bluuebunny/crossref_metadata_2025 huggingface dataset:
A well-behaved theoretical framework for ReaxFF reactive force fields
Authors: Furman David , Wales David J.
Published: July 2020

In recent work, we have presented a new ReaxFF formulation with a superior conservation of energy in reactive molecular dynamics simulations. The key ingredient in the approach involved the tapering of bond order and bond distance discontinuities using Hermite polynomials. This Communication extends the previous formulation by alleviating additional sources of numerical instability in the original formalism. These “numerical pathologies” are rooted in the counting of lone-pair electrons, the sum of bond orders between atoms that form a valence angle, and the definition of a torsional potential. Based on a theoretical analysis, new functions that mitigate these limitations are designed and validated. The extent of their transferability with previous parameterizations is discussed. The new enhancements provide further gains in numerical stability to facilitate exploration of reactive energy landscapes.
A framework for quantitative analysis of spectral data in two channels
Authors: Ryan Duncan P. , Dunlap Megan K. , Majumder Somak , Werner James H. , Hollingsworth Jennifer A. , Gelfand Martin P. , Van Orden Alan , Goodwin Peter M.
Published: July 2020

Simultaneous acquisition of emission intensity from two channels in dual-color fluorescence measurements can be used to determine the spectral properties of an emitter. We detail a method to extract quantitative information from dual-color measurements by considering two models: a single spectral component model for peak wavelength determination and a dual spectral component model for relative strength determination. The former model is useful for spectral characterization and establishing heterogeneity within an emitter species, while the latter model is useful for analyzing energy transfer efficiency. Both models are formalized to yield probability distributions that reflect uncertainties due to shot noise. We applied these analysis tools to single-particle measurements of CdSe/CdS quantum dots. Isolated emitters had narrow spectral-intensity distributions that reflected their static emission profiles and fluorescence stability. Small assemblies of mixed donor/acceptor particles exhibited dynamic behavior where emission configuration changes reveal different spectral characteristics due to energy transfer.
Titratable Martini model for constant pH simulations
Authors: Grünewald Fabian , Souza Paulo C. T. , Abdizadeh Haleh , Barnoud Jonathan , de Vries Alex H. , Marrink Siewert J.
Published: July 2020

In this work, we deliver a proof of concept for a fast method that introduces pH effects into classical coarse-grained (CG) molecular dynamics simulations. Our approach is based upon the latest version of the popular Martini CG model to which explicit proton mimicking particles are added. We verify our approach against experimental data involving several different molecules and different environmental conditions. In particular, we compute titration curves, pH dependent free energies of transfer, and lipid bilayer membrane affinities as a function of pH. Using oleic acid as an example compound, we further illustrate that our method can be used to study passive translocation in lipid bilayers via protonation. Finally, our model reproduces qualitatively the expansion of the macromolecule dendrimer poly(propylene imine) as well as the associated pKa shift of its different generations. This example demonstrates that our model is able to pick up collective interactions between titratable sites in large molecules comprising many titratable functional groups.
Phase transition of Bi5Ti3FeO15 ceramics discovered by Raman spectroscopy and in situ synchrotron XRD under stress field
Authors: Bian Mengyun , Ye Yan , Cui Anyang , Jiang Kai , Bai Wei , Dong Hongliang , Chen Bin , Hu Zhigao , Chu Junhao
Published: July 2020

Bi5Ti3FeO15 (BTFO) ceramics have been widely studied as a multiferroic material with some potential applications. However, the effect of the stress field on BTFO ceramics with complex lattice structures is unknown. Here, we use pressure-dependent Raman scattering spectroscopy to study the structure/phase transition of BTFO samples. Because the phonon mode changes significantly, there could be a phase transition in the range of 4.5–14.8 GPa. In order to further prove the occurrence of phase transition, we carried out in situ high-pressure angular dispersion x-ray diffraction (XRD), which clearly proved the structural evolution of BTFO: orthorhombic crystal A21am transformed into tetragonal I4/mmm. Note that the results from the XRD experiment are self-consistent with the data derived from Raman spectroscopy. It provides an effective method to explore the phase transition of complex oxide structures under high pressure.
Optimising camera trap height and model increases detection and individual identification rates for a small mammal, the numbat (
Authors: Seidlitz Anke , Bryant Kate A. , Armstrong Nicola J. , Calver Michael , Wayne Adrian F.
Published: July 2020

Camera traps are widely used to collect data for wildlife management, but species-specific testing is crucial. We conducted three trials to optimise camera traps for detecting numbats (Myrmecobius fasciatus), a 500–700-g mammal. We compared detection rates from (1) Reconyx PC900 camera traps installed at heights ranging from 10–45 cm, and (2) Reconyx PC900, Swift 3C standard and wide-angle camera traps with differing detection zone widths. Finally, we compared elevated, downward-angled time-lapse cameras installed at heights ranging from 1–2 m to obtain dorsal images for individual numbat identification. Camera traps set at 25 cm had the highest detection rates but missed 40% of known events. During model comparison, Swift 3C wide-angle camera traps recorded 89%, Swift 3C standard 51%, and Reconyx PC900 37% of known events. The number of suitable images from elevated, downward-angled cameras, depicting dorsal fur patterns, increased with increasing camera height. The use of well regarded camera trap brands and generic recommendations for set-up techniques cannot replace rigorous, species-specific testing. For numbat detection, we recommend the Swift 3C wide-angle model installed at 25-cm height. For individual numbat identification, elevated, downward-angled time-lapse cameras were useful; however, more research is needed to optimise this technique.
Effects of thyroid hormone on ovarian cell apoptosis in the rat
Authors: Wang Qiaozhi , Ma Xiaoshu , Zhang Cheng
Published: July 2020

