bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Fundamentality of Fit
Authors: Howard Christopher 
Published: July 2019

Abstract
Many authors, including Derek Parfit, T. M. Scanlon, and Mark Schroeder, favor a “reasons-first” ontology of normativity, which treats reasons as normatively fundamental. Others, most famously G. E. Moore, favor a “value-first” ontology, which treats value or goodness as normatively fundamental. Chapter 10 argues that both the reasons-first and value-first ontologies should be rejected because neither can account for all of the normative reasons that, intuitively, there are. It advances an ontology of normativity, originally suggested by Franz Brentano and A. C. Ewing, according to which fittingness is normatively fundamental. The normative relation of fittingness is the relation in which a response stands to an object when the object merits—or is worthy of—that response. The author argues that his “fittingness-first” ontology is no less parsimonious than either the reasons- or the value-first ontology, but it can plausibly accommodate the existence of all the normative reasons there are. It therefore provides a superior ontology of normativity.
Dualism and Development
Authors: Nattrass Nicoli , Seekings Jeremy 
Published: July 2019

AbstractChapter 2 discusses the Lewis model of development with surplus labour and the ongoing relevance of his dualist approach as demonstrated in the industrialization of Hong Kong, India, Bangladesh, etc. We show, using examples from the South African clothing manufacturing industry, that relatively high- and low-wage firms exist in the same industry by using different technologies and targeting different product markets. There is no necessary ‘race to the bottom’. Industrial policy can usefully promote competitiveness across a range of technologies, supporting labour-intensive technologies (especially in contexts of high unemployment) without undermining firms in more skill- and capital-intensive niches. The chapter concludes with a discussion of the implications of unemployment for development strategy, and for the relationship between development and inequality.
The Moral Economy of Low-Wage Work
Authors: Nattrass Nicoli , Seekings Jeremy 
Published: July 2019

AbstractChapter 5 considers the debate over ‘sweatshops’ in the clothing manufacturing industry, arguing that the moral economy of rival positions entails different understandings of the relationship between wages, profits, and employment. Many contemporary arguments reflect those made over a century earlier in Britain and the US. However, whereas the British Fabian socialists sought (and achieved) the simultaneous expansion of labour protection and welfare support for the unemployed, the contemporary anti-sweatshop movement focusses solely on wages. By the early twentieth century in Britain, those who lost their jobs because of rising minimum wages could expect support from the welfare system. In twenty-first-century surplus labour countries, the unemployed fall through what meagre welfare nets exist. In this context, the potential trade-off between wages and employment matters for poverty and inequality. Chapter 5 also reviews the evidence on the impact of rising minimum wages on employment both internationally and in South Africa. The impact is typically neutral or mildly negative, suggesting that policymakers are generally careful about not raising minimum wages excessively. There is, however, evidence that it is mostly unskilled workers who lose jobs when job losses occur.
Minimal
n
-noids in hyperbolic and anti-de Sitter 3-space
Authors: Bobenko Alexander I. , Heller Sebastian , Schmitt Nicholas 
Published: July 2019

We construct minimal surfaces in hyperbolic and anti-de Sitter 3-space with the topology of a
n
-punctured sphere by loop group factorization methods. The end behaviour of the surfaces is based on the asymptotics of Delaunay-type surfaces, i.e. rotational symmetric minimal cylinders. The minimal surfaces in H
3
extend to Willmore surfaces in the conformal 3-sphere
S
3
= H
3
∪S
2
∪H
3
.
Quantification of Conflicts of Interest in an Online Point-of-Care Clinical Support Website
Authors: Chopra Ambica C. , Tilberry Stephanie , Sternat Kaitlyn E. , Chung Daniel Y. , Nichols Stephanie D. , Piper Brian J. 
Published: July 2019

AbstractOnline medical reference websites are utilized by health care providers to enhance their education and decision making. However, these resources may not adequately reveal pharmaceutical-author interactions and their potential conflicts of interest (CoIs). This investigation: 1) evaluates the correspondence of two well-utilized CoI databases: the Centers for Medicare and Medicaid Services Open Payments (CMSOP) and ProPublica’s Dollars for Docs (PDD) and 2) quantifies CoIs among authors of a publically available point of care clinical support website. Two data sources were used: the hundred most common drugs and the top fifty causes of death. These topics were entered into a freely available database. The authors (N = 139) were then input into CMSOP and PDD and compensation and number of payment were determined for 2013-2015. The subset of highly compensated authors that also reported “Nothing to disclose” were further examined. There was a high degree of similarity between CMSOP and PDD for compensation (R2 ≥ 0.998) and payment number (R2 ≥ 0.992). The amount received was 1.4% higher in CMSOP ($4,059,194) than in PDD ($4,002,891). The articles where the authors had received the greatest compensation were in neurology (Parkinson’s Disease = $1,810,032), oncology (Acute Lymphoblastic Leukemia = $616,727), and endocrinology (Type I Diabetes = $377,388). Two authors reporting “Nothing to disclose” received appreciable and potentially relevant compensation. CMSOP and PDD produced almost identical results. CoIs were common among authors but self-reporting may be an inadequate reporting mechanism. Recommendations are offered for improving the CoI transparency of pharmaceutical-author interactions in point-of-care electronic resources.
Actigraphic Screening for Rapid Eye Movement Sleep Behavior Disorder
Authors: Kristián Šandala , Simona Dostálová , Jiří Nepožitek , Losada Veronika Ibarburu Lorenzo y , Petr Dušek , Evžen Růžička , Karel Šonka , David Kemlink 
Published: July 2019

AbstractBackgroundThe patients suffering of the rapid eye movement sleep behavior disorder (RBD) are in high risk of developing a neurodegenerative disorder, most frequently from the group of alpha-synucleinopathies, such as Parkinson’s disease (PD), Dementia with Lewy Bodies (DLB) or multiple system atrophy (MSA). The definitive diagnosis of RBD is based on polysomnographic investigation. Actigraphy is much easier to perform and reflects condition in patient’s home environment.The aimsThe aim of this study was to find suitable biomarkers for RBD, which can be detectable by actigraphic recording.MethodsHigh resolution actigraphic recording (MotionWatch, CamNtech ltd.) and confirming polysomnographic recording was performed on 45 RBD patients, 30 patients with other sleep-related motor disorders and 20 healthy controls. Each individual file was analysed by software testing for amount of sleep (MotionWare 1.1.20) and secondly for periodic motor activity (PLMS analysis 1.0.16). The 13-item patient self-rating RBD screening questionnaire (RBD-SQ) translated to Czech language was also used for screening purposes. We used an RBD-SQ score of five points as a positive test result, as suggested by the original publication of the scale.ResultsWhen using the actigraphic sleep detection, we encountered significant differences mostly on non-dominant hand, related to sleep fragmentation - most notably increased percentage of Short immobile bouts (47.0% vs. 28.0%, p<0.0001), increased Fragmentation index (72.5 vs. 40.7, p<0.0001) and decreased percentage of Sleep efficiency (72.1% vs. 86.8%, p<0.0001)in RBD subjects compared to other sleep disorders and controls. When analyzing periodic motor activity, we also found surprisingly more periodic hand movements (p=0.028, corrected for multiple testing), but differences on lower extremities using either measurement were not significant. The discrimination function based on RBD-SQ and Short immobile bouts % could allocate correctly the RBD status in 87.6% of cases with Wilks Lambda 0.435 and p<0.0001.ConclusionIn our single-center study in patients from the Czech population, we found that actigraphic recording from upper extremities shows consistently more prominent sleep fragmentation in RBD patients compared to other sleep diagnoses or healthy controls. Actigraphy may be useful in broader screening for RBD.
Pathway Association Studies Tool
Authors: Thrash Adam , Tang Juliet D. , DeOrnellis Mason , Peterson Daniel G. , Warburton Marilyn L. 
Published: July 2019

