bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Cease and desist?’ The persistence of Marlboro brand imagery in racing video games
Authors: Forsyth Susan , McDaniel Patricia A
Published: February 2020

Background

Since 1972, Philip Morris (PM) has sponsored motorsports. Racing video games are a popular genre among youth and often emulate the branding of their real-life counterparts, potentially exposing youth to tobacco imagery. We examined racing video games for the presence of Marlboro imagery and explored the history of efforts to remove or regulate such imagery.

Methods

We searched the Truth Tobacco Industry documents for relevant documents and used information from video game-related websites and game play videos to identify racing video games that contained Marlboro trademarks and imagery. We also collected information on the Entertainment Software Ratings Board’s (ESRB) tobacco-specific and overall game ratings.

Findings

In 1989, negative publicity surrounding the presence of Marlboro logos in racing games led PM to threaten legal action against two game makers for copyright infringement. PM also launched a media campaign promoting this intervention as evidence of its commitment to youth smoking prevention. Nonetheless, we identified 219 video games from 1979 to 2018 that contained Marlboro trademarks and/or Marlboro-sponsored drivers and livery. Among the games in our sample with an ESRB game rating, all but one received an ‘E,’ indicating appropriateness for everyone, and all but three lacked tobacco content descriptors.

Conclusion

Racing video games have been and continue to be a vehicle for exposing adolescents to the Marlboro brand. Because voluntary efforts by PM and the video game industry to prevent youth exposure to tobacco brands in video games have been ineffective, USA and international policy-makers should prohibit tobacco content in video games.
Effect of technological voids on swelling behaviour of compacted bentonite–claystone mixture
Authors: Zeng Zhixiong , Cui Yu-Jun , Zhang Feng , Conil Nathalie , Talandier Jean
Published: February 2020

The effect of technological voids on the swelling pressure of compacted MX80 bentonite–Callovo-Oxfordian (COx) claystone mixture was investigated by simulating the technological voids with a pre-defined space between the compacted disks of the mixture. Both axial and radial swelling pressures were monitored. After the tests, the microstructure of samples at different positions was investigated using mercury intrusion porosimetry (MIP), together with the determination of dry density and water content. Results showed that two main processes, filling and homogenization, occurred during soil hydration. In the filling process, the initial technological voids were gradually filled and the axial swelling pressure tended to increase. In the homogenization process, the samples had a sealing zone and a swelling zone. The sealing zone was characterized by a lower dry density than the expected final dry density while the swelling zone was characterized by a larger one. From the MIP results, the sealing zone showed larger inaccessible-pore, medium-pore, and large-pore void ratios and a lower small-pore void ratio than the swelling zone. Over time, the medium and large pores in the sealing zone were compressed, while the small pores in the swelling zone decreased. The stabilized axial swelling pressure followed a unique relationship with the expected final dry density. Moreover, the swelling pressure anisotropy was found to decrease as the technological voids increased.
Effects of microorganism within organic matter on the mechanical behaviour of solidified municipal dredged mud
Authors: Deng Yongfeng , Wu Jun , Tan Yunzhi , Cui Yujun , Tang Chao-sheng , Zhou Annan
Published: February 2020

Municipal mud consists of organic matter naturally deposited in a microbial-rich environment, and its common pre-treatment in the laboratory is normally different from that in situ. In this study, an improved pre-loading method and the common pre-treatment method (by air or oven drying) were first applied to investigate the effect of microorganisms within organic matter on performance of the solidified soils. Results reveal that (i) Atterberg limits in the pre-loading method were higher than those in the drying method; (ii) the time-dependent strength became stable for the solidified soils pre-treated by the drying method, while strength decreased for the soils pre-treated by the pre-loading method; (iii) pH value of solidified soils by the pre-loading method decreased more significantly. After excluding the possible porosity influence on solidified soils, the effects of microorganisms within organic matter were investigated by microbial identification tests, including fluorescence detection and high-throughput sequencing. The pre-treatment procedure changed the vitality and diversity of microorganisms, leading to a rebalance between acid erosion and cement hydration during long-term curing. At the end, the long-term strength of the solidified municipal mud by the traditional pre-treatment method (by air or oven drying) could be overevaluated.
Study of the $${{^{25}}}$$Mg(d,p)$${{^{26}}}$$Mg reaction to constrain the $${{^{25}}}$$Al(p,$${\gamma }$$)$${{^{26}}}$$Si resonant reaction rates in nova burning conditions
Authors: Hamill C. B. , Woods P. J. , Kahl D. , Longland R. , Greene J. P. , Marshall C. , Portillo F. , Setoodehnia K.
Published: February 2020

