bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preparing the next gravitational million-body simulations: evolution of single and binary stars in
nbody6++gpu
,
mocca
, and
mcluster
Authors: Kamlah A W H , Leveque A , Spurzem R , Arca Sedda M , Askar A , Banerjee S , Berczik P , Giersz M , Hurley J , Belloni D , Kühmichel L , Wang L 
Published: December 2021

ABSTRACT
We present the implementation of updated stellar evolution recipes in the codes nbody6++gpu, mocca, and mcluster. We test them through numerical simulations of star clusters containing 1.1 × 105 stars (with 2.0 × 104 in primordial hard binaries) performing high-resolution direct N-body (nbody6++gpu) and Monte Carlo (mocca) simulations to an age of 10 Gyr. We compare models implementing either delayed or core-collapse supernovae mechanisms, a different mass ratio distribution for binaries, and white dwarf (WD) natal kicks enabled/disabled. Compared to nbody6++gpu, the mocca models appear to be denser, with a larger scatter in the remnant masses, and a lower binary fraction on average. The mocca models produce more black holes (BHs) and helium WDs, while nbody6++gpu models are characterized by a much larger amount of WD–WD binaries. The remnant kick velocity and escape speed distributions are similar for the BHs and neutron stars (NSs), and some NSs formed via electron-capture supernovae, accretion-induced collapse, or merger-induced collapse escape the cluster in all simulations. The escape speed distributions for the WDs, on the other hand, are very dissimilar. We categorize the stellar evolution recipes available in nbody6++gpu into four levels: the one implemented in previous nbody6++gpu and mocca versions (level A), state-of-the-art prescriptions (level B), some in a testing phase (level C), and those that will be added in future versions of our codes.
Investigation of the orbital period and mass relations for W UMa-type contact systems
Authors: Poro A , Sarabi S , Zamanpour S , Fotouhi S , Davoudi F , Khakpash S , Salehian S Ranjbar , Madayen T , Foroutanfar A , Bakhshi E , Mahdavi N S , Alicavus F , Farahani A Mazidabadi , Sabbaghian G , Hosseini R S , Aryaeefar A , Hemati M 
Published: December 2021

ABSTRACT
New relationships between the orbital period and some parameters of W Ursae Majoris (W UMa)-type systems are presented in this study. To investigate the relationships, we calculated the absolute parameters of a sample of 118 systems. For this purpose, we used the parallax values obtained from the Gaia Early Data Release 3 star catalogue for more precise calculations. The other required parameters, including the light-curve solutions and the orbital period, were derived from previous research. For some relationships, we added 86 systems from another study with an orbital period of less than 0.6 d to our sample, allowing us to increase the number of systems to 204. Therefore, the mass (M) values of each component along with all the other absolute parameters were recalculated for these contact systems. We used the Markov chain Monte Carlo approach in order to gain the new orbital period–mass relations (P–M) per component, and added the temperature (T) to the process to acquire the new orbital period–temperature (P–T1) relation. We presented the orbital period behaviour in terms of log(g) by new relations for each component. We have also obtained a model between the orbital period, the mass of the primary component, and temperature (P–M1–T1) using the artificial neural network method. Additionally, we present a model for the relationship between the orbital period and the mass ratio (P–q) by fitting a multilayer perceptron regression model to a sample of the data collected from the literature.
XMM–Newton detection of soft time lags in the TDE candidate AT 2018fyk
Authors: Zhang Wenda 
Published: December 2021

ABSTRACT
In this letter, we report a tentative detection of soft time lags (i.e. variability of softer photons lags behind the variability of harder photons) in one XMM–Newton observation of the tidal disruption event (TDE) candidate AT 2018fyk while the source was in the hard spectral state. The lags are detected at $6.51\times 10^{-5}~\rm Hz$. The amplitude of the lags with respect to 0.5 − 1 keV monotonically decreases with the photon energy, from $\sim 1200~\rm s$ at 0.3 − 0.5 keV to $\sim -4200~\rm s$ at 3 − 5 keV (in our convention, a positive lag means lagging behind the reference band). We find that the amplitude is proportional to the logarithm of the energy separation between the examined band and the reference band. The energy-dependent covariance spectrum indicates that the correlated variability is more likely to be associated with the non-thermal radiation. The soft lags are difficult to reconcile with the reverberation scenario that are used to explain the soft lags in active galactic nuclei. On the other hand, the observed soft lags are consistent with the picture that the soft X-rays are down-scattered hard X-rays by the outflow as predicted by ‘unification’ models of TDEs.
Influencing Perceptions of Harm of Waterpipe Tobacco Smoking Among One Member of Couples Who Use Waterpipe
Authors: Lipkus Isaac M , Sanders Camilla , Mays Darren 
Published: December 2021