AbstractBackgroundIn recent years, a bioinformatics method for interpreting GWAS data using metabolic pathway analysis has been developed and successfully used to find significant pathways and mechanisms explaining phenotypic traits of interest in plants. However, the many scripts implementing this method were not straightforward to use, had to be customized for each project, required user supervision, and took more than 24 hours to process data. PAST (Pathway Association Study Tool), a new implementation of this method, has been developed to address these concerns.ResultsPAST is implemented as a package for the R language. Two user-interfaces are provided; PAST can be run by loading the package in R and calling its methods, or by using an R Shiny guided user interface. In testing, PAST completed analyses in approximately one hour by processing data in parallel. PAST has many user-specified options for maximum customization. PAST produces the same results as the previously developed method.ConclusionsIn order to promote a powerful new method of pathway analysis that interprets GWAS data to find biological mechanisms associated with traits of interest, we developed a more accessible and user friendly tool. This tool is more efficient and requires less knowledge of programming languages to use than previous methods. Moreover, it produces similar results in significantly less time. These attributes make PAST accessible to researchers interested in associating metabolic pathways with GWAS datasets to better understand the genetic architecture and mechanisms affecting phenotype.
Modular Thermal Control of Protein Dimerization
Authors: Piraner Dan I. , Wu Yan , Shapiro Mikhail G. 
Published: July 2019

ABSTRACTProtein-protein interactions and protein localization are essential mechanisms of cellular signal transduction. The ability to externally control such interactions using chemical and optogenetic methods has facilitated biological research and provided components for the engineering of cell-based therapies and materials. However, chemical and optical methods are limited in their ability to provide spatiotemporal specificity in light-scattering tissues. To overcome these limitations, we present “thermomers,” modular protein dimerization domains controlled with temperature – a form of energy that can be delivered to cells both globally and locally in a wide variety of in vitro and in vivo contexts. Thermomers are based on a sharply thermolabile coiled-coil protein, which we engineered to heterodimerize at a tunable transition temperature within the biocompatible range of 37–42 °C. When fused to other proteins, thermomers can reversibly control their association, as demonstrated via membrane localization in mammalian cells. This technology enables remote control of intracellular protein-protein interactions with a form of energy that can be delivered with spatiotemporal precision in a wide range of biological, therapeutic and living material scenarios.
Improving interpretability of deep learning models: splicing codes as a case study
Authors: Jha Anupama , Aicher Joseph K. , Singh Deependra , Barash Yoseph 
Published: July 2019

AbstractDespite the success and fast adaptation of deep learning models in a wide range of fields, lack of interpretability remains an issue, especially in biomedical domains. A recent promising method to address this limitation is Integrated Gradients (IG), which identifies features associated with a prediction by traversing a linear path from a baseline to a sample. We extend IG with nonlinear paths, embedding in latent space, alternative baselines, and a framework to identify important features which make it suitable for interpretation of deep models for genomics.
The CIViC knowledge model and standard operating procedures for curation and clinical interpretation of variants in cancer
Authors: Danos Arpad M. , Krysiak Kilannin , Barnell Erica K. , Coffman Adam C. , McMichael Joshua F. , Kiwala Susanna , Spies Nicholas C. , Sheta Lana M. , Pema Shahil P. , Kujan Lynzey , Clark Kaitlin A. , Wollam Amber Z. , Rao Shruti , Ritter Deborah I. , Sonkin Dmitriy , Raca Gordana , Kim Raymond H. , Wagner Alex H. , Madhavan Subha , Griffith Malachi , Griffith Obi L. 
Published: July 2019