The rate of the $$^{25}$$25Al(p, $$\gamma $$γ)$$^{26}$$26Si reaction is one of the few key remaining nuclear uncertainties required for predicting the production of the cosmic $$\gamma $$γ-ray emitter $$^{26}$$26Al in explosive burning in novae. This reaction rate is dominated by three key resonances ($$J^{\pi }=0^{+}$$Jπ=0+, $$1^{+}$$1+ and $$3^{+}$$3+) in $$^{26}$$26Si. Only the $$3^{+}$$3+ resonance strength has been directly constrained by experiment. A high resolution measurement of the $$^{25}$$25Mg(d, p) reaction was used to determine spectroscopic factors for analog states in the mirror nucleus, $$^{26}$$26Mg. A first spectroscopic factor value is reported for the $$0^{+}$$0+ state at 6.256 MeV, and a strict upper limit is set on the value for the $$1^{+}$$1+ state at 5.691 MeV, that is incompatible with an earlier ($$^{4}$$4He, $$^{3}$$3He) study. These results are used to estimate proton partial widths, and resonance strengths of analog states in $$^{26}$$26Si contributing to the $$^{25}$$25Al(p, $$\gamma $$γ)$$^{26}$$26Si reaction rate in nova burning conditions.
Elastic differential cross-section $${\mathrm{d}}\sigma /{\mathrm{d}}t$$ at $$\sqrt{s}=2.76\hbox { TeV}$$ and implications on the existence of a colourless C-odd three-gluon compound state
Authors: Antchev G. , Aspell P. , Atanassov I. , Avati V. , Baechler J. , Barrera C. Baldenegro , Berardi V. , Berretti M. , Bossini E. , Bottigli U. , Bozzo M. , Burkhardt H. , Cafagna F. S. , Catanesi M. G. , Csanád M. , Csörgő T. , Deile M. , De Leonardis F. , Doubek M. , Druzhkin D. , Eggert K. , Eremin V. , Ferro F. , Fiergolski A. , Garcia F. , Georgiev V. , Giani S. , Grzanka L. , Hammerbauer J. , Ivanchenko V. , Kašpar J. , Kopal J. , Kundrát V. , Lami S. , Latino G. , Lauhakangas R. , Lindsey C. , Lokajíček M. V. , Losurdo L. , Vetere M. Lo , Rodríguez F. Lucas , Macrí M. , Malawski M. , Minafra N. , Minutoli S. , Naaranoja T. , Nemes F. , Niewiadomski H. , Novák T. , Oliveri E. , Oljemark F. , Oriunno M. , Österberg K. , Palazzi P. , Passaro V. , Peroutka Z. , Procházka J. , Quinto M. , Radermacher E. , Radicioni E. , Ravotti F. , Robutti E. , Royon C. , Ruggiero G. , Saarikko H. , Scribano A. , Smajek J. , Snoeys W. , Sziklai J. , Taylor C. , Tcherniaev E. , Turini N. , Vacek V. , Welti J. , Williams J.
Published: February 2020

The proton–proton elastic differential cross section $${\mathrm{d}}\sigma /{\mathrm{d}}t$$dσ/dt has been measured by the TOTEM experiment at $$\sqrt{s}=2.76\hbox { TeV}$$s=2.76TeV energy with $$\beta ^{*}=11\hbox { m}$$β∗=11m beam optics. The Roman Pots were inserted to 13 times the transverse beam size from the beam, which allowed to measure the differential cross-section of elastic scattering in a range of the squared four-momentum transfer (|t|) from 0.36 to $$0.74\hbox { GeV}^{2}$$0.74GeV2. The differential cross-section can be described with an exponential in the |t|-range between 0.36 and $$0.54\hbox { GeV}^{2}$$0.54GeV2, followed by a diffractive minimum (dip) at $$|t_{\mathrm{dip}}|=(0.61\pm 0.03)\hbox { GeV}^{2}$$|tdip|=(0.61±0.03)GeV2 and a subsequent maximum (bump). The ratio of the $${\mathrm{d}}\sigma /{\mathrm{d}}t$$dσ/dt at the bump and at the dip is $$1.7\pm 0.2$$1.7±0.2. When compared to the proton–antiproton measurement of the D0 experiment at $$\sqrt{s} = 1.96\hbox { TeV}$$s=1.96TeV, a significant difference can be observed. Under the condition that the effects due to the energy difference between TOTEM and D0 can be neglected, the result provides evidence for the exchange of a colourless C-odd three-gluon compound state in the t-channel of the proton–proton and proton–antiproton elastic scattering.
“Stationary” Schrödinger equation in quantum cosmology
Authors: Gorobey N. , Lukyanenko A. , Shavrin A.
Published: February 2020

The conditional principle of extremum in quantum cosmology is formulated for a positive functional of the energy density of space, in which gravitational constraints serve as additional conditions. The extremum conditions determine the discrete spectrum of the “stationary” state of the universe with the corresponding values of the energy density of space. A dynamic interpretation of solutions is proposed, in which the quantum number of the energy density plays the role of cosmic time. In the self-consistent harmonic approximation, the quantum dynamics of the anisotropic model of the Bianchi IX universe is considered.
Black hole in balance with dark matter
Authors: Meierovich Boris E.
Published: February 2020

Equilibrium of a gravitating scalar field inside a black hole compressed to the state of a boson matter, in balance with a longitudinal vector field (dark matter) from outside is considered. Analytical consideration, confirmed numerically, shows that there exist static solutions of Einstein’s equations with arbitrary high total mass of a black hole, where the component of the metric tensor [Formula: see text] changes its sign twice. The balance of the energy-momentum tensors of the scalar field and the longitudinal vector field at the interface ensures the equilibrium of these phases. Considering a gravitating scalar field as an example, the internal structure of a black hole is revealed. Its phase equilibrium with the longitudinal vector field, describing dark matter on the periphery of a galaxy, determines the dependence of the velocity on the plateau of galaxy rotation curves on the mass of a black hole, located in the center of a galaxy.
Improve the spectral clustering by integrating a new modularity similarity index and out-of-sample extension
Authors: Shen Dongqin , Li Xiuyi , Yan Guan
Published: February 2020

