Salivary gland tumors (SGT) are a group of highly heterogeneous head and neck malignancies with widely varied clinical outcomes and no standard effective treatments. The CRTC1-MAML2 fusion oncogene, ...encoded by a recurring chromosomal translocation t(11;19)(q14-21;p12-13), is a frequent genetic alteration found in >50% of mucoepidermoid carcinomas (MEC), the most common malignant SGT. In this study, we aimed to define the role of the CRTC1-MAML2 oncogene in the maintenance of MEC tumor growth and to investigate critical downstream target genes and pathways for therapeutic targeting of MEC. By performing gene expression analyses and functional studies via RNA interference and pharmacological modulation, we determined the importance of the CRTC1-MAML2 fusion gene and its downstream AREG-EGFR signaling in human MEC cancer cell growth and survival in vitro and in vivo using human MEC xenograft models. We found that CRTC1-MAML2 fusion oncogene was required for the growth and survival of fusion-positive human MEC cancer cells in vitro and in vivo. The CRTC1-MAML2 oncoprotein induced the upregulation of the epidermal growth factor receptor (EGFR) ligand Amphiregulin (AREG) by co-activating the transcription factor CREB, and AREG subsequently activated EGFR signaling in an autocrine manner that promoted MEC cell growth and survival. Importantly, CRTC1-MAML2-positive MEC cells were highly sensitive to EGFR signaling inhibition. Therefore, our study revealed that aberrantly activated AREG-EGFR signaling is required for CRTC1-MAML2-positive MEC cell growth and survival, suggesting that EGFR-targeted therapies will benefit patients with advanced, unresectable CRTC1-MAML2-positive MEC.
The radial velocity (RV) is a basic physical quantity that can be determined through the Doppler shift of the spectrum of a star. The precision of the RV measurement depends on the resolution of the ...spectrum we used and the accuracy of wavelength calibration. In this work, radial velocities of the Large Sky Area Multi-Object Fibre Spectroscopic Telescope-II (LAMOST-II) medium-resolution (R ∼ 7500) spectra are measured for 1,594,956 spectra (each spectrum has two wavebands) through matching with templates. A set of RV standard stars are used to recalibrate the zero point of the measurement, and some reference sets with RVs derived from medium-/high-resolution observations are used to evaluate the accuracy of the measurement. By comparing with reference sets, the accuracy of our measurement can get 0.0277 km s−1 with respect to radial velocities of standard stars. The intrinsic precision is estimated with the multiple observations of single stars, which can be achieved to 1.36 km s−1, 1.08 km s−1, and 0.91 km s−1 for the spectra at signal-to-noise levels of 10, 20, and 50, respectively.
A new methodology based on tensor algebra that uses a higher order singular value decomposition to perform three-dimensional voxel reconstruction from a series of temporal images obtained using ...dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is proposed. Principal component analysis (PCA) is used to robustly extract the spatial and temporal image features and simultaneously de-noise the datasets. Tumour segmentation on enhanced scaled (ES) images performed using a fuzzy C-means (FCM) cluster algorithm is compared with that achieved using the proposed tensorial framework. The proposed algorithm explores the correlations between spatial and temporal features in the tumours. The multi-channel reconstruction enables improved breast tumour identification through enhanced de-noising and improved intensity consistency. The reconstructed tumours have clear and continuous boundaries; furthermore the reconstruction shows better voxel clustering in tumour regions of interest. A more homogenous intensity distribution is also observed, enabling improved image contrast between tumours and background, especially in places where fatty tissue is imaged. The fidelity of reconstruction is further evaluated on the basis of five new qualitative metrics. Results confirm the superiority of the tensorial approach. The proposed reconstruction metrics should also find future applications in the assessment of other reconstruction algorithms.
Background and purpose
Orolingual angioedema (OA) is an uncommon but potentially life‐threatening complication of treatment with recombinant tissue plasminogen activator (rt‐PA; alteplase) during ...acute ischaemic stroke. This study aimed to determine the incidence of rt‐PA‐related OA in an Asian stroke population and the risk of pre‐stroke anti‐hypertensive drug use for development of this complication.
Methods
A multi‐center stroke registry was used to identify the pre‐stroke medications of acute ischaemic stroke patients receiving intravenous rt‐PA from January 2002 to December 2013. The clinical manifestations of rt‐PA‐related OA were recorded and the incidence of this complication was determined. The risks of pre‐stroke use of different anti‐hypertensive agents for the occurrence of rt‐PA‐related OA were determined from this study and from a meta‐analysis.
