which reveal that, although he undoubtedly owes much in theme and language to Rabelais, Du Fail deploys many images and figures of speech that are not found in Rabelais and that may well reflect the influence of the region in which he is writing.
The solar-like ‘Second Spectrum’ and polarized metal lines in the emission of the post-AGB binary 89 Herculis
Authors: Leone F , Gangi M , Giarrusso M , Scalia C , Cecconi M , Cosentino R , Ghedina A , Munari M , Scuderi S 
Published: July 2018

ABSTRACT
We studied the polarized spectrum of the post-AGB binary system 89 Herculis on the basis of data collected with the high-resolution Catania Astrophysical Observatory Spectropolarimeter, HArps-North POlarimeter and Echelle SpectroPolarimetric Device for the Observation of Stars. We find the existence of linear polarization in the strongest metal lines in absorption and with low excitation potentials. Signals are characterized by complex Q and U morphologies varying with the orbital period. We rule out magnetic fields, continuum depolarization due to pulsations and hot spots as the possible origin of this ‘Second Solar Spectrum’-like behaviour. The linear polarization we detected in the Caii 8662-Å line is clear evidence of optical pumping polarization and rules out scattering polarization from free electrons of the circumbinary environment. In the framework of optical pumping due to the secondary star, the observed periodic properties of the spectral line polarization can be justified by two jets, with a flow velocity of a few tens of km s−1, at the basis of that hourglass structure characterizing 89 Herculis. We also discovered linear polarization across the emission profile of metal lines. Numerical simulations show that these polarized profiles could be formed in an undisrupted circumbinary disc rotating at ≤10 km s−1 and with an orientation in the sky in agreement with optical and radio interferometric results. We conclude that the study of aspherical envelopes, the origin of which is not yet completely understood, of PNe and already present in post-AGBs can benefit from high-resolution spectropolarimetry and that this technique can shape envelopes still too far away for interferometry.