bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating Exposure Intensity Based on Odor
Authors: Nicas Mark , Neuhaus John
Published: October 2021

The odor detection threshold for a chemical typically varies widely across population members, and the values can be described by a lognormal distribution. Assuming that the parameters of a chemical’s odor detection threshold distribution can be estimated, a method is presented to retrospectively estimate exposure intensity based on detecting the chemical’s odor. The context is a single exposure period involving a single air contaminant. In brief, where k out of n identically exposed persons detect the chemical’s odor, the best estimate of the chemical’s concentration in air corresponds to the k ÷ n fractile of the odor detection threshold distribution. Where n is small and/or k ÷ n is close to zero or one, exact 100×(1−α)% confidence bounds for the fractile estimate can be computed without using the normal distribution assumption. In addition, statistical uncertainty in the parameter estimates of the chemical’s odor detection threshold distribution can be considered via a parametric bootstrap procedure, such that an overall 100×(1−α)% confidence interval on the chemical’s concentration in air is obtained. The method is illustrated for benzene. Analysis of the available benzene odor detection threshold literature provides best estimates of a population geometric mean equal to 37.8 ppm and geometric standard deviation equal to 1.92. In a hypothetical example in which two out of six workers detect the odor of benzene, the point estimate of the benzene exposure level is 28.5 ppm, and the approximate one-sided lower 95% confidence limit is 8.2 ppm. The present analysis also makes clear that odor does not provide an adequate warning of excessive levels of airborne benzene.
HyperAttentionDTI: improving drug–protein interaction prediction by sequence-based deep learning with attention mechanism
Authors: Zhao Qichang , Zhao Haochen , Zheng Kai , Wang Jianxin
Published: October 2021

Motivation

Identifying drug–target interactions (DTIs) is a crucial step in drug repurposing and drug discovery. Accurately identifying DTIs in silico can significantly shorten development time and reduce costs. Recently, many sequence-based methods are proposed for DTI prediction and improve performance by introducing the attention mechanism. However, these methods only model single non-covalent inter-molecular interactions among drugs and proteins and ignore the complex interaction between atoms and amino acids.

Results

In this article, we propose an end-to-end bio-inspired model based on the convolutional neural network (CNN) and attention mechanism, named HyperAttentionDTI, for predicting DTIs. We use deep CNNs to learn the feature matrices of drugs and proteins. To model complex non-covalent inter-molecular interactions among atoms and amino acids, we utilize the attention mechanism on the feature matrices and assign an attention vector to each atom or amino acid. We evaluate HpyerAttentionDTI on three benchmark datasets and the results show that our model achieves significantly improved performance compared with the state-of-the-art baselines. Moreover, a case study on the human Gamma-aminobutyric acid receptors confirm that our model can be used as a powerful tool to predict DTIs.

Availability and implementation

The codes of our model are available at https://github.com/zhaoqichang/HpyerAttentionDTI and https://zenodo.org/record/5039589.

Supplementary information

Supplementary data are available at Bioinformatics online.
PMCE: efficient inference of expressive models of cancer evolution with high prognostic power
Authors: Angaroni Fabrizio , Chen Kevin , Damiani Chiara , Caravagna Giulio , Graudenzi Alex , Ramazzotti Daniele
Published: October 2021

Motivation

Driver (epi)genomic alterations underlie the positive selection of cancer subpopulations, which promotes drug resistance and relapse. Even though substantial heterogeneity is witnessed in most cancer types, mutation accumulation patterns can be regularly found and can be exploited to reconstruct predictive models of cancer evolution. Yet, available methods can not infer logical formulas connecting events to represent alternative evolutionary routes or convergent evolution.

Results

We introduce PMCE, an expressive framework that leverages mutational profiles from cross-sectional sequencing data to infer probabilistic graphical models of cancer evolution including arbitrary logical formulas, and which outperforms the state-of-the-art in terms of accuracy and robustness to noise, on simulations. The application of PMCE to 7866 samples from the TCGA database allows us to identify a highly significant correlation between the predicted evolutionary paths and the overall survival in 7 tumor types, proving that our approach can effectively stratify cancer patients in reliable risk groups.

Availability and implementation

PMCE is freely available at https://github.com/BIMIB-DISCo/PMCE, in addition to the code to replicate all the analyses presented in the manuscript.

Supplementary information

Supplementary data are available at Bioinformatics online.
875 Using Stress Testing to Identify Vulnerabilities in Artificial Intelligence Models for the Identification of Culprit Carotid Lesions in Cerebrovascular Events
Authors: Le E , Tarkin J , Evans N , Chowdhury M , Rudd J
Published: October 2021

Introduction

Carotid atherosclerosis is a major risk factor for ischaemic stroke, a leading cause of death. Carotid CT angiography (CTA) is commonly performed following a stroke or transient ischaemic attack (TIA) to help guide patient management in secondary prevention of stroke. Deep learning algorithms can help extract greater information from scans.