Follicle development is a complicated process regulated by thyroid hormone (TH). TH dysregulation is associated with reproductive disorders; however, the mechanism underlying these relationships remains unclear. Glucose-related protein 78 (GRP78) is a well-characterised endoplasmic reticulum stress protein related to ovarian cell apoptosis. To clarify whether GRP78 is regulated by TH and the involvement of GRP78 in follicle development, we established rat models of hypothyroidism and hyperthyroidism and investigated the effects of TH dysregulation on levels of GRP78, C/EBP homologous protein (CHOP) and cleaved caspase-3. TH dysregulation decreased levels of GRP78 and increased those of CHOP and cleaved caspase-3 in both rat models. However, treatment with equine chorionic gonadotrophin reversed these effects, as well as granulosa cell apoptosis induced by TH dysregulation. Together, these results provide evidence that TH dysregulation alters the GRP78 expression profile, triggering the apoptotic signalling pathway, and suggest that GRP78 is a novel mediator of TH in follicle development.
Reinforcement by realignment in diachronic construction grammar
Authors: Kuo Yueh Hsin
Published: July 2020

This paper suggests thatxiē‘some’ in Mandarin Chinese originated as a quantifier but became a classifier in theyi‘one’ construction viarealignment, orchange in inheritancein diachronic construction grammar. This change has createdyi xiē, semantically equivalent toxiē, therefore it is also a case of reinforcement in the sense of Jespersen’s Cycle. However, this study argues thatyi xiēhas not necessarily undergone grammaticalisation. Generalising the analysis, two types of reinforcement are proposed: reinforcement by innovation and by realignment. The former involves grammaticalisation, but the latter may not. The study highlights the importance of higher-level generalisations in language change.
Recent advances in regulating cholesterol and bile acid metabolism
Authors: Sato Ryuichiro
Published: July 2020

Cholesterol is an important component of lipids in animal membranes. All living cells can synthesize cholesterol, but the amount of synthesis is not sufficient, and therefore cholesterol synthesized in the liver is delivered to extrahepatic tissues as a form of LDL. The liver is a primary organ to not only synthesize but also catabolize cholesterol into bile acids, which ends up to excrete with the feces. The synthetic and catabolic pathways are precisely regulated under the negative-feedback control system under the transcriptional regulation driven by several transcription factors such as the sterol regulatory element-binding proteins (SREBPs), the liver x receptor, and the farnesoid x receptor. This review summarizes various findings including our recent discoveries in the molecular mechanism of activation of SREBP that is involved in the regulation of hepatic cholesterol biosynthesis, and a novel function of the metabolic end product of cholesterol, bile acids, in skeletal muscles.
PTEN dephosphorylates Abi1 to promote epithelial morphogenesis
Authors: Qi Yanmei , Liu Jie , Chao Joshua , Greer Peter A. , Li Shaohua
Published: July 2020

The tumor suppressor PTEN is essential for early development. Its lipid phosphatase activity converts PIP3 to PIP2 and antagonizes the PI3K–Akt pathway. In this study, we demonstrate that PTEN’s protein phosphatase activity is required for epiblast epithelial differentiation and polarization. This is accomplished by reconstitution of PTEN-null embryoid bodies with PTEN mutants that lack only PTEN’s lipid phosphatase activity or both PTEN’s lipid and protein phosphatase activities. Phosphotyrosine antibody immunoprecipitation and mass spectrometry were used to identify Abi1, a core component of the WASP-family verprolin homologous protein (WAVE) regulatory complex (WRC), as a new PTEN substrate. We demonstrate that PTEN dephosphorylation of Abi1 at Y213 and S216 results in Abi1 degradation through the calpain pathway. This leads to down-regulation of the WRC and reorganization of the actin cytoskeleton. The latter is critical to the transformation of nonpolar pluripotent stem cells into the polarized epiblast epithelium. Our findings establish a link between PTEN and WAVE-Arp2/3–regulated actin cytoskeletal dynamics in epithelial morphogenesis.
Effective equation of state in modified gravity and observational constraints
Authors: Arora Simran , Meng Xin-he , Pacif S K J , Sahoo P K
Published: July 2020

In this article, the bulk viscosity is introduced in a modified gravity model. The gravitational action has a general f(R, T) form, where R and T are the curvature scalar and the trace of energy momentum tensor respectively. An effective equation of state (EoS) has been investigated in the cosmological evolution with bulk viscosity. In the present scenario, the Hubble parameter which has a scaling relation with the redshift can be obtained generically. The role of deceleration parameter q and EoS parameter ω is discussed to explain the late-time accelerating expansion of the Universe. The statefinder parameters and Om diagnostic analysis are discussed for our obtained model to distinguish from other dark energy models together with the analysis of energy conditions and velocity of sound for the model. We have also numerically investigated the model by detailed maximum likelihood analysis of 580 type Ia supernovae from Union 2.1 compilation datasets and updated 57 Hubble datasets (31 data points from differential age method and 26 points from BAO and other methods). It is with efforts found that the present model is in good agreement with observations.
Quantum geometry from higher gauge theory
Authors: Asante Seth K , Dittrich Bianca , Girelli Florian , Riello Aldo , Tsimiklis Panagiotis
Published: July 2020

