bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Resampling Approach for Correcting Systematic Spatiotemporal Biases for Multiple Variables in a Changing Climate
Authors: Mehrotra R. , Sharma A. 
Published: January 2019

AbstractSystematic biases in climate model simulations are commonly addressed using univariate bias correction algorithms that involve matching of mean, variance, and quantiles. These approaches work well for a single variable and location and effectively mimic the observed temporal structure in the corrected series. The intervariable, interspace, and high‐ or low‐frequency temporal dependencies that characterize observed hydrological records are often left untouched and lead to substantial biases in applications such as catchment modeling where their correct representation is critical. In the approach presented here, changes in the dependence attributes are ascertained by resampling of the historical ranks into what these might resemble in the future. The proposed approach is not limited in terms of the number of variables, grid points in space, and the time scale considered. Most importantly, it maintains the shift in dependence and other attributes between the current and the future climate as ascertained by a climate model. The approach is illustrated using daily time series of temperature, precipitation, relative humidity, and wind speed simulated by a regional climate model at 8,910 grid points over Australia. Spatial, temporal, and cross‐variable dependence attributes of the corrected simulations at daily and aggregated time scales are compared against quantile mapping and substantial improvements in performance identified. Resampling of corrected ranks offers a very simple, flexible, and effective general purpose multivariate, multitime, and multilocation bias correction alternative for current and future climate. As the approach works in three dimensions, space, time, and variables, it is denoted as 3DBC, or three‐dimensional bias correction.
The biogenic amines putrescine and cadaverine show in vitro cytotoxicity at concentrations that can be found in foods
Authors: del Rio Beatriz , Redruello Begoña , Linares Daniel M. , Ladero Victor , Ruas-Madiedo Patricia , Fernandez Maria , Martin M. Cruz , Alvarez Miguel A. 
Published: January 2019

AbstractPutrescine and cadaverine are among the most common biogenic amines (BA) in foods, but it is advisable that their accumulation be avoided. Present knowledge about their toxicity is, however, limited; further research is needed if qualitative and quantitative risk assessments for foods are to be conducted. The present work describes a real-time analysis of the cytotoxicity of putrescine and cadaverine on intestinal cell cultures. Both BA were cytotoxic at concentrations found in BA-rich foods, although the cytotoxicity threshold for cadaverine was twice that of putrescine. Their mode of cytotoxic action was similar, with both BA causing cell necrosis; they did not induce apoptosis. The present results may help in establishing legal limits for both putrescine and cadaverine in food.
Systems Biology Approach to Identify Novel Genomic Determinants for Pancreatic Cancer Pathogenesis
Authors: Khatri Indu , Ganguly Koelina , Sharma Sunandini , Carmicheal Joseph , Kaur Sukhwinder , Batra Surinder K. , Bhasin Manoj K. 
Published: January 2019

AbstractPancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with a 5-year survival rate of <8%. Its dismal prognosis stems from inefficient therapeutic modalities owing to the lack of understanding about pancreatic cancer pathogenesis. Considering the molecular complexity and heterogeneity of PDAC, identification of novel molecular contributors involved in PDAC onset and progression using global “omics” analysis will pave the way to improved strategies for disease prevention and therapeutic targeting. Meta-analysis of multiple miRNA microarray datasets containing healthy controls (HC), chronic pancreatitis (CP) and PDAC cases, identified 13 miRNAs involved in the progression of PDAC. These miRNAs showed dysregulation in both tissue as well as blood samples, along with progressive decrease in expression from HC to CP to PDAC. Gene-miRNA interaction analysis further elucidated 5 miRNAs (29a/b, 27a, 130b and 148a) that are significantly downregulated in conjunction with concomitant upregulation of their target genes throughout PDAC progression. Among these, miRNA-29a/b targeted genes were found to be most significantly altered in comparative profiling of HC, CP and PDAC, indicating its involvement in malignant evolution. Further, pathway analysis suggested direct involvement of miRNA-29a/b in downregulating the key pathways associated with PDAC development and metastasis including focal adhesion signaling and extracellular matrix organization. Our systems biology data analysis, in combination with real-time PCR validation indicates direct functional involvement of miRNA-29a in PDAC progression and is a potential prognostic marker and therapeutic candidate for patients with progressive disease.
Internal surface electric charge characterization of mesoporous silica
Authors: Sen Tumcan , Barisik Murat 
Published: January 2019

AbstractMesoporous silica is an emerging technology to solve problems of existing and to support projected revolutionary applications ranging from targeted drug delivery to artificial kidney. However, one of the major driving mechanisms, electric charging of internal mesoporous surfaces, has not been characterized yet. In the nanoscale confinements of mesoporous structures made of pore throats and pore voids, surface charges diverge from existing theoretical calculations and show local variation due to two occurrences. First, when the size of pore throat becomes comparable with the thickness of ionic layering forming on throats’ surfaces, ionic layers from opposite surfaces overlap so that ionic concentration on the surface becomes different than Boltzmann distribution predicts, and there will no longer be an equilibrium of zero electric potential at pore throat centers. Second, when this non zero potential inside throats becomes different than the potential of pore voids, ionic diffusion from void to throat creates axial ionic variation on surfaces. For such a case, we performed a pore level analysis on mesoporous internal surface charge at various porosities and ionic conditions. Pore parameters strongly affected the average internal charge which we characterized as a function of overlap ratio and porosity, first time in literature. Using this, a phenomenological model was developed as an extension of the existing theory to include nano-effects, to predict the average mesoporous internal surface charge as a function of EDL thickness, pore size and porosity.
The brittle-ductile transition in active volcanoes
Authors: Parisio Francesco , Vinciguerra Sergio , Kolditz Olaf , Nagel Thomas 
Published: January 2019

AbstractContrasting deformation mechanisms precede volcanic eruptions and control precursory signals. Density increase and high uplifts consistent with magma intrusion and pressurization are in contrast with dilatant responses and reduced surface uplifts observed before eruptions. We investigate the impact that the rheology of rocks constituting the volcanic edifice has on the deformation mechanisms preceding eruptions. We propose a model for the pressure and temperature dependent brittle-ductile transition through which we build a strength profile of the shallow crust in two idealized volcanic settings (igneous and sedimentary basement). We have performed finite element analyses in coupled thermo-hydro-mechanical conditions to investigate the influence of static diking on the local brittle-ductile transition. Our results show that in active volcanoes: (i) dilatancy is an appropriate indicator for the brittle-ductile transition; (ii) the predicted depth of the brittle-ductile transition agrees with the observed attenuated seismicity; (iii) seismicity associated with diking is likely to be affected by ductile deformation mode caused by the local temperature increase; (iv) if failure occurs within the edifice, it is likely to be brittle-dilatant with strength and stiffness reduction that blocks stress transfers within the volcanic edifice, ultimately damping surface uplifts.
Metabolome and transcriptome-wide effects of the carbon storage regulator A in enteropathogenic Escherichia coli
Authors: Berndt Volker , Beckstette Michael , Volk Marcel , Dersch Petra , Brönstrup Mark 
Published: January 2019

AbstractThe carbon storage regulator A (CsrA) is a conserved global regulatory system known to control central carbon pathways, biofilm formation, motility, and pathogenicity. The aim of this study was to characterize changes in major metabolic pathways induced by CsrA in human enteropathogenic Escherichia coli (EPEC) grown under virulence factor-inducing conditions. For this purpose, the metabolomes and transcriptomes of EPEC and an isogenic ∆csrA mutant derivative were analyzed by untargeted mass spectrometry and RNA sequencing, respectively. Of the 159 metabolites identified from untargeted GC/MS and LC/MS data, 97 were significantly (fold change ≥ 1.5; corrected p-value ≤ 0.05) regulated between the knockout and the wildtype strain. A lack of csrA led to an accumulation of fructose-6-phosphate (F6P) and glycogen synthesis pathway products, whereas metabolites in lower glycolysis and the citric acid cycle were downregulated. Associated pathways from the citric acid cycle like aromatic amino acid and siderophore biosynthesis were also negatively influenced. The nucleoside salvage pathways were featured by an accumulation of nucleosides and nucleobases, and a downregulation of nucleotides. In addition, a pronounced downregulation of lyso-lipid metabolites was observed. A drastic change in the morphology in the form of vesicle-like structures of the ∆csrA knockout strain was visible by electron microscopy. Colanic acid synthesis genes were strongly (up to 50 fold) upregulated, and the abundance of colanic acid was 3 fold increased according to a colorimetric assay. The findings expand the scope of pathways affected by the csrA regulon and emphasize its importance as a global regulator.
Peptidoglycan binding protein (PGBP)-modified magnetic nanobeads for efficient magnetic capturing of Staphylococcus aureus associated with sepsis in blood
Authors: Lim Jaewoo , Choi Jongmin , Guk Kyeonghye , Son Seong Uk , Lee Do Kyung , Yeom Soo-Jin , Kang Taejoon , Jung Juyeon , Lim Eun-Kyung 
Published: January 2019

AbstractPeptidoglycan-binding protein-modified magnetic nanobeads (PGBP-MNBs) were prepared for efficient magnetic capturing of Staphylococcus aureus (S. aureus), which is associated with sepsis, using the binding affinity of PGBP for the peptidoglycan (PG) layer on S. aureus. These PGBP-MNBs can simply capture S. aureus in plasma within 1 hr or even 15 min. Importantly, they also can capture various types of Gram-positive bacteria, such as Bacillus cereus and methicillin-resistant and methicillin-susceptible S. aureus (MRSA and MSSA). We believe that PGBP-based systems will be used to develop diagnostic systems for Gram-positive bacteria-related diseases.
Genetically distinct glioma stem-like cell xenografts established from paired glioblastoma samples harvested before and after molecularly targeted therapy
Authors: Tanaka Shota , Luk Samantha , Kiyokawa Juri , Onozato Maristela L. , Iafrate A. John , Shah Khalid , Martuza Robert L. , Rabkin Samuel D. , Batchelor Tracy T. , Cahill Daniel P. , Chi Andrew S. , Wakimoto Hiroaki 
Published: January 2019

AbstractIntratumoural heterogeneity underlies tumour escape from molecularly targeted therapy in glioblastoma. A cell-based model preserving the evolving molecular profiles of a tumour during treatment is key to understanding the recurrence mechanisms and development of strategies to overcome resistance. In this study, we established a matched pair of glioblastoma stem-like cell (GSC) cultures from patient glioblastoma samples before and after epidermal growth factor receptor (EGFR)-targeted therapy. A patient with recurrent glioblastoma (MGG70R) harboring focal, high-level EGFR amplification received the irreversible EGFR tyrosine kinase inhibitor dacomitinib. The tumour that subsequently recurred (MGG70RR) showed diploid EGFR, suggesting inhibitor-mediated elimination of EGFR-amplified tumour cells and propagation of EGFR non-amplified cell subpopulations. The MGG70R-GSC line established from MGG70R formed xenografts retaining EGFR amplification and EGFR overexpression, while MGG70RR-GSC established from MGG70RR generated tumours that lacked EGFR amplification and EGFR overexpression. MGG70R-GSC-derived intracranial xenografts were more proliferative than MGG70RR-GSC xenografts, which had upregulated mesenchymal markers, mirroring the pathological observation in the corresponding patient tumours. In vitro MGG70R-GSC was more sensitive to EGFR inhibitors than MGG70RR-GSC. Thus, these molecularly distinct GSC lines recapitulated the subpopulation alteration that occurred during glioblastoma evasion of targeted therapy, and offer a valuable model facilitating therapeutic development for recurrent glioblastoma.
Identification of wheat stress-responding genes and TaPR-1-1 function by screening a cDNA yeast library prepared following abiotic stress
Authors: Wang Jingyi , Mao Xinguo , Wang Ruitong , Li Ang , Zhao Guangyao , Zhao Jinfeng , Jing Ruilian 
Published: January 2019

AbstractAbiotic stress significantly impacts growth and yield of crop plants. It is imperative for crop improvement to discover and utilize stress-tolerant functional genes. In this study, genes responding to abiotic stresses, such as freezing, salt and osmotic stress, were screened from a cDNA yeast library that was constructed from the drought- and heat-tolerant wheat variety Hanxuan 10. After screening for surviving clones we isolated 7,249, 4,313 and 4,469 raw sequences, corresponding to 4,695, 2,641 and 2,771 genes following each treatment. Venn diagrams revealed 377 overlapping genes. GO analysis suggested that these genes were mainly involved in the metabolic and stress signal pathways. KEGG pathway enrichment analysis indicated that the isolated genes predominantly belonged to pathways concerning energy and metabolism. Overlapping gene TaPR-1-1 within the pathogenesis-related (PR) protein family was selected for detailed characterization. Although previous studies had shown that PR genes function during pathogen attack, our results demonstrated that TaPR-1-1 expression was also induced by freezing, salinity, and osmotic stresses. Overexpression in yeast and Arabidopsis showed that TaPR-1-1 conferred tolerance to these stresses. We concluded that screening cDNA yeast libraries following abiotic stress is an efficient way to identify stress-tolerance genes.
History and future of shotgun glycomics
Authors: Smith David F. , Cummings Richard D. , Song Xuezheng 
Published: January 2019

AbstractGlycans in polysaccharides and glycoconjugates of the hydrophilic exterior of all animal cells participate in signal transduction, cellular adhesion, intercellular signaling, and sites for binding of pathogens largely through protein–glycan interactions. Microarrays of defined glycans have been used to study the binding specificities of biologically relevant glycan-binding proteins (GBP), but such arrays are limited by their lack of diversity or relevance to the GBP being investigated. Shotgun glycan microarrays are made up of structurally undefined glycans that were released from natural sources, labeled with bifunctional reagents so that they can be monitored during their purification using multidimensional chromatographic procedures, stored as a tagged glycan library (TGL) and subsequently printed onto microarrays at equal molar concentrations. The shotgun glycan microarray is then interrogated with a biologically relevant GBP and the corresponding glycan ligands can be retrieved from the TGL for detailed structural analysis and further functional analysis. Shotgun glycomics extended the defined glycan microarray to a discovery platform that supports functional glycomic analyses and may provide a useful process for ultimately defining the human glycome.
Hereditary diseases of coenzyme A thioester metabolism
Authors: Yang Hao , Zhao Chen , Wang Youlin , Wang Shu Pei , Mitchell Grant A. 
Published: January 2019

Abstract
Coenzyme A (CoA) thioesters (acyl-CoAs) are essential intermediates of metabolism. Inborn errors of acyl-CoA metabolism include a large fraction of the classical organic acidemias. These conditions can involve liver, muscle, heart and brain, and can be fatal. These conditions are increasingly detected by newborn screening. There is a renewed interest in CoA metabolism and in developing effective new treatments. Here, we review theories of the pathophysiology in relation to mitochondrial CoA sequestration, toxicity and redistribution (CASTOR).
Lossy flat‐passband signal‐interference microstrip filter
Authors: Gómez‐García Roberto , Muñoz‐Ferreras José‐María , Yang Li , Feng Wenjie 
Published: January 2019

A type of lossy transversal‐signal‐interference planar bandpass filter (BPF) with a flattened passband is reported in this Letter. The authors exploit in‐series‐cascaded transversal filtering sections composed of two in‐parallel transmission‐line segments and series‐type lossy hybrid resonators connected at their inputoutput accesses. The resistors of these lossy resonators by dissipating part of the RF‐input‐signal energy in the BPF passband region following a complementary frequency‐variation profile with regard to the one associated with conventional substrate filter loss allow obtaining an overall flattened transmission band. To experimentally validate the proposed approach, a 2 GHz microstrip prototype of a sharp‐rejection lossy signal‐interference BPF with a flattened passband is developed and characterised.
A 10-M⊙ YSO with a Keplerian disk and a nonthermal radio jet
Authors: Moscadelli L. , Sanna A. , Cesaroni R. , Rivilla V. M. , Goddi C. , Rygl K. L. J. 
Published: January 2019