Spectral clustering is one of the most important data processing methods which has been wildly applied to machine learning, computer vision, pattern recognition and image processing. However, one of the main drawbacks of spectral clustering is the fact that the clustering model is defined only for primal data without clear extension to out-of-sample data. To improve its efficiency, in this paper, we proposed a new modularity-based method for spectral clustering with out-of-sample extension. First, kernel independent component analysis is used to solve the demixing matrix on Stiefel manifold in order to extract high-order irrelevant data feature. Then, a new modularity similarity measure-based spectral mapping algorithm is proposed, which allows the clustering model to be directly extended to out-of-sample data. Based on above analysis, we present a spectral clustering algorithm with out-of-sample extension. Experimental results show our method has better performance compared with other related algorithms in different datasets.
Novel Polyacrylonitrile-Based C/Co-Ru Metal-Carbon Nanocomposites as Effective Catalysts for Ethanol Steam Reforming
Authors: Efimov M. N. , Mironova E. Yu. , Pavlov A. A. , Vasilev A. A. , Muratov D. G. , Dzidziguri E. L. , Yaroslavtsev A. B. , Karpacheva G. P.
Published: February 2020

One-step preparation method of metal-carbon nanocomposites based on bimetallic Co–Ru nanoparticles supported and IR carbonized polyacrylonitrile was proposed. IR pyrolysis of the precursor based on joint solution of polyacrylonitrile and metal compounds leads to the simultaneous formation of carbon support and bimetallic metal nanoparticles. The metal reduction occures due to the release of hydrogen during decomposition of backbone polymer chain. Furthermore, IR radiation shortens fabrication time significantly. It was shown that the presence of cobalt and ruthenium in the system provides the creation of alloy Co–Ru nanoparticles. In addition, cobalt provides a formation of structured carbon shells around bimetallic nanoparticles. The nanocomposites were tested as catalysts for the hydrogen production through ethanol steam reforming. The dependence of structural and functional properties on the metal loading was demonstrated. The high yield of hydrogen was recorded for all three samples, whereas the by-product yield was relatively low.
Omnithermal Perfect Simulation for Multi-server Queues
Authors: Connor Stephen
Published: February 2020

A number of perfect simulation algorithms for multi-server First Come First Served queues have recently been developed. Those of Connor and Kendall [6] and Blanchet et al. [4] use dominated Coupling from the Past (domCFTP) to sample from the equilibrium distribution of the Kiefer--Wolfowitz workload vector for stable
M
/
G
/
c
and
GI
/
GI
/
c
queues, respectively, using Random Assignment queues as dominating processes. In this article, we answer a question posed by Connor and Kendall [6] by demonstrating how these algorithms may be modified to carry out domCFTP
simultaneously
for a range of values of
c
(the number of servers).
An Integrated Method for Simultaneous Calibration and Parameter Selection in Computer Models
Authors: Yuan Jun , Ng Szu Hui
Published: February 2020

For many large and complex computer models, there usually exist a large number of unknown parameters. To improve the computer model's predictive performance for more reliable and confident decision making, two important issues have to be addressed. The first is to calibrate the computer model and the second is to select the most influential set of parameters. However, these two issues are often addressed independently, which may waste computational effort. In this article, a Gaussian process-based Bayesian method is first proposed to simultaneously calibrate and select parameters in stochastic computer models. The whole procedure can be conducted more efficient by sharing the data information between these two steps. To further ease the computational burden, an approximation approach based on a weighted normal approximation is proposed to evaluate the posteriors in the proposed Bayesian method. A sequential approximation procedure is further proposed to improve the approximation accuracy by allocating the sequential design points more appropriately. The efficiency and accuracy of the proposed approaches are compared in a building energy model and a pandemic influenza simulation model.
Enhancing Response Predictions with a Joint Gaussian Process Model for Stochastic Simulation Models
Authors: Wang Songhao , Ng Szu hui
Published: February 2020

The stochastic Gaussian process model has been widely used in stochastic simulation metamodeling. In practice, the performance of this model can be largely affected by the noise in the observations. In this article, we propose an approach to mitigate the impact of the noisy observations by jointly modeling the response of interest with a correlated but less-noisy auxiliary response. The main idea is to leverage on and learn from the correlated and more accurate response to improve the prediction. To achieve this, we extend the existing deterministic multi-response model for stochastic simulation to jointly model the two responses, use some simplified examples to show the benefit of the proposed model, and investigate the input estimation of this model. Quantile prediction is used to illustrate the efficiency of the proposed approach by jointly modeling it with the expectation, which typically has a less noisy estimator compared with that of the quantile. Several numerical examples are then conducted, and the results show that the joint model can provide better performance. These promising results illustrate the potential of this joint model especially in situations where the response of interest is much noisier or when observations are scarce. We further propose a two-stage design approach based on the multi-response model to more efficiently utilize limited computing budget to improve predictions. We also see from these designs the benefits of the joint model, where the more accurate auxiliary response observations can be used to improve the response of interest.
Securing the Boot Process
Authors: Frazelle Jessie
Published: February 2020

The goal of a hardware root of trust is to verify that the software installed in every component of the hardware is the software that was intended. This way you can verify and know without a doubt whether a machine’s hardware or software has been hacked or overwritten by an adversary. In a world of modchips, supply chain attacks, evil maid attacks, cloud provider vulnerabilities in hardware components, and other attack vectors it has become more and more necessary to ensure hardware and software integrity.
Confinement and Diffusion of Small Molecules in a Molecular-Scale Tunnel
Authors: Chavan Kanchan Suklal , Barton Scott Calabrese
Published: February 2020

