bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contradictory mRNA and protein misexpression of EEF1A1 in ductal breast carcinoma due to cell cycle regulation and cellular stress
Authors: Lin Cheng-Yu , Beattie Alexandra , Baradaran Behzad , Dray Eloise , Duijf Pascal H. G. 
Published: September 2018

AbstractEncoded by EEF1A1, the eukaryotic translation elongation factor eEF1α1 strongly promotes the heat shock response, which protects cancer cells from proteotoxic stress, following for instance oxidative stress, hypoxia or aneuploidy. Unexpectedly, therefore, we find that EEF1A1 mRNA levels are reduced in virtually all breast cancers, in particular in ductal carcinomas. Univariate and multivariate analyses indicate that EEF1A1 mRNA underexpression independently predicts poor patient prognosis for estrogen receptor-positive (ER+) cancers. EEF1A1 mRNA levels are lowest in the most invasive, lymph node-positive, advanced stage and postmenopausal tumors. In sharp contrast, immunohistochemistry on 100 ductal breast carcinomas revealed that at the protein level eEF1α1 is ubiquitously overexpressed, especially in ER+ , progesterone receptor-positive and lymph node-negative tumors. Explaining this paradox, we find that EEF1A1 mRNA levels in breast carcinomas are low due to EEF1A1 allelic copy number loss, found in 27% of tumors, and cell cycle-specific expression, because mRNA levels are high in G1 and low in proliferating cells. This also links estrogen-induced cell proliferation to clinical observations. In contrast, high eEF1α1 protein levels protect tumor cells from stress-induced cell death. These observations suggest that, by obviating EEF1A1 transcription, cancer cells can rapidly induce the heat shock response following proteotoxic stress, and survive.
Neural Signatures of the Configural Superiority Effect and Fundamental Emergent Features in Human Vision
Authors: Costa Thiago Leiros , Orsten-Hooge Kimberley , Gaudêncio Rêgo Gabriel , Wagemans Johan , R Pomerantz James , Sérgio Boggio Paulo 
Published: September 2018

AbstractThe concepts of grouping, emergence, and superadditivity (when a whole is qualitatively different from the sum of its parts) are critical in Gestalt psychology and essential to properly understand the information processing mechanisms underlying visual perception. However, very little is known about the neural processes behind these phenomena (particularly in terms of their generality vs. specificity and their time-course). Here, we used the configural superiority effect as a way to define “emergence” and “emergent features” operationally, employing an approach that can isolate different emergent features and compare them on a common scale. By assessing well-established event related potentials in a HD-EEG system, we found that the critical processes behind configural superiority and superadditive Gestalt phenomena are present in the window between 100 and 200 ms after stimulus onset and that these effects seem to be driven by specific attentional selection mechanisms. Also, some emergent features seem to be differentially processed in different brain hemispheres. These results shed new light on the issues of the generality vs. specificity of the neural correlates of different Gestalt principles, the hemispheric asymmetries in the processing of hierarchical image structure and the role of the N1 ERP component in reflecting feature selective mechanisms.
Kondo-like transport and magnetic field effect of charge carrier fluctuations in granular aluminum oxide thin films
Authors: Barone C. , Rotzinger H. , Mauro C. , Dorer D. , Münzberg J. , Ustinov A. V. , Pagano S. 
Published: September 2018

AbstractGranular aluminum oxide is an attractive material for superconducting quantum electronics. However, its low-temperature normal state transport properties are still not fully understood, while they could be related to the unconventional phenomenon of the superconductivity in this material. In order to obtain useful information on this aspect, a detailed study of charge carrier fluctuations has been performed in granular aluminum oxide films. The results of electric noise measurements indicate the presence of a Kondo-type spin-flip scattering mechanism for the conducting electrons in the normal state, at low temperatures. Moreover, the magnetic field dependence of the noise amplitude suggests that interface magnetic moments are the main source of fluctuations. The identification of the nature of fluctuation processes is a mandatory requirement for the improvement of quality and performance of quantum devices.
Computational measurement of tumor immune microenvironment in gastric adenocarcinomas
Authors: Chang Young Hwan , Heo You Jeong , Cho Junhun , Song Sang Yong , Lee Jeeyun , Kim Kyoung-Mee 
Published: September 2018

AbstractThe use of four groups of tumor immune microenvironments (TME) based on PD-L1 and tumor-infiltrating T lymphocytes (TIL) is a reliable biomarker for anti-PD-1/PD-L1 inhibitor therapy. We classified the TME in 241 gastric cancers which were subdivided according to 40 EBV+, 76 microsatellite instability-high (MSI-H), and 125 EBV-/microsatellite-stable (MSS) subtypes by quantitative image analysis (QIA) and correlated the results with mRNA expression levels. The mean PD-L1 ratio and CD8 ratio in EBV+, MSI-H, and EBV−/MSS GCs were significantly different (P < 0.006). The PD-L1 ratio and CD8 ratio obtained by QIA correlated well with the RNA levels of PD-L1 (r = 0.63) and CD8 (r = 0.67), respectively. The TME were type I (PD-L1H/CD8H) in 45, type II (PD-L1L/CD8L) in 106, type III (PD-L1H/CD8L) in 8, and type IV (PD-L1L/CD8H) in 82 cases. The type I TME was significantly associated with high TIL (P = 3.0E-11) and EBV+ status (P = 8.55E-08). In conclusion, QIA results correlated well with the mRNA expression levels and classified TME of gastric cancers.
Attenuation of melanogenesis by Nymphaea nouchali (Burm. f) flower extract through the regulation of cAMP/CREB/MAPKs/MITF and proteasomal degradation of tyrosinase
Authors: Alam Md Badrul , Ahmed Arif , Motin Md Abdul , Kim Sunghwan , Lee Sang-Han 
Published: September 2018

AbstractMedicinal plants have been used to treat diseases from time immemorial. We aimed to examine the efficacy of the ethyl acetate fraction of Nymphaea nouchali flower extract (NNFE) against melanogenesis process, and the underlying mechanisms in vitro and in vivo. Paper spray ionisation mass spectroscopy and (+) mode electrospray ionisation revealed the presence of seven flavonoids, two spermidine alkaloids, 3,4,8,9,10-pentahydroxy-dibenzo[b,d]pyran-6-one, and shoyuflavone C in NNFE. NNFE (100 µg/mL) significantly inhibited the monophenolase and diphenolase activities of mushroom tyrosinase at 94.90 ± 0.003% and 93.034 ± 0.003%, respectively. NNFE significantly suppressed cellular tyrosinase activity and melanin synthesis in vitro in melan-a cells and in vivo in HRM2 hairless mice. Furthermore, NNFE inhibited tyrosinase (TYR), tyrosinase-related protein (TYRP)-1, TYRP-2, and microphthalmia-associated transcription factor (MITF) expression, thereby blocking melanin synthesis. In particular, NNFE suppressed cAMP production with subsequent downregulation of CREB phosphorylation. Additionally, it stimulated MAP kinase phosphorylation (p38, JNK, and ERK1/2) and the proteasomal debasement pathway, leading to degradation of tyrosinase and MITF and the suppression of melanin production. Moreover, selective inhibitors of ERK1/2, JNK, and p38 attenuated NNFE inhibitory effects on melanogenesis, and MG-132 (a proteasome inhibitor) prevented the NNFE-induced decline in tyrosinase protein levels. In conclusion, these findings indicate that NNFE is a potential therapy for hyperpigmentation.
Serotonin receptor type 1B constitutes a therapeutic target for MDS and CMML
Authors: Banús-Mulet Antònia , Etxabe Amaia , Cornet-Masana Josep Maria , Torrente Miguel Ángel , Lara-Castillo María Carmen , Palomo Laura , Nomdedeu Meritxell , Díaz-Beyá Marina , Solé Francesc , Nomdedeu Benet , Esteve Jordi , Risueño Ruth M. 
Published: September 2018

AbstractMyelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are chronic myeloid clonal neoplasms. To date, the only potentially curative therapy for these disorders remains allogeneic hematopoietic progenitor cell transplantation (HCT), although patient eligibility is limited due to high morbimortality associated with this procedure coupled with advanced age of most patients. Dopamine receptors (DRs) and serotonin receptors type 1 (HTR1s) were identified as cancer stem cell therapeutic targets in acute myeloid leukemia. Given their close pathophysiologic relationship, expression of HTR1s and DRs was interrogated in MDS and CMML. Both receptors were differentially expressed in patient samples compared to healthy donors. Treatment with HTR1B antagonists reduced cell viability. HTR1 antagonists showed a synergistic cytotoxic effect with currently approved hypomethylating agents in AML cells. Our results suggest that HTR1B constitutes a novel therapeutic target for MDS and CMML. Due to its druggability, the clinical development of new regimens based on this target is promising.
Extra Strain Rates in an unsteady spilling breaking wave
Authors: Lucarelli Alessia , Lugni Claudio , Falchi Massimo , Felli Mario , Brocchini Maurizio 
Published: September 2018

