bluuebunny/crossref_metadata_2025_split huggingface dataset:
Druggable negative allosteric site of P2X3 receptors
Authors: Wang Jin , Wang Yao , Cui Wen-Wen , Huang Yichen , Yang Yang , Liu Yan , Zhao Wen-Shan , Cheng Xiao-Yang , Sun Wang-Sheng , Cao Peng , Zhu Michael X. , Wang Rui , Hattori Motoyuki , Yu Ye 
Published: April 2018

SignificanceAllosteric regulation, produced by the binding of a ligand at an allosteric site topographically distinct from the orthosteric site, represents a direct and efficient means for modulation of biological macromolecule function. Because allosteric modulators have advantages over classic orthosteric ligands as therapeutic agents, understanding the mechanism underlying allosteric modulation may open new therapeutic avenues. Here, we focused on allosteric regulation of P2X receptors, which are implicated in diverse pathophysiological processes, such as blood clotting, pain sensation, inflammation, and rheumatoid arthritis. Combining structural determination, molecular modeling, and mutagenesis, we identified a druggable allosteric site on P2X3. Our findings will facilitate the development of novel therapeutics targeting these receptors.
HFSP: high speed homology-driven function annotation of proteins
Authors: Mahlich Yannick , Steinegger Martin , Rost Burkhard , Bromberg Yana 
Published: April 2018

Abstract

Motivation
The rapid drop in sequencing costs has produced many more (predicted) protein sequences than can feasibly be functionally annotated with wet-lab experiments. Thus, many computational methods have been developed for this purpose. Most of these methods employ homology-based inference, approximated via sequence alignments, to transfer functional annotations between proteins. The increase in the number of available sequences, however, has drastically increased the search space, thus significantly slowing down alignment methods.

Results
Here we describe homology-derived functional similarity of proteins (HFSP), a novel computational method that uses results of a high-speed alignment algorithm, MMseqs2, to infer functional similarity of proteins on the basis of their alignment length and sequence identity. We show that our method is accurate (85% precision) and fast (more than 40-fold speed increase over state-of-the-art). HFSP can help correct at least a 16% error in legacy curations, even for a resource of as high quality as Swiss-Prot. These findings suggest HFSP as an ideal resource for large-scale functional annotation efforts.

Supplementary information
Supplementary data are available at Bioinformatics online.
comoRbidity: an R package for the systematic analysis of disease comorbidities
Authors: Gutiérrez-Sacristán Alba , Bravo Àlex , Giannoula Alexia , Mayer Miguel A , Sanz Ferran , Furlong Laura I 
Published: April 2018

Abstract

Motivation
The study of comorbidities is a major priority due to their impact on life expectancy, quality of life and healthcare cost. The availability of electronic health records (EHRs) for data mining offers the opportunity to discover disease associations and comorbidity patterns from the clinical history of patients gathered during routine medical care. This opens the need for analytical tools for detection of disease comorbidities, including the investigation of their underlying genetic basis.

Results
We present comoRbidity, an R package aimed at providing a systematic and comprehensive analysis of disease comorbidities from both the clinical and molecular perspectives. comoRbidity leverages from (i) user provided clinical data from EHR databases (the clinical comorbidity analysis) and (ii) genotype-phenotype information of the diseases under study (the molecular comorbidity analysis) for a comprehensive analysis of disease comorbidities. The clinical comorbidity analysis enables identifying significant disease comorbidities from clinical data, including sex and age stratification and temporal directionality analyses, while the molecular comorbidity analysis supports the generation of hypothesis on the underlying mechanisms of the disease comorbidities by exploring shared genes among disorders. The open-source comoRbidity package is a software tool aimed at expediting the integrative analysis of disease comorbidities by incorporating several analytical and visualization functions.

Availability and implementation
https://bitbucket.org/ibi_group/comorbidity

Supplementary information
Supplementary data are available at Bioinformatics online.
CONICS integrates scRNA-seq with DNA sequencing to map gene expression to tumor sub-clones
Authors: Müller Sören , Cho Ara , Liu Siyuan J , Lim Daniel A , Diaz Aaron 
Published: April 2018

Abstract

Motivation
Single-cell RNA-sequencing (scRNA-seq) has enabled studies of tissue composition at unprecedented resolution. However, the application of scRNA-seq to clinical cancer samples has been limited, partly due to a lack of scRNA-seq algorithms that integrate genomic mutation data.

Results
To address this, we present

CONICS
COpy-Number analysis In single-Cell RNA-Sequencing. CONICS is a software tool for mapping gene expression from scRNA-seq to tumor clones and phylogenies, with routines enabling: the quantitation of copy-number alterations in scRNA-seq, robust separation of neoplastic cells from tumor-infiltrating stroma, inter-clone differential-expression analysis and intra-clone co-expression analysis.

Availability and implementation
CONICS is written in Python and R, and is available from https://github.com/diazlab/CONICS.

Supplementary information
Supplementary data are available at Bioinformatics online.
GlycoStore: a database of retention properties for glycan analysis
Authors: Zhao Sophie , Walsh Ian , Abrahams Jodie L , Royle Louise , Nguyen-Khuong Terry , Spencer Daniel , Fernandes Daryl L , Packer Nicolle H , Rudd Pauline M , Campbell Matthew P 
Published: April 2018

Abstract

Summary
GlycoStore is a curated chromatographic, electrophoretic and mass-spectrometry composition database of N-, O-, glycosphingolipid (GSL) glycans and free oligosaccharides associated with a range of glycoproteins, glycolipids and biotherapeutics. The database is built on publicly available experimental datasets from GlycoBase developed in the Oxford Glycobiology Institute and then the National Institute for Bioprocessing Research and Training (NIBRT). It has now been extended to include recently published and in-house data collections from the Bioprocessing Technology Institute (BTI) A*STAR, Macquarie University and Ludger Ltd. GlycoStore provides access to approximately 850 unique glycan structure entries supported by over 8500 retention positions determined by: (i) hydrophilic interaction chromatography (HILIC) ultra-high performance liquid chromatography (U/HPLC) and reversed phase (RP)-U/HPLC with fluorescent detection; (ii) porous graphitized carbon (PGC) chromatography in combination with ESI-MS/MS detection; and (iii) capillary electrophoresis with laser induced fluorescence detection (CE-LIF). GlycoStore enhances many features previously available in GlycoBase while addressing the limitations of the data collections and model of this popular resource. GlycoStore aims to support detailed glycan analysis by providing a resource that underpins current workflows. It will be regularly updated by expert annotation of published data and data obtained from the project partners.

Availability and implementation
http://www.glycostore.org

Supplementary information
Supplementary data are available at Bioinformatics online.
MARDy: Mycology Antifungal Resistance Database
Authors: Nash Anthony , Sewell Thomas , Farrer Rhys A , Abdolrasouli Alireza , Shelton Jennifer M G , Fisher Matthew C , Rhodes Johanna 
Published: April 2018

Abstract

Summary
The increase of antifungal drug resistance is a major global human health concern and threatens agriculture and food security; in order to tackle these concerns, it is important to understand the mechanisms that cause antifungal resistance. The curated Mycology Antifungal Resistance Database (MARDy) is a web-service of antifungal drug resistance mechanisms, including amino acid substitutions, tandem repeat sequences and genome ploidy. MARDy is implemented on a Linux, Apache, MySQL and PHP web development platform and includes a local installation of BLASTn of the database of curated genes.

Availability and implementation
MARDy can be accessed at http://www.mardy.net and is free to use. The complete database can be retrieved, ordered by organism, gene and drug. Missing or new mycological antifungal resistance data can be relayed to the development team through a contribute entry form. Updates and news will be publicized via a dedicated Twitter feed: @MARDYfungi.
Spatial quantification of the synaptic activity phenotype across large populations of neurons with Markov random fields
Authors: Robinson Sean , Courtney Michael J 
Published: April 2018

Abstract

Motivation
The collective and co-ordinated synaptic activity of large neuronal populations is relevant to neuronal development as well as a range of neurological diseases. Quantification of synaptically-mediated neuronal signalling permits further downstream analysis as well as potential application in target validation and in vitro screening assays. Our aim is to develop a phenotypic quantification for neuronal activity imaging data of large populations of neurons, in particular relating to the spatial component of the activity.

