bluuebunny/crossref_metadata_2025_split huggingface dataset:
DDT - Drug Discovery Tool: a fast and intuitive graphics user interface for docking and molecular dynamics analysis
Authors: Aureli Simone , Di Marino Daniele , Raniolo Stefano , Limongelli Vittorio 
Published: July 2019

Abstract

Motivation
The ligand/protein binding interaction is typically investigated by docking and molecular dynamics (MD) simulations. In particular, docking-based virtual screening (VS) is used to select the best ligands from database of thousands of compounds, while MD calculations assess the energy stability of the ligand/protein binding complexes. Considering the broad use of these techniques, it is of great demand to have one single software that allows a combined and fast analysis of VS and MD results. With this in mind, we have developed the Drug Discovery Tool (DDT) that is an intuitive graphics user interface able to provide structural data and physico-chemical information on the ligand/protein interaction.

Results
DDT is designed as a plugin for the Visual Molecular Dynamics (VMD) software and is able to manage a large number of ligand/protein complexes obtained from AutoDock4 (AD4) docking calculations and MD simulations. DDT delivers four main outcomes: i) ligands ranking based on an energy score; ii) ligand ranking based on a ligands’ conformation cluster analysis; iii) identification of the aminoacids forming the most occurrent interactions with the ligands; iv) plot of the ligands’ center-of-mass coordinates in the Cartesian space. The flexibility of the software allows saving the best ligand/protein complexes using a number of user-defined options.

Availability and implementation
DDT_site_1 (alternative DDT_site_2); the DDT tutorial movie is available here.

Supplementary information
Supplementary data are available at Bioinformatics online.
The influence of heterogeneous codon frequencies along sequences on the estimation of molecular adaptation
Authors: Del Amparo Roberto , Vicens Alberto , Arenas Miguel 
Published: July 2019

Abstract

Motivation
The nonsynonymous/synonymous substitution rate ratio (dN/dS) is a commonly used parameter to quantify molecular adaptation in protein-coding data. It is known that the estimation of dN/dS can be biased if some evolutionary processes are ignored. In this concern, common ML methods to estimate dN/dS assume invariable codon frequencies among sites, despite this characteristic is rare in nature, and it could bias the estimation of this parameter.

Results
Here we studied the influence of variable codon frequencies among genetic regions on the estimation of dN/dS. We explored scenarios varying the number of genetic regions that differ in codon frequencies, the amount of variability of codon frequencies among regions and the nucleotide frequencies at each codon position among regions. We found that ignoring heterogeneous codon frequencies among regions overall leads to underestimation of dN/dS and the bias increases with the level of heterogeneity of codon frequencies. Interestingly, we also found that varying nucleotide frequencies among regions at the first or second codon position leads to underestimation of dN/dS while variation at the third codon position leads to overestimation of dN/dS. Next, we present a methodology to reduce this bias based on the analysis of partitions presenting similar codon frequencies and we applied it to analyze four real datasets. We conclude that accounting for heterogeneous codon frequencies along sequences is required to obtain realistic estimates of molecular adaptation through this relevant evolutionary parameter.

Availability and implementation
The applied frameworks for the computer simulations of protein-coding data and estimation of molecular adaptation are SGWE and PAML, respectively. Both are publicly available and referenced in the study.

Supplementary information
Supplementary data are available at Bioinformatics online.
A trans-fatty acid-rich diet promotes liver tumorigenesis in HCV core gene transgenic mice
Authors: Hu Xiao , Wang Xiaojing , Jia Fangping , Tanaka Naoki , Kimura Takefumi , Nakajima Takero , Sato Yoshiko , Moriya Kyoji , Koike Kazuhiko , Gonzalez Frank J , Nakayama Jun , Aoyama Toshifumi 
Published: July 2019

Abstract
Excess consumption of trans-fatty acid (TFA), an unsaturated fatty acid containing trans double bonds, is a major risk factor for cardiovascular disease and metabolic syndrome. However, little is known about the link between TFA and hepatocellular carcinoma (HCC) despite it being a frequent form of cancer in humans. In this study, the impact of excessive dietary TFA on hepatic tumorigenesis was assessed using hepatitis C virus (HCV) core gene transgenic mice that spontaneously developed HCC. Male transgenic mice were treated for 5 months with either a control diet or an isocaloric TFA-rich diet that replaced the majority of soybean oil with shortening. The prevalence of liver tumors was significantly higher in TFA-rich diet-fed transgenic mice compared with control diet-fed transgenic mice. The TFA-rich diet significantly increased the expression of pro-inflammatory cytokines, as well as oxidative and endoplasmic reticulum stress, and activated nuclear factor-kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (NRF2), leading to high p62/sequestosome 1 (SQSTM1) expression. Furthermore, the TFA diet activated extracellular signal-regulated kinase (ERK) and stimulated the Wnt/β-catenin signaling pathway, synergistically upregulating cyclin D1 and c-Myc, driving cell proliferation. Excess TFA intake also promoted fibrogenesis and ductular reaction, presumably contributing to accelerated liver tumorigenesis. In conclusion, these results demonstrate that a TFA-rich diet promotes hepatic tumorigenesis, mainly due to persistent activation of NF-κB and NRF2-p62/SQSTM1 signaling, ERK and Wnt/β-catenin pathways and fibrogenesis. Therefore, HCV-infected patients should avoid a TFA-rich diet to prevent liver tumor development.
Graded Dalbavancin Challenge in a Patient With Severe Vancomycin Hypersensitivity Reaction
Authors: Ishizuka Kelly T , Tran Thao K , Ayars Andrew G , Chau Alice S , Chan Jeannie D 
Published: July 2019

Abstract
Cross-reactivity should be considered when treating patients with a previous hypersensitivity reaction within the same class of antibiotics that share similar chemical structures. This case report describes a patient with severe hypersensitivity reaction to vancomycin who successfully tolerated a dalbavancin graded challenge.
Monitoring of cerebral oximetry in patients with postural orthostatic tachycardia syndrome
Authors: Kharraziha Isabella , Holm Hannes , Bachus Erasmus , Melander Olle , Sutton Richard , Fedorowski Artur , Hamrefors Viktor 
Published: July 2019

Abstract

Aims
Postural orthostatic tachycardia syndrome (POTS) is a disorder of unknown aetiology characterized by orthostatic intolerance and tachycardia with diverse other symptoms, including neurocognitive deficits. Cerebral oximetry non-invasively measures cerebral tissue saturation (SctO2) and has been shown to be informative in syncope evaluation. We aimed to assess SctO2 in POTS patients and those with normal response to orthostatic provocation, relative to haemodynamic parameters and symptoms.

Methods and results
Thirty-four patients with POTS (29.1 ± 9.5 years; 26 females) and 34 age-/sex-matched controls with normal head-up tilt tests (HUTs) were included. SctO2 at rest and during HUT were compared between POTS and controls. The relation between SctO2, systolic blood pressure (SBP), and heart rate (HR) during HUT was linearly assessed. SctO2 values were related to dizziness or syncope during HUT. The minimum SctO2-value during HUT was lower (65.4 ± 5.6 vs. 68.2 ± 4.2%, P = 0.023) and changes in SctO2 from supine to minimum HUT value were more pronounced in POTS patients (−5.7 ± 2.9% vs. −4.3 ± 2.1%, P = 0.028). Decrease in SBP from supine to minimum HUT value (P = 0.004) and increase in HR from supine to HUT value at 3 min (P = 0.022) correlated with more pronounced SctO2 decrease in POTS but not controls. SctO2 did not predict syncope or dizziness during HUT.

Conclusion
Postural orthostatic tachycardia syndrome patients have lower cerebral tissue saturation during orthostatic provocation compared with those subjects having normal haemodynamic response to tilt. Orthostatic decrease in cerebral saturation only weakly correlates with HR increase and does not predict vasovagal reflex in POTS. Other hitherto unknown factors may affect cerebral tissue saturation in POTS.
Inactivated Rabies Virus–Based Ebola Vaccine Preserved by Vaporization Is Heat-Stable and Immunogenic Against Ebola and Protects Against Rabies Challenge
Authors: Kurup Drishya , Fisher Christine R , Smith Todd G , Abreu-Mota Tiago , Yang Yong , Jackson Felix R , Gallardo-Romero Nadia , Franka Richard , Bronshtein Victor , Schnell Matthias J 
Published: July 2019