AbstractWe analyze the extra strain rates that characterize a curved, thin mixing layer induced at an unsteady spilling breaker. We focus on the flow curvature, which induces some extra rates of strain that should be accounted for in algebraic-type turbulence closures. The comparison between the analytical formulation proposed by Brocchini and co-workers for a single-phase turbulent thin layer of fluid and the data, obtained from a Particle Image Velocimetry (PIV) dedicated experimental program, reveals that the order of magnitude of the extra rates of strain induced by the streamline curvature, is comparable with that of the simple shear. This differs from what observed for the geometric curvature terms and from what occurs at hydraulic jumps, typically used to model steady breakers.
The population genomics of yellowfin tuna (Thunnus albacares) at global geographic scale challenges current stock delineation
Authors: Pecoraro Carlo , Babbucci Massimiliano , Franch Rafaella , Rico Ciro , Papetti Chiara , Chassot Emmanuel , Bodin Nathalie , Cariani Alessia , Bargelloni Luca , Tinti Fausto 
Published: September 2018

AbstractYellowfin tuna, Thunnus albacares, is one of the most important seafood commodities in the world. Despite its great biological and economic importance, conflicting evidence arises from classical genetic and tagging studies concerning the yellowfin tuna population structure at local and global oceanic scales. Access to more powerful and cost effective genetic tools would represent the first step towards resolving the population structure of yellowfin tuna across its distribution range. Using a panel of 939 neutral Single Nucleotide Polymorphisms (SNPs), and the most comprehensive data set of yellowfin samples available so far, we found genetic differentiation among the Atlantic, Indian and Pacific oceans. The genetic stock structure analysis carried out with 33 outlier SNPs, putatively under selection, identified discrete populations within the Pacific Ocean and, for the first time, also within the Atlantic Ocean. Stock assessment approaches that consider genetic differences at neutral and adaptive genomic loci should be routinely implemented to check the status of the yellowfin tuna, prevent illegal trade, and develop more sustainable management measures.
Enhanced Sensitivity of Patient-Derived Pediatric High-Grade Brain Tumor Xenografts to Oncolytic HSV-1 Virotherapy Correlates with Nectin-1 Expression
Authors: Friedman Gregory K. , Bernstock Joshua D. , Chen Dongquan , Nan Li , Moore Blake P. , Kelly Virginia M. , Youngblood Samantha L. , Langford Catherine P. , Han Xiaosi , Ring Eric K. , Beierle Elizabeth A. , Gillespie G. Yancey , Markert James M. 
Published: September 2018

AbstractPediatric high-grade brain tumors and adult glioblastoma are associated with significant morbidity and mortality. Oncolytic herpes simplex virus-1 (oHSV) is a promising approach to target brain tumors; oHSV G207 and M032 (encodes human interleukin-12) are currently in phase I clinical trials in children with malignant supratentorial brain tumors and adults with glioblastoma, respectively. We sought to compare the sensitivity of patient-derived pediatric malignant brain tumor and adult glioblastoma xenografts to these clinically-relevant oHSV. In so doing we found that pediatric brain tumors were more sensitive to the viruses and expressed significantly more nectin-1 (CD111) than adult glioblastoma. Pediatric embryonal and glial tumors were 74-fold and 14-fold more sensitive to M002 and 16-fold and 6-fold more sensitive to G207 than adult glioblastoma, respectively. Of note, pediatric embryonal tumors were more sensitive than glial tumors. Differences in sensitivity may be due in part to nectin-1 expression, which predicted responses to the viruses. Treatment with oHSV resulted in prolonged survival in both pediatric and adult intracranial patient-dervied tumor xenograft models. Our results suggest that pediatric brain tumors are ideal targets for oHSV and that brain tumor expression of nectin-1 may be a useful biomarker to predict patient response to oHSV.
Multidirectional digital scanned light-sheet microscopy enables uniform fluorescence excitation and contrast-enhanced imaging
Authors: Glaser Adam K. , Chen Ye , Yin Chengbo , Wei Linpeng , Barner Lindsey A. , Reder Nicholas P. , Liu Jonathan T. C. 
Published: September 2018