Results
A total of 559 patients received intravenous rt‐PA over a 12‐year period. Five patients (two males) developed OA after rt‐PA administration. The incidence of OA amongst these patients was 0.89% (95% confidence interval 0.29%–2.09%), which was lower than that obtained by meta‐analysis (1.9%). Amongst pre‐stroke anti‐hypertensive medications, angiotensin‐converting enzyme (ACE) inhibitors were found in this study to have the highest relative risk for rt‐PA‐related OA (17.1; 95% confidence interval 3.0–96.9). Meta‐analysis also revealed that pre‐stroke use of ACE inhibitors was associated with a high relative risk of OA after intravenous rt‐PA (12.9; 95% confidence interval 4.5–37.0).
Conclusions
The incidence of rt‐PA‐related OA in the Asian population is lower than that in the Caucasian population. Pre‐stroke use of ACE inhibitors significantly increases the risk of this complication.
Six rumen-fistulated dairy cows were used in 2 trials to validate the technique for the collection of ruminal fluid by an oral stomach tube (OST). Trial 1 was conducted to compare the differences of ...ruminal fermentation parameters among rumen sites (cranial dorsal, cranial ventral, central, ventral, caudal dorsal, and caudal ventral). The ruminal fluid was collected once per day for 3 consecutive days through rumen cannula (RC). The samples were analyzed for pH, volatile fatty acids (VFA), ammonia N, sodium, potassium, calcium, chloride, and phosphorus concentrations. The ruminal fermentation parameters varied significantly among rumen sites. Compared with the central or ventral rumen, the cranial dorsal rumen had significantly higher pH, ammonia, and sodium concentrations and lower acetate, propionate, and butyrate concentrations, indicating that the sampling site may be one of the main factors contributing to the difference in ruminal fermentation parameters between the samples collected via the OST and RC. In trial 2, the fermentation parameters of ruminal fluid collected via OST at 2 insertion depths (180 or 200cm) were compared with those of ruminal fluid collected via RC (ventral sac). Ruminal fluid was collected once per week at 5 to 6h after morning feeding. When the OST was inserted to a depth of 180cm, the OST head was located in the cranial dorsal (atrium) of the rumen. The ruminal fluid collected via the OST had higher pH and sodium concentrations but lower VFA, potassium, calcium, and phosphorus concentrations than that collected via RC. However, when the OST was inserted to a depth of 200cm, the OST head could pass through the front rumen pillar and reach the central rumen for sampling. No differences were found in pH, VFA, ammonia N, and ion concentrations between the samples collected via the 2 sampling methods. These results indicated that the OST should be inserted to reach the central rumen to obtain representative rumen fluid samples.
This Letter reports a measurement of the flux and energy spectrum of electron antineutrinos from six 2.9 GWth nuclear reactors with six detectors deployed in two near (effective baselines 512 and 561 ...m) and one far (1579 m) underground experimental halls in the Daya Bay experiment. Using 217 days of data, 296 721 and 41 589 inverse β decay (IBD) candidates were detected in the near and far halls, respectively. The measured IBD yield is (1.55±0.04) ×10(-18) cm(2) GW(-1) day(-1) or (5.92±0.14) ×10(-43) cm(2) fission(-1). This flux measurement is consistent with previous short-baseline reactor antineutrino experiments and is 0.946±0.022 (0.991±0.023) relative to the flux predicted with the Huber-Mueller (ILL-Vogel) fissile antineutrino model. The measured IBD positron energy spectrum deviates from both spectral predictions by more than 2σ over the full energy range with a local significance of up to ∼4σ between 4-6 MeV. A reactor antineutrino spectrum of IBD reactions is extracted from the measured positron energy spectrum for model-independent predictions.
Since the commercialization of lithium secondary batteries in the early of 1990s, their development has been rapid. Nowadays, improving the preparation technology and electrochemical performance of ...their electrode materials is a major focus in research and development of the materials, power sources and chemistry. Sol–gel methods are a promising way to prepare electrode materials due to their evident advantages over traditional methods, for example, homogeneous mixing at the atomic or molecular level, lower synthesis temperature, shorter heating time, better crystallinity, uniform particle distribution and smaller particle size at nanometer level. In this paper, latest progress in the preparation of electrode materials by sol–gel methods is reviewed, including cathodic ones, e.g., lithium cobalt oxides, lithium nickel oxides, spinel and layered lithium manganese oxides, vanadium oxides and ferrous phosphates, and anodic ones, e.g., tin oxides and titanium oxides. Compared with those prepared by traditional solid-state reaction, the structure stability of the prepared electrode materials and the behavior of lithium intercalation and de-intercalation are much improved. As a result, the prepared products provide better electrochemical performance including reversible capacity, cycling behavior and rate capability. In addition, sol–gel methods can be used to prepare new kinds of electrode materials such as nanowires of LiCoO
2 and nanotubes of V
2O
5, which cannot be easily created by the traditional methods. Further development and application of sol–gel methods will bring about new and better electrode materials, meaning a great promotion to lithium secondary batteries.