Higher gauge theories play a prominent role in the construction of 4D topological invariants and have been long ago proposed as a tool for 4D quantum gravity. The Yetter lattice model and its continuum counterpart, the BFCG theory, generalize BF theory to 2-gauge groups and—when specialized to 4D and the Poincaré 2-group—they provide an exactly solvable topologically-flat version of 4D general relativity. The 2-Poincaré Yetter model was conjectured to be equivalent to a state sum model of quantum flat spacetime developed by Baratin and Freidel after work by Korepanov (KBF model). This conjecture was motivated by the origin of the KBF model in the theory of two-representations of the Poincaré 2-group. Its proof, however, has remained elusive due to the lack of a generalized Peter–Weyl theorem for 2-groups. In this work we prove this conjecture. Our proof avoids the Peter–Weyl theorem and rather leverages the geometrical content of the Yetter model. Key for the proof is the introduction of a kinematical boundary Hilbert space on which 1- and two-Lorentz invariance is imposed. Geometrically this allows the identification of (quantum) tetrad variables and of the associated (quantum) Levi-Civita connection. States in this Hilbert space are labelled by quantum numbers that match the two-group representation labels. Our results open exciting opportunities for the construction of new representations of quantum geometries. Compared to loop quantum gravity, the higher gauge theory framework provides a quantum representation of the ADM—Regge initial data, including an identification of the intrinsic and extrinsic curvature. Furthermore, it leads to a version of the diffeomorphism and Hamiltonian constraints that acts on the vertices of the discretization, thus providing a prospect for a quantum realization of the hypersurface deformation algebra in 4D.
Quantum field theory on global anti-de Sitter space-time with Robin boundary conditions
Authors: Morley Thomas , Taylor Peter , Winstanley Elizabeth
Published: July 2020

We compute the vacuum polarization for a massless, conformally coupled scalar field on the covering space of global, four-dimensional, anti-de Sitter space-time. Since anti-de Sitter space is not globally hyperbolic, boundary conditions must be applied to the scalar field. We consider general Robin (mixed) boundary conditions for which the classical evolution of the field is well-defined and stable. The vacuum expectation value of the square of the field is not constant unless either Dirichlet or Neumann boundary conditions are applied. We also compute the thermal expectation value of the square of the field. For Dirichlet boundary conditions, both thermal and vacuum expectation values approach the same well-known limit on the space-time boundary. For all other Robin boundary conditions (including Neumann boundary conditions), the vacuum and thermal expectation values have the same limit on the space-time boundary, but this limit does not equal that in the Dirichlet case.
Heavy ion induced single-event-transient effects in nanoscale ferroelectric vertical tunneling transistors by TCAD simulation
Authors: Tian Guoliang , Bi Jinshun , Xu Gaobo , Xi Kai , Yang Xueqin , Yin Huaxiang , Xu Qiuxia , Wang Wenwu
Published: July 2020

Tunnel field-effect transistors (TFETs) are strong candidates for ‘Internet of Things’ electronic devices, due to their ultra-low power consumption. In this work, we propose a novel nanoscale silicon-on-insulator double-gate ferroelectric tunneling ﬁeld-eﬀect transistor (SOI DG-FeTFET), and single-event-transient (SET) eﬀects are investigated by means of two-dimensional technology computer-aided design simulations. In addition, we perform systematic analysis and comparison with a silicon-on-insulator double-gate ferroelectric ﬁeld-eﬀect transistor (SOI DG-FeET) . The simulation results show that the peak value of the drain transient current achieved by our DG-FeTFET is up to 2.72 × 10–4 A at 10 MeV·cm2 mg−1, which is much higher than the on-state current (I
on) ∼ 7.63 × 10−5 A at V
d = 0.5 V. Moreover, our results show that the DG-FeTFET is more susceptible to SET eﬀects than FeFET. The results also show that the bipolar ampliﬁcation eﬀect can be neglected, and that the drift-diﬀusion mechanism is dominant in the carrier collection process in the DG-FeTFET. The transient responses of the single event eﬀect are also strongly correlated with the strike location of heavy ions, with the most sensitive part being close to the area where interband tunneling occurs and the electric ﬁeld is the strongest. These analyses may prove relevant for applications SOI DG-FeTFETs/FeFETs in environments where radiation is present.
Experimental evidence of intrabeam scattering in a free-electron laser driver
Authors: Di Mitri S , Perosa G , Brynes A , Setija I , Spampinati S , Williams P H , Wolski A , Allaria E , Brussaard S , Giannessi L , Penco G , Rebernik P R , Trovò M
Published: July 2020

The effect of multiple small-angle Coulomb scattering, or intrabeam scattering (IBS) is routinely observed in electron storage rings over the typical damping time scale of milliseconds. So far, IBS has not been observed in single pass electron accelerators because charge density orders of magnitude higher than in storage rings would be needed. We show that such density is now available at high brightness electron linacs for free-electron lasers (FELs). We report measurements of the beam energy spread in the FERMI linac in the presence of the microbunching instability, which are consistent with a revisited IBS model for single pass systems. We also show that neglecting the hereby demonstrated effect of IBS in the parameter range typical of seeded VUV and soft x-ray FELs, results in too conservative a facility design, or failure to realise the accessible potential performance. As an example, an optimization of the FERMI parameters driven by an experimentally benchmarked model, opens the door to the extension of stable single spectral line emission to the water window (2.3–4.4 nm), with far-reaching implications for experiments in a variety of disciplines, ranging from physics and chemistry to biology and material sciences, and including nonlinear x-ray optics based on the four-wave-mixing approach.
What are the best combinations of fuel-vehicle technologies to mitigate climate change and air pollution effects across the United States?
Authors: Tong Fan , Azevedo Inês M L
Published: July 2020

The transportation sector is the largest contributor to CO2 emissions and a major source of criteria air pollutants in the United States. The impact of climate change and that of air pollution differ in space and time, but spatially-explicit, systematic evaluations of the effectiveness of alternative fuels and advanced vehicle technologies in mitigating both climate change and air pollution are lacking. In this work, we estimate the life cycle monetized damages due to greenhouse gas emissions and criteria air pollutant emissions for different types of passenger-moving vehicles in the United States. We find substantial spatial variability in the monetized damages for all fuel-vehicle technologies studied. None of the fuel-vehicle technologies leads simultaneously to the lowest climate change damages and the lowest air pollution damages across all U.S. counties. Instead, the fuel-vehicle technology that best mitigates climate change in one region is different from that for the best air quality (i.e. the trade-off between decarbonization and air pollution mitigation). For example, for the state of Pennsylvania, battery-electric cars lead to the lowest population-weighted-average climate change damages (a climate change damage of 0.87 cent/mile and an air pollution damage of 1.71 cent/mile). In contrast, gasoline hybrid-electric cars lead to the lowest population-weighted-average air pollution damages (a climate change damage of 0.92 cent/mile and an air pollution damage of 0.77 cent/mile). Vehicle electrification has great potential to reduce climate change damages but may increase air pollution damages substantially in regions with high shares of coal-fired power plants compared to conventional vehicles. However, clean electricity grid could help battery electric vehicles to achieve low damages in both climate change and air pollution.
Are biodiversity losses valued differently when they are caused by human activities? A meta-analysis of the non-use valuation literature
Authors: Nobel Anne , Lizin Sebastien , Brouwer Roy , Bruns Stephan B , Stern David I , Malina Robert
Published: July 2020

Many countries committed to climate action by adopting the Paris Agreement and Sustainable Development Goals in 2015. This study synthesizes 40 years of scientific evidence of what may be an important benefit of these commitments: the non-use value of biodiversity conservation. The synthesis investigates whether biodiversity values can be integrated into climate change damage estimates based on non-use valuation studies of different threats to biodiversity. In the absence of estimates of public willingness to pay (WTP) to avoid the adverse impacts of anthropogenic climate change on biodiversity, we synthesize non-use values for biodiversity conservation from stated preference studies that account for a heterogeneous set of biodiversity threats. We test whether biodiversity non-use values are affected by the threats that policies aim to address, be it human activities or other threats. We estimate meta-regression models in which we explain the variation in these non-use values by accounting for the observed heterogeneity in good, methodology, sample, and context characteristics. We estimate meta-regression models using 159 observations from 62 publications. The models suggest that non-use values for biodiversity conservation addressing human impacts may be larger than those addressing other threats. We also find that non-use values are generally not sensitive to which biodiversity indicators, habitat types, or taxonomic groups are valued. We predict that the mean annual WTP for avoiding human-caused biodiversity losses ranges from 0.2 to 0.4% of GDP per capita. Our findings suggest that state-of-the-art climate change damage functions in integrated assessment models may underestimate actual damage costs because they do not incorporate the premium that the public is willing to pay to avoid human-caused biodiversity losses.
Climate and growing season variability impacted the intensity and distribution of Fremont maize farmers during and after the Medieval Climate Anomaly based on a statistically downscaled climate model
Authors: Thomson Marcus J , MacDonald Glen M
Published: July 2020

The rise and decline of many complex, pre-European maize-farming cultures in the American Southwest coincides with the warm, climatically quiescent Medieval Climate Anomaly (MCA, ca. 850–1350 CE) and transition to the cool, hydrologically variable Little Ice Age (LIA, ca. 1350–1850 CE). The effects of drought on early subsistence agriculture in the Southwest is well studied, but the impact of temperature stress and variability on the growth of maize crops and which areas were most resilient to such stress remain open questions. We statistically downscaled outputs from a paleo-climate model experiment (CESM1 LME) to map changes to cumulative growing degree days for maize (GDD, 30/10 °C) and precipitation over Utah between 850 and 1449 CE, and downscaled GDD changes to local Fremont Culture archaeological site occupations from radiocarbon-dated contexts mapped as spatially discrete kernel density estimates of summed probability distributions (SPDs). We then analyzed correspondences between Fremont SPDs and GDD/precipitation between 850 and 1449 CE. In general, we found (1) high Fremont occupation intensity coincident with GDD that is less volatile than the long term average, and low occupation intensity coincident with, or following, periods of volatile GDD; (2) intensified occupation of high-elevation sites during the MCA, followed by a retreat to lower elevation sites coincident with a sudden rise in annual temperature volatility and increasing drought conditions; and (3) these occupation changes occurred in spite of the greater temperatures and variability in GDD at low-elevation sites. We found evidence that increased inter-annual variability of growing seasons prior to the onset of the LIA, was likely a determinant of Fremont subsistence strategy decision making, and high-elevation site occupation. The most resilient Fremont occupations in the face of these challenges were sited where growing season lengths were least variable.
Hydrology is the key factor for nitrogen export from tile-drained catchments under consistent land-management
Authors: Bauwe Andreas , Kahle Petra , Tiemeyer Bärbel , Lennartz Bernd
Published: July 2020

In this study, 14 years of climate, stream flow, land management, nitrate-nitrogen (NO3
–N) load and concentration data were analyzed to identify potential drivers for NO3
–N losses at two tile-drained catchments under cropland use in northeastern Germany. Mean (±standard deviation) annual NO3
–N concentrations were 9.7 ± 2.9 (drainage plot) and 6.8 ± 2.4 mg l−1 (ditch catchment), while mean annual NO3
–N loads amounted to 22 ± 16 and 20 ± 16 kg ha−1, respectively. Significant positive relationships between annual discharge and annual NO3
–N losses underlined the importance of hydrologic conditions on NO3
–N export mechanisms. No direct relationships were found between N soil surface surpluses and NO3
–N losses. Any possible impact of N soil surface surpluses on NO3
–N export rates was overridden by the hydro-meteorological conditions in the catchment. Positive correlations between the climatic water balance and NO3
–N losses suggest that agricultural catchments with similar characteristics as ours may face—without countermeasures—increased N losses in the future as regional climate projections predict wetter winters in the coming decades. Our analysis has further shown that effects of land management strategies aiming at reducing N losses into surface waters might only become visible with a delay of years or even decades.
Predicting Sediment transport in sewers using integrative harmony search-ANN model and factor analysis
Authors: Zounemat-Kermani Mohammad , Fadaee Marzieh , Adarsh S , Hinkelmann Reinhard
Published: July 2020

This study evaluates the performance of an integrated version of artificial neural network namely HS-ANN (which is a combination of neural network and heuristic harmony search algorithm) as an alternative approach to predict the sediment transport in terms of sediment volumetric concentration (Cv) in sewer pipe systems. To overcome the complexities of choosing the optimum number of the input variables and to consider the effective parameters of the model, the factor analysis technique is utilized. In addition to the HS-ANN model, an empirical equation, as well as a multiple linear regression model, are also considered. The mean square error (RMSE), mean absolute percentage error (MAPE), and Pearson correlation coefficients (PCC) are used for evaluating the accuracy of the applied models. As the comparisons demonstrate, the HS-ANN model (PCC = 0.97) is more accurate than the existing empirical equation and MLR model and could be successfully employed in predicting sediment transport in sewer networks.
Excess Soluble fms-like Tyrosine Kinase 1 Correlates With Endothelial Dysfunction and Organ Failure in Critically Ill Coronavirus Disease 2019 Patients
Authors: Dupont Vincent , Kanagaratnam Lukshe , Goury Antoine , Poitevin Gaël , Bard Mathieu , Julien Gauthier , Bonnivard Michel , Champenois Vanessa , Noel Violaine , Mourvillier Bruno , Nguyen Philippe
Published: July 2020

Excess soluble fms-like tyrosine kinase 1 (sFlt-1), a soluble inhibitor of vascular endothelial growth factor pathway, has been demonstrated to promote endothelial dysfunction. Here, we demonstrate that sFlt-1 plasma levels correlate with respiratory symptom severity, expression of endothelial dysfunction biomarker, and incidence of organ failure in coronavirus disease 2019 patients.

Clinical Trials Registration: NCT04394195.
Implications of Efavirenz Pharmacogenetics When Switching From Efavirenz- to Dolutegravir-containing Antiretroviral Regimens
Authors: Haas David W , Acosta Edward P
Published: July 2020

Many patients switch from efavirenz- to dolutegravir-based regimens. In a phase 1 dolutegravir-efavirenz interaction study, mean dolutegravir minimum concentration decreased by 60% and 85% among CYP2B6 normal and slow/intermediate metabolizers, respectively. Mean efavirenz half-life was 2.7 times greater in slow vs normal metabolizers. Slow metabolizers will experience more prolonged subtherapeutic dolutegravir concentrations.
Severe Acute Respiratory Syndrome Coronavirus 2 Infects and Damages the Mature and Immature Olfactory Sensory Neurons of Hamsters
Authors: Zhang Anna Jinxia , Lee Andrew Chak-Yiu , Chu Hin , Chan Jasper Fuk-Woo , Fan Zhimeng , Li Can , Liu Feifei , Chen Yanxia , Yuan Shuofeng , Poon Vincent Kwok-Man , Chan Chris Chung-Sing , Cai Jian-Piao , Wu Kenneth Lap-Kei , Sridhar Siddharth , Chan Ying-Shing , Yuen Kwok-Yung
Published: July 2020

Background

Coronavirus disease 2019 (COVID-19) is primarily an acute respiratory tract infection. Distinctively, a substantial proportion of COVID-19 patients develop olfactory dysfunction. Especially in young patients, loss of smell can be the first or only symptom. The roles of inflammatory obstruction of the olfactory clefts, inflammatory cytokines affecting olfactory neuronal function, destruction of olfactory neurons or their supporting cells, and direct invasion of olfactory bulbs in causing olfactory dysfunction are uncertain.