AbstractLight-sheet fluorescence microscopy (LSFM) has emerged as a powerful method for rapid and optically efficient 3D microscopy. Initial LSFM designs utilized a static sheet of light, termed selective plane illumination microscopy (SPIM), which exhibited shadowing artifacts and deteriorated contrast due to light scattering. These issues have been addressed, in part, by multidirectional selective plane illumination microscopy (mSPIM), in which rotation of the light sheet is used to mitigate shadowing artifacts, and digital scanned light-sheet microscopy (DSLM), in which confocal line detection is used to reject scattered light. Here we present a simple and passive multidirectional digital scanned light-sheet microscopy (mDSLM) architecture that combines the benefits of mSPIM and DSLM. By utilizing an elliptical Gaussian beam with increased angular diversity in the imaging plane, mDSLM provides mitigation of shadowing artifacts and contrast-enhanced imaging of fluorescently labeled samples.
Tailoring of low grade coal to fluorescent nanocarbon structures and their potential as a glucose sensor
Authors: B Manoj , Raj Ashlin M. , Thomas George C. 
Published: September 2018

AbstractLignite is an abundantly utilized feedstock for the facile synthesis of fluorescent carbon dots and carbon nanomaterials. Its value is appreciated as an energy source for combustion for long time. Herein we report a novel top-down strategy to synthesis lignite based fluorescent nano carbon structures by combined acidic oxidation and chemical reflux. The nanocarbon crystallites in lignite are converted to oxygenated nano carbon dots and graphene sheets. They exhibited stable fluorescence property in the visible region depending on their size, functionalities and defects which were highly stable in all the pH conditions. These nanocarbon structures are an effective probe for fluorescent sensing of label-free and selective detection of glucose ions with detection limit as low as 0.125 mM, promising real-world sensor applications. These findings establish a scalable method for the production of fluorescent carbon based glucose sensor from lignite.
Novel Clade C-I Clostridium difficile strains escape diagnostic tests, differ in pathogenicity potential and carry toxins on extrachromosomal elements
Authors: Ramírez-Vargas Gabriel , López-Ureña Diana , Badilla Adriana , Orozco-Aguilar Josué , Murillo Tatiana , Rojas Priscilla , Riedel Thomas , Overmann Jörg , González Gabriel , Chaves-Olarte Esteban , Quesada-Gómez Carlos , Rodríguez César 
Published: September 2018

AbstractThe population structure of Clostridium difficile currently comprises eight major genomic clades. For the highly divergent C-I clade, only two toxigenic strains have been reported, which lack the tcdA and tcdC genes and carry a complete locus for the binary toxin (CDT) next to an atypical TcdB monotoxin pathogenicity locus (PaLoc). As part of a routine surveillance of C. difficile in stool samples from diarrheic human patients, we discovered three isolates that consistently gave negative results in a PCR-based screening for tcdC. Through phenotypic assays, whole-genome sequencing, experiments in cell cultures, and infection biomodels we show that these three isolates (i) escape common laboratory diagnostic procedures, (ii) represent new ribotypes, PFGE-types, and sequence types within the Clade C-I, (iii) carry chromosomal or plasmidal TcdBs that induce classical or variant cytopathic effects (CPE), and (iv) cause different levels of cytotoxicity and hamster mortality rates. These results show that new strains of C. difficile can be detected by more refined techniques and raise questions on the origin, evolution, and distribution of the toxin loci of C. difficile and the mechanisms by which this emerging pathogen causes disease.
The eICU Collaborative Research Database, a freely available multi-center database for critical care research
Authors: Pollard Tom J. , Johnson Alistair E. W. , Raffa Jesse D. , Celi Leo A. , Mark Roger G. , Badawi Omar 
Published: September 2018

