bluuebunny/crossref_metadata_2025_split huggingface dataset:
Schiller on Freedom and Aesthetic Value: Part I
Authors: Matherne Samantha , Riggle Nick 
Published: February 2020

Abstract
In his Letters on the Aesthetic Education of Man, Friedrich Schiller draws a striking connection between aesthetic value and individual and political freedom, claiming that, ‘it is only through beauty that man makes his way to freedom’. However, contemporary ways of thinking about freedom and aesthetic value make it difficult to see what the connection could be. Through a careful reconstruction of the Letters, we argue that Schiller’s theory of aesthetic value serves as the key to understanding not only his view of aesthetic engagement, but also his distinctive account of individual and political freedom. In Part I, we develop a reconstruction of Schiller's view that aesthetic value is the only path to individual freedom and in Part II we analyze how Schiller connects aesthetic value to political freedom. In the end, we show that Schiller defends a non-hedonic, action-oriented, communitarian theory of aesthetic value and a theory of freedom that makes the aesthetic not just supererogatory but fundamental for any fully autonomous life. Although we have lost touch with this way of thinking about aesthetic value and freedom, we submit that it is illuminating for contemporary thinking about both.
A survey of gene expression meta-analysis: methods and applications
Authors: Toro-Domínguez Daniel , Villatoro-García Juan Antonio , Martorell-Marugán Jordi , Román-Montoya Yolanda , Alarcón-Riquelme Marta E , Carmona-Sáez Pedro 
Published: February 2020

AbstractThe increasing use of high-throughput gene expression quantification technologies over the last two decades and the fact that most of the published studies are stored in public databases has triggered an explosion of studies available through public repositories. All this information offers an invaluable resource for reuse to generate new knowledge and scientific findings. In this context, great interest has been focused on meta-analysis methods to integrate and jointly analyze different gene expression datasets. In this work, we describe the main steps in the gene expression meta-analysis, from data preparation to the state-of-the art statistical methods. We also analyze the main types of applications and problems that can be approached in gene expression meta-analysis studies and provide a comparative overview of the available software and bioinformatics tools. Moreover, a practical guide for choosing the most appropriate method in each case is also provided.
FluPhenotype—a one-stop platform for early warnings of the influenza A virus
Authors: Lu Congyu , Cai Zena , Zou Yuanqiang , Zhang Zheng , Chen Wenjun , Deng Lizong , Du Xiangjun , Wu Aiping , Yang Lei , Wang Dayan , Shu Yuelong , Jiang Taijiao , Peng Yousong 
Published: February 2020

Abstract

Motivation
Newly emerging influenza viruses keep challenging global public health. To evaluate the potential risk of the viruses, it is critical to rapidly determine the phenotypes of the viruses, including the antigenicity, host, virulence and drug resistance.

Results
Here, we built FluPhenotype, a one-stop platform to rapidly determinate the phenotypes of the influenza A viruses. The input of FluPhenotype is the complete or partial genomic/protein sequences of the influenza A viruses. The output presents five types of information about the viruses: (i) sequence annotation including the gene and protein names as well as the open reading frames, (ii) potential hosts and human-adaptation-associated amino acid markers, (iii) antigenic and genetic relationships with the vaccine strains of different HA subtypes, (iv) mammalian virulence-related amino acid markers and (v) drug resistance-related amino acid markers. FluPhenotype will be a useful bioinformatic tool for surveillance and early warnings of the newly emerging influenza A viruses.

Availability and implementation
It is publicly available from: http://www.computationalbiology.cn : 18888/IVEW.

Supplementary information
Supplementary data are available at Bioinformatics online.
Polar labeling: silver standard algorithm for training disease classifiers
Authors: Wagholikar Kavishwar B , Estiri Hossein , Murphy Marykate , Murphy Shawn N 
Published: February 2020

Abstract

Motivation
Expert-labeled data are essential to train phenotyping algorithms for cohort identification. However expert labeling is time and labor intensive, and the costs remain prohibitive for scaling phenotyping to wider use-cases.