AbstractManually curated variant knowledgebases and their associated knowledge models are serving an increasingly important role in distributing and interpreting variants in cancer. These knowledgebases vary in their level of public accessibility, and the complexity of the models used to capture clinical knowledge. CIViC (Clinical Interpretations of Variants in Cancer - www.civicdb.org) is a fully open, free-to-use cancer variant interpretation knowledgebase that incorporates highly detailed curation of evidence obtained from peer-reviewed publications. Currently, the CIViC knowledge model consists of four main components: Genes, Variants, Evidence Items, and Assertions. Each component has an associated knowledge model and methods for curation. Gene and Variant data contextualize the genomic region(s) involved in the clinical statement. Evidence Items provide structured associations between variants and their clinically predictive/therapeutic, prognostic, diagnostic, predisposing, and functional implications. Finally, CIViC Assertions summarize collections of CIViC Evidence Items for a specific Disease, Variant, and Clinical Significance with incorporation of clinical and technical guidelines. Here we present the CIViC knowledge model, curation standard operating procedures, and detailed examples to support community-driven curation of cancer variants.
Restoration of wild-type motility to flagellin-knockoutEscherichia coli
Authors: Thomson Nicholas M. , Pallen Mark J. 
Published: July 2019

AbstractFlagellin is the major constituent of the flagellar filament and faithful restoration of wild-type motility to flagellin mutants may be beneficial for studies of flagellar biology and biotechnological exploitation of the flagellar system. Therefore, we explored the restoration of motility by flagellin expressed from a variety of combinations of promoter, plasmid copy number and induction strength. Motility was only partially restored using the tightly regulated rhamnose promoter, but wild-type motility was achieved with the T5 promoter, which, although leaky, allowed titration of induction strength. Motility was little affected by plasmid copy number when dependent on inducible promoters. However, plasmid copy number was important when expression was controlled by the nativeE. coliflagellin promoter. Motility was poorly correlated with flagellin transcription levels, but strongly correlated with the amount of flagellin associated with the flagellar filament, suggesting that excess monomers are either not exported or not assembled into filaments. This study provides a useful reference for further studies of flagellar function and a simple blueprint for similar studies with other proteins.
Heterogeneities in intrinsic excitability and frequency-dependent response properties of granule cells across the blades of the rat dentate gyrus
Authors: Mishra Poonam , Narayanan Rishikesh 
Published: July 2019

ABSTRACTThe dentate gyrus (DG), the input gate to the hippocampus proper, is anatomically segregated into three different sectors, namely the suprapyramidal blade, the crest region and the infrapyramidal blade. Although there are well-established differences between these sectors in terms of neuronal morphology, connectivity patterns and activity levels, differences in electrophysiological properties of granule cells within these sectors have remained unexplored. Here, employing somatic whole-cell patch-clamp recordings from the rat DG, we demonstrate that granule cells in these sectors manifest considerable heterogeneities in their intrinsic excitability, temporal summation, action potential characteristics and frequency-dependent response properties. Across sectors, these neurons showed positive temporal summation of their responses to inputs mimicking excitatory postsynaptic currents, and showed little to no sag in their voltage responses to pulse currents. Consistently, the impedance amplitude profile manifested low-pass characteristics and the impedance phase profile lacked positive phase values at all measured frequencies, voltages and for all sectors. Granule cells in all sectors exhibited class I excitability, with broadly linear firing rate profiles, and granule cells in the crest region fired significantly less action potentials compared to those in the infrapyramidal blade. Finally, we found weak pairwise correlations across the 18 different measurements obtained individually from each of the three sectors, providing evidence that these measurements are indeed reporting distinct aspects of neuronal physiology. Together, our analyses show that granule cells act as integrators of afferent information, and emphasize the need to account for the considerable physiological heterogeneities in assessing their roles in information encoding and processing.
Molecular mechanism of mitochondrial phosphatidate transfer by Ups1/Mdm35
Authors: Lu Jiuwei , Chan Kevin , Yu Leiye , Fan Jun , Zhai Yujia , Sun Fei 
Published: July 2019

