bluuebunny/crossref_metadata_2025_split huggingface dataset:
Convergence of virulence and multidrug resistance in a single plasmid vector in multidrug-resistant Klebsiella pneumoniae ST15
Authors: Lam Margaret M. C. , Wyres Kelly L. , Wick Ryan R. , Judd Louise M. , Fostervold Aasmund , Holt Kathryn E. , Löhr Iren Høyland 
Published: November 2018

SYNOPSISBackgroundMultidrug resistance (MDR) and hypervirulence (hv) are typically observed in separate Klebsiella pneumoniae populations. However, convergent strains with both properties have been documented and potentially pose a high risk to public health in the form of invasive infections with limited treatment options.ObjectivesTo characterize the genetic determinants of virulence and antimicrobial resistance (AMR) in two ESBL-producing K. pneumoniae isolates belonging to the international MDR clone ST15.MethodsThe complete genome sequences of both isolates, including their plasmids, were resolved using Illumina and Oxford Nanopore sequencing.ResultsBoth isolates carried large mosaic plasmids in which AMR and virulence loci have converged within the same vector. These closely related mosaic hv-MDR plasmids include sequences typical of the K. pneumoniae virulence plasmid 1 (KpVP-1; including aerobactin synthesis locus iuc) fused with sequences typical of IncFIIK conjugative AMR plasmids. One hv-MDR plasmid carried three MDR elements encoding the ESBL gene blaCTX-M-15 and eight other AMR genes (blaTEM, aac3’-IIa, aph3’-Ia, dfrA1, satA2, blaSHV, sul1, aadA1). The other carried remnants of these elements encoding blaTEM and aac3’-IIa, and blaCTX-M-15 was located in a second plasmid in this isolate. The two isolates originated from patients hospitalized in Norway but have epidemiological and genomic links to Romania.ConclusionsThe presence of both virulence and AMR determinants on a single vector enables simultaneous transfer in a single event and potentially rapid emergence of hv-MDR K. pneumoniae clones. This highlights the importance of monitoring for such convergence events with stringent genomic surveillance.
AnnoTree: visualization and exploration of a functionally annotated microbial tree of life
Authors: Mendler Kerrin , Chen Han , Parks Donovan H. , Hug Laura A. , Doxey Andrew C. 
Published: November 2018

AbstractBacterial genomics has revolutionized our understanding of the microbial tree of life; however, mapping and visualizing the distribution of functional traits across bacteria remains a challenge. Here, we introduce AnnoTree - an interactive, functionally annotated bacterial tree of life that integrates taxonomic, phylogenetic, and functional annotation data from nearly 24,000 bacterial genomes. AnnoTree enables visualization of millions of precomputed genome annotations across the bacterial phylogeny, thereby allowing users to explore gene distributions as well as patterns of gene gain and loss across bacteria. Using AnnoTree, we examined the phylogenomic distributions of 28,311 gene/protein families, and measured their phylogenetic conservation, patchiness, and lineage-specificity. Our analyses revealed widespread phylogenetic patchiness among bacterial gene families, reflecting the dynamic evolution of prokaryotic genomes. Genes involved in phage infection/defense, mobile elements, and antibiotic resistance dominated the list of most patchy traits, as well as numerous intriguing metabolic enzymes that appear to have undergone frequent horizontal transfer. We anticipate that AnnoTree will be a valuable resource for exploring gene histories across bacteria, and will act as a catalyst for biological and evolutionary hypothesis generation.
Assessment of bilateral knee pain from MR imaging using deep neural networks
Authors: Chang Gary H. , Felson David T. , Qiu Shangran , Capellini Terence D. , Kolachalama Vijaya B. 
Published: November 2018

ABSTRACTBackground and objectiveIt remains difficult to characterize pain in knee joints with osteoarthritis solely by radiographic findings. We sought to understand how advanced machine learning methods such as deep neural networks can be used to analyze raw MRI scans and predict bilateral knee pain, independent of other risk factors.MethodsWe developed a deep learning framework to associate information from MRI slices taken from the left and right knees of subjects from the Osteoarthritis Initiative with bilateral knee pain. Model training was performed by first extracting features from two-dimensional (2D) sagittal intermediate-weighted turbo spin echo slices. The extracted features from all the 2D slices were subsequently combined to directly associate using a fused deep neural network with the output of interest as a binary classification problem.ResultsThe deep learning model resulted in predicting bilateral knee pain on test data with 70.1% mean accuracy, 51.3% mean sensitivity, and 81.6% mean specificity. Systematic analysis of the predictions on the test data revealed that the model performance was consistent across subjects of different Kellgren-Lawrence grades.ConclusionThe study demonstrates a proof of principle that a machine learning approach can be applied to associate MR images with bilateral knee pain.SIGNIFICANCE AND INNOVATIONKnee pain is typically considered as an early indicator of osteoarthritis (OA) risk. Emerging evidence suggests that MRI changes are linked to pre-clinical OA, thus underscoring the need for building image-based models to predict knee pain. We leveraged a state-of-the-art machine learning approach to associate raw MR images with bilateral knee pain, independent of other risk factors.
NEPRE: a Scoring Function for Protein Structures based on Neighbourhood Preference
Authors: Liu Siyuan , Xiang Xilun , Liu Haiguang 
Published: November 2018