Results
We present an approach referred to as polar labeling (PL), to create silver standard for training machine learning (ML) for disease classification. We test the hypothesis that ML models trained on the silver standard created by applying PL on unlabeled patient records, are comparable in performance to the ML models trained on gold standard, created by clinical experts through manual review of patient records. We perform experimental validation using health records of 38 023 patients spanning six diseases. Our results demonstrate the superior performance of the proposed approach.

Availability and implementation
We provide a Python implementation of the algorithm and the Python code developed for this study on Github.

Supplementary information
Supplementary data are available at Bioinformatics online.
InterLig: improved ligand-based virtual screening using topologically independent structural alignments
Authors: Mirabello Claudio , Wallner Björn 
Published: February 2020

Abstract

Motivation
In the past few years, drug discovery processes have been relying more and more on computational methods to sift out the most promising molecules before time and resources are spent to test them in experimental settings. Whenever the protein target of a given disease is not known, it becomes fundamental to have accurate methods for ligand-based virtual screening, which compares known active molecules against vast libraries of candidate compounds. Recently, 3D-based similarity methods have been developed that are capable of scaffold hopping and to superimpose matching molecules.

Results
Here, we present InterLig, a new method for the comparison and superposition of small molecules using topologically independent alignments of atoms. We test InterLig on a standard benchmark and show that it compares favorably to the best currently available 3D methods.

Availability and implementation
The program is available from http://wallnerlab.org/InterLig.

Supplementary information
Supplementary data are available at Bioinformatics online.
Baloxavir: A Novel Antiviral Agent in the Treatment of Influenza
Authors: Abraham George M , Morton Jacob B , Saravolatz Louis D 
Published: February 2020

Abstract
Baloxavir marboxil (formerly S-033188) is a prodrug of baloxavir acid (S-033447) and inhibits cap-dependent endonuclease, an essential protein involved in the initiation of viral transcription by cleaving capped mRNA bound to PB2. Its adverse event profile is comparable to oseltamivir but is still vulnerable to resistance. The single-dose baloxavir marboxil is an appealing antiviral regimen for the treatment of influenza among outpatients when compared with longer, twice-daily regimens of oral and inhaled neuraminidase inhibitors. This review focuses on the mode of action, antiviral activity, pharmacokinetics, clinical indications, and safety profiles of this drug. Considerations for formulary addition and its place in therapy are also discussed.
Moderate but not severe hypothermia causes pro-arrhythmic changes in cardiac electrophysiology
Authors: Dietrichs Erik S , McGlynn Karen , Allan Andrew , Connolly Adam , Bishop Martin , Burton Francis , Kettlewell Sarah , Myles Rachel , Tveita Torkjel , Smith Godfrey L 
Published: February 2020

Abstract

Aims
Treatment of arrhythmias evoked by hypothermia/rewarming remains challenging, and the underlying mechanisms are unclear. This in vitro experimental study assessed cardiac electrophysiology in isolated rabbit hearts at temperatures occurring in therapeutic and accidental hypothermia.

Methods and results
Detailed ECG, surface electrogram, and panoramic optical mapping were performed in isolated rabbit hearts cooled to moderate (31°C) and severe (17°C) hypothermia. Ventricular activation was unchanged at 31°C while action potential duration (APD) was significantly prolonged (176.9 ± 4.2 ms vs. 241.0 ± 2.9 ms, P &lt; 0.05), as was ventricular repolarization. At 17°C, there were proportionally similar delays in both activation and repolarization. These changes were reflected in the QRS and QT intervals of ECG recordings. Ventricular fibrillation threshold was significantly reduced at 31°C (16.3 ± 3.1 vs. 35 ± 3.5 mA, P &lt; 0.05) but increased at 17°C (64.2 ± 9.9, P &lt; 0.05). At 31°C, transverse conduction was relatively unchanged by cooling compared to longitudinal conduction, but at 17°C both transverse and longitudinal conduction were proportionately reduced to a similar extent. The gap junction uncoupler heptanol had a larger relative effect on transverse than longitudinal conduction and was able to restore the transverse/longitudinal conduction ratio, returning ventricular fibrillation threshold to baseline values (16.3 ± 3.1 vs. 36.3 ± 4.3 mA, P &lt; 0.05) at 31°C. Rewarming to 37°C restored the majority of the electrophysiological parameters.

Conclusions
Moderate hypothermia does not significantly change ventricular conduction time but prolongs repolarization and is pro-arrhythmic. Further cooling to severe hypothermia causes parallel changes in ventricular activation and repolarization, changes which are anti-arrhythmic. Therefore, relative changes in QRS and QT intervals (QR/QTc) emerge as an ECG-biomarker of pro-arrhythmic activity. Risk for ventricular fibrillation appears to be linked to the relatively low temperature sensitivity of ventricular transmural conduction, a conclusion supported by the anti-arrhythmic effect of heptanol at 31°C.
A Novel Approach to Investigate the Effect of Tree Reconstruction Artifacts in Single-Gene Analysis Clarifies Opsin Evolution in Nonbilaterian Metazoans
Authors: Fleming James F , Feuda Roberto , Roberts Nicholas W , Pisani Davide 
Published: February 2020

AbstractOur ability to correctly reconstruct a phylogenetic tree is strongly affected by both systematic errors and the amount of phylogenetic signal in the data. Current approaches to tackle tree reconstruction artifacts, such as the use of parameter-rich models, do not translate readily to single-gene alignments. This, coupled with the limited amount of phylogenetic information contained in single-gene alignments, makes gene trees particularly difficult to reconstruct. Opsin phylogeny illustrates this problem clearly. Opsins are G-protein coupled receptors utilized in photoreceptive processes across Metazoa and their protein sequences are roughly 300 amino acids long. A number of incongruent opsin phylogenies have been published and opsin evolution remains poorly understood. Here, we present a novel approach, the canary sequence approach, to investigate and potentially circumvent errors in single-gene phylogenies. First, we demonstrate our approach using two well-understood cases of long-branch attraction in single-gene data sets, and simulations. After that, we apply our approach to a large collection of well-characterized opsins to clarify the relationships of the three main opsin subfamilies.
Who benefits most from extending financial protection for cataract surgery in Vietnam? An extended cost-effectiveness analysis of small incision surgery
Authors: Essue Beverley M , Jan Stephen , Phuc Huynh Tan , Dodson Sarity , Armstrong Kirsten , Laba Tracey-Lea 
Published: February 2020

Abstract
Treatment costs remain a barrier for having timely cataract surgery in Vietnam, particularly for females and the poor, despite significant progress in achieving universal health coverage (UHC). This study evaluated the potential impact, on health and financial protection, of eliminating medical and non-medical out-of-pocket costs associated with cataract surgery. An extended cost-effectiveness analysis (ECEA) was conducted with a societal perspective. The ECEA modelled how many more disability-adjusted life years (DALYs) and cases of catastrophic health expenditure (CHE) and medical impoverishment could be averted across income quintiles and between males and females. Two programmes were evaluated: (1) eliminating medical out-of-pocket costs for small incision cataract surgery and (2) Programme A plus a voucher programme covering non-medical out-of-pocket costs. Compared with current, the incremental cost per year of Programme A was estimated to be $833 396 and $1 641 835 for Programme B, each representing &lt;0.01% of total health care spending in 2016. Males and females in the richest income quintiles would avert more DALYs than those in the poorest quintiles. For both programmes, most cases of CHE would be averted by individuals in the poorest income quintile. Programme B would avert the most CHE cases overall and females would have a greater share of benefits. All cases of impoverishing medical expenditure would be averted by individuals in the poorest quintile (A: 115 cases and B: 493 cases) for both programmes. The cost to avert each case of CHE with Programme A ranged from $67 to $292 and $100 to $232 for Programme B. We found a pro-rich health distribution and a pro-poor CHE distribution associated with eliminating out-of-pocket costs of cataract surgery in Vietnam. A programme that addressed both medical and non-medical out-of-pocket costs could have the greatest impact on improving financial protection in this population, particularly among the poorest income quintiles and for females. This study supports the concordance between the objectives of UHC and gender equity.
The Proliferation of Joint Interpretation Clauses in New International Investment Agreements: A Mixed Blessing?
Authors: Marotti Loris 
Published: February 2020

Abstract
Joint interpretation clauses (JICs) are among the most controversial control mechanisms on the interpretative powers of tribunals brought by the current wave of reform of the investor–State dispute settlement system (ISDS). Literally proliferating in the new generation of international investment agreements (IIAs), these clauses give contracting States the power to issue joint interpretations (JIs) that are expressly recognized as binding upon dispute settlement bodies and may even be issued in relation to matters pending before such bodies. This article discusses several issues raised by the ‘authentic interpretation’ enhanced by JICs. In the first part, JICs are assessed against the background of the general rule on treaty interpretation, including, in particular, subsequent agreements under article 31(3)(a) of the 1969 Vienna Convention on the Law of Treaties. The second part of the article addresses the tensions between judicial bodies and treaty parties sharing the interpretative authority over IIAs and investigates whether there are any limitations on the interpretative powers of States under JICs. The third part is devoted to the impact of JIs on the proper conduct of investment arbitration proceedings, considering the participation of private actors (the investors) in the proceedings and the ‘dual role’ of States (as treaty parties and respondents) in this field. The concluding part of the article speculates whether a greater institutionalization of the international investment regime is likely to prompt more frequent forms of judicial reactions against ‘ill-perceived’ JIs and fuel the tension between States and dispute settlement bodies.
Pericardial Adipose Tissue Volume Is Independently Associated With Human Immunodeficiency Virus Status and Prior Use of Stavudine, Didanosine, or Indinavir
Authors: Knudsen Andreas D , Krebs-Demmer Lisanne , Bjørge Natascha I D , Elming Marie B , Gelpi Marco , Sigvardsen Per E , Lebech Anne-Mette , Fuchs Andreas , Kühl Jørgen T , Køber Lars , Lundgren Jens , Nordestgaard Børge G , Kofoed Klaus F , Nielsen Susanne D 
Published: February 2020

AbstractBackgroundIncreased pericardial adipose tissue is associated with higher risk of cardiovascular disease. We aimed to determine whether human immunodeficiency virus (HIV) status was independently associated with larger pericardial adipose tissue volume and to explore possible HIV-specific risk factors.MethodsPersons with HIV (PWH) were recruited from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study and matched 1:1 on age and sex to uninfected controls. Pericardial adipose tissue volume was measured using cardiac computed tomography.ResultsA total of 587 PWH and 587 controls were included. Median age was 52 years, and 88% were male. Human immunodeficiency virus status was independently associated with 17 mL (95% confidence interval [CI], 10–23; P &lt; .001) larger pericardial adipose tissue volume. Larger pericardial adipose tissue volume was associated with low CD4+ nadir and prior use of stavudine, didanosine, and indinavir. Among PWH without thymidine analogue or didanosine exposure, time since initiating combination antiretroviral treatment (per 5-year use) was associated with l6 mL (95% CI, −6 to −25; P = .002) lower pericardial adipose tissue volume.ConclusionsHuman immunodeficiency virus status was independently associated with larger pericardial adipose tissue volume. Severe immunodeficiency, stavudine, didanosine, and indinavir were associated with larger pericardial adipose tissue volume. Persons with HIV with prior exposure to these drugs may constitute a distinct cardiovascular risk population.
Image-based extrusion with realistic surface wrinkles
Authors: Ragragui Anouar , Ouazzani Chahdi Adnane , Halli Akram , Satori Khalid 
Published: February 2020

Abstract
Per-pixel extrusion mapping is an image-based modeling and rendering technique that can be used in a large variety of computer graphic applications. This technique makes it possible to create geometries without polygonal meshes by extrusion of a basic form stored in a 2D binary image. It is available in four versions: basic extrusion, outward extrusion, beveled extrusion, and chamfered extrusion, and all allow the production of satisfactory results in terms of interactivity or visual quality. The problem is that the extruded surfaces do not exhibit microrelief effects and have a lack of realistic superficial wrinkles. To solve this problem, we proposed in this paper a combination of the per-pixel extrusion mapping and the bump mapping in order to add a microrelief effect to extruded surfaces without changing the basic geometry. For the real-time synchronization between the depth scaling of the microreliefs and the resulting shading, we proposed to use a scale factor to further disturb the normal in a function of depths.
Computer-aided SPT-based reliability model for probability of liquefaction using hybrid PSO and GA
Authors: Goharzay Maral , Noorzad Ali , Ardakani Ahmadreza Mahboubi , Jalal Mostafa 
Published: February 2020