Multi-step reaction cascades can be designed to include channeling mechanisms, which provide electrostatic or steric control over intermediate transport such that intermediates do not escape to the bulk between active sites. Physical confinement of the intermediate pathway between sites retains intermediate from bulk access and thus provides high transport efficiency. In this work, we use molecular dynamics to study the transport of intermediates (charged oxalate and neutral ethanol) inside a nanochannel represented by a single-walled carbon nanotube (SWCNT). This approach reveals that solvent orientation highly impacts intermediate transport. At small nanochannel diameter near 1 nm, highly structured solvent water and Knudsen diffusion decreases effective intermediate diffusivity. Finally, modified SWCNT termini with electrostatically-charged carboxylate groups are shown to increase intermediate retention for both charged and uncharged intermediates by up to five-fold. When catalyst sites are located within the nanochannel, decreased diffusion rate and increased retention time will enhance cascade efficiency.
P14ARF inhibits regional inflammation and vascularization in intervertebral disc degeneration by upregulating TIMP3
Authors: He Mingwei , Pang Jinlei , Sun Haiyan , Zheng Guanrong , Lin Yan , Ge Weipeng
Published: February 2020

In this study, we identified P14 alternate reading frame (P14ARF) as a novel regulator of inflammation and vascularization in intervertebral disk degeneration (IVDD). We collected IVD tissues from IVDD patients and normal individuals for analysis of P14ARF expression. We also induced experimental IVDD by needle puncture injuries in the caudal intervertebral disks of Sprague-Dawley (SD) rats and achieved recombinant adenovirus-mediated P14ARF overexpression in experimental IVDD rats. Regulation relationships between P14ARF and tissue inhibitors of metalloproteinases-3 (TIMP3) were confirmed in P14ARF-overexpressed and TIMP3-depleted nucleus pulposus (NP) cells. Tube formation in vitro was evaluated in coculture systems of human umbilical vein endothelial cells (HUVECs) and rat degenerated NP cells (DNPCs). Inflammatory response was assessed from levels of TNF-α, IL-1β, and IL-6 and neovascularization from expression of endothelial growth factor (VEGF). The P14ARF and TIMP3 were downregulated in degenerated IVD tissue derived from patients and experimental IVDD rats. Overexpressed P14ARF suppressed inflammatory cytokine levels and vascularization. There was decreased in vitro tube formation in response to P14ARF overexpression and TIMP3 elevation. Finally, attenuated inflammatory responses and suppression of VEGF were achieved by P14ARF-mediated promotion of TIMP3 in rat DNPCs. Taken together, the present study reveals that P14ARF/TIMP3 modulation of inflammatory response and vascularization in the context of IVDD highlights a potential target for future therapeutic strategies.
Synemin-related skeletal and cardiac myopathies: an overview of pathogenic variants
Authors: Paulin Denise , Hovhannisyan Yeranuhi , Kasakyan Serdar , Agbulut Onnik , Li Zhenlin , Xue Zhigang
Published: February 2020

This review analyzes data concerning patients with cardiomyopathies or skeletal myopathies associated with a variation in the intermediate filament (IF) synemin gene ( SYNM), also referred to as desmuslin ( DMN). Molecular studies demonstrate that synemin copolymerizes with desmin and vimentin IF and interacts with vinculin, α-actinin, α-dystrobrevin, dystrophin, talin, and zyxin. It has been found that synemin is an A-kinase-anchoring protein (AKAP) that anchors protein kinase A (PKA) and modulates the PKA-dependent phosphorylation of several cytoskeletal substrates such as desmin. Because several IF proteins, including desmin, have been implicated in human genetic disorders such as dominant or recessive congenital and adult-onset myopathy, synemin becomes a significant candidate for cardiac and skeletal myopathies of unknown etiology. Because SYNM is a new candidate gene that displays numerous sequence polymorphisms, in this review, we summarize the genetic and clinical literature about SYNM mutations. Protein-changing variants (missense, frameshifts, nonsense) were further evaluated based on structural modifications and amino acid interactions. We present in silico modeling of helical salt-bridges between residues to evaluate the impact of the synemin networks crucial to interactions with cytoskeletal proteins. Finally, a discussion is featured regarding certain variants that may contribute to the disease state.
PDGFRα and αSMA mark two distinct mesenchymal cell populations involved in parenchymal and vascular remodeling in pulmonary fibrosis
Authors: Biasin Valentina , Crnkovic Slaven , Sahu-Osen Anita , Birnhuber Anna , El Agha Elie , Sinn Katharina , Klepetko Walter , Olschewski Andrea , Bellusci Saverio , Marsh Leigh M. , Kwapiszewska Grazyna
Published: February 2020

Pulmonary fibrosis is characterized by pronounced collagen deposition and myofibroblast expansion, whose origin and plasticity remain elusive. We utilized a fate-mapping approach to investigate α-smooth muscle actin (αSMA)+ and platelet-derived growth factor receptor α (PDGFRα)+ cells in two lung fibrosis models, complemented by cell type-specific next-generation sequencing and investigations on human lungs. Our data revealed that αSMA+ and PDGFRα+ cells mark two distinct mesenchymal lineages with minimal transdifferentiation potential during lung fibrotic remodeling. Parenchymal and perivascular fibrotic regions were populated predominantly with PDGFRα+ cells expressing collagen, while αSMA+ cells in the parenchyma and vessel wall showed variable expression of collagen and the contractile protein desmin. The distinct gene expression profile found in normal conditions was retained during pathologic remodeling. Cumulatively, our findings identify αSMA+ and PDGFRα+ cells as two separate lineages with distinct gene expression profiles in adult lungs. This cellular heterogeneity suggests that anti-fibrotic therapy should target diverse cell populations.
Renovascular hypertension elevates pulmonary ventilation in rats by carotid body-dependent mechanisms
Authors: Melo Mariana Rosso , Gasparini Silvia , Silva Elaine F. , Karlen-Amarante Marlusa , Speretta Guilherme F. , Lauar Mariana R. , Pedrino Gustavo R. , Menani Jose V. , Colombari Debora S. A. , Zoccal Daniel B. , Colombari Eduardo
Published: February 2020

The two kidney-one clip (2K1C) renovascular hypertension depends on the renin-angiotensin system and sympathetic overactivity. The maintenance of 2K1C hypertension also depends on inputs from the carotid bodies (CB), which when activated stimulate the respiratory activity. In the present study, we investigated the importance of CB afferent activity for the ventilatory responses in 2K1C hypertensive rats and for phrenic and hypoglossal activities in in situ preparations of normotensive rats treated with angiotensin II. Silver clips were implanted around the left renal artery of male Holtzman rats (150 g) to induce renovascular hypertension. Six weeks after clipping, hypertensive 2K1C rats showed, in conscious state, elevated resting tidal volume and minute ventilation compared with the normotensive group. 2K1C rats also presented arterial alkalosis, urinary acidification, and amplified hypoxic ventilatory response. Carotid body removal (CBR), 2 wk before the experiments (4th week after clipping), significantly reduced arterial pressure and pulmonary ventilation in 2K1C rats but not in normotensive rats. Intra-arterial administration of angiotensin II in the in situ preparation of normotensive rats increased phrenic and hypoglossal activities, responses that were also reduced after CBR. Results show that renovascular hypertensive rats exhibit increased resting ventilation that depends on CB inputs. Similarly, angiotensin II increases phrenic and hypoglossal activities in in situ preparations of normotensive rats, responses that also depend on CB inputs. Results suggest that mechanisms that depend on CB inputs in renovascular hypertensive rats or during angiotensin II administration in normotensive animals increase respiratory drive.
Structure and function of crocodilian hemoglobins and allosteric regulation by chloride, ATP, and CO2
Authors: Fago Angela , Natarajan Chandrasekhar , Pettinati Martín , Hoffmann Federico G. , Wang Tobias , Weber Roy E. , Drusin Salvador I. , Issoglio Federico , Martí Marcelo A. , Estrin Darío , Storz Jay F.
Published: February 2020

Hemoglobins (Hbs) of crocodilians are reportedly characterized by unique mechanisms of allosteric regulatory control, but there are conflicting reports regarding the importance of different effectors, such as chloride ions, organic phosphates, and CO2. Progress in understanding the unusual properties of crocodilian Hbs has also been hindered by a dearth of structural information. Here, we present the first comparative analysis of blood properties and Hb structure and function in a phylogenetically diverse set of crocodilian species. We examine mechanisms of allosteric regulation in the Hbs of 13 crocodilian species belonging to the families Crocodylidae and Alligatoridae. We also report new amino acid sequences for the α- and β-globins of these taxa, which, in combination with structural analyses, provide insights into molecular mechanisms of allosteric regulation. All crocodilian Hbs exhibited a remarkably strong sensitivity to CO2, which would permit effective O2unloading to tissues in response to an increase in metabolism during intense activity and diving. Although the Hbs of all crocodilians exhibit similar intrinsic O2-affinities, there is considerable variation in sensitivity to Cl−ions and ATP, which appears to be at least partly attributable to variation in the extent of NH2-terminal acetylation. Whereas chloride appears to be a potent allosteric effector of all crocodile Hbs, ATP has a strong, chloride-independent effect on Hb-O2affinity only in caimans. Modeling suggests that allosteric ATP binding has a somewhat different structural basis in crocodilian and mammalian Hbs.
Long-term blood pressure lowering and cGMP-activating actions of the novel ANP analog MANP
Authors: Chen Yang , Schaefer Jacob J. , Iyer Seethalakshmi R. , Harders Gerald E. , Pan Shuchong , Sangaralingham S. Jeson , Chen Horng H. , Redfield Margaret M. , Burnett John C.
Published: February 2020