AbstractCritical care patients are monitored closely through the course of their illness. As a result of this monitoring, large amounts of data are routinely collected for these patients. Philips Healthcare has developed a telehealth system, the eICU Program, which leverages these data to support management of critically ill patients. Here we describe the eICU Collaborative Research Database, a multi-center intensive care unit (ICU)database with high granularity data for over 200,000 admissions to ICUs monitored by eICU Programs across the United States. The database is deidentified, and includes vital sign measurements, care plan documentation, severity of illness measures, diagnosis information, treatment information, and more. Data are publicly available after registration, including completion of a training course in research with human subjects and signing of a data use agreement mandating responsible handling of the data and adhering to the principle of collaborative research. The freely available nature of the data will support a number of applications including the development of machine learning algorithms, decision support tools, and clinical research.
The Mount Sinai cohort of large-scale genomic, transcriptomic and proteomic data in Alzheimer's disease
Authors: Wang Minghui , Beckmann Noam D. , Roussos Panos , Wang Erming , Zhou Xianxiao , Wang Qian , Ming Chen , Neff Ryan , Ma Weiping , Fullard John F. , Hauberg Mads E. , Bendl Jaroslav , Peters Mette A. , Logsdon Ben , Wang Pei , Mahajan Milind , Mangravite Lara M. , Dammer Eric B. , Duong Duc M. , Lah James J. , Seyfried Nicholas T. , Levey Allan I. , Buxbaum Joseph D. , Ehrlich Michelle , Gandy Sam , Katsel Pavel , Haroutunian Vahram , Schadt Eric , Zhang Bin 
Published: September 2018

AbstractAlzheimer’s disease (AD) affects half the US population over the age of 85 and is universally fatal following an average course of 10 years of progressive cognitive disability. Genetic and genome-wide association studies (GWAS) have identified about 33 risk factor genes for common, late-onset AD (LOAD), but these risk loci fail to account for the majority of affected cases and can neither provide clinically meaningful prediction of development of AD nor offer actionable mechanisms. This cohort study generated large-scale matched multi-Omics data in AD and control brains for exploring novel molecular underpinnings of AD. Specifically, we generated whole genome sequencing, whole exome sequencing, transcriptome sequencing and proteome profiling data from multiple regions of 364 postmortem control, mild cognitive impaired (MCI) and AD brains with rich clinical and pathophysiological data. All the data went through rigorous quality control. Both the raw and processed data are publicly available through the Synapse software platform.
69–78 GHz ESD‐protected SiGe BiCMOS PA with 30 dB automatic level control for mm‐wave 5G applications
Authors: Wang Keping , Qiu Lei , Wang Zhigong 
Published: September 2018

A silicon–germanium BiCMOS E‐band power amplifier (PA) for millimetre‐waves for Gbit/s data rates in fifth‐generation cellular wireless backhaul networks is presented. A 69–78 GHz transmission‐line PA is demonstrated by integrating an electrostatic discharge (ESD) and a power detector together. To save this area, a transmission‐line‐based power coupler is shared by the ESD and the power detector. The ESD achieves an insertion loss of <1.5 dB in the frequency range of 17–100 GHz. The linear‐in‐dB output characteristic of the power detector is achieved by an exponential voltage convertor. The designed PA measured a maximum gain of 18.6 dB with 3 dB bandwidth of 68.9–78.7 GHz. The input return loss is better than −10 dB from 50 to 81 GHz. It delivers 10 dBm saturated output power at 73.4 GHz. Transmission line pulsing (TLP) measurement result shows that the voltage is clamped below 6 V even under 10 A ESD current.
Optimal velocity prediction for fuel economy improvement of connected vehicles
Authors: Barik Biswajit , Krishna Bhat Pradeep , Oncken Joseph , Chen Bo , Orlando Joshua , Robinette Darrell 
Published: September 2018

With the advancement of vehicle‐to‐vehicle and vehicle‐to‐infrastructure technologies, more and more real‐time information regarding traffic and transportation system will be available to vehicles. This paper presents the development of a novel algorithm that uses available velocity bounds and powertrain information to generate an optimal velocity trajectory over a prediction horizon. When utilised by a vehicle, this optimal velocity trajectory reduces fuel consumption. The objective of this optimisation problem is to reduce dynamic losses, required tractive force, and completing trip distance with a given travel time. Sequential quadratic programming method is employed for this nonlinearly constrained optimisation problem. When applied to a GM Volt‐2, the generated velocity trajectory saves fuel compared to a real‐world drive cycle. The simulation results confirm the fuel consumption reduction with the rule‐based mode selection and the energy management strategy of a GM Volt 2 model in Autonomie.