AbstractIn this paper, an approach for soil liquefaction evaluation using probabilistic method based on the world-wide SPT databases has been presented. In this respect, the parameters’ uncertainties for liquefaction probability have been taken into account. A calibrated mapping function is developed using Bayes’ theorem in order to capture the failure probabilities in the absence of the knowledge of parameter uncertainty. The probability models provide a simple, but also efficient decision-making tool in engineering design to quantitatively assess the liquefaction triggering thresholds. Within an extended framework of the first-order reliability method considering uncertainties, the reliability indices are determined through a well-performed meta-heuristic optimization algorithm called hybrid particle swarm optimization and genetic algorithm to find the most accurate liquefaction probabilities. Finally, the effects of the level of parameter uncertainty on liquefaction probability, as well as the quantification of the limit state model uncertainty in order to incorporate the correct model uncertainty, are investigated in the context of probabilistic reliability analysis. The results gained from the presented probabilistic model and the available models in the literature show the fact that the developed approach can be a robust tool for engineering design and analysis of liquefaction as a natural disaster.
Modeling and assessing cyber resilience of smart grid using Bayesian network-based approach: a system of systems problem
Authors: Ibne Hossain Niamat Ullah , Nagahi Morteza , Jaradat Raed , Shah Chiranjibi , Buchanan Randy , Hamilton Michael 
Published: February 2020

Abstract
Due to the widespread of new technologies, the modern electric power system has become much more complex and uncertain. The Integration of technologies in the electric power system has increased the exposure of cyber threats and correlative susceptibilities from malicious cyber-attacks. To better address these cyber risks and minimize the effects of the power system outage, this research identifies the potential causes and mitigation techniques for the smart grid (SG) and assesses the overall cyber resilience of smart grid systems using a Bayesian network approach. Bayesian network is a powerful analytical tool predominantly used in risk, reliability, and resilience assessment under uncertainty. The quantification of the model is examined, and the results are analyzed through different advanced techniques such as predictive inference reasoning and sensitivity analysis. Different scenarios have been developed and analyzed to identify critical variables that are susceptible to the cyber resilience of a smart grid system of systems. Insight drawn from these analyses suggests that overall cyber resilience of the SG system of systems is dependent upon the status of identified factors, and more attention should be directed towards developing the countermeasures against access domain vulnerability. The research also shows the efficacy of a Bayesian network to assess and enhance the overall cyber resilience of the smart grid system of systems.
Identification of an Emergent Pathogen, Bartonella vinsonii, Using Next-Generation Sequencing in a Patient With Culture-Negative Endocarditis
Authors: Downey Rachel D , Russo Susan M , Hauger Sarmistha B , Murphey Donald K , Marx Grace , Huynh Thanhthao , Denison Amy M , Quirt Rachel , Bailey Ann , Fernandez Marisol 
Published: February 2020

Abstract
Diagnosis and treatment of culture negative endocarditis remains a challenge. This report describes a rare cause of endocarditis in humans, Bartonella vinsonii, identified through next generation sequencing of plasma microbial cell-free DNA with confirmation of cardiac valve tissue infection through immunohistochemical staining and polymerase chain reaction.
Inside the ‘Red Circle’: the production of China’s corporate legal elite
Authors: Zhu Jingqi , Zhao Yang , Liu Sida 
Published: February 2020

AbstractThis article examines the production of corporate legal elite through a systematic analysis of the profiles of the first three cohorts of partners in nine elite corporate law firms in Beijing. We argue that the social production of the Chinese corporate legal elite is primarily an outcome of domestic social factors rather than international factors. It is characterized by local elite recruitment from elite universities and endogenous elite circulation within the Red Circle firms. International credentials and work experience come only secondary to education and work experience in elite Chinese law schools and law firms for achieving elite status in the profession. Yet, international experience plays a role in promoting gender equality in elite professional service firms. This article contributes to the study of globalization and elite production in professional service firms by investigating how local and global forces manifest themselves in elite production in a major emerging market.