Based on the cardiac hormone atrial natriuretic peptide (ANP) and its seminal role in blood pressure (BP) homeostasis, we investigated the chronic BP lowering actions of a novel ANP analog currently entering clinical trials for hypertension. Previous reports demonstrate that this analog MANP activates the guanylyl cyclase A receptor (GC-A) and results in more potent biological actions compared with ANP; thus, it may represent a new therapeutic drug for hypertension. A major goal of this study was to establish that chronic subcutaneous delivery of MANP is feasible and hypotensive together with cGMP effects. We investigated the BP-lowering and cGMP-activating actions of acute and chronic subcutaneous delivery in normal and hypertensive rats. Furthermore, we explored vascular mechanisms of MANP in human aortic smooth muscle cells (HASMC) and ex vivo in isolated arteries. In normal rats with a single subcutaneous injection, MANP promoted robust dose-dependent BP-lowering actions and natriuresis, together with cGMP activation. Most importantly in hypertensive rats, once-a-day subcutaneous injection of MANP for 7 days induced cGMP elevation and long-term BP reduction compared with vehicle. Mechanistically, in HASMC, MANP activated cGMP and attenuated angiotensin II-mediated increases in intracellular Ca2+levels while directly vasorelaxing arterial rings. Our study demonstrates for the first time the effectiveness of subcutaneous administration of MANP for 7 days and provides innovative, vascular mechanisms of BP regulation supporting its continued development as a novel therapeutic for hypertension.
Object and place information processing by CA1 hippocampal neurons of C57BL/6J mice
Authors: Ásgeirsdóttir Herborg N. , Cohen Sarah J. , Stackman Robert W.
Published: February 2020

Medial and lateral entorhinal cortices convey spatial/contextual and item/object information to the hippocampus, respectively. Whether the distinct inputs are integrated as one cognitive map by hippocampal neurons to represent location and the objects therein, or whether they remain as parallel outputs, to be integrated in a downstream region, remains unclear. Principal, or complex spike bursting, neurons of hippocampus exhibit location-specific firing, and it is likely that the activity of “place cells” supports spatial memory/navigation in rodents. Consistent with cognitive map theory, the activity of CA1 hippocampal neurons is also critical for nonspatial memory, such as object recognition. However, the degree to which CA1 neuronal activity represents the associations of object-context or object-in-place memory is not well understood. Here, the contributions of mouse CA1 neuronal activity to object recognition memory and the emergence of object-place conjunctive representations were tested using in vivo recordings and functional inactivation. Independent of arena configuration, CA1 place fields were stable throughout testing and object-place representations were not identified in CA1, although the number of fields per cell increased during object sessions, and few object-related firing CA1 neurons (nonplace) were recorded. The results of the inactivation studies confirmed the significant contribution of CA1 neuronal activity to object recognition memory when a delay of 20 min, but not 5 min, was imposed between encoding and retrieval. Together, our results confirm the delay-dependent contribution of the CA1 region to object memory and suggest that object information is processed in parallel with the ongoing spatial mapping function that is a hallmark of hippocampal memory.

NEW & NOTEWORTHY We developed variations of the object recognition task to examine the contribution of mouse CA1 neuronal activity to object memory and the degree to which object-context conjunctive representations are formed during object training. Our results indicate that, within the CA1 region, object information is processed in a parallel but delay-dependent manner, with ongoing spatial mapping.
Neural entrainment to music is sensitive to melodic spectral complexity
Authors: Wollman Indiana , Arias Pablo , Aucouturier Jean-Julien , Morillon Benjamin
Published: February 2020

During auditory perception, neural oscillations are known to entrain to acoustic dynamics but their role in the processing of auditory information remains unclear. As a complex temporal structure that can be parameterized acoustically, music is particularly suited to address this issue. In a combined behavioral and EEG experiment in human participants, we investigated the relative contribution of temporal (acoustic dynamics) and nontemporal (melodic spectral complexity) dimensions of stimulation on neural entrainment, a stimulus-brain coupling phenomenon operationally defined here as the temporal coherence between acoustical and neural dynamics. We first highlight that low-frequency neural oscillations robustly entrain to complex acoustic temporal modulations, which underscores the fine-grained nature of this coupling mechanism. We also reveal that enhancing melodic spectral complexity, in terms of pitch, harmony, and pitch variation, increases neural entrainment. Importantly, this manipulation enhances activity in the theta (5 Hz) range, a frequency-selective effect independent of the note rate of the melodies, which may reflect internal temporal constraints of the neural processes involved. Moreover, while both emotional arousal ratings and neural entrainment were positively modulated by spectral complexity, no direct relationship between arousal and neural entrainment was observed. Overall, these results indicate that neural entrainment to music is sensitive to the spectral content of auditory information and indexes an auditory level of processing that should be distinguished from higher-order emotional processing stages.

NEW & NOTEWORTHY Low-frequency (<10 Hz) cortical neural oscillations are known to entrain to acoustic dynamics, the so-called neural entrainment phenomenon, but their functional implication in the processing of auditory information remains unclear. In a behavioral and EEG experiment capitalizing on parameterized musical textures, we disentangle the contribution of stimulus dynamics, melodic spectral complexity, and emotional judgments on neural entrainment and highlight their respective spatial and spectral neural signature.
Associations of Alpha and Beta Interhemispheric EEG Coherences with Indices of Attentional Control and Academic Performance
Authors: Gorantla Vasavi R. , Tedesco Sarah , Chandanathil Merin , Maity Sabyasachi , Bond Vernon , Lewis Courtney , Millis Richard M.
Published: February 2020