AbstractIntroductionWaterpipe tobacco smoking (WTS) often occurs socially, increasing health risks for the smoker and others through secondhand smoke effects. While messages on WTS harms enhance perceived risks for self, whether these messages elevate perceived risks for others, such as one’s romantic partner who engages in WTS, is unclear. We tested this idea by surveying one member of dual-smoking couples who engages in WTS.Aims and MethodsAs part of an online study, we enrolled adults ages 18–30 who engaged in WTS and were in a committed relationship of at least 6 months whose partner engaged in WTS. Participants were randomized to a control arm or to one of two arms consisting of watching a brief video on health harms or overcoming myths about WTS, respectively. Outcomes were perceived harms and measures of desire and probability of quitting for self and partner.ResultsParticipants (N = 238) who watched either video, compared with participants who did not watch a video, reported greater perceived health risks for self and partner and that their own WTS harmed their partner. Participants who watched either video reported a greater desire to quit for themselves, perceived that their partner had a greater desire to quit, and reported a higher likelihood of quitting together in the next 6 months.ConclusionsBrief videos containing risk-based messaging increase young adult waterpipe tobacco smokers’ perceived harms and desire to quit for self and partner. This can be a useful strategy to motivate cessation in couples who engage in WTS.ImplicationsThis study shows for the first time that at least among one member of dual-smoking couples who engages in WTS, brief videos on harms of WTS influences perceived harms and motivation to quit for the self and one’s partner. This can be a useful strategy to promote cessation.
Classification of EEG Signals Reveals a Focal Aftereffect of 10 Hz Motor Cortex Transcranial Alternating Current Stimulation
Authors: Tzvi Elinor , Alizadeh Jalal , Schubert Christine , Classen Joseph 
Published: December 2021

Abstract
Transcranial alternating current stimulation (tACS) modulates oscillations in a frequency- and location-specific manner and affects cognitive and motor functions. This effect appears during stimulation as well as “offline,” following stimulation, presumably reflecting neuroplasticity. Whether tACS produces long-lasting aftereffects that are physiologically meaningful, is still of current debate. Thus, for tACS to serve as a reliable method for modulating activity within neural networks, it is important to first establish whether “offline” aftereffects are robust and reliable. In this study, we employed a novel machine-learning approach to detect signatures of neuroplasticity following 10-Hz tACS to two critical nodes of the motor network: left motor cortex (lMC) and right cerebellum (rCB). To this end, we trained a classifier to distinguish between signals following lMC-tACS, rCB-tACS, and sham. Our results demonstrate better classification of electroencephalography (EEG) signals in both theta (θ, 4–8 Hz) and alpha (α, 8–13 Hz) frequency bands to lMC-tACS compared with rCB-tACS/sham, at lMC-tACS stimulation location. Source reconstruction allocated these effects to premotor cortex. Stronger correlation between classification accuracies in θ and α in lMC-tACS suggested an association between θ and α efffects. Together these results suggest that EEG signals over premotor cortex contains unique signatures of neuroplasticity following 10-Hz motor cortex tACS.
Circular RNA circ_0002984 Promotes Cell Proliferation and Migration by Regulating miR-181b-5p/Vascular Endothelial Growth Factor Axis and PI3K-AKT Signaling Pathway in Oxidized Low-Density Lipoprotein–Treated Vascular Smooth Muscle Cells
Authors: Wang Xichun , Ma Chong , Hou Xiaojun , Zhang Ge , Huang Yueping 
Published: December 2021

Abstract:
RNAs (circRNAs) play critical roles in many diseases, including atherosclerosis (AS). However, the role and underlying mechanism of circ_0002984 in AS remain unclear. Vascular smooth muscle cells (VSMCs) treated with oxidized low-density lipoprotein (ox-LDL) were used as a AS cell model. Quantitative real-time polymerase chain reaction was conducted to detect the expression of circ_0002984, miR-181b-5p and vascular endothelial growth factor A (VEGFA). Cell proliferation was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide assay and 5-ethynyl-2′-deoxyuridine assays. Cell migration was assessed using wound healing assay and transwell assay. All protein levels were analyzed by western blot assay. The interaction between miR-181b-5p and circ_0002984 or VEGFA was confirmed by dual-luciferase reporter, RNA Immunoprecipitation, and RNA pull-down assays. Circ_0002984 and VEGFA were overexpressed, and miR-181b-5p was downregulated in serum of AS patients and ox-LDL–stimulated VSMCs. Circ_0002984 silencing inhibited ox-LDL–induced proliferation and migration in VSMCs. MiR-181b-5p was a target of circ_0002984, and miR-181b-5p inhibition counteracted the suppressing effects of circ_0002984 downregulation on proliferation and migration in ox-LDL–stimulated VSMCs. Additionally, VEGFA was a downstream target of miR-181b-5p and VEGFA upregulation abolished the suppressive influence of miR-181b-5p on proliferation and migration in ox-LDL–exposed VSMCs. Furthermore, circ_0002984 depletion blocked phosphatidylinositol 3 kinase-AKT signaling pathway by regulating miR-181b-5p and VEGFA. Circ_0002984 downregulation suppressed cell proliferation and migration by regulating miR-181b-5p/VEGFA axis and phosphatidylinositol 3 kinase-AKT pathway in ox-LDL–stimulated VEGFA, providing a new mechanism for AS pathogenesis.
Predictive Factors for Humoral Response After 2-dose SARS-CoV-2 Vaccine in Solid Organ Transplant Patients
Authors: Marion Olivier , Del Bello Arnaud , Abravanel Florence , Faguer Stanislas , Esposito Laure , Laure Hebral Anne , Bellière Julie , Izopet Jacques , Kamar Nassim 
Published: December 2021

Background.
A weak immunogenicity has been reported in solid organ transplant (SOT) recipients after 2 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. The aim of this retrospective study was to identify the predictive factors for humoral response in SOT patients.

Methods.
Three hundred and ninety-three SOT patients from our center with at least 4 wk of follow-up after 2 doses of mRNA-based vaccine were included in this study. Anti-SARS-Cov-2 spike protein antibodies were assessed before and after vaccination.

Results.
Anti-SARS-CoV-2 antibodies were detected in 34% of the patients: 33.7% of kidney transplant patients, 47.7% of liver transplant patients, and 14.3% of thoracic transplant patients (P = 0.005). Independent predictive factors for humoral response after vaccination were male gender, a longer period between transplantation and vaccination, liver transplant recipients, a higher lymphocyte count at baseline, a higher estimated glomerular filtration rate and receiving the tacrolimus + everolimus ± steroids combination. Conversely, the nondevelopment of anti-SARS-CoV-2 antibodies after vaccination was associated with younger patients, thoracic organ recipients, induction therapy recipients, and tacrolimus + mycophenolic acid ± steroids recipients.

Conclusions.
The immunosuppressive regimen is a modifiable predictive factor for humoral response to SARS-CoV-2 vaccine.
Deafferentation of Olfactory Bulb in Subjects Dying with COVID-19
Authors: Tremblay Cécilia , Beach Thomas G. , Intorcia Anthony J. , Walker Jessica E. , Arce Richard A. , Sue Lucia I. , Nelson Courtney M. , Borja Claryssa I. , Suszczewicz Katsuko E. , Cline Madison P. , Hemmingsen Spencer J. , Qiji Sanaria H. , Desforges Marc , Serrano Geidy E. 
Published: December 2021