ABSTRACTProtein structure prediction relies on two major components, a method to generate good models that are close to the native structure and a scoring function that can select the good models. Based on the statistics from known structures in the protein data bank, a statistical energy function is derived to reflect the amino acid neighbourhood preferences. The neighbourhood of one amino acid is defined by its contacting residues, and the energy function is determined by the neighbhoring residue types and relative positions. A scoring algorithm, Nepre, has been implemented and its performance was tested with several decoy sets. The results show that the Nepre program can be applied in model ranking to improve the success rate in structure predictions.
Comprehensive evaluation of computational cell-type quantification methods for immuno-oncology
Authors: Sturm Gregor , Finotello Francesca , Petitprez Florent , Zhang Jitao David , Baumbach Jan , Fridman Wolf H. , List Markus , Aneichyk Tatsiana 
Published: November 2018

AbstractMotivationThe composition and density of immune cells in the tumor microenvironment profoundly influence tumor progression and success of anti-cancer therapies. Flow cytometry, immunohistochemistry staining, or single-cell sequencing is often unavailable such that we rely on computational methods to estimate the immune-cell composition from bulk RNA-sequencing (RNA-seq) data. Various methods have been proposed recently, yet their capabilities and limitations have not been evaluated systematically. A general guideline leading the research community through cell type deconvolution is missing.ResultsWe developed a systematic approach for benchmarking such computational methods and assessed the accuracy of tools at estimating nine different immune- and stromal cells from bulk RNA-seq samples. We used a single-cell RNA-seq dataset of ∼11,000 cells from the tumor microenvironment to simulate bulk samples of known cell type proportions, and validated the results using independent, publicly available gold-standard estimates. This allowed us to analyze and condense the results of more than a hundred thousand predictions to provide an exhaustive evaluation across seven computational methods over nine cell types and ∼1,800 samples from five simulated and real-world datasets. We demonstrate that computational deconvolution performs at high accuracy for well-defined cell-type signatures and propose how fuzzy cell-type signatures can be improved. We suggest that future efforts should be dedicated to refining cell population definitions and finding reliable signatures.AvailabilityA snakemake pipeline to reproduce the benchmark is available at https://github.com/grst/immune_deconvolution_benchmark. An R package allows the community to perform integrated deconvolution using different methods (https://grst.github.io/immunedeconv).Contactg.sturm@tum.deSupplementary informationSupplementary data are available at Bioinformatics online.
Architectural principles for Hfq/Crc-mediated regulation of gene expression
Authors: Pei Xue-Yuan , Dendooven Tom , Sonnleitner Elisabeth , Chen Shaoxia , Bläsi Udo , Luisi Ben F. 
Published: November 2018

SUMMARYThe global regulator Hfq facilitates the action of regulatory RNAs in post-transcription gene regulation in many Gram-negative bacteria.In Pseudomonas aeruginosa, Hfq, in conjunction with the catabolite repression protein Crc, was shown to form a complex that directly inhibits translation of target transcripts during carbon catabolite repression. Here, we describe and validate high-resolution cryo-EM structures of the cooperative assembly of Hfq and Crc bound to a translation initiation site. The core assembly is formed through interactions of two cognate RNAs, two Hfq hexamers and a Crc pair. Additional Crc protomers can be recruited to form higher-order assemblies with demonstratedin vivoactivity. The structures indicate a distinctive RNA conformation and a pattern of repeating motifs that confer regulatory function. This study not only reveals for the first time how Hfq cooperates with a partner protein to regulate translation but also provides a novel structural basis to explain how an RNA code can guide global regulators to interact cooperatively and regulate many different RNA targets.
Abrogation of Stem Loop Binding Protein (Slbp) function leads to a failure of cells to transition from proliferation to differentiation, retinal coloboma and midline axon guidance deficits
Authors: Turner Kate , Hoyle Jacqueline , Valdivia Leonardo E , Cerveny Kara , Hart Wendy , Mangoli Maryam , Geisler Robert , Rees Michele , Houart Corinne , Poole Richard J. , Wilson Stephen W , Gestri Gaia 
Published: November 2018

AbstractThrough forward genetic screening for mutations affecting visual system development, we identified prominent coloboma and cell-autonomous retinal neuron differentiation, lamination and retinal axon projection defects ineisspalte(ele) mutant zebrafish. Additional axonal deficits were present, most notably at midline axon commissures. Genetic mapping and cloning of theelemutation showed that the affected gene isslbp, which encodes a conserved RNA stem-loop binding protein involved in replication dependent histone mRNA metabolism. Cells throughout the central nervous system remained in the cell cycle inelemutant embryos at stages when, and locations where, post-mitotic cells have differentiated in wild-type siblings. Indeed, RNAseq analysis showed down-regulation of many genes associated with neuronal differentiation. This was coincident with changes in the levels and spatial localisation of expression of various genes implicated, for instance, in axon guidance, that likely underlie specificelephenotypes. These results suggest that many of the cell and tissue specific phenotypes inelemutant embryos are secondary to altered expression of modules of developmental regulatory genes that characterise, or promote transitions in, cell state and require the correct function of Slbp-dependent histone and chromatin regulatory genes.Author SummaryCongenital deficits of eye formation are common in humans and to help understand the genetic basic of such conditions, we are studying zebrafish with comparable eye defects. We identified defects in both the shaping of the eye and in its connections to the brain ineisspaltemutant fish. Further analyses revealed additional deficits in the brain, most notably a severe reduction in neurons and their connections. We find that this is due to an inability of the cells that generate neurons to transition from proliferation to neuronal differentiation. By using a sequencing approach to compare mutant embryos to their normal siblings, we identified the affected gene asslbp, which encodes a protein that binds the mRNAs of other genes important for cell proliferation. This sequencing approach revealed the full extent of changes in gene expression in the mutant, helping us to better understand why the nervous system defects occur. Our study suggests that in the absence of Slbp function, cells lose the ability to transition from the proliferative to the differentiated state and this leads to additional defects in the eyes and brain.
Chemo- and regioselective [3 + 2]-cycloadditions of thiocarbonyl ylides: crystal structures of trans-8-benzoyl-1,1,3,3-tetramethyl-7-trifluoromethyl-5-thiaspiro[3.4]octan-2-one and trans-3-benzoyl-2,2-diphenyl-4-(trifluoromethyl)tetrahydrothiophene
Authors: Linden Anthony , Mlostoń Grzegorz , Grzelak Paulina , Heimgartner Heinz 
Published: November 2018

The title compounds, C19H21F3O2S and C24H19F3OS, were prepared via chemo- and regioselective [3 + 2]-cycloadditions of the respective thiocarbonyl ylides (thiocarbonyl S-methanides), generated in situ, with (E)-4,4,4-trifluoro-1-phenylbut-2-en-1-one. The thiophene ring in the crystal structure of each compound has an envelope conformation. The largest differences between the two molecular structures is in the bond lengths about the quaternary C atom of the thiophene ring; in the spirocyclic structure, the C—C bonds to the spiro C atom in the cyclobutane ring are around 1.60 Å, although this is also observed in related structures. In the same structure, weak intermolecular C—H...X (X = S, O) interactions link the molecules into extended ribbons running parallel to the [001] direction. In the other structure, weak C—H...π interactions link the molecules into sheets parallel to the (010) plane.
Aerodynamic and structural design for the development of a MALE UAV
Authors: Panagiotou Pericles , Giannakis Efstratios , Savaidis Georgios , Yakinthos Kyros 
Published: November 2018

Purpose
The purpose of this paper is to present the preliminary design of a medium altitude long endurance (MALE) unmanned aerial vehicle (UAV), focusing on the interaction between the aerodynamic and the structural design studies.

Design/methodology/approach
The classic layout theory was used, adjusted for the needs of unmanned aircraft, including aerodynamic calculations, presizing methods and CFD, to estimate key aerodynamic and stability coefficients. Considering the structural aspects, a combination of layout, finite element methods and custom parameterized design tools were used, allowing automatic reshapes of the skin and the internal structural parts, which are mainly made of composite materials. Interaction loops were defined between the aforementioned studies to optimize the performance of the aerial vehicle, maximize the aerodynamic efficiency and reduce the structural weight.

Findings
The complete design procedure of a UAV is shown, starting from the final stages of conceptual design, up to the point where the detail design and mechanical drawings initiated.

Practical implications
This paper presents a complete view of a design study of a MALE UAV, which was successfully constructed and flight-tested.

Originality/value
This study presents a complete, synergetic approach between the configuration layout, aerodynamic and structural aspects of a MALE UAV.
Cold flow studies in a vortex thrust chamber
Authors: T.N. Rajesh , Sarvoththama Jothi T.J. , T. Jayachandran 
Published: November 2018

Purpose
The purpose of this paper is to estimate the chamber pressure and flow behaviour in a vortex thrust chamber (VTC) during the cold flow with hydrogen and oxygen as propellants.