Methods

We investigated the location for the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the olfactory epithelium (OE) to the olfactory bulb in golden Syrian hamsters.

Results

After intranasal inoculation with SARS-CoV-2, inflammatory cell infiltration and proinflammatory cytokine/chemokine responses were detected in the nasal turbinate tissues. The responses peaked between 2 and 4 days postinfection, with the highest viral load detected at day 2 postinfection. In addition to the pseudo-columnar ciliated respiratory epithelial cells, SARS-CoV-2 viral antigens were also detected in the mature olfactory sensory neurons labeled by olfactory marker protein, in the less mature olfactory neurons labeled by neuron-specific class III β-tubulin at the more basal position, and in the sustentacular cells, resulting in apoptosis and severe destruction of the OE. During the entire course of infection, SARS-CoV-2 viral antigens were not detected in the olfactory bulb.

Conclusions

In addition to acute inflammation at the OE, infection of mature and immature olfactory neurons and the supporting sustentacular cells by SARS-CoV-2 may contribute to the unique olfactory dysfunction related to COVID-19, which is not reported with SARS-CoV-2.
Finite-element EM modelling on hexahedral grids with an FD solver as a pre-conditioner
Authors: Yavich Nikolay , Zhdanov Michael S
Published: July 2020

The finite-element (FE) method is one of the most powerful numerical techniques for modelling 3-D electromagnetic fields. At the same time, there still exists the problem of efficient and economical solution of the respective system of FE equations in the frequency domain. In this paper, we concentrate on modelling with adapted hexahedral or logically rectangular grids. These grids are easy to generate, yet they are flexible enough to incorporate real topography and seismic horizons. The goal of this work is to show how a finite-difference (FD) solver can be used as a pre-conditioner for hexahedral FE modelling. Applying the lowest order Nédélec elements, we present a novel pre-conditioned iterative solver for the arising system of linear equations that combines an FD solver and simple smoothing procedure. The particular FD solver that we use relies on the implicit factorization of the horizontally layered earth matrix. We assessed runtime and accuracy of the presented approach on synthetic and real resistivity models (topography of the Black Sea continental slope). We further compared performance of our program versus publicly available Mare2DEM, ModEM and MUMPS programs/libraries. Our examples involve plane-wave and controlled source modelling. The numerical examples demonstrate that the presented approach is fast and robust for models with moderate contrast, supports highly deformed cells, and is quite memory-economical.
ISOGlyP: de novo prediction of isoform-specific mucin-type O-glycosylation
Authors: Mohl Jonathon E , Gerken Thomas A , Leung Ming-Ying
Published: July 2020

Mucin-type O-glycosylation is one of the most common posttranslational modifications of proteins. The abnormal expression of various polypeptide GalNAc-transferases (GalNAc-Ts) which initiate and define sites of O-glycosylation are linked to many cancers and other diseases. Current O-glycosyation prediction programs utilize O-glycoproteomics data obtained without regard to the transferase isoform (s) responsible for the glycosylation. With 20 different GalNAc-Ts in humans, having an ability to predict and interpret O-glycosylation sites in terms of specific GalNAc-T isoforms is invaluable.

To fill this gap, ISOGlyP (Isoform-Specific O-Glycosylation Prediction) has been developed. Using position-specific enhancement values generated based on GalNAc-T isoform-specific amino acid preferences, ISOGlyP predicts the propensity that a site would be glycosylated by a specific transferase. ISOGlyP gave an overall prediction accuracy of 70% against in vivo data, which is comparable to that of the NetOGlyc4.0 predictor. Additionally, ISOGlyP can identify the known effects of long- and short-range prior glycosylation and can generate potential peptide sequences selectively glycosylated by specific isoforms.

ISOGlyP is freely available for use at ISOGlyP.utep.edu. The code is also available on GitHub (https://github.com/jonmohl/ISOGlyP).
Interferon-Induced Macrophage-Derived Exosomes Mediate Antiviral Activity Against Hepatitis B Virus Through miR-574-5p
Authors: Wu Wenyu , Wu Di , Yan Weiming , Wang Yongli , You Jie , Wan Xiaoyang , Xi Dong , Luo Xiaoping , Han Meifang , Ning Qin
Published: July 2020

Background

Interferon alfa (IFN-α) has been proved effective in treating chronic hepatitis B (CHB), owing to its ability to suppress hepatitis B surface antigen and hepatitis B virus (HBV) covalently closed circular DNA. However, the underlying mechanisms are unclear.

Methods

We investigated the antiviral activities of exosomes from responders and nonresponders to pegylated IFN-α (PegIFN-α) as well as the supernatants of IFN-α–treated macrophages derived from THP-1 (the human leukemia monocyte cell line). Then the expression profiles of exosomal microRNAs (miRNAs) were analyzed using miRNA sequencing. The luciferase reporter assay was used to locate the binding position of HBV genomic sequence targeted by the identified miRNA.