Introduction. Heretofore, research on optimizing academic performance has suffered from an inability to translate what is known about an individual’s learning behaviors to how effectively they are able to use the critical nodes and hubs in their cerebral cortex for learning. A previous study from our laboratory suggests that lower theta-beta ratios (TBRs) measured by EEG may be associated with higher academic performance in a medical school curriculum. Methods. In this study, we tested the hypothesis that TBR and academic performance may be correlated with EEG coherence, a measure of brain connectivity. We analyzed the interhemispheric coherences of the subjects involved in our prior study. TBR and coherence measurements were made at 19 scalp electrode recording sites and 171 electrode combinations with eyes open and closed (EO, EC). Control data were acquired during a session of acclimation to the research protocol 3 d before an initial examination in anatomy-physiology (control exam) and were repeated five weeks later, 3 d before a second exam covering different anatomy-physiology topics (comparison exam). Results. Between the control and comparison exams, beta coherences increased significantly at the frontal pole, frontal, parietal, midtemporal, posterior temporal, and occipital recording sites under the EO condition and at the inferior frontal, central, midtemporal, and posterior temporal sites under the EC condition. Alpha coherences increased significantly at the same sites and under the same EO/EC conditions as found for the beta coherences. The beta coherences were negatively correlated with the TBR and were positively correlated with the comparison exam score at the midfrontal electrode site (F3-F4) but only under the EO condition. Beta and alpha coherences at the midfrontal, inferior frontal midtemporal, posterior temporal, and occipital sites were also negatively correlated with the average TBR under the EO condition. Conclusions. Lower TBR, an indicator of attentional control, was associated with higher alpha and beta interhemispheric coherences measured with eyes open at sites overlying the frontal, temporal, and occipital cortices. Changes in EEG coherences and TBRs might be useful as neurophysiological measures of neuroplasticity and the efficacy of strategies for preventing academic underachievement and treatments for improving academic performance.
High Glucose Exacerbates TNF-α-Induced Proliferative Inhibition in Human Periodontal Ligament Stem Cells through Upregulation and Activation of TNF Receptor 1
Authors: Zhu Wenjun , Qiu Qihong , Luo Haoyuan , Zhang Fuping , Wu Juan , Zhu Xiaorui , Liang Min
Published: February 2020

Objective. This research is aimed at investigating how high glucose affects the proliferation and apoptosis in periodontal ligament stem cells (PDLSCs) in the presence of TNF-α. Methods. PDLSCs obtained from periodontal healthy permanent teeth were treated under either high-glucose condition (30 mmol/L, G30 group) or normal glucose condition (5.6 mmol/L, G5.6 group) in the presence or absence of TNF-α (10 ng/ml) for 2 to 6 days. Cell proliferation and cell cycle were evaluated by CCK-8, EdU incorporation assay, and flow cytometry. Cell apoptosis was assessed by annexin V/PI staining. Protein expression was detected by western blotting. Cellular ROS expression was evaluated by CellROX labeling and flow cytometry. Specific antibodies targeting TNFR1 and TNFR2 were used to block TNF-α signaling. Vitamin C was also used to verify if the blockage of ROS can rescue PDLSCs in the presence of high glucose and TNF-α. Results. CCK-8 assay showed that high glucose exacerbated TNF-α-induced cell viability inhibition (57.0%, 85.2%, and 100% for the G30+TNF-α group, G5.6+TNF-α group, and control group, respectively) on day 6. High glucose increased protein expression of TNFR1 compared with the control group on day 2 (1.24-fold) and day 6 (1.26-fold). Blocking TNFR1 totally reversed the proliferative inhibition in G30+TNF-α group. The addition of vitamin C or TNFR1 antibody totally reversed the elevation of intracellular ROS expression caused by high glucose and TNF-α. Vitamin C partially restored cell proliferation in the presence of high glucose and TNF-α. Conclusion. High glucose exacerbates TNF-α-induced proliferative inhibition in human periodontal ligament stem cells through the upregulation and activation of TNF receptor 1. Inhibition of intracellular ROS expression by vitamin C partially rescues PDLSCs in terms of cell proliferation.
Xuan Bi Tong Yu Fang Promotes Angiogenesis via VEGF‐Notch1/Dll4 Pathway in Myocardial Ischemic Rats
Authors: Li Shuangdi , Dong Jingrong , Ta Guang , Liu Yinghui , Cui Junfeng , Li Xiaohui , Song Jing , Liu Aidong , Cheng Guangyu
Published: February 2020

Objective. To investigate the effect of Xuan Bi Tong Yu Fang (XBTYF) on angiogenesis via the vascular endothelial growth factor‐ (VEGF‐) Notch1/delta‐like 4 (Dll4) pathway. Materials and Methods. Sixty Sprague‐Dawley rats were randomly divided into six groups: control, sham‐operated, myocardial ischemia model, and XBTYF treatment at 3.2, 1.6, and 0.8 g/kg. Electrocardiography was performed to evaluate the successful establishment of the model. Hematoxylin‐eosin staining and transmission electron microscopy were carried out to observe the morphology and mitochondrial structure in myocardial cells, respectively. TUNEL staining was performed to assess the degree of cell apoptosis. The expression of VEGF‐A, Notch1, Dll4, Bcl2, Bax, caspase 3, caspase 9, and cytochrome‐c (Cyt‐c) was observed by western blot. Results. XBTYF inhibited changes to the morphology and mitochondrial structure in cardiomyocyte and reduced cell apoptosis. Compared with the model group, XBTYF at all doses (3.2, 1.6, and 0.8 g/kg) reduced the expression of Notch1, Dll4, Bax, caspase 3, caspase 9, and Cyt‐c, whereas expression of VEGF‐A and Bcl2 was increased. Conclusion. XBTYF attenuated mitochondrial damage and cell apoptosis while promoting the angiogenesis of cardiomyocyte. The associated mechanism may be related to the VEGF‐Notch1/Dll4 pathway.
Exploring the Mesenchymal Stem Cell Secretome for Corneal Endothelial Proliferation
Authors: Van den Bogerd Bert , Zakaria Nadia , Matthyssen Steffi , Koppen Carina , Ní Dhubhghaill Sorcha
Published: February 2020

Ex vivo grown human corneal endothelial cells (HCEnC) are a new emerging treatment option to treat visually impaired patients aimed at alleviating the current global donor shortage. Expanding HCEnC is still challenging, and obtaining cells in sufficient quantities is a limiting factor. It is already known that conditioned medium obtained from bone marrow mesenchymal stem cells can stimulate the proliferation of endothelial cells. The aim of this study was to take this work a step further to identify some of the underlying factors responsible. We confirmed the stimulatory effect of the mesenchymal stem cell secretome seen previously and separated the exosomes from the soluble proteins using size exclusion chromatography. We demonstrated the presence of exosomes and soluble proteins in the early and late fractions, respectively, with transmission electron microscopy and protein assays. Proliferation studies demonstrated that growth stimulation could be reproduced with the later protein-rich fractions but not with the exosome-rich fraction. Antibody assays revealed the presence of the secreted proteins EGF, IGFBP2, and IGFBP6 in protein-high fractions, but the growth enhancement was not seen with purified protein formulations. In conclusion, we confirmed the stimulatory effect of stem cell-conditioned medium and have determined that the effect was attributable to the proteins rather than to the exosomes. We were not able to reproduce the growth stimulation, however, with the pure recombinant protein candidates tested. Specific identification of the underlying proteins using proteomics could render a bioactive protein that can be used for ex vivo expansion of cells or as an in vivo drug to treat early corneal endothelial damage.
A Bayesian Hierarchical Model for the Spatial Analysis of Carbon Monoxide Pollution Extremes in Mexico City
Authors: Jiménez-Hernández José del Carmen , López-Cerino Marisol , Aguirre-Salado Alejandro Ivan
Published: February 2020

Air pollution by carbon monoxide is a serious problem that affects many cities around the world, and the theory of extreme values has played a crucial role in the study of this issue. In this paper, we proposed a Bayesian hierarchical spatial model of extreme values to evaluate the risk of extreme events of air pollution due to carbon monoxide in the metropolitan area of Mexico City. Spatial trends are modeled through of a Gaussian process for the generalized extreme value (GEV) distribution parameters, and prediction maps are produced for each of these. The results show a marginal spatial behavior for the location, scale, and shape parameters of GEV distribution, which indicate the existence of local variations that would not be possible to model using only stationary models. A return map of the maximum concentrations with a return period of one year is obtained. We found that the return levels for a one-year return period of CO concentration above 8 ppm in the Metropolitan Area of the Valley of Mexico are concentrated in the central part of this region, and the areas with the lowest estimates are distributed in the periphery. In addition, a quantile-quantile (QQ) plot between the theoretical and empirical quantiles was provided, which showed a very good fit of data to the proposed model.
Disseminated Endometriosis and Low-Grade Endometrioid Stromal Sarcoma in a Patient with a History of Uterine Morcellation for Adenomyosis
Authors: Stefanko Daniel P. , Eskander Ramez , Aisagbonhi Omonigho
Published: February 2020

Morcellation of benign uterine tumors allows for removal of the tumors via minimally invasive laparoscopic procedures. However, in rare cases, morcellation has been associated with upstaging of unexpected malignancies. Morcellation has also been associated with dissemination of benign pathologic processes such as endometriosis and leiomyomas. Endometrial stromal sarcoma typically arises in the uterine cavity, although cases of extrauterine endometrioid stromal sarcoma arising out of foci of endometriosis have been reported. Dissemination of endometrial stromal sarcomas can be an unintended consequence of morcellation procedures, as can dissemination of endometriosis, from which endometrioid stromal sarcomas can arise. Herein, we report a case of a 55-year-old woman who was found to have disseminated endometriosis and low-grade endometrioid stromal sarcoma, with bowel and liver parenchymal metastasis, 7 years after undergoing supracervical hysterectomy with unconfined uterine morcellation for adenomyosis. Our case highlights the potential for malignant transformation of disseminated adenomyosis/endometriosis and the importance of patient counseling and shared decision-making prior to morcellation procedures.
Natural Tooth Pontic Using Recent Adhesive Technologies: An Esthetic and Minimally Invasive Prosthetic Solution
Authors: Augusti Davide , Augusti Gabriele , Ionescu Andrei , Brambilla Eugenio , Re Dino
Published: February 2020

An implant-supported crown represents an established and validated option for single-tooth replacement; however, a restorative solution should be selected according to a wide number of factors including patient’s desire, expectations, specific clinical conditions, and financial possibilities. The aim of this case report is to describe a conservative rehabilitation strategy for the replacement of a periodontally compromised mandibular incisor: the extracted natural tooth was used as a pontic bonded to adjacent elements with polyethylene fiber and resin composite. This way, a chairside fabrication of a resin-bonded fiber-reinforced prosthesis is possible, using the patient’s own tooth. After showing a satisfactory functional and esthetic result, advantages and pitfalls of this technique along with available data on the literature regarding the natural tooth pontic are addressed. Both patients and clinicians should be aware of minimally invasive, successful solutions for single-tooth replacement; whether indicated or necessary, the natural tooth pontic technique leaves open other treatment options for the future.