bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural stem cells deriving from chick embryonic hindbrain recapitulate hindbrain development in culture
Authors: Peretz Yuval , Kohl Ayelet , Slutsky Natalia , Komlos Marko , Varshavsky Stas , Sela-Donenfeld Dalit
Published: September 2018

Neural stem cells (NSCs) are self-renewing multipotent cells that line the neural-tube and generate all the nervous system. Understanding NSC biology is fundamental for neurodevelopmental research and therapy. Many studies emphasized the need to culture NSCs, which are typically purified from mammalian embryonic/adult brains. These sources are somewhat limited in terms of quantity, availability and animal ethical guidelines. Therefore, new sources are needed. The chick is a powerful system for experimental embryology which contributed enormously to neurodevelopmental concepts. Its accessibility, genetic/molecular manipulations, and homology to other vertebrates, makes it valuable for developmental biology research. Recently, we identified a population of NSCs in the chick hindbrain. It resides in rhombomere-boundaries, expresses Sox2 and generates progenitors and neurons. Here, we investigated whether these cells can recapitulate hindbrain development in culture. By developing approaches to propagate and image cells, manipulate their growth-conditions and separate them into subpopulations, we demonstrate the ordered formation of multipotent and self-renewing neurospheres that maintain regional identity and display differential stem/differentiation/proliferation properties. Live imaging revealed new cellular dynamics in the culture. Collectively, these NSC cultures reproduce major aspects of hindbrain development in-vitro, proposing the chick as a model for culturing hindbrain-NSCs that can be directly applied to other neural-tube domains and species.
A new approach to obtain pure and active proteins from Lactococcus lactis protein aggregates
Authors: Gifre-Renom L. , Cano-Garrido O. , Fàbregas F. , Roca-Pinilla R. , Seras-Franzoso J. , Ferrer-Miralles N. , Villaverde A. , Bach À. , Devant M. , Arís A. , Garcia-Fruitós E.
Published: September 2018

The production of pure and soluble proteins is a complex, protein-dependent and time-consuming process, in particular for those prone-to-aggregate and/or difficult-to-purify. Although Escherichia coli is widely used for protein production, recombinant products must be co-purified through costly processes to remove lipopolysaccharide (LPS) and minimize adverse effects in the target organism. Interestingly, Lactococcus lactis, which does not contain LPS, could be a promising alternative for the production of relevant proteins. However, to date, there is no universal strategy to produce and purify any recombinant protein, being still a protein-specific process. In this context and considering that L. lactis is also able to form functional protein aggregates under overproduction conditions, we explored the use of these aggregates as an alternative source of soluble proteins. In this study, we developed a widely applicable and economically affordable protocol to extract functional proteins from these nanoclusters. For that, two model proteins were used: mammary serum amyloid A3 (M-SAA3) and metalloproteinase 9 (MMP-9), a difficult-to-purify and a prone-to-aggregate protein, respectively. The results show that it is possible to obtain highly pure, soluble, LPS-free and active recombinant proteins from L. lactis aggregates through a cost-effective and simple protocol with special relevance for difficult-to-purify or highly aggregated proteins.
The 40Ar/39Ar dating of quartz: new insights into the metallogenic chronology of the Jinchang gold deposit and its geological significance
Authors: Shi Kaituo , Wang Keyong , Yu Haijun , Wang Zhigao , Ma Xueli , Bai Xiujuan , Wang Rui
Published: September 2018

The Jinchang gold deposit has been extensively studied, but precise dates for its formation are debated. Native gold mainly occurs as inclusions within pyrite and quartz. In this study, we analysed quartz crystals coeval with gold precipitation from two different types of mineralization using the ArgusVI multi-collector noble gas mass spectrometer by the stepwise crushing technique to resolve the timing and genesis of gold mineralization. 40Ar/39Ar dating of quartz samples (J12Q) from breccia ore yields a plateau age of 109.87 ± 0.86 Ma, and an inverse isochron age of 109.87 ± 0.88 Ma. Quartz samples (J18Q) from vein ore yields a slightly younger plateau age of 107.76 ± 0.85 Ma, with an inverse isochron age of 107.76 ± 0.92 Ma. These dates place the ore-forming age of the Jinchang gold deposit at 107~110 Ma, much younger than previously published radiometric ages, suggesting the gold mineralization is spatio-temporally associated with the granite porphyry. The formation of the Jinchang gold deposit is consistent with the regional late Mesozoic porphyry-epithermal gold mineralization event in the Yanbian-Dongning area. Finally, our study shows that 40Ar/39Ar of quartz can be used as a powerful tool to date the formation ages of hydrothermal ore deposits.
Comparative Investigations of Social Context-Dependent Dominance in Captive Chimpanzees (Pan troglodytes) and Wild Tibetan Macaques (Macaca thibetana)
Authors: Funkhouser Jake A. , Mayhew Jessica A. , Sheeran Lori K. , Mulcahy John B. , Li Jin-Hua
Published: September 2018

Theoretical definitions of dominance, how dominance is structured and organized in nature, and how dominance is measured have varied as investigators seek to classify and organize social systems in gregarious species. Given the variability in behavioral measures and statistical methods used to derive dominance rankings, we conducted a comparative analysis of dominance using existing statistical techniques to analyze dominance ranks, social context-dependent dominance structures, the reliability of statistical analyses, and rank predictability of dominance structures on other social behaviors. We investigated these topics using behavioral data from captive chimpanzees (Pan troglodytes) and wild Tibetan macaques (Macaca thibetana). We used a combination of all-occurrence, focal-animal, and instantaneous scan sampling to collect social, agonistic, and associative data from both species. We analyzed our data to derive dominance ranks, test rank reliability, and assess cross-context predictability using various statistical analyses. Our results indicate context-dependent dominance and individual social roles in the captive chimpanzee group, one broadly defined dominance structure in the Tibetan macaque group, and high within-context analysis reliability but little cross-context predictability. Overall, we suggest this approach is preferable over investigations of dominance where only a few behavioral metrics and statistical analyses are utilized with little consideration of rank reliability or cross-context predictability.
Personality Profiles Are Associated with Functional Brain Networks Related to Cognition and Emotion
Authors: Mulders Peter , Llera Alberto , Tendolkar Indira , van Eijndhoven Philip , Beckmann Christian
Published: September 2018

Personality factors as defined by the “five-factor model” are some of the most investigated characteristics that underlie various types of complex behavior. These are, however, often investigated as isolated traits that are conceptually independent, yet empirically are typically strongly related to each other. We apply Independent Component Analysis to these personality factors as measured by the NEO-FFI in 471 healthy subjects from the Human Connectome Project to investigate independent personality profiles that incorporate all five original factors. Subsequently we examine how these profiles are related to patterns of resting-state brain activity in specific networks-of-interest related to cognition and emotion. We find that a personality profile of contrasting openness and agreeableness is associated with engagement of a subcortical-medial prefrontal network and the dorsolateral prefrontal cortex. Likewise, a profile of contrasting extraversion and conscientiousness is associated with activity in the precuneus. This study shows a novel approach to investigating personality and how it is related to patterns of activity in the resting brain.
MicroRNAs delivery into human cells grown on 3D-printed PLA scaffolds coated with a novel fluorescent PAMAM dendrimer for biomedical applications
Authors: Paolini Alessandro , Leoni Luca , Giannicchi Ilaria , Abbaszadeh Zeinab , D’Oria Valentina , Mura Francesco , Dalla Cort Antonella , Masotti Andrea
Published: September 2018

Many advanced synthetic, natural, degradable or non-degradable materials have been employed to create scaffolds for cell culture for biomedical or tissue engineering applications. One of the most versatile material is poly-lactide (PLA), commonly used as 3D printing filament. Manufacturing of multifunctional scaffolds with improved cell growth proliferation and able to deliver oligonucleotides represents an innovative strategy for controlled and localized gene modulation that hold great promise and could increase the number of applications in biomedicine. Here we report for the first time the synthesis of a novel Rhodamine derivative of a poly-amidoamine dendrimer (G = 5) able to transfect cells and to be monitored by confocal microscopy that we also employed to coat a 3D-printed PLA scaffold. The coating do not modify the oligonucleotide binding ability, toxicity or transfection properties of the scaffold that is able to increase cell proliferation and deliver miRNA mimics (i.e., pre-mir-503) into human cells. Although further experiments are required to optimize the dendrimer/miRNA ratio and improve transfection efficiency, we demonstrated the effectiveness of this promising and innovative 3D-printed transfection system to transfer miRNAs into human cells for future biomedical applications.
Effective Radiative Properties of Tilted Metallic Nanorod Arrays Considering Polarization Coupling
Authors: Lattery Dustin M. , Kim Mingeon , Choi Jongin , Lee Bong Jae , Wang Xiaojia
Published: September 2018

With the advent of new nanomanufacturing techniques has come the rise of the field of nanophotonics and an increased need to determine optical properties of novel structures. Commercial software packages are able to estimate the behavior, but require large resources and heavy computational time. By combining coordinate transforms and Effective Medium Theory (EMT), an effective relative permittivity tensor is defined and further exploited to calculate the polarization-coupled Fresnel coefficients through Maxwell’s equations. A uniaxial simplification is made to show the case of tilted nanorod arrays. To demonstrate the flexibility of this system, the interfacial reflectance has been calculated for both s- and p-polarizations as well as the coupled case with the volume filling fractions of f = 0.10 and 0.30 for silver (Ag) and titanium (Ti) nanorods, and a scenario of a Ag nanorod array with polymethyl methacrylate (PMMA) as the surrounding medium. The exact results computed by the finite-difference time-domain method justify the validity of EMT with polarization coupling taken into account. The effects of incidence angle and azimuthal angle on reflectance are also discussed. The relatively simple nature of this approach allows for fast estimations of the optical properties of various nanostructures.
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

Encoded 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

The 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

Granular 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

The 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

Medicinal 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

Myelodysplastic 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

We 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

Yellowfin 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

Pediatric 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

Light-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

Lignite 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

The 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

Critical 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

Alzheimer’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.
In situ analytical characterization and chemical imaging of tablet coatings using laser induced breakdown spectroscopy (LIBS)
Authors: Zou Lanfang , Kassim Brittany , Smith Joseph P. , Ormes James D. , Liu Yong , Tu Qiang , Bu Xiaodong
Published: September 2018

The first report that describes direct visualization and quantitative evaluation of the coating uniformity using the LIBS-based 3D chemical imaging technique.
Handheld battery-operated sample preparation device for qPCR nucleic acid detections using simple contactless pouring
Authors: Mulberry Geoffrey , Vuillier Alissa , Vaidya Manjusha , Sugaya Kiminobu , Kim Brian N.
Published: September 2018

Sample preparation is an essential process that precedes nucleic acid detections which use quantitative polymerase chain reaction (qPCR).
An electrochemical sensor based on Fe3O4@PANI nanocomposites for sensitive detection of Pb2+ and Cd2+
Authors: Kong Ying , Wu Tingting , Wu Di , Zhang Yong , Wang Yaoguang , Du Bin , Wei Qin
Published: September 2018

In this study, an easy-to-use electrochemical sensor was developed for the quantitative detection of lead ions (Pb2+) and cadmium ions (Cd2+).
Unimicellar hyperstars as multi-antigen cancer nanovaccines displaying clustered epitopes of immunostimulating peptides
Authors: Kakwere Hamilton , Ingham Elizabeth S. , Allen Riley , Mahakian Lisa M. , Tam Sarah M. , Zhang Hua , Silvestrini Matthew T. , Lewis Jamal S. , Ferrara Katherine W.
Published: September 2018

Multi-antigen bearing biodegradable unimicellar nanovaccines based on hyperstar macromolecular chimeras for cancer therapy.
Diastereoselective synthesis of 1,3-disubstituted isoindolines and sultams via bronsted acid catalysis
Authors: Tao Ye , Gilbertson Scott R.
Published: September 2018

Isoindolines and sultams formed under mild conditions.
Molecular hydrides of divalent ytterbium supported by a macrocyclic ligand: synthesis, structure and olefin hydrofunctionalization catalysis
Authors: Schuhknecht Danny , Truong Khai-Nghi , Spaniol Thomas P. , Maron Laurent , Okuda Jun
Published: September 2018

Cationic ytterbium hydrides [(Me4TACD)2Yb2H(2+n)](2−n)+ (n = 0, 1) catalyzed the H2/D2 isotope exchange as well as hydrogenation and hydrosilylation of 1-hexene.
C–H functionalisation of aldehydes using light generated, non-stabilised diazo compounds in flow
Authors: Dingwall Paul , Greb Andreas , Crespin Lorène N. S. , Labes Ricardo , Musio Biagia , Poh Jian-Siang , Pasau Patrick , Blakemore David C. , Ley Steven V.
Published: September 2018

Here we explore further the use of oxadiazolines, non-stabilised diazo precursors which are bench stable, in direct, non-catalytic, aldehyde C–H functionalisation reactions under UV photolysis in flow and free from additives.
Towards rational design of RAD51-targeting prodrugs: platinumIV–artesunate conjugates with enhanced cytotoxicity against BRCA-proficient ovarian and breast cancer cells
Authors: Zhang Shuren , Yuan Hao , Guo Yan , Wang Kun , Wang Xiaoyong , Guo Zijian
Published: September 2018

PtIV–Artesunate prodrugs target the homologous recombination protein RAD51 and exhibit higher cytotoxicity against BRCA-proficient ovarian and breast cancer cells than cisplatin.
ESIPT-based fluorescence probe for the rapid detection of peroxynitrite ‘AND’ biological thiols
Authors: Wu Luling , Han Hai-Hao , Liu Liyuan , Gardiner Jordan E. , Sedgwick Adam C. , Huang Chusen , Bull Steven D. , He Xiao-Peng , James Tony D.
Published: September 2018

An ESIPT-based ‘AND’ logic fluorescence probe (GSH-ABAH) was developed for the simultaneous detection of ONOO−‘AND’ biological thiols.
Bayesian analysis of single-particle tracking data using the nested-sampling algorithm: maximum-likelihood model selection applied to stochastic-diffusivity data
Authors: Thapa Samudrajit , Lomholt Michael A. , Krog Jens , Cherstvy Andrey G. , Metzler Ralf
Published: September 2018

We employ Bayesian statistics using the nested-sampling algorithm to compare and rank multiple models of ergodic diffusion (including anomalous diffusion) as well as to assess their optimal parameters forin silico-generated and experimental time-series.
Anomalous diffusion of polystyrene from an attractive substrate based on all-atom simulation
Authors: Zhang Bingjie , Cao Xiuli , Zhou Ge , Zhao Nanrong
Published: September 2018

The diffusion of polystyrene (PS) polymer chains from a hydroxy (–OH)-terminated Si surface with different grafting densities ϕG is studied based on all-atom simulation.
Computational investigation of gas detection and selectivity on TiS3 nanoflakes supported by experimental evidence
Authors: Aryanpour Masoud , Rafiefard Nassim , Hosseini-Shokouh Seyed Hossein , Fardindoost Somayeh , Iraji zad Azam
Published: September 2018

Detection of gas molecules by the (001) surface of TiS3 is predicted via adsorption profiles, a useful analysis tool compiled based on ab initio calculations.
Elaborate design of polymeric nanocomposites with Mg(ii)-buffering nanochannels for highly efficient and selective removal of heavy metals from water: case study for Cu(ii)
Authors: Sun Qina , Yang Yujia , Zhao Zhixue , Zhang Qingrui , Zhao Xinmei , Nie Guangze , Jiao Tifeng , Peng Qiuming
Published: September 2018

Zr/Mg oxide-PS was designed to extend the applicability of nanostructured metal oxide bearing composites to Cu(ii) removal in acidic wastewaters.
Catalytic production of hexane-1,2,5,6-tetrol from bio-renewable levoglucosanol in water: effect of metal and acid sites on (stereo)-selectivity
Authors: Krishna Siddarth H. , De bruyn Mario , Schmidt Zachary R. , Weckhuysen Bert M. , Dumesic James A. , Huber George W.
Published: September 2018

We report on a new route to produce hexane-1,2,5,6-tetrol from cellulose-derived levoglucosanol using metal and acid catalysts.
Nanostructure of the deep eutectic solvent/platinum electrode interface as a function of potential and water content
Authors: Hammond Oliver S. , Li Hua , Westermann Christian , Al-Murshedi Azhar Y. M. , Endres Frank , Abbott Andrew P. , Warr Gregory G. , Edler Karen J. , Atkin Rob
Published: September 2018

Addition of water increases the DES interfacial nanostructure up to ∼40 wt%. This differs starkly from ionic liquids, where addition of small amounts of water rapidly decreases the interfacial nanostructure.
Supramolecular fluorescent sensor array for simultaneous qualitative and quantitative analysis of quaternary ammonium herbicides
Authors: Liu Chang , Wang Peng , Liu Xueke , Yi Xiaotong , Zhou Zhiqiang , Liu Donghui
Published: September 2018

A supramolecular fluorescent sensor array was firstly used to simultaneously qualitatively and quantitatively analyze quaternary ammonium herbicides.
Enantioselective open-tubular capillary electrochromatography using a β-cyclodextrin–gold nanoparticles–polydopamine coating as a stationary phase
Authors: Zhou Li , Zhang Bo , Li Shuang , Yu Jia , Guo Xingjie
Published: September 2018

A novel β-cyclodextrin–gold nanoparticles–polydopamine modified open tubular column was prepared for the chiral separation of enantiomers in capillary electrochromatography.
Dual functionalized natural biomass carbon dots from lychee exocarp for cancer cell targetable near-infrared fluorescence imaging and photodynamic therapy
Authors: Xue Mingyue , Zhao Jingjin , Zhan Zhihua , Zhao Shulin , Lan Chuanqing , Ye Fanggui , Liang Hong
Published: September 2018

Dual functionalized natural biomass carbon dots from lychee exocarp were fabricated for cancer cell targetable near-infrared fluorescence imaging and photodynamic therapy.
Self-supported nickel–cobalt nanowires as highly efficient and stable electrocatalysts for overall water splitting
Authors: Xu Hui , Wei Jingjing , Zhang Min , Wang Jin , Shiraishi Yukihide , Tian Lin , Du Yukou
Published: September 2018

The Ni1Co1O2 NWs//Ni1Co1P NWs couple is highly active and stable for overall water electrolysis with a low voltage of 1.58 V at 10 mA cm−2, showing extraordinary promise for practical overall water splitting electrolysis.
Thermo- and photo-modulation of exciplex fluorescence in a 3D spin crossover Hofmann-type coordination polymer
Authors: Delgado Teresa , Meneses-Sánchez Manuel , Piñeiro-López Lucía , Bartual-Murgui Carlos , Muñoz M. Carmen , Real José Antonio
Published: September 2018

Inclusion of pyrene in the pores of a 3D iron(ii) spin-crossover Hofmann-type material allows thermal and light-induced ON–OFF switching of the resulting exciplex luminescence and provides an analytical tool to control the spin-state of the iron(ii) nodes.
Reductive cleavage of CC bonds as a new strategy for turn-on dual fluorescence in effective sensing of H2S
Authors: Wang Chunfei , Cheng Xiaoxiang , Tan Jingyun , Ding Zhaoyang , Wang Wenjing , Yuan Daqiang , Li Gang , Zhang Hongjie , Zhang Xuanjun
Published: September 2018

Four effective probes with turn-off to turn-on fluorescence switches were successfully applied for sensing H2S.
Facile folding of insulin variants bearing a prosthetic C-peptide prepared by α-ketoacid-hydroxylamine (KAHA) ligation
Authors: Boross Gábor N. , Shimura Satomi , Besenius Melissa , Tennagels Norbert , Rossen Kai , Wagner Michael , Bode Jeffrey W.
Published: September 2018

Ester forming KAHA-ligation and a traceless prosthetic C-peptide provides a modular platform for the synthesis and folding of insulin variants.
Sulphur edge and vacancy assisted nitrogen–phosphorus co-doped exfoliated tungsten disulfide: a superior electrocatalyst for hydrogen evolution reaction
Authors: Maiti Anurupa , Srivastava Suneel Kumar
Published: September 2018

Schematic representation of the steps involved in fabrication of PNEWS2.
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.
Sensor fusion for vehicle tracking based on the estimated probability
Authors: Lee Chang Joo , Kim Kyeong Eun , Lim Myo Taeg
Published: September 2018