ABSTRACTThere have been clinical descriptions of diverse neurological effects in COVID-19 disease, involving up to 36% of patients. It appears likely that most of these are not caused by viral brain invasion but by systemic accompaniments of critical illness such as coagulopathy, deleteriously upregulated immune response, autoimmune mechanisms, hypoxia or multiorgan failure. Anosmia or hyposmia is present in a majority of COVID-19 patients, and there is early and severe involvement of the nasopharyngeal mucosa and olfactory epithelium. Preliminary studies by our group have found massive gene expression changes in olfactory bulb, but the magnitude of these changes are not different between subjects with detectable versus non-detectable olfactory bulb SARS-CoV-2 RNA. As spontaneous discharge of olfactory epithelial afferents dictates intra-olfactory bulb neurophysiological activity and connectivity, we hypothesized that olfactory bulb deafferentation during COVID-19 is responsible for a large fraction of our observed olfactory bulb transcriptional changes. As the olfactory marker protein (OMP-1) is a specific marker of olfactory epithelial afferents to the olfactory bulb and is severely depleted in animal model lesions of olfactory epithelium, we quantified OMP-1-immunoreactivity in the olfactory bulb of subjects dying with or without COVID-19. Additionally, we quantified olfactory bulb tyrosine hydroxylase (TH), which is often also reduced after olfactory epithelium lesions, and SNAP-25, a pan-synaptic marker. COVID-19 cases (n = 18) were generally elderly and were not significantly different in age or gender distribution from the non-COVID-19 cases (n = 28). Both COVID-19 and non-COVID-19 cases had a wide range of neuropathological diagnoses. The area occupied by OMP-1 immunoreactivity in COVID-19 cases was significantly less, about 60% of that in control cases but amongst subjects with COVID-19, there was no significant difference between OBT-SARS-CoV-2-PCR-positive and negative cases. There were no significant group differences for TH or SNAP-25, supporting a selective effect for OMP-1. We suggest that olfactory dysfunction, and some of the COVID-19-associated transcriptional changes that we have reported for the olfactory bulb and amygdala, may be due to olfactory bulb deafferentation and subsequent transsynaptic effects. Additionally, animal models of olfactory bulb deafferentation or bulbectomy indicate a possibility for widespread changes in interconnected brain regions, providing a possible substrate for diverse post-acute COVID-19 neurological sequelae.
Engineered ACE2 counteracts vaccine-evading SARS-CoV-2 Omicron variant
Authors: Ikemura Nariko , Taminishi Shunta , Inaba Tohru , Arimori Takao , Motooka Daisuke , Katoh Kazutaka , Kirita Yuhei , Higuchi Yusuke , Li Songling , Suzuki Tatsuya , Itoh Yumi , Ozaki Yuki , Nakamura Shota , Matoba Satoaki , Standley Daron M , Okamoto Toru , Takagi Junichi , Hoshino Atsushi 
Published: December 2021

AbstractThe novel SARS-CoV-2 variant, Omicron (B.1.1.529) contains an unusually high number of mutations (>30) in the spike protein, raising concerns of escape from vaccines, convalescent sera and therapeutic drugs. Here we analyze the alteration of neutralizing titer with Omicron pseudovirus. Sera obtained 3 months after double BNT162b2 vaccination exhibit approximately 18-fold lower neutralization titers against Omicron than parental virus. Convalescent sera from Alpha and Delta patients allow similar levels of breakthrough by Omicron. Domain-wise analysis using chimeric spike revealed that this efficient evasion was primarily achieved by mutations clustered in the receptor-binding domain, but that multiple mutations in the N-terminal domain contributed as well. Omicron escapes a therapeutic cocktail of imdevimab and casirivimab, whereas sotrovimab, which targets a conserved region to avoid viral mutation, remains effective. The ACE2 decoy is another virus-neutralizing drug modality that is free, at least in theory, from complete escape. Deep mutational analysis demonstrated that, indeed, engineered ACE2 prevented escape for each single-residue mutation in the receptor-binding domain, similar to immunized sera. Engineered ACE2 neutralized Omicron comparable to Wuhan and also showed a therapeutic effect against Omicron infection in hamsters and human ACE2 transgenic mice. Like previous SARS-CoV-2 variants, some sarbecoviruses showed high sensitivity against engineered ACE2, confirming the therapeutic value against diverse variants, including those that are yet to emerge.One Sentence SummaryOmicron, carrying ∼30 mutations in the spike, exhibits effective immune evasion but remains highly susceptible to blockade by engineered ACE2.
Allosteric Determinants of the SARS-CoV-2 Spike Protein Binding with Nanobodies: Examining Mechanisms of Mutational Escape and Sensitivity of the Omicron Variant
Authors: Verkhivker Gennady 
Published: December 2021