Context. To constrain present star formation models, we need to simultaneously establish the dynamical and physical properties of disks and jets around young stars.
Aims. We previously observed the star-forming region G16.59−0.05 through interferometric observations of both thermal and maser lines, and identified a high-mass young stellar object (YSO) which is surrounded by an accretion disk and drives a nonthermal radio jet. Our goals are to establish the physical conditions of the environment hosting the high-mass YSO and to study the kinematics of the surrounding gas in detail.
Methods. We performed high-angular-resolution (beam FWHM ≈ 0′′.15) 1.2-mm continuum and line observations towards G16.59−0.05 with the Atacama Large Millimeter Array (ALMA).
Results. The main dust clump, with size ≈104 au, is resolved into four distinct, relatively compact (diameter ~2000 au) millimeter (mm) sources. The source harboring the high-mass YSO is the most prominent in molecular emission. By fitting the emission profiles of several unblended and optically thin transitions of CH3OCH3 and CH3OH, we derived gas temperatures inside the mm sources in the range 42–131 K, and calculated masses of 1–5 M⊙. A well-defined Local Standard of Rest (LSR) velocity (VLSR) gradient is detected in most of the high-density molecular tracers at the position of the high-mass YSO, pinpointed by compact 22-GHz free-free emission. This gradient is oriented along a direction forming a large (≈70°) angle with the radio jet, traced by elongated 13-GHz continuum emission. The butterfly-like shapes of the P–V plots and the linear pattern of the emission peaks of the molecular lines at high velocity confirm that this VLSR gradient is due to rotation of the gas in the disk surrounding the high-mass YSO. The disk radius is ≈500 au, and the VLSR distribution along the major axis of the disk is well reproduced by a Keplerian profile around a central mass of 10 ± 2 M⊙. The position of the YSO is offset by ≳0′′.1 from the axis of the radio jet and the dust emission peak. To explain this displacement we argue that the high-mass YSO could have moved from the center of the parental mm source owing to dynamical interaction with one or more companions.
Quality of extracellular vesicle images by transmission electron microscopy is operator and protocol dependent
Authors: Rikkert L. G. , Nieuwland R. , Terstappen L. W. M. M. , Coumans F. A. W. 
Published: January 2019

ABSTRACTTransmission electron microscopy (TEM) has nanometre resolution and can be used to distinguish single extracellular vesicles (EVs) from non‐EV particles. TEM images of EVs are a result of operator image selection. To which extent operator image selection reflects the overall sample quality, and to which extent the images are comparable and reproducible, is unclear. In a first attempt to improve the comparability and reproducibility of TEM to visualise EVs, we compared operator image selection to images taken at predefined locations from the same grids, using four EV TEM preparation protocols, a single EV‐containing sample and a single TEM instrument. Operator image selection leads to high‐quality images that are more similar between the protocols. In contrast, images taken at predefined locations reveal differences between the protocols, for example in number of EVs per image and background quality. From the evaluated protocols, for only one protocol the operator image selection is comparable to the TEM images taken at predefined locations. Taken together, operator image selection can be used to demonstrate the presence of EVs in a sample, but seem less suitable to demonstrate the quality of a sample. Because images taken at predefined locations reflect the overall quality of the EV‐containing sample rather than the presence of EVs alone, this is a first step to improve the comparability and reproducibility of TEM for monitoring the quality of EV‐containing samples.
An accurate and powerful method for copy number variation detection
Authors: Xiao Feifei , Luo Xizhi , Hao Ning , Niu Yue S , Xiao Xiangjun , Cai Guoshuai , Amos Christopher I , Zhang Heping 
Published: January 2019

Abstract

Motivation
Integration of multiple genetic sources for copy number variation detection (CNV) is a powerful approach to improve the identification of variants associated with complex traits. Although it has been shown that the widely used change point based methods can increase statistical power to identify variants, it remains challenging to effectively detect CNVs with weak signals due to the noisy nature of genotyping intensity data. We previously developed modSaRa, a normal mean-based model on a screening and ranking algorithm for copy number variation identification which presented desirable sensitivity with high computational efficiency. To boost statistical power for the identification of variants, here we present a novel improvement that integrates the relative allelic intensity with external information from empirical statistics with modeling, which we called modSaRa2.

Results
Simulation studies illustrated that modSaRa2 markedly improved both sensitivity and specificity over existing methods for analyzing array-based data. The improvement in weak CNV signal detection is the most substantial, while it also simultaneously improves stability when CNV size varies. The application of the new method to a whole genome melanoma dataset identified novel candidate melanoma risk associated deletions on chromosome bands 1p22.2 and duplications on 6p22, 6q25 and 19p13 regions, which may facilitate the understanding of the possible roles of germline copy number variants in the etiology of melanoma.

Availability and implementation
http://c2s2.yale.edu/software/modSaRa2 or https://github.com/FeifeiXiaoUSC/modSaRa2.

Supplementary information
Supplementary data are available at Bioinformatics online.