ABSTRACTCardiolipin plays many important roles for mitochondrial physiological function and is synthesized from phosphatidic acid (PA) at inner mitochondrial membrane (IMM). PA synthesized from endoplasmic reticulum needs to transfer to IMM via outer mitochondrial membrane (OMM). The transfer of PA between IMM and OMM is mediated by Ups1/Mdm35 protein family. Although there are many structures of this family available, the detailed molecular mechanism of how PA is transferred between membranes is yet unknown. Here, we report another crystal structures of Ups1/Mdm35 in the authentic monomeric apo state and the DHPA bound state. By combining subsequent all-atom molecular dynamics simulations, extensive structural comparisons and biophysical assays, we discovered the conformational changes of Ups1/Mdm35, identified key structural elements and residues during membrane binding and PA entry. We found the monomeric Ups1 on membrane is an important transit for the success of PA transfer, and the equilibrium between monomeric Ups1 and Ups1/Mdm35 complex on membrane affects the PA transfer rate and can be regulated by many factors including environmental pH.
Application of a gut-immune co-culture system for the study of N-glycan-dependent host-pathogen interactions ofCampylobacter jejuni
Authors: Zamora Cristina Y. , Ward Elizabeth M. , Kester Jemila C. , Kelly Chen Wen Li , Velazquez Jason G. , Griffith Linda G. , Imperiali Barbara 
Published: July 2019

AbstractAn in vitro gut-immune co-culture model with apical and basal accessibility, designed to more closely resemble a human intestinal microenvironment, was employed to study the role of the Nlinked protein glycosylation (Pgl) pathway in Campylobacter jejuni pathogenicity. The gutimmune co-culture (GIC) was developed to model important aspects of the human small intestine by the inclusion of mucin producing goblet cells, human enterocytes, and dendritic cells, bringing together a mucus-containing epithelial monolayer with elements of the innate immune system. The utility of the system was demonstrated by characterizing host-pathogen interactions facilitated by N-linked glycosylation, such as host epithelial barrier functions, bacterial invasion and immunogenicity. Changes in human intestinal barrier functions in the presence of 11168 C. jejuni (wildtype) strains were quantified using GICs. The glycosylationdeficient strain 11168 ΔpglE was 100-fold less capable of adhering to and invading this intestinal model in cell infectivity assays. Quantification of inflammatory signaling revealed that 11168ΔpglE differentially modulated inflammatory responses in different intestinal microenvironments, suppressive in some but activating in others. Virulence-associated outer membrane vesicles produced by wildtype and 11168ΔpglE C. jejuni were shown to have differential composition and function, with both leading to immune system activation when provided to the gut-immune co-culture model. This analysis of aspects of C. jejuni infectivity in the presence and absence of its N-linked glycome, is enabled by application of the gut-immune model and we anticipate that this system will be applicable to further studies of C. jejuni and other enteropathogens of interest.
Auditory contrast gain control predicts perceptual performance and is not dependent on cortical activity
Authors: Lohse Michael , Bajo Victoria M. , King Andrew J. , Willmore Ben D.B. 
Published: July 2019

AbstractNeural adaptation enables sensory information to be represented optimally in the brain despite large fluctuations over time in the statistics of the environment. Auditory contrast gain control represents an important example, which is thought to arise primarily from cortical processing. We find, however, that neurons in both the auditory thalamus and midbrain of mice show robust contrast gain control, and that this is implemented independently of cortical activity. Although neurons at each level exhibit contrast gain control to similar degrees, adaptation time constants become longer at later stages of the processing hierarchy, resulting in progressively more stable representations. We also show that auditory discrimination thresholds in human listeners compensate for changes in contrast, and that the strength of this perceptual adaptation can be predicted from physiological measurements. Contrast adaptation is therefore a robust property of both the subcortical and cortical auditory system and accounts for the short-term adaptability of perceptual judgments.