AbstractStructural and biochemical studies have recently revealed a range of rationally engineered nanobodies with efficient neutralizing capacity against SARS-CoV-2 virus and resilience against mutational escape. In this study, we performed a comprehensive computational analysis of the SARS-CoV-2 spike trimer complexes with Nb6, VHH E and bi-paratopic VHH VE nanobodies. We combined atomistic dynamics and collective motions analysis with binding free energy scanning, perturbation-response scanning and network centrality analysis to examine mechanisms of nanobody-induced allosteric modulation and cooperativity in the SARS-CoV-2 spike trimer complexes with these nanobodies. By quantifying energetic and allosteric determinants of the SARS-CoV-2 spike protein binding with nanobodies, we also examined nanobody-induced modulation of escaping mutations and the effect of the Omicron variant on nanobody binding. The mutational scanning analysis supported the notion that E484A mutation can have a significant detrimental effect on nanobody binding and result in Omicron-induced escape from nanobody neutralization. Our findings showed that SARS-CoV-2 spike protein may exploit plasticity of specific allosteric hotspots to generate escape mutants that alter response to binding without compromising activity. The network analysis supported these findings showing that VHH VE nanobody binding can induce long-range couplings between the cryptic binding epitope and ACE2-binding site through a broader ensemble of communication paths that is less dependent on specific mediating centers and therefore may be less sensitive to mutational perturbations of functional residues. The results suggest that binding affinity and long-range communications of the SARS-CoV-2 complexes with nanobodies can be determined by structurally stable regulatory centers and conformationally adaptable hotspots that are allosterically coupled and collectively control resilience to mutational escape.
Machine learning guided design of high affinity ACE2 decoys for SARS-CoV-2 neutralization
Authors: Chan Matthew C. , Chan Kui. K. , Procko Erik , Shukla Diwakar 
Published: December 2021

AbstractA potential therapeutic candidate for neutralizing SARS-CoV-2 infection is engineering high-affinity soluble ACE2 decoy proteins to compete for binding of the viral spike (S) protein. Previously, a deep mutational scan of ACE2 was performed and has led to the identification of a triple mutant ACE2 variant, named ACE22.v.2.4, that exhibits nanomolar affinity binding to the RBD domain of S. Using a recently developed transfer learning algorithm, TLmutation, we sought to identified other ACE2 variants, namely double mutants, that may exhibit similar binding affinity with decreased mutational load. Upon training a TLmutation model on the effects of single mutations, we identified several ACE2 double mutants that bind to RBD with tighter affinity as compared to the wild type, most notably, L79V;N90D that binds RBD with similar affinity to ACE22.v.2.4. The successful experimental validation of the double mutants demonstrated the use transfer and supervised learning approaches for engineering protein-protein interactions and identifying high affinity ACE2 peptides for targeting SARS-CoV-2.
An empirical evaluation of genotype imputation of ancient DNA
Authors: Ausmees Kristiina , Sanchez-Quinto Federico , Jakobsson Mattias , Nettelblad Carl 
Published: December 2021

ABSTRACTWith capabilities of sequencing ancient DNA to high coverage often limited by sample quality or cost, imputation of missing genotypes presents a possibility to increase power of inference as well as cost-effectiveness for the analysis of ancient data. However, the high degree of uncertainty often associated with ancient DNA poses several methodological challenges, and performance of imputation methods in this context has not been fully explored. To gain further insights, we performed a systematic evaluation of imputation of ancient data using Beagle 4.0 and reference data from phase 3 of the 1000 Genomes project, investigating the effects of coverage, phased reference and study sample size. Making use of five ancient samples with high-coverage data available, we evaluated imputed data with respect to accuracy, reference bias and genetic affinities as captured by PCA. We obtained genotype concordance levels of over 99% for data with 1x coverage, and similar levels of accuracy and reference bias at levels as low as 0.75x. Our findings suggest that using imputed data can be a realistic option for various population genetic analyses even for data in coverage ranges below 1x. We also show that a large and varied phased reference set as well as the inclusion of low- to moderate-coverage ancient samples can increase imputation performance, particularly for rare alleles. In-depth analysis of imputed data with respect to genetic variants and allele frequencies gave further insight into the nature of errors arising during imputation, and can provide practical guidelines for post-processing and validation prior to downstream analysis.