Results
We extend the use of Markov random field (MRF) models to achieve this aim. In particular, we consider Bayesian posterior densities of model parameters in Gaussian MRFs to directly model changes in calcium fluorescence intensity rather than using spike trains. The basis of our model is defining neuron ‘neighbours’ by the relative spatial positions of the neuronal somata as obtained from the image data whereas previously this has been limited to defining an artificial square grid across the field of view and spike binning. We demonstrate that our spatial phenotypic quantification is applicable for both in vitro and in vivo data consisting of thousands of neurons over hundreds of time points. We show how our approach provides insight beyond that attained by conventional spike counting and discuss how it could be used to facilitate screening assays for modifiers of disease-associated defects of communication between cells.

Availability and implementation
We supply the MATLAB code and data to obtain all of the results in the paper.

Supplementary information
Supplementary data are available at Bioinformatics online.
Decomposition Spaces and Restriction Species
Authors: Gálvez-Carrillo Imma , Kock Joachim , Tonks Andrew 
Published: April 2018

Abstract
We show that Schmitt’s restriction species (such as graphs, matroids, posets, etc.) naturally induce decomposition spaces (a.k.a. unital $2$-Segal spaces), and that their associated coalgebras are an instance of the general construction of incidence coalgebras of decomposition spaces. We introduce directed restriction species that subsume Schmitt’s restriction species and also induce decomposition spaces. Whereas ordinary restriction species are presheaves on the category of finite sets and injections, directed restriction species are presheaves on the category of finite posets and convex maps. We also introduce the notion of monoidal (directed) restriction species, which induce monoidal decomposition spaces and hence bialgebras, most often Hopf algebras. Examples of this notion include rooted forests, directed graphs, posets, double posets, and many related structures. A prominent instance of a resulting incidence bialgebra is the Butcher–Connes–Kreimer Hopf algebra of rooted trees. Both ordinary and directed restriction species are shown to be examples of a construction of decomposition spaces from certain cocartesian fibrations over the category of finite ordinals that are also cartesian over convex maps. The proofs rely on some beautiful simplicial combinatorics, where the notion of convexity plays a key role. The methods developed are of independent interest as techniques for constructing decomposition spaces.
Clinicopathological predictors for progression of chronic kidney disease in nephrosclerosis: a biopsy-based cohort study
Authors: Yamanouchi Masayuki , Hoshino Junichi , Ubara Yoshifumi , Takaichi Kenmei , Kinowaki Keiichi , Fujii Takeshi , Ohashi Kenichi , Mise Koki , Toyama Tadashi , Hara Akinori , Shimizu Miho , Furuichi Kengo , Wada Takashi 
Published: April 2018

Abstract

Background
Biopsy-based studies on nephrosclerosis are lacking and the clinicopathological predictors for progression of chronic kidney disease (CKD) are not well established.

Methods
We retrospectively assessed 401 patients with biopsy-proven nephrosclerosis in Japan. Progression of CKD was defined as new-onset end-stage renal disease, decrease of estimated glomerular filtration rate (eGFR) by  ≥50% or doubling of serum creatinine, and the sub-distribution hazard ratio (SHR) with 95% confidence interval (CI) for CKD progression was determined for various clinical and histological characteristics in competing risks analysis. The incremental value of pathological information for predicting CKD progression was assessed by calculating Harrell’s C-statistics, the Akaike information criterion (AIC), net reclassification improvement and integrated discrimination improvement.

Results
During a median follow-up period of 5.3 years, 117 patients showed progression of CKD and 10 patients died before the defined kidney event. Multivariable sub-distribution hazards model identified serum albumin (SHR 0.48; 95% CI 0.35–0.67), hemoglobin A1c (SHR 0.71; 95% CI 0.54–0.94), eGFR (SHR 0.98; 95% CI 0.97–0.99), urinary albumin/creatinine ratio (UACR) (SHR 1.18; 95% CI 1.08–1.29), percentage of segmental/global glomerulosclerosis (%GS) (SHR 1.01; 95% CI 1.00–1.02) and interstitial fibrosis and tubular atrophy (IFTA) (SHR 1.52; 95% CI 1.20–1.92) as risk factors for CKD progression. The C-statistic of a model with only clinical variables was improved by adding %GS (0.790 versus 0.796, P < 0.01) and IFTA (0.790 versus 0.811, P < 0.01). The reclassification statistic was also improved after adding the biopsy data to the clinical data. The model including IFTA was superior, with the lowest AIC.

Conclusions
The study implies that in addition to the traditional markers of eGFR and UACR, we may explore the markers of serum albumin and hemoglobin A1c, which are widely available but not routinely measured in patients with nephrosclerosis, and the biopsy data, especially the data on the severity of interstitial damage, for the better prediction of CKD progression in patients with nephrosclerosis.
In the Beginning, All the World Was America
Authors: Ince Onur Ulas 
Published: April 2018

Abstract
This chapter offers an analysis of John Locke’s theory of property in the context of Atlantic colonial capitalism. Breaking with interpretations that center on Locke’s theory of labor, the chapter identifies Locke’s theory of money as the linchpin of his liberal justification of English colonization in America. It brings into conversation the colonial interpretations of Locke with the earlier economic debates on the place of natural law, morality, and accumulation of capital in Locke’s theory of property. It argues that by predicating property and improvement on monetization, Locke construes the absence of monetization in America as the sign that the continent remains in the state of “natural common” open to nonconsensual appropriation. By invoking a fictive “universal tacit consent of mankind” as the origin of money, Locke bridges the gap between his liberal theory of private property and the illiberality of extralegal colonial expansion in the New World.
Letters from Sydney
Authors: Ince Onur Ulas 
Published: April 2018

Abstract
This chapter examines Wakefield’s political economic arguments and policy proposals for the colonial settlement of Australasia as a systematic solution to the demographic problems of overpopulation in Britain and underpopulation in Britain’s colonies. It is argued that Wakefield’s theory of “systematic colonization” aimed to protect the British capitalist civilization from social revolution at home and frontier barbarism in the colonies. Equating capitalist civilization with wage labor, Wakefield planned for the creation of a legally free yet structurally dependent colonial labor force. This would be achieved by imposing preemptive crown rights and artificially inflated prices on colonial lands, which would prevent poor emigrants from becoming landowners and force them to work for colonial capitalists. Cognizant of the illiberality of instituting colonial wage servitude by the imperial state, Wakefield fabricated a utilitarian myth of “contractual dispossession,” recasting systematic colonization and colonial proletarianization as the enforcement of an original “settler contract” among colonists.
All at Sea
Authors: Livermore Roy 
Published: April 2018

Abstract
According to first-generation plate tectonics, sea-floor spreading was nice and simple. Plates were pulled apart at mid-ocean ridges, and weak mantle rocks rose to fill the gap and began to melt. The resulting basaltic magma ascended into the crust, where it ponded to form linear ‘infinite onion’ magma chambers beneath the mid-ocean tennis-ball seam. At frequent intervals, vertical sheets of magma rose from these chambers to the surface, where they erupted to form new ocean floor or solidified to form dykes, in the process acquiring a magnetization corresponding to the geomagnetic field at the time. Mid-ocean ridge axes were defined by rifted valleys and divided into segments by transform faults with offsets of tens to hundreds of kilometres, resulting in the staircase pattern seen on maps of the ocean floor. All mid-ocean ridges were thus essentially identical. Such a neat and elegant theory was bound to be undermined as new data were acquired in the oceans.
Mesomedes’Hymn to the Sun
Authors: Psaroudakes Stelios 
Published: April 2018

AbstractThis chapter investigates the relationship between the lyrics and the music of Mesomedes’ Hymn to the Sun. There are many instances of word painting in music. The chapter argues that Mesomedes’ Hymn to the Sun is a piece of music well thought through by the composer. The song’s melodic contours reflect and accentuate the meaning of the words, which can affectively be brought forth in sound if the performer is musically sensitive and is aware of the word-melody relationships. It is argued that the song was most probably composed for monodic performance.
Humans as a Service
Authors: Prassl Jeremias 
Published: April 2018