The Human Connectome Project (HCP) seeks to map the structural and functional connections between network elements in the human brain. Magnetoencephalography (MEG) provides a temporally rich source ...of information on brain network dynamics and represents one source of functional connectivity data to be provided by the HCP. High quality MEG data will be collected from 50 twin pairs both in the resting state and during performance of motor, working memory and language tasks. These data will be available to the general community. Additionally, using the cortical parcellation scheme common to all imaging modalities, the HCP will provide processing pipelines for calculating connection matrices as a function of time and frequency. Together with structural and functional data generated using magnetic resonance imaging methods, these data represent a unique opportunity to investigate brain network connectivity in a large cohort of normal adult human subjects. The analysis pipeline software and the dynamic connectivity matrices that it generates will all be made freely available to the research community.
•Millisecond resolution dynamic connectivity will be provided to the HCP using MEG•MEG data will be collected at rest and during motor and cognitive task performance•Task paradigms are matched to tfMRI designs to provide cross-modal information•A number of connectivity metrics will be implemented at both sensor and source levels•Automated processing pipelines will be made publically available
Since the birth of the lithium ion battery in the early 1990s, its development has been very rapid and it has been widely applied as power source for a lot of light and high value electronics due to ...its significant advantages over traditional rechargeable battery systems. Recent research demonstrates the importance of surface structural features of electrode materials for their electrochemical performance, and in this paper the latest progress on this aspect is reviewed. Electrode materials are either anodic or cathodic ones. The former mainly include graphitic carbons, whose surfaces can be modified by mild oxidation, deposition of metals and metal oxides, coating with polymers and other kinds of carbons. Through these modifications, the surface structures of the graphitic carbon anodes are improved, and these improvements include: (1) smoothing the active edge surfaces by removing some reactive sites and/or defects on the graphite surface, (2) forming a dense oxide layer on the graphite surface, and (3) covering active edge structures on the graphite surface. Meanwhile, other accompanying changes occur: (1) production of nanochannels/micropores, (2) an increase in the electronic conductivity, (3) an inhibition of structural changes during cycling, (4) a reduction of the thickness of the SEI (solid-electrolyte-interface) layer, and (5) an increase in the number of host sites for lithium storage. As a result, the direct contact of graphite with the electrolyte solution is prevented, its surface reactivity with electrolytes, the decomposition of electrolytes, the co-intercalation of the solvated lithium ions and the charge-transfer resistance are decreased, and the movement of graphene sheets is inhibited. When the surfaces of cathode materials, mainly including LiCoO
2, LiNiO
2 and LiMn
2O
4, are coated with oxides such as MgO, Al
2O
3, ZnO, SnO
2, ZrO
2, Li
2O⋅2B
2O
3 glass and other electroactive oxides, the coating can prevent their direct contact with the electrolyte solution, suppress the phase transitions, improve the structural stability, and decrease the disorder of cations in the crystal sites. As a result, side reactions and the amount of the heat production during cycling are decreased. Simultaneously, other effects are observed such as: (1) suppression of the dissolution of Mn
2+, (2) higher conductivity, and (3) removal of HF from the electrolyte solution. Consequently, after the above-mentioned effective coating, marked improvements in the electrochemical performance of the electrode materials including the reversible capacity, the coulombic efficiency in the first cycle, the cycling behavior, and the high rate capability have been achieved. However, many surface science issues are still remaining open, e.g., mechanisms of these coatings and different actions of different coatings, and some further directions are suggested for the surface modification of the electrode materials.
To explore the characteristics of Helicobacter pylori resistance in China and the association between antibiotic resistance and several clinical factors.
H. pylori strains were collected from ...patients in 13 provinces or cities in China between 2010 and 2016. Demographic data including type of disease, geographic area, age, gender and isolation year were collected to analyse their association with antibiotic resistance. Antibiotic resistance was detected using the Etest test and the Kirby-Bauer disc diffusion method.
H. pylori were successfully cultured from 1117 patients. The prevalence of metronidazole, clarithromycin (CLA), azithromycin, levofloxacin (LEV), moxifloxacin, amoxicillin (AMO), tetracycline and rifampicin resistance was 78.2, 22.1, 23.3, 19.2, 17.2, 3.4, 1.9 and 1.5%, respectively. No resistance to furazolidone was observed. The resistance rates to LEV and moxifloxacin were higher in strains isolated from patients with gastritis compared to those with duodenal ulcer and among women. Compared to patients ≥40 years old, younger patients exhibited lower resistance rates to CLA, azithromycin, LEV and moxifloxacin. The resistance rates to CLA and AMO were higher in strains isolated more recently, and we also found that the prevalence of resistance to metronidazole, CLA, azithromycin and AMO were significantly different among different regions of China.
The resistance rates to metronidazole, CLA and LEV were high in China. Patient age, gender, disease and location were associated with the resistance of H. pylori to some antibiotics. Furazolidone, AMO and tetracycline are better choices for H. pylori treatment in China.
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