Design/methodology/approach
Experiments are carried out in a VTC with a different mixture ratio of hydrogen and oxygen. The pressures developed inside the VTC are measured. Numerical simulations are carried out to understand the flow patterns of fuel and oxidizer inside the VTC.

Findings
The chamber pressure is influenced by the type of injection of propellant and mixture ratio. Tangential injection of propellant is the key parameter for an increase of the chamber pressure of the VTC.

Research limitations/implications
The pressure measurements are carried out in cold flow conditions without combustion happening in the VTC.

Practical implications
The practical implication is that when the combustion in the VTC ceases, the thrust generated due to the propellants in cold flow conditions can be assessed.

Originality/value
The VTC with the tangential injection of propellant generates higher chamber pressure.
Combustion chamber design and reaction modeling for aero turbo-shaft engine
Authors: Marudhappan Raja , Udayagiri Chandrasekhar , Reddy Koni Hemachandra 
Published: November 2018

Purpose
The purpose of this paper is to formulate a structured approach to design an annular diffusion flame combustion chamber for use in the development of a 1,400 kW range aero turbo shaft engine. The purpose is extended to perform numerical combustion modeling by solving transient Favre Averaged Navier Stokes equations using realizable two equation k-e turbulence model and Discrete Ordinate radiation model. The presumed shape β-Probability Density Function (β-PDF) is used for turbulence chemistry interaction. The experiments are conducted on the real engine to validate the combustion chamber performance.

Design/methodology/approach
The combustor geometry is designed using the reference area method and semi-empirical correlations. The three dimensional combustor model is made using a commercial software. The numerical modeling of the combustion process is performed by following Eulerian approach. The functional testing of combustor was conducted to evaluate the performance.

Findings
The results obtained by the numerical modeling provide a detailed understanding of the combustor internal flow dynamics. The transient flame structures and streamline plots are presented. The velocity profiles obtained at different locations along the combustor by numerical modeling mostly go in-line with the previously published research works. The combustor exit temperature obtained by numerical modeling and experiment are found to be within the acceptable limit. These results form the basis of understanding the design procedure and opens-up avenues for further developments.

Research limitations/implications
Internal flow and combustion dynamics obtained from numerical simulation are not experimented owing to non-availability of adequate research facilities.

Practical implications
This study contributes toward the understanding of basic procedures and firsthand experience in the design aspects of combustors for aero-engine applications. This work also highlights one of the efficient, faster and economical aero gas turbine annular diffusion flame combustion chamber design and development.

Originality/value
The main novelty in this work is the incorporation of scoops in the dilution zone of the numerical model of combustion chamber to augment the effectiveness of cooling of combustion products to obtain the desired combustor exit temperature. The use of polyhedral cells for computational domain discretization in combustion modeling for aero engine application helps in achieving faster convergence and reliable predictions. The methodology and procedures presented in this work provide a basic understanding of the design aspects to the beginners working in the gas turbine combustors particularly meant for turbo shaft engines applications.
Chinese investment in the USA and US–China relations
Authors: Zhu Zhiqun 
Published: November 2018

Purpose
The purpose of this paper is to analyze the rationale, strategies and significance of Chinese investment in the USA and its impact on US–China relations.

Design/methodology/approach
Through empirical analysis, this preliminary study examines the rationale, strategies and impact of Chinese investment in the USA.

Findings
Chinese investment has promoted economic growth in both countries, but it faces several challenges including security concerns and cultural clashes.

Originality/value
This paper is one of the first, comprehensive studies of the topic.
Information asymmetries and agricultural credit
Authors: Zegarra Luis Felipe 
Published: November 2018

Purpose
The purpose of this paper is to analyze the functioning of the rural credit market of Lima from 1825 to 1865, paying special attention to the effect of information asymmetries on the access to rural credit.

Design/methodology/approach
The article relies on primary sources for the study of the early credit market of Lima. In particular, the study relies on a sample of notarized loans for 1825–1865 and on property tax reports, collected from the National Archives of Peru, to determine the effect of information asymmetries, collateral and regional lending on access to credit. The article also analyzes the legal system of Peru during this period to determine whether property rights were well protected and so collateral could be used in the rural credit market.

Findings
A revision of the legislation shows that the legal system had some deficiencies, but allowed landlords and tenants to use their assets as collateral. Tax reports show that landlords and tenants owned valuable capital that could be used as collateral. Evidence from notarized loans shows that information asymmetries severely restricted inter-regional lending. In Lima, however, notaries played a role as financial intermediaries, providing the information about potential borrowers and allowing landlords and tenants to access credit. As a result, access to credit was significant for landlords and tenants.

Originality/value
This paper is one of the few historical studies on the role of information asymmetries in the allocation of rural credit in Latin America. It contributes to our understanding of credit markets prior to the creation of banks.