AbstractBackgroundEbola virus (EBOV) is a highly lethal member of the Filoviridae family associated with human hemorrhagic disease. Despite being a sporadic disease, it caused a large outbreak in 2014–2016 in West Africa and another outbreak recently in the Democratic Republic of Congo. Several vaccine candidates are currently in preclinical and clinical studies but none are stable without cold chain storage.MethodsWe used preservation by vaporization (PBV), a novel processing technology to heat-stabilize FiloRab1 (inactivated rabies-based Ebola vaccine), a candidate Ebola vaccine, and stored the vials at temperatures ranging from 4°C to 50°C for 10 days to 12 months. We immunized Syrian hamsters with the best long-term stable FiloRab1 PBV vaccines and challenged them with rabies virus (RABV).ResultsSyrian hamsters immunized with FiloRab1 PBV–processed vaccines stored at temperatures of 4°C and 37°C for 6 months, and at 50°C for 2 weeks, seroconverted against both RABV-G and EBOV-GP. Notably, all of the FiloRab1 PBV vaccines proved to be 100% effective in a RABV challenge model.ConclusionsWe successfully demonstrated that the FiloRab1 PBV vaccines are stable and efficacious for up to 6 months when stored at temperatures ranging from 4°C to 37°C and for up to 2 weeks at 50°C.
Eliminating Hepatitis C Virus Among Human Immunodeficiency Virus–Infected Men Who Have Sex With Men in Berlin: A Modeling Analysis
Authors: Martin Natasha K , Jansen Klaus , an der Heiden Matthias , Boesecke Christoph , Boyd Anders , Schewe Knud , Baumgarten Axel , Lutz Thomas , Christensen Stefan , Thielen Alexander , Mauss Stefan , Rockstroh Jürgen K , Skaathun Britt , Ingiliz Patrick 
Published: July 2019

Abstract

Background
Despite high hepatitis C virus (HCV) treatment rates, HCV incidence among human immunodeficiency virus (HIV)–infected men who have sex with men (HIV-infected MSM) in Germany rose before HCV direct-acting antivirals (DAAs). We model what intervention can achieve the World Health Organization (WHO) elimination target of an 80% reduction in HCV incidence by 2030 among HIV-infected MSM in Berlin.

Methods
An HCV transmission model among HIV-diagnosed MSM was calibrated to Berlin (rising HCV incidence and high rates of HCV testing and treatment). We modeled the HCV incidence among HIV-diagnosed MSM in Berlin until 2030 (relative to 2015 WHO baseline) under scenarios of DAA scale-up with or without behavior change (among HIV-diagnosed MSM and/or all MSM).

Results
Continuing current treatment rates will marginally reduce the HCV incidence among HIV-diagnosed MSM in Berlin by 2030. Scaling up DAA treatment rates, beginning in 2018, to 100% of newly diagnosed HCV infections within 3 months of diagnosis and 25% each year of previously diagnosed and untreated HCV infections could reduce the HCV incidence by 61% (95% confidence interval, 55.4%–66.7%) by 2030. The WHO target would likely be achieved by combining DAA scale-up with a 40% reduction in HCV transmission among HIV-diagnosed MSM and a 20% reduction among HIV-undiagnosed or HIV-uninfected MSM.

Discussion
HCV elimination among HIV-infected MSM in Berlin likely requires combining DAA scale-up with moderately effective behavioral interventions to reduce risk among all MSM.
Interventions in Live Poultry Markets for the Control of Avian Influenza: A Systematic Review and Meta-analysis
Authors: Shi Naiyang , Huang Jinxin , Zhang Xuefeng , Bao Changjun , Yue Na , Wang Qiang , Cui Tingting , Zheng Mengyun , Huo Xiang , Jin Hui 
Published: July 2019

AbstractBackgroundThis review aimed to provide constructive suggestions for the control and management of avian influenza through quantitative and qualitative evaluation of the impact of different live poultry market (LPM) interventions.MethodsBoth English and Chinese language databases were searched for articles that were published on or before 9 November 2018. After extraction and assessment of the included literature, Stata14.0 was applied to perform a meta-analysis to explore the impacts of LPM interventions.ResultsA total of 19 studies were identified. In total, 224 human, 3550 poultry, and 13 773 environment samples were collected before the intervention; 181 people, 4519 poultry, and 9562 environments were sampled after LPM interventions. Avian influenza virus (AIV) detection rates in the LPM environment (odds ratio [OR], 0.393; 95% confidence interval [CI], 0.262–0.589) and the incidence of AIV infection (OR, 0.045; 95% CI, 0.025–0.079) were significantly lower after LPM interventions, while interventions were not significantly effective in reducing AIV detection in poultry samples (OR, 0.803; 95% CI, 0.403–1.597).ConclusionsLPM interventions can reduce AIV human infections and the detection rate of AIV in market environments.
From Wealth to Power? The Failure of Layered Reforms in India's Defense Sector
Authors: Weiss Moritz 
Published: July 2019