The track‐to‐track fusion (T2TF) algorithm is currently an attractive fusion methodology in the industry because the algorithm can reflect the reliability of sensor tracks. However, the T2TF algorithm cannot be applied when the probability information of the sensor is unknown. The aim of this study is to exploit the T2TF algorithm even in the absence of the probability information of the sensor. The covariance is estimated using the recursive equations of the Kalman filter. In addition, a novel track‐association approach using the total similarity is developed to improve association performance. The total similarity complements the defects of the track disposition and the estimated track history. Finally, by fusing the associated tracks using the estimated covariance, the T2TF algorithm is successfully applied to sensors with an unknown covariance. The fusion results are then evaluated using the correct association rate and the optimal subpattern assignment metric. The simulation results obtained show the superiority of the proposed algorithm under three scenarios.
Closed‐loop hierarchical control strategies for connected and autonomous hybrid electric vehicles with random errors
Authors: Qiu Shaolin , Qiu Lihong , Qian Lijun , Abdollahi Zoleikha , Pisu Pierluigi
Published: September 2018

This study presents a closed‐loop hierarchical control strategy for a group of connected and autonomous hybrid electric vehicles (HEVs) with the purpose of optimising fuel economy while guaranteeing traffic mobility and vehicle safety. In the hierarchical control architecture, a decentralised stochastic model predictive control (SMPC)‐based higher level controller incorporating signal phase and timing information is formulated to optimise the velocity profile of each vehicle, and an adaptive equivalent consumption minimisation strategy based lower level controller is employed for the energy management control of the HEVs. Creatively, random errors of the control variable are considered in the SMPC framework. The errors are discretised and modelled as a Markov process and the state transition matrix of the errors is generated randomly to capture the error transition dynamics. To solve the SMPC problem more efficiently, a scenario‐based SMPC is employed. Moreover, the propulsion and recuperation efficiencies of the lower level controller are calculated at each time step with measurable variables, and fed back to the higher level controller for velocity optimisation in next time step. Simulation results validate the control effectiveness and advantages of the proposed control architecture.
Robust shifting control of a motor‐transmission integrated system considering anti‐jerking and speed regulation for electric vehicles
Authors: Chai Benben , Zhang Jianwu , Wu Shaofang
Published: September 2018

Electric drive system with directly coupled traction motor and two‐speed transmission is a good choice for electric vehicles because of the potential in energy efficiency improvement and motor size reduction. Here, a control hierarchy of the electric powertrain has been applied, which comprises an optimal shift schedule at entire driving cycles as well as torque and speed control of the traction motor at the certain shift process. Firstly, the energy‐saving shift schedule is investigated by dynamic programming methods. Then, bench tests of the integrated motor‐transmission system are conducted. The oscillation of driveline and unsatisfied speed regulation of the traction motor are observed in the experiment results, which will deteriorate the shift performance. Therefore, an anti‐jerking robust controller is designed to attenuate the vibration of the powertrain and a robust speed controller is proposed to enhance the speed synchronisation capability of the traction motor. Simulation results indicate that the obtained shift schedule is effective to improve the energy efficiency and the robust shift process control can enhance the drive ability.
Comparative study on the economy of hybrid mining trucks for open‐pit mining
Authors: Jin Chun , Yi Tong , Shen Yanhua , Khajepour Amir , Meng Qingyong
Published: September 2018

The mining trucks with heavy loads are widely used in open‐pit mines, which are usually under working conditions where the recoverable potential energy accounts for more than 1/3 of the traction energy. Therefore, it is important to study the existing energy recovery technologies suitable for mining trucks. This work presents a comparative study on the economy of a mining truck by integrating four different energy storage systems (ESS): battery, supercapacitor, hydraulic accumulator, and air tank combining with the existing internal combustion engine to form a hybrid mining truck. First, recent applications and features of the four ESSs in vehicles are discussed. Next, the configurations of four types of partial hybrid mining trucks are presented. In addition, this project compares different configurations by the total benefit over 10 years of operation. The compressed‐air ESS with full capacity obtained the best benefit under medium and heavy load scenarios, which is more applicable to the actual situations. Therefore, it will be beneficial to turn the conventional electric‐driving mining truck into a compressed‐air hybrid.