Results

Exosomes from PegIFN-α–treated patients, particularly responders, as well as the supernatants of IFN-α–treated macrophages exhibited anti-HBV activities, as manifested by the suppression of hepatitis B surface antigen, hepatitis B e antigen, HBV DNA, and covalently closed circular DNA levels in HBV-related cell lines. PegIFN-α treatment up-regulated exosomal hsa-miR-193a-5p, hsa-miR-25-5p, and hsa-miR-574-5p, which could partially inhibit HBV replication and transcription, and hsa-miR-574-5p reduced pregenomic RNA and polymerase messenger RNA levels by binding to the 2750–2757 position of the HBV genomic sequence.

Conclusions

Exosomes can transfer IFN-α–related miRNAs from macrophages to HBV-infected hepatocytes, and they exhibit antiviral activities against HBV replication and expression.
Why International Organizations Commit to Liberal Norms
Authors: Tallberg Jonas , Lundgren Magnus , Sommerer Thomas , Squatrito Theresa
Published: July 2020

Recent decades have witnessed the emergence and spread of a broad range of liberal norms in global governance, among them sustainable development, gender equality, and human security. While existing scholarship tells us a lot about the trajectories of particular norms, we know much less about the broader patterns and sources of commitments to liberal norms by international organizations (IOs). This article offers the first comparative large-N analysis of such commitments, building on a unique dataset on IO policy decisions over the time period 1980–2015. Distinguishing between deep norm commitment and shallow norm recognition, the analysis produces several novel findings. We establish that IOs’ deeper commitments to liberal norms primarily are driven by internal conditions: democratic memberships and institutional designs more conducive to norm entrepreneurship. In contrast, legitimacy standards in the external environment of IOs, often invoked in existing research, mainly account for shallower recognition or “talk” of norms.
Digestibility of amino acids and concentrations of metabolizable energy and net energy are greater in high-shear dry soybean expellers than in soybean meal when fed to growing pigs
Authors: Rodriguez Diego A , Lee Su A , Stein Hans H
Published: July 2020

Soybean expellers may be produced by dry extrusion and mechanical oil pressing of soybeans, but there is limited information about the nutritional value of expellers produced via this procedure. Therefore, 2 experiments were conducted to test the hypothesis that standardized ileal digestibility (SID) of CP and amino acids (AA), apparent total tract digestibility (ATTD) of energy and total dietary fiber (TDF), and concentrations of DE, ME, and NE are greater in soybean expellers than in soybean meal (SBM) when fed to growing pigs. Pigs were the offspring of Line 359 boars mated to Camborough females (Pig Improvement Company, Hendersonville, TN). In experiment 1, nine growing barrows (initial BW: 55.98 kg ± 13.75 kg) with T-cannulas installed in the distal ileum were allotted to 1 of 3 diets using a triplicated 3 × 3 Latin square design with 3 periods. Two diets were formulated to contain 35% soybean expellers or 33% SBM as the sole source of AA. A N-free diet was used to determine basal endogenous losses of AA. Ileal digesta were collected on days 6 and 7 of each 7-d period. Results indicated that the SID of most indispensable and dispensable AA were greater (P < 0.05) or tended (P < 0.10) to be greater in soybean expellers than in SBM. In experiment 2, a corn-based diet and 2 diets based on corn and each of the 2 soybean products were formulated. Twenty-four growing barrows (initial BW: 44.88 kg ± 2.17 kg) were allotted to 1 of the 3 diets with 8 pigs per diet. Urine and fecal samples were collected for 4 d after 5 d of adaptation. Results indicated that the ATTD of energy and TDF was not different between soybean expellers and SBM, but the ATTD of TDF in the 2 soybean products was greater (P < 0.05) than in corn. Concentrations of DE and ME in soybean expellers were greater (P < 0.05) compared with corn or SBM. Soybean expellers had greater (P < 0.05) calculated NE compared with SBM, but there was no difference in NE between corn and soybean expellers. In conclusion, values for SID of most AA and DE, ME, and NE in soybean expellers were greater than in SBM.
A new family and superfamily for the southern giant crab of Australia, Pseudocarcinus gigas (Lamarck, 1818) (Decapoda: Brachyura)
Authors: Ng Peter K L , Davie Peter J F
Published: July 2020

The Australian southern giant crab, Pseudocarcinus gigas (Lamarck, 1818), has traditionally been placed in the families Oziidae Dana, 1851 or Menippidae Ortmann, 1893 (superfamily Eriphioidea MacLeay, 1838). Previous genetic studies questioned the validity of this classification as the molecular markers placed it far from all eriphioid lineages. A morphological re-examination of P. gigas shows that it possesses a suite of unusual characters in the structure of the antennae, antennules, epistome, carapace, pereopods, thoracic sternum, and vulvae that show it is different from other Eriphioidea as well as all other extant heterotremes, confirming the genetic results. A new family, Pseudocarcinidae, and a new superfamily, Pseudocarcinoidea, both monotypic, are here established for P. gigas.
Comparing fitness measures and the influence of age of first reproduction in Columbian ground squirrels
Authors: Rubach Kristin K , Dobson F Stephen , Zinner Bertram , Murie Jan O , Viblanc Vincent A
Published: July 2020

The timing of life-history traits may have strong influences on the evolution of life cycles and on population demography. This is especially true of the age at which females first reproduce (Cole’s principle). We examined whether the age at which females first reproduce influences fitness in Columbian ground squirrels (Urocitellus columbianus), for which females varied in the age at which they initially produce weaned offspring, from ages 1 through 5 years. With 148 females with complete known life spans in a 28-year data set, we examined four fitness measures: individual fitness (λ ind), individual fitness relative to the pattern of growth of the population (λ rel), lifetime reproductive success (LRS), and LRS relative to the total LRS for each female’s cohort (LRSrel). These metrics were calculated for offspring produced at the time of weaning and offspring that survived to emerge after their first hibernation period. Individual fitness (λ ind) was significantly associated with population growth during a female’s lifetime (λ Leslie; R2 = 0.523, P < 0.0001), indicating the need to adjust individual fitness for demonstrated changes in population growth and thus producing a relative individual fitness index (λ rel). We regressed λ rel on age at first reproduction, and found significant selection favoring earlier reproductive success (β ± SE = −0.20 ± 0.06; R2 = 0.306, P < 0.0001). When using an earlier (offspring at weaning) versus later (those that survived their first hibernation) measure of fecundity, we found that the latter introduced considerable variation, likely environmental, into the estimate of selection. This greatly weakened the regression of relative fitness on the age at first successful reproduction. LRS and LRSrel exhibited nonsignificant changes with age at first reproduction. Finally, those females that reproduced successfully at younger ages had similar litter sizes but significantly shorter life spans than females that matured when older, perhaps reflecting costs to early reproduction.
High-resolution VLA low radio frequency observations of the Perseus cluster: radio lobes, mini-halo, and bent-jet radio galaxies
Authors: Gendron-Marsolais M , Hlavacek-Larrondo J , van Weeren R J , Rudnick L , Clarke T E , Sebastian B , Mroczkowski T , Fabian A C , Blundell K M , Sheldahl E , Nyland K , Sanders J S , Peters W M , Intema H T
Published: July 2020

We present the first high-resolution 230–470 MHz map of the Perseus cluster obtained with the Karl G. Jansky Very Large Array. The high dynamic range and resolution achieved have allowed the identification of previously unknown structures in this nearby galaxy cluster. New hints of sub-structures appear in the inner radio lobes of the brightest cluster galaxy NGC 1275. The spurs of radio emission extending into the outer X-ray cavities, inflated by past nuclear outbursts, are seen for the first time at these frequencies, consistent with spectral aging. Beyond NGC 1275, we also analyse complex radio sources harboured in the cluster. Two new distinct, narrowly collimated jets are visible in IC 310, consistent with a highly projected narrow-angle tail radio galaxy infalling into the cluster. We show how this is in agreement with its blazar-like behaviour, implying that blazars and bent-jet radio galaxies are not mutually exclusive. We report the presence of filamentary structures across the entire tail of NGC 1265, including two new pairs of long filaments in the faintest bent extension of the tail. Such filaments have been seen in other cluster radio sources such as relics and radio lobes, indicating that there may be a fundamental connection between all these radio structures. We resolve the very narrow and straight tail of CR 15 without indication of double jets, so that the interpretation of such head–tail sources is yet unclear. Finally, we note that only the brightest western parts of the mini-halo remain, near NGC 1272 and its bent double jets.
On the distribution of fluxes of gamma-ray blazars: hints for a stochastic process?
Authors: Tavecchio F , Bonnoli G , Galanti G
Published: July 2020

We examine a model for the observed temporal variability of powerful blazars in the γ-ray band in which the dynamics is described in terms of a stochastic differential equation, including the contribution of a deterministic drift and a stochastic term. The form of the equation is motivated by the current astrophysical framework, accepting that jets are powered through the extraction of the rotational energy of the central supermassive black hole mediated by magnetic fields supported by a so-called magnetically arrested accretion disc. We apply the model to the γ-ray light curves of several bright blazars and we infer the parameters suitable to describe them. In particular, we examine the differential distribution of fluxes (dN/dFγ) and we show that the predicted probability density function for the assumed stochastic equation naturally reproduces the observed power-law shape at large fluxes $\mathrm{ d}N/\mathrm{ d}F_{\gamma } \propto F_{\gamma }^{-\alpha }$ with α > 2.
Alignment and quantification of ChIP-exo crosslinking patterns reveal the spatial organization of protein–DNA complexes
Authors: Yamada Naomi , Rossi Matthew J , Farrell Nina , Pugh B Franklin , Mahony Shaun
Published: July 2020

The ChIP-exo assay precisely delineates protein–DNA crosslinking patterns by combining chromatin immunoprecipitation with 5′ to 3′ exonuclease digestion. Within a regulatory complex, the physical distance of a regulatory protein to DNA affects crosslinking efficiencies. Therefore, the spatial organization of a protein–DNA complex could potentially be inferred by analyzing how crosslinking signatures vary between its subunits. Here, we present a computational framework that aligns ChIP-exo crosslinking patterns from multiple proteins across a set of coordinately bound regulatory regions, and which detects and quantifies protein–DNA crosslinking events within the aligned profiles. By producing consistent measurements of protein–DNA crosslinking strengths across multiple proteins, our approach enables characterization of relative spatial organization within a regulatory complex. Applying our approach to collections of ChIP-exo data, we demonstrate that it can recover aspects of regulatory complex spatial organization at yeast ribosomal protein genes and yeast tRNA genes. We also demonstrate the ability to quantify changes in protein–DNA complex organization across conditions by applying our approach to analyze Drosophila Pol II transcriptional components. Our results suggest that principled analyses of ChIP-exo crosslinking patterns enable inference of spatial organization within protein–DNA complexes.