Abstract
The rise of the gig economy is disrupting business models across the globe. Platforms’ digital work intermediation has had a profound impact on traditional conceptions of the employment relationship. The completion of ‘tasks’, ‘gigs’, or ‘rides’ in the (digital) crowd fundamentally challenges our understanding of work in modern labour markets: gone are the stable employment relationships between firms and workers, replaced by a world in which everybody can be ‘their own boss’ and enjoy the rewards—and face the risks—of independent businesses. Is this the future of work? What are the benefits and challenges of crowdsourced work? How can we protect consumers and workers without stifling innovation? Humans as a Service provides a detailed account of the growth and operation of gig-economy platforms, and develops a blueprint for solutions to the problems facing on-demand workers, platforms, and their customers. Following a brief introduction to the growth and operation of on-demand platforms across the world, the book scrutinizes competing narratives about ‘gig’ work. Drawing on a wide range of case studies, it explores how claims of ‘disruptive innovation’ and ‘micro-entrepreneurship’ often obscure the realities of precarious work under strict algorithmic surveillance, and the return to a business model that has existed for centuries. Humans as a Service shows how employment law can address many of these problems: gigs, tasks, and rides are work—and should be regulated as such. A concluding chapter demonstrates the broader benefits of a level playing field for consumers, taxpayers, and innovative entrepreneurs.
Work on Demand
Authors: Adams-Prassl Jeremias 
Published: April 2018

Abstract
This chapter explores how the gig economy works. It looks at some of the most important platforms and illustrates their central role in shaping transactions between consumers and workers. Digital work intermediation, in particular, is key to understanding the gig economy: here, platforms’ sophisticated algorithms connect workers and customers, and exercise ongoing control over the ensuing relationships. The chapter then charts the astonishing variety and global growth of the gig economy, with a particular emphasis on how platforms make money, from improved matchmaking to regulatory arbitrage. Finally, this chapter turns to the broader impacts of digital work intermediation, considering how platforms go beyond mere matchmaking to shape the experiences of workers and consumers.
The Innovation Paradox
Authors: Adams-Prassl Jeremias 
Published: April 2018

Abstract
This chapter turns to the innovation narrative. It argues that, as far as work is concerned, gig-economy innovation is a myth. The software and hardware on which apps and platforms draw are often the direct result of truly revolutionary innovation and breakthroughs, from GPS locators and the Internet to powerful processors that fit into the palm of your hand. This is the innovation paradox: contrary to the industry’s claims, the underlying business model is anything but novel, as illustrations ranging from nineteenth-century homework in the ‘sweated trades’ to dock labour in the early twentieth century demonstrate. The gig economy is but the latest (and perhaps the most extreme) example of labour market practices that have been around for centuries, with low-skilled tasks instead of complex jobs, powerful intermediaries controlling large workforces, and hybrid arrangements between open market and closed hierarchies replacing the traditional binary contract of employment.
Primitive Equations Model
Authors: Zeitlin Vladimir 
Published: April 2018

AbstractThe chapter gives the foundations of modelling of large-scale atmospheric and oceanic motions and presents the ‘primitive equations’ (PE) model. After a concise reminder on general fluid mechanics, the main hypotheses leading to the PE model are explained, together with the tangent-plane (so-called f and beta plane) approximations, and ‘traditional’ approximation to the hydrodynamical equations on the rotating sphere. PE are derived in parallel for the ocean and for the atmosphere. It is then shown that, with a judicious choice of the vertical coordinate, the ‘pseudo-height’, in the atmosphere, these two sets of equations are practically equivalent. The main properties of PE are derived and the key concepts of wave–vortex dichotomy, and of slow and fast motions, are explained. The essential notion of potential vorticity is introduced and its conservation by fluid masses is demonstrated. Inertia–gravity waves are explained and their properties presented. Limitations of the hydrostatic hypothesis are demonstrated.