AbstractThis article puts forward a historical institutionalist explanation of how rising powers translate increased wealth into military strength. It develops microfoundations for path dependence and applies them empirically as an approach to defense procurement. The Indian government layered market reforms onto a state-run defense sector. It aimed to exploit competition in its massive acquisition of combat fighter aircraft after 2007. Yet, despite formal rule changes and overwhelming material benefits, government reformers ultimately failed and returned to an intergovernmental purchase in 2015. I develop two mechanisms to explain this instance of failed institutional change in India. First, the reform's structural misfit created uncertainty, as some of the prerequisites for a market such as sound legal protection and private actors were absent. Second, the government reformers were reluctantly supported at the outset by a coalition of so-called opportunists, which neither fully embraced nor strongly opposed institutional reforms. When problems resulting from the misfit multiplied and promised benefits vanished, however, this coalition dissolved and layering failed. A process-tracing analysis and the triangulation of a diverse set of data substantiate this explanation. The article contributes to debates on institutional change as well as to those on rising powers and the constraints they face in their attempts to transform growing wealth into military strength. Most significantly, it specifies a causal pathway along which state institutions shape the defense policies of rising powers. Layered reforms may fail not only when faced by defenders of the status quo; opportunists may suffice to defeat them.
Wave propagation effect on differential image motion monitor measurements
Authors: Kornilov Victor , Safonov Boris 
Published: July 2019

ABSTRACT
The differential image motion monitor (DIMM) is widely used to measure the atmospheric optical turbulence (OT) integral over the line of sight. However, it is known that because of the wave propagation effect, the DIMM’s sensitivity falls with the distance to the turbulent layer and the variance of differential image motion is only approximately proportional to the OT integral. In this paper, we study this problem using the formalism of so-called weighting functions (WFs). We develop a method for calculating these WFs, including the case of the wide spectral band of detected radiation. The effect of underestimating the OT integral for different DIMM devices involved in previous site-testing campaigns is estimated using real measurements of OT vertical profiles. For instruments with small apertures (4–6 cm), the underestimation is ≈10 per cent, whereas for larger devices with apertures of 8–10 cm, the underestimation is less than 5 per cent, on average. This leads to a negative bias in seeing estimation of 7 and 3 per cent, respectively.
On neutralization of charged black holes
Authors: Gong Yi , Cao Zhoujian , Gao He , Zhang Bing 
Published: July 2019

Abstract
For non-spinning, charged (Reissner–Nordström) black holes, the particles with an opposite sign of charge with respect to that of the black hole will be pulled into the black hole by the extra electromagnetic force. Such a hole will be quickly neutralized so that there should not exist significantly charged, non-spinning black holes in the universe. The case of spinning, charged (Kerr–Newmann, KN) black holes is more complicated. For a given initial position and initial velocity of the particle, an oppositely charged particle does not always more easily fall into the black hole than a neutral particle. The possible existence of a magnetosphere further complicate the picture. One therefore cannot straightforwardly conclude that a charged spinning black hole will be neutralized. In this paper, we make the first step to investigate the neutralization of KN black holes without introducing a magnetosphere. We track the particle trajectories under the influence of the curved space–time and the electromagnetic field carried by the spinning, charged black hole. A statistical method is used to investigate the neutralization problem. We find a universal dependence of the falling probability into the black hole on the charge of the test particle, with the oppositely charged particles having a higher probability of falling. We therefore conclude that charged, spinning black holes without a magnetosphere should be quickly neutralized, consistent with people’s intuition. The neutralization problem of KN black holes with a corotating force-free magnetosphere is subject to further studies.
The global star formation law by supernova feedback
Authors: Dekel Avishai , Sarkar Kartick C , Jiang Fangzhou , Bournaud Frederic , Krumholz Mark R , Ceverino Daniel , Primack Joel R 
Published: July 2019

ABSTRACT
We address a simple model where the Kennicutt–Schmidt (KS) relation between the macroscopic densities of star formation rate (SFR, ρsfr) and gas (n) in galactic discs emerges from self-regulation of the SFR via supernova feedback. It arises from the physics of supernova bubbles, insensitive to the microscopic SFR recipe and not explicitly dependent on gravity. The key is that the filling factor of SFR-suppressed supernova bubbles self-regulates to a constant, f ∼ 0.5. Expressing the bubble fading radius and time in terms of n, the filling factor is $f\propto S\, n^{-s}$ with s ≃ 1.5, where S is the supernova rate density. A constant f thus refers to ρsfr ∝ n1.5, with a density-independent SFR efficiency per free-fall time ∼0.01. The self-regulation to f ∼ 0.5 and the convergence to a KS relation independent of the local SFR recipe are demonstrated in cosmological and isolated-galaxy simulations using different codes and recipes. In parallel, the spherical analysis of bubble evolution is generalized to clustered supernovae, analytically and via simulations, yielding s ≃ 1.5 ± 0.5. An analysis of photoionized bubbles about pre-supernova stars yields a range of KS slopes but the KS relation is dominated by the supernova bubbles. Superbubble blowouts may lead to an alternative self-regulation by outflows and recycling. While the model is oversimplified, its simplicity and validity in the simulations may argue that it captures the origin of the KS relation.
The i-process yields of rapidly accreting white dwarfs from multicycle He-shell flash stellar evolution models with mixing parametrizations from 3D hydrodynamics simulations
Authors: Denissenkov Pavel A , Herwig Falk , Woodward Paul , Andrassy Robert , Pignatari Marco , Jones Samuel 
Published: July 2019

ABSTRACT
We have modelled the multicycle evolution of rapidly accreting CO white dwarfs (RAWDs) with stable H burning intermittent with strong He-shell flashes on their surfaces for 0.7 ≤ MRAWD/M⊙ ≤ 0.75 and [Fe/H] ranging from 0 to −2.6. We have also computed the i-process nucleosynthesis yields for these models. The i process occurs when convection driven by the He-shell flash ingests protons from the accreted H-rich surface layer, which results in maximum neutron densities Nn, max ≈ 1013–1015 cm−3. The H-ingestion rate and the convective boundary mixing (CBM) parameter ftop adopted in the one-dimensional nucleosynthesis and stellar evolution models are constrained through three-dimensional (3D) hydrodynamic simulations. The mass ingestion rate and, for the first time, the scaling laws for the CBM parameter ftop have been determined from 3D hydrodynamic simulations. We confirm our previous result that the high-metallicity RAWDs have a low mass retention efficiency ($\eta \lesssim 10{{\ \rm per\ cent}}$). A new result is that RAWDs with [Fe/H] $\lesssim -2$ have $\eta \gtrsim 20{{\ \rm per\ cent}}$; therefore, their masses may reach the Chandrasekhar limit and they may eventually explode as SNeIa. This result and the good fits of the i-process yields from the metal-poor RAWDs to the observed chemical composition of the CEMP-r/s stars suggest that some of the present-day CEMP-r/s stars could be former distant members of triple systems, orbiting close binary systems with RAWDs that may have later exploded as SNeIa.
Time-scale of twin-peak quasi-periodic oscillations and mass of accreting neutron stars
Authors: Török Gabriel , Goluchová Kateřina , Šrámková Eva , Urbanec Martin , Straub Odele 
Published: July 2019

ABSTRACT
Einstein’s general relativity predicts that orbital motion of accreted gas approaching a neutron star (NS) in a NS low-mass X-ray binary (LMXB) system occurs on a time-scale proportional to the NS mass. Radiation of the gas accounts for most of the observed LMXBs variability. In more than a dozen of sources twin-peak quasi-periodic oscillations (QPOs) have been observed. Inspired by the expected proportionality between periods of orbital motion and NS mass we present a straightforward comparison among these sources. We investigate relations between QPO periods and their ratios and identify characteristic time-scales of QPOs associated with individual sources. These time-scales are likely determined by the relative mass of each NS. We show that the characteristic time-scale of the millisecond pulsar XTE J1807.4−294 is longer than for most other NS LMXBs. Consequently, models of QPOs that consider geodesic orbital frequencies imply that the X-ray pulsars’ mass has to be about $50{{\ \rm per\ cent}}$ higher than the average mass of other sources. Consideration of other X-ray pulsars indicates that the exceptionality of XTE J1807.4−294 cannot be related to NS magnetic field in any simple manner. We suggest that QPOs observed in this source can help to discriminate between the proposed versions of the NS equation of state.