Method

The dataset comprised CTA scans from 40 culprit and 40 non-culprit carotid arteries of patients with recent stroke/TIA, and 40 carotid arteries of asymptomatic patients without previous stroke/TIA. A 3D convolutional neural network was trained to classify carotid artery type. Each input comprised 14 axial CTA carotid patches (centred around the carotid artery) concatenated together to form a 3D volume (capturing ∼3cm of artery). 75% of the dataset was used for training and 25% for internal validation. Following training, computer vision operations were applied to input images to assess their impact on the model’s classification decisions.

Results

The model achieved 100% accuracy on the training set and 67% on the internal validation set. However, after subjecting input images to image operations, vulnerabilities in the deep learning model were revealed, even when using input images from the training set. For example, using a Gaussian blur filter with sigma 1.0 was sufficient to change classification decisions, as was horizontally flipping the image.

Conclusions

Deep learning has exceptional capabilities for learning, however the risk with such high-capacity models is failure to learn relevant features from the data. Stress testing provides a viable method to further evaluate deep learning models before clinical deployment.
Untold diversity of floral rewards inCypella(Tigridieae: Iridaceae) and related genera: distribution and anatomy
Authors: Pastori Tamara , Kuhn Sofia Aumond , De Souza-Chies Tatiana Teixeira , Silvério Adriano , Mastroberti Alexandra Antunes , Eggers Lilian , Chauveau Olivier , Mariath Jorge Ernesto De Araujo
Published: October 2021

Floral rewards are important elements in plant–pollinator interactions and can play an essential role in the diversification of species. The identification of these rewards has been neglected in species of Tigridieae (Iridaceae), one of the few angiosperm groups to offer lipids, considered a specialized reward. We identify and characterize the secretory structures of floral rewards in Cypella and related genera (Calydorea, Catila, Herbertia, Onira and Kelissa). Our results reveal that there are trichomatic elaiophores in the tepals of Cypella, Kelissa, Onira and Herbertia and staminal nectaries in the connectives of the anthers of Cypella and Onira. There is an unusual combination of floral rewards in Cypella and Onira, demonstrating a unique pattern in Iridaceae of the American continent.
Severe Dysbiosis and Specific Haemophilus and Neisseria Signatures as Hallmarks of the Oropharyngeal Microbiome in Critically Ill Coronavirus Disease 2019 (COVID-19) Patients
Authors: de Castilhos Juliana , Zamir Eli , Hippchen Theresa , Rohrbach Roman , Schmidt Sabine , Hengler Silvana , Schumacher Hanna , Neubauer Melanie , Kunz Sabrina , Müller-Esch Tonia , Hiergeist Andreas , Gessner André , Khalid Dina , Gaiser Rogier , Cullin Nyssa , Papagiannarou Stamatia M , Beuthien-Baumann Bettina , Krämer Alwin , Bartenschlager Ralf , Jäger Dirk , Müller Michael , Herth Felix , Duerschmied Daniel , Schneider Jochen , Schmid Roland M , Eberhardt Johann F , Khodamoradi Yascha , Vehreschild Maria J G T , Teufel Andreas , Ebert Matthias P , Hau Peter , Salzberger Bernd , Schnitzler Paul , Poeck Hendrik , Elinav Eran , Merle Uta , Stein-Thoeringer Christoph K
Published: October 2021

Background

At the entry site of respiratory virus infections, the oropharyngeal microbiome has been proposed as a major hub integrating viral and host immune signals. Early studies suggested that infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with changes of the upper and lower airway microbiome, and that specific microbial signatures may predict coronavirus disease 2019 (COVID-19) illness. However, the results are not conclusive, as critical illness can drastically alter a patient’s microbiome through multiple confounders.

Methods

To study oropharyngeal microbiome profiles in SARS-CoV-2 infection, clinical confounders, and prediction models in COVID-19, we performed a multicenter, cross-sectional clinical study analyzing oropharyngeal microbial metagenomes in healthy adults, patients with non-SARS-CoV-2 infections, or with mild, moderate, and severe COVID-19 (n = 322 participants).

Results

In contrast to mild infections, patients admitted to a hospital with moderate or severe COVID-19 showed dysbiotic microbial configurations, which were significantly pronounced in patients treated with broad-spectrum antibiotics, receiving invasive mechanical ventilation, or when sampling was performed during prolonged hospitalization. In contrast, specimens collected early after admission allowed us to segregate microbiome features predictive of hospital COVID-19 mortality utilizing machine learning models. Taxonomic signatures were found to perform better than models utilizing clinical variables with Neisseria and Haemophilus species abundances as most important features.

Conclusions

In addition to the infection per se, several factors shape the oropharyngeal microbiome of severely affected COVID-19 patients and deserve consideration in the interpretation of the role of the microbiome in severe COVID-19. Nevertheless, we were able to extract microbial features that can help to predict clinical outcomes.
FDA Public Workshop Summary—Coccidioidomycosis (Valley Fever): Considerations for Development of Antifungal Drugs
Authors: O’Shaughnessy Elizabeth , Yasinskaya Yuliya , Dixon Cheryl , Higgins Karen , Moore Jason , Reynolds Kellie , Ampel Neil M , Angulo David , Blair Janis E , Catanzaro Antonino , Galgiani John N , Garvey Edward , Johnson Royce , Larwood David J , Lewis Gareth , Purdie Rob , Rex John H , Shubitz Lisa F , Stevens David A , Page Stephen J , Shukla Sunita J , Farley John J , Nambiar Sumathi
Published: October 2021

Coccidioidomycosis is a fungal disease endemic to the southwestern United States, Mexico, and Central and South America. Prevalence rates are increasing steadily, and new endemic areas of Coccidioides are emerging. Standard treatment is often administered for months to decades, and intolerance to medications and treatment failures are common. No new treatments for coccidioidomycosis have been approved in the United States in nearly 40 years. On 5 August 2020, the US Food and Drug Administration convened experts in coccidioidomycosis from academia, industry, patient groups, and other government agencies to discuss the disease landscape and strategies to facilitate product development for treatment of coccidioidomycosis. This article summarizes the key topics concerning drug development for coccidioidomycosis presented by speakers and panelists during the workshop, such as unmet need, trial designs, endpoints, incentives, research and development support, and collaborations to facilitate antifungal drug development.
How microbial glycosyl hydrolase activity in the gut mucosa initiates microbial cross-feeding
Authors: Berkhout Maryse D , Plugge Caroline M , Belzer Clara
Published: October 2021

The intestinal epithelium is protected from direct contact with gut microbes by a mucus layer. This mucus layer consists of secreted mucin glycoproteins. The outer mucus layer in the large intestine forms a niche that attracts specific gut microbiota members of which several gut commensals can degrade mucin. Mucin glycan degradation is a complex process that requires a broad range of glycan degrading enzymes, as mucin glycans are intricate and diverse molecules. Consequently, it is hypothesized that microbial mucin breakdown requires concerted action of various enzymes in a network of multiple resident microbes in the gut mucosa. This review investigates the evolutionary relationships of microbial carbohydrate-active enzymes that are potentially involved in mucin glycan degradation and focuses on the role that microbial enzymes play in the degradation of gut mucin glycans in microbial cross-feeding and syntrophic interactions.
El espejismo de Baena: Luces y sombras de un derecho administrativo comparado latinoamericanoBaena’s mirage: Lights and shades of comparative administrative law in Latin America
Authors: García-Huidobro Luis Eugenio , Guidi Sebastián
Published: October 2021

In the context of a growing interest in comparative administrative law in Latin America, an emerging academic project asserts the existence of a “common administrative law” in the region, inspired by the so-called ius constitutionale commune in Latin America. In this essay, we examine the impact of the Baena decision (Inter-American Court of Human Rights, 2001) on the administrative regimes of Argentina, Chile, and Mexico so as to reveal the limitations of such a project. We speculate that the limited impact of this decision can be explained by particular characteristics germane to administrative law that tend to be overlooked from a constitutionalist optic. Finally, we draw from our case studies to make methodological recommendations to those who want to undertake comparative administrative law studies in the region.
SARS-CoV-2 Psychiatric Sequelae: A Review of Neuroendocrine Mechanisms and Therapeutic Strategies
Authors: Hornick Mary G , Olson Margaret E , Jadhav Arun L
Published: October 2021

From the earliest days of the coronavirus disease 2019 (COVID-19) pandemic, there have been reports of significant neurological and psychological symptoms following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. This narrative review is designed to examine the potential psychoneuroendocrine pathogenic mechanisms by which SARS-CoV-2 elicits psychiatric sequelae as well as to posit potential pharmacologic strategies to address and reverse these pathologies. Following a brief overview of neurological and psychological sequelae from previous viral pandemics, we address mechanisms by which SARS-CoV-2 could enter or otherwise elicit changes in the CNS. We then examine the hypothesis that COVID-19–induced psychiatric disorders result from challenges to the neuroendocrine system, in particular the hypothalamic-pituitary-adrenal stress axis and monoamine synthesis, physiological mechanisