bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Open-Source Storage Solution for Cryo-Electron Microscopy Samples
Authors: Ultee Eveline , Schenkel Fred , Yang Wen , Brenzinger Susanne , Depelteau Jamie S. , Briegel Ariane 
Published: January 2018

AbstractCryo-electron microscopy (cryo-EM) enables the study of biological structures in situ in great detail and to solve protein structures at Ångstrom level resolution. Due to recent advances in instrumentation and data processing, the field of cryo-EM is a rapidly growing. Access to facilities and national centers that house the state-of-the-art microscopes is limited due to the ever-rising demand, resulting in long wait times between sample preparation and data acquisition. To improve sample storage, we have developed a cryo-storage system with an efficient, high storage capacity that enables sample storage in a highly organized manner. This system is simple to use, cost-effective and easily adaptable for any type of grid storage box and dewar and any size cryo-EM laboratory.
Efficacy of MEK inhibition in a K-Ras-driven cholangiocarcinoma preclinical model
Authors: Dong Mingjie , Liu Xianqiong , Evert Katja , Utpatel Kirsten , Peters Michele , Zhang Shanshan , Xu Zhong , Che Li , Cigliano Antonio , Ribback Silvia , Dombrowski Frank , Cossu Antonio , Gordan John , Calvisi Diego F. , Evert Matthias , Liu Yan , Chen Xin 
Published: January 2018

AbstractIntrahepatic cholangiocarcinoma (iCCA) is a deadly malignancy with limited treatment options. Gain-of-function mutations in K-Ras is a very frequent alteration, occurring in ~15 to 25% of human iCCA patients. Here, we established a new iCCA model by expressing activated forms of Notch1 (NICD) and K-Ras (K-RasV12D) in the mouse liver (K-Ras/NICD mice). Furthermore, we investigated the therapeutic potential of MEK inhibitors in vitro and in vivo using human CCA cell lines and K-Ras/NICD mice, respectively. Treatment with U0126, PD901, and Selumetinib MEK inhibitors triggered growth restraint in all CCA cell lines tested, with the most pronounced growth suppressive effects being observed in K-Ras mutant cells. Growth inhibition was due to reduction in proliferation and massive apoptosis. Furthermore, treatment of K-Ras/NICD tumor-bearing mice with PD901 resulted in stable disease. At the molecular level, PD901 efficiently inhibited ERK activation in K-Ras/NICD tumor cells, mainly leading to increased apoptosis. Altogether, our study demonstrates that K-Ras/NICD mice represent a novel and useful preclinical model to study K-Ras-driven iCCA development and the effectiveness of MEK inhibitors in counteracting this process. Our data support the usefulness of MEK inhibitors for the treatment of human iCCA.
PCDHGA9 acts as a tumor suppressor to induce tumor cell apoptosis and autophagy and inhibit the EMT process in human gastric cancer
Authors: Weng Junyong , Xiao Jingbo , Mi Yushuai , Fang Xu , Sun Yahuang , Li Shanbao , Qin Zhiwei , Li Xu , Liu Tingting , Zhao Senlin , Zhou Lisheng , Wen Yugang 
Published: January 2018

AbstractThe results of a cDNA array revealed that protocadherin gamma subfamily A, 9 (PCDHGA9) was significantly decreased in SGC-7901 gastric cancer (GC) cells compared with GES-1 normal gastric cells and was strongly associated with the Wnt/β-catenin and transforming growth factor-β (TGF-β)/Smad2/3 signaling pathway. As a member of the cadherin family, PCDHGA9 functions in both cell–cell adhesion and nuclear signaling. However, its role in tumorigenicity or metastasis has not been reported. In the present study, we found that PCDHGA9 was decreased in GC tissues compared with corresponding normal mucosae and its expression was correlated with the GC TNM stage, the UICC stage, differentiation, relapse, and metastasis (p < 0.01). Multivariate Cox analysis revealed that PCDHGA9 was an independent prognostic indicator for overall survival (OS) and disease-free survival (DFS) (p < 0.01). The effects of PCDHGA9 on GC tumor growth and metastasis were examined both in vivo and in vitro. PCDHGA9 knockdown promoted GC cell proliferation, migration, and invasion, whereas PCDHGA9 overexpression inhibited GC tumor growth and metastasis but induced apoptosis, autophagy, and G1 cell cycle arrest. Furthermore, PCDHGA9 suppressed epithelial–mesenchymal transition (EMT) induced by TGF-β, decreased the phosphorylation of Smad2/3, and inhibited the nuclear translocation of pSmad2/3. Our results suggest that PCDHGA9 might interact with β-catenin to prevent β-catenin from dissociating in the cytoplasm and translocating to the nucleus. Moreover, PCDHGA9 overexpression restrained cell proliferation and reduced the nuclear β-catenin, an indicator of Wnt/β-catenin pathway activation, suggesting that PCDHGA9 negatively regulates Wnt signaling. Together, these data indicate that PCDHGA9 acts as a tumor suppressor with anti-proliferative activity and anti-invasive ability, and the reduction of PCDHGA9 could serve as an independent prognostic biomarker in GC.
Sensitivity to lunar cycles prior to the 2007 eruption of Ruapehu volcano
Authors: Girona Társilo , Huber Christian , Caudron Corentin 
Published: January 2018

AbstractA long-standing question in Earth Science is the extent to which seismic and volcanic activity can be regulated by tidal stresses, a repeatable and predictable external excitation induced by the Moon-Sun gravitational force. Fortnightly tides, a ~14-day amplitude modulation of the daily tidal stresses that is associated to lunar cycles, have been suggested to affect volcano dynamics. However, previous studies found contradictory results and remain mostly inconclusive. Here we study how fortnightly tides have affected Ruapehu volcano (New Zealand) from 2004 to 2016 by analysing the rolling correlation between lunar cycles and seismic amplitude recorded close to the crater. The long-term (~1-year) correlation is found to increase significantly (up to confidence level of 5-sigma) during the ~3 months preceding the 2007 phreatic eruption of Ruapehu, thus revealing that the volcano is sensitive to fortnightly tides when it is prone to explode. We show through a mechanistic model that the real-time monitoring of seismic sensitivity to lunar cycles may help to detect the clogging of active volcanic vents, and thus to better forecast phreatic volcanic eruptions.
In vivo fluorescence bioimaging of ascorbic acid in mice: Development of an efficient probe consisting of phthalocyanine, TEMPO, and albumin
Authors: Yokoi Takanori , Otani Takayuki , Ishii Kazuyuki 
Published: January 2018

AbstractAfter a groundbreaking study demonstrated that a high dose of ascorbic acid selectively kills cancer cells, the compound has been tested in the clinic against various forms of cancers, with some success. However, in vivo tracing of intravenously injected ascorbic acid has not been achieved. Herein, we successfully imaged ascorbic acid intravenously injected into mice based on the discovery of a novel, highly sensitive, and appropriately selective fluorescent probe consisting of silicon phthalocyanine (SiPc) and two 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) radicals, i.e., R2c. The radicals in this R2c were encapsulated in dimeric bovine serum albumin, and the sensitivity was >100-fold higher than those of other R2c-based probes. Ascorbic acid intravenously injected into mice was efficiently transported to the liver, heart, lung, and cholecyst. The present results provide opportunities to advance the use of ascorbic acid as cancer therapy.
Repression of Akt3 gene transcription by the tumor suppressor RIZ1
Authors: Liu Qingnan , Qu Xiaotian , Xie Xiaolei , He Pei , Huang Shi 
Published: January 2018

AbstractRIZ1 has been studied as a tumor suppressor and may play a role in metabolic diseases related to the Western style diet, such as cancer and obesity. The Akt pathway is known to play a role in both cancer and obesity, and a link between Akt and RIZ1 has also been found. To better understand the role of RIZ1 in obesity and cancer, we investigated how RIZ1 regulates the expression of Akt3. We found that overexpression of RIZ1 in HEK293 cells reduced the expression of Akt3 protein. Luciferase reporter activity of Akt3 gene promoter was significantly reduced in cells co-transfected with RIZ1. Recombinant proteins of RIZ1 was able to bind the Akt3 promoter in vitro, and chromatin immunoprecipitation assay also demonstrated the ability of RIZ1 binding to the Akt3 promoter in vivo. Overexpression of RIZ1 increased H3K9 methylation on the Akt3 promoter. These results identify Akt3 as a target of RIZ1 regulation and expand our understanding of the Akt pathway in cancer and obesity.
Decoherence and control of a qubit in spin baths: an exact master equation study
Authors: Jing Jun , Wu Lian-Ao 
Published: January 2018

AbstractIn spin-based nanosystems for quantum information processing, electron spin qubits are subject to decoherence due to their interactions with nuclear spin environments. In this paper, we present an exact master equation for a central spin-1/2 system in time-dependent external fields and coupled to a spin-half bath in terms of hyperfine interaction. The master equation provides a unified description for free and controlled dynamics of the central spin and is formally independent of the details and size of spin environments. Different from the previous approaches, the master equation remains exact even in the presence of external control fields. Using the parameters for realistic nanosystems with nonzero nuclear spins, such as GaAs, we investigate the Overhauser’s effect on the decoherence dynamics of the central spin under different distributions of bath-spin frequencies and system-bath coupling strengths. Furthermore, we apply the leakage elimination operator, in a nonperturbative manner, to this system to suppress the decoherence induced by hyperfine interaction.
Central and cerebral haemodynamic changes after antihypertensive therapy in ischaemic stroke patients: A double-blind randomised trial
Authors: Choi Mun Hee , Lee Jin Soo , Lee Sung Eun , Lee Seong-Joon , Yoon Dukyong , Park Rae Woong , Hong Ji Man 
Published: January 2018

AbstractCentral and cerebral haemodynamic parameters can vary under similar brachial blood pressure (BP). We aimed to investigate the effects of antihypertensive agents on central and cerebral haemodynamic parameters in hypertensive patients with ischaemic stroke. The Fimasartan, Atenolol, and Valsartan On haemodynamic paRameters (FAVOR) study was conducted in a prospective, double-blinded manner. One hundred five patients were randomly administered atenolol, valsartan, or fimasartan during 12 weeks. We measured brachial, central, cerebral haemodynamic parameters and plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at baseline and after 12-week. Baseline haemodynamic parameters were balanced among the three groups. Even with similar brachial BP reduction, significantly lower central systolic BP (atenolol; 146.5 ± 18.8 vs. valsartan; 133.5 ± 20.7 vs. fimasartan; 133.6 ± 19.8 mmHg, p = 0.017) and augmentation index values (89.8 ± 13.2 vs. 80.6 ± 9.2 vs. 79.2 ± 11.6%; p = 0.001) were seen in the angiotensin receptor blockers (ARBs) groups. The pulsatility index on transcranial Doppler was significantly reduced in valsartan (p = 0.002) and fimasartan group (p = 0.008). Plasma NT-proBNP level was also significantly decreased in ARB groups, especially for the fimasartan group (37.8 ± 50.6 vs. 29.2 ± 36.9 vs.19.2 ± 27.8 pg/mL; p = 0.006). These findings suggest that short-term ARB administration would be favourable for ischaemic stroke patients with hypertension, permitting effective reduction of central pressure and dampening of cerebral pulsatility.
Inhibiting cancer cell hallmark features through nuclear export inhibition
Authors: Sun Qingxiang , Chen Xueqin , Zhou Qiao , Burstein Ezra , Yang Shengyong , Jia Da 
Published: January 2018

AbstractTreating cancer through inhibition of nuclear export is one of the best examples of basic research translation into clinical application. Nuclear export factor chromosomal region maintenance 1 (CRM1; Xpo1 and exportin-1) controls cellular localization and function of numerous proteins that are critical for the development of many cancer hallmarks. The diverse actions of CRM1 are likely to explain the broad ranging anti-cancer potency of CRM1 inhibitors observed in pre-clinical studies and/or clinical trials (phase I–III) on both advanced-stage solid and hematological tumors. In this review, we compare and contrast the mechanisms of action of different CRM1 inhibitors, and discuss the potential benefit of unexplored non-covalent CRM1 inhibitors. This emerging field has uncovered that nuclear export inhibition is well poised as an attractive target towards low-toxicity broad-spectrum potent anti-cancer therapy.
Cosmic ray and neutrino emission from gamma-ray bursts with a nuclear cascade
Authors: Biehl D. , Boncioli D. , Fedynitch A. , Winter W. 
Published: January 2018

Aim. We discuss neutrino and cosmic ray emission from gamma-ray bursts (GRBs) with the injection of nuclei, where we take into account that a nuclear cascade from photodisintegration can fully develop in the source. Our main objective is to test whether recent results from the IceCube and the Pierre Auger Observatory can be accommodated within the paradigm that GRBs are the sources of ultra-high-energy cosmic rays (UHECRs).
Methods. We simulate this scenario in a combined source-propagation model. While our key results are obtained using an internal shock model of the source, we discuss how the secondary emission from a GRB shell can be interpreted in terms of other astrophysical models.
Results. We demonstrate that the expected neutrino flux from GRBs weakly depends on the injection composition for the same injection spectra and luminosities, which implies that prompt neutrinos from GRBs can efficiently test the GRB-UHECR paradigm even if the UHECRs are nuclei. We show that the UHECR spectrum and composition, as measured by the Pierre Auger Observatory, can be self-consistently reproduced. In an attempt to describe the energy range including the ankle, we find tension with the IceCube bounds from the GRB stacking analyses. In an alternative scenario, where only the UHECRs beyond the ankle originate from GRBs, the requirement for a joint description of cosmic ray and neutrino observations favors lower luminosities, which does not correspond to the typical expectation from γ-ray observations.
Refraction in exoplanet atmospheres
Authors: Alp D. , Demory B.-O. 
Published: January 2018

Context.Refraction deflects photons that pass through atmospheres, which affects transit light curves. Refraction thus provides an avenue to probe physical properties of exoplanet atmospheres and to constrain the presence of clouds and hazes. In addition, an effective surface can be imposed by refraction, thereby limiting the pressure levels probed by transmission spectroscopy.Aims.The main objective of the paper is to model the effects of refraction on photometric light curves for realistic planets and to explore the dependencies on atmospheric physical parameters. We also explore under which circumstances transmission spectra are significantly affected by refraction. Finally, we search for refraction signatures in photometric residuals inKeplerdata.Methods.We use the model of Hui & Seager (2002, ApJ, 572, 540) to compute deflection angles and refraction transit light curves, allowing us to explore the parameter space of atmospheric properties. The observational search is performed by stacking large samples of transit light curves fromKepler.Results.We find that out-of-transit refraction shoulders are the most easily observable features, which can reach peak amplitudes of ~10 parts per million (ppm) for planets around Sun-like stars. More typical amplitudes are a few ppm or less for Jovians and at the sub-ppm level for super-Earths. In-transit, ingress, and egress refraction features are challenging to detect because of the short timescales and degeneracies with other transit model parameters. Interestingly, the signal-to-noise ratio of any refraction residuals for planets orbiting Sun-like hosts are expected to be similar for planets orbiting red dwarfs and ultra-cool stars. We also find that the maximum depth probed by transmission spectroscopy is not limited by refraction for weakly lensing planets, but that the incidence of refraction can vary significantly for strongly lensing planets. We find no signs of refraction features in the stackedKeplerlight curves, which is in agreement with our model predictions.
Chromospheric heating during flux emergence in the solar atmosphere
Authors: Leenaarts Jorrit , de la Cruz Rodríguez Jaime , Danilovic Sanja , Scharmer Göran , Carlsson Mats 
Published: January 2018

Context. The radiative losses in the solar chromosphere vary from 4 kW m−2 in the quiet Sun, to 20 kW m−2 in active regions. The mechanisms that transport non-thermal energy to and deposit it in the chromosphere are still not understood.
Aim. We aim to investigate the atmospheric structure and heating of the solar chromosphere in an emerging flux region.
Methods. We have used observations taken with the CHROMIS and CRISP instruments on the Swedish 1-m Solar Telescope in the Ca II K , Ca II 854.2 nm, Hα, and Fe I 630.1 nm and 630.2 nm lines. We analysed the various line profiles and in addition perform multi-line, multi-species, non-local thermodynamic equilibrium (non-LTE) inversions to estimate the spatial and temporal variation of the chromospheric structure.
Results. We investigate which spectral features of Ca II K contribute to the frequency-integrated Ca II K brightness, which we use as a tracer of chromospheric radiative losses. The majority of the radiative losses are not associated with localised high-Ca II K-brightness events, but instead with a more gentle, spatially extended, and persistent heating. The frequency-integrated Ca II K brightness correlates strongly with the total linear polarization in the Ca II 854.2 nm, while the Ca II K profile shapes indicate that the bulk of the radiative losses occur in the lower chromosphere. Non-LTE inversions indicate a transition from heating concentrated around photospheric magnetic elements below log τ500 = −3 to a more space-filling and time-persistent heating above log τ500 = −4. The inferred gas temperature at log τ500 = −3.8 correlates strongly with the total linear polarization in the Ca II 854.2 nm line, suggesting that that the heating rate correlates with the strength of the horizontal magnetic field in the low chromosphere.
Molecular characterization of latent GDF8 reveals mechanisms of activation
Authors: Walker Ryan G. , McCoy Jason C. , Czepnik Magdalena , Mills Melanie J. , Hagg Adam , Walton Kelly L. , Cotton Thomas R. , Hyvönen Marko , Lee Richard T. , Gregorevic Paul , Harrison Craig A. , Thompson Thomas B. 
Published: January 2018

Significance
GDF8 is a signaling protein that inhibits muscle mass. Inhibitors of GDF8 are highly sought as therapeutics for the treatment of muscle-wasting diseases. During synthesis, GDF8 is made as a precursor where the signaling segment is cleaved from the N-terminal prodomain, which remains associated and inhibits signaling. Activation involves an additional cleavage of the prodomain. We demonstrate GDF8 signaling could be gained through a conformational change where the prodomain remains associated with the signaling segment. Alteration of the prodomain can weaken the interactions causing GDF8 to signal, thus alleviating inhibition by the prodomain. This study illuminates how GDF8 transitions from an inhibited state to an active state—information that will help to understand the mechanism of GDF8 signaling.
Primer3_masker: integrating masking of template sequence with primer design software
Authors: Kõressaar Triinu , Lepamets Maarja , Kaplinski Lauris , Raime Kairi , Andreson Reidar , Remm Maido 
Published: January 2018

Abstract

Summary
Designing PCR primers for amplifying regions of eukaryotic genomes is a complicated task because the genomes contain a large number of repeat sequences and other regions unsuitable for amplification by PCR. We have developed a novel k-mer based masking method that uses a statistical model to detect and mask failure-prone regions on the DNA template prior to primer design. We implemented the software as a standalone software primer3_masker and integrated it into the primer design program Primer3.

Availability and implementation
The standalone version of primer3_masker is implemented in C. The source code is freely available at https://github.com/bioinfo-ut/primer3_masker/ (standalone version for Linux and macOS) and at https://github.com/primer3-org/primer3/ (integrated version). Primer3 web application that allows masking sequences of 196 animal and plant genomes is available at http://primer3.ut.ee/.

Supplementary information
Supplementary data are available at Bioinformatics online.
Where can a Trappist-1 planetary system be produced?
Authors: Haworth Thomas J , Facchini Stefano , Clarke Cathie J , Mohanty Subhanjoy 
Published: January 2018

AbstractWe study the evolution of protoplanetary discs that would have been precursors of a Trappist-1-like system under the action of accretion and external photoevaporation in different radiation environments. Dust grains swiftly grow above the critical size below which they are entrained in the photoevaporative wind, so although gas is continually depleted, dust is resilient to photoevaporation after only a short time. This means that the ratio of the mass in solids (dust plus planetary) to the mass in gas rises steadily over time. Dust is still stripped early on, and the initial disc mass required to produce the observed 4 M⊕ of Trappist-1 planets is high. For example, assuming a Fatuzzo & Adams distribution of UV fields, typical initial disc masses have to be &gt;30 per cent the stellar (which are still Toomre Q stable) for the majority of similar mass M dwarfs to be viable hosts of the Trappist-1 planets. Even in the case of the lowest UV environments observed, there is a strong loss of dust due to photoevaporation at early times from the weakly bound outer regions of the disc. This minimum level of dust loss is a factor of 2 higher than that which would be lost by accretion on to the star during 10 Myr of evolution. Consequently, even in these least irradiated environments, discs that are viable Trappist-1 precursors need to be initially massive (&gt;10 per cent of the stellar mass).
Chandra X-ray constraints on the candidate Ca-rich gap transient SN 2016hnk
Authors: Sell P H , Arur K , Maccarone T J , Kotak R , Knigge C , Sand D J , Valenti S 
Published: January 2018

Abstract
We present a Chandra observation of SN 2016hnk, a candidate Ca-rich gap transient. This observation was specifically designed to test whether or not this transient was the result of the tidal detonation of a white dwarf by an intermediate-mass black hole. Since we detect no X-ray emission 28 d after the discovery of the transient, as predicted from fall-back accretion, we rule out this model. Our upper limit of ∼10 M⊙ does not allow us to rule out a neutron star or stellar-mass black hole detonator due limits on the sensitivity of Chandra to soft X-rays and unconstrained variables tied to the structure of super-Eddington accretion discs. Together with other Chandra and multiwavelength observations, our analysis strongly argues against the intermediate-mass black hole tidal detonation scenario for Ca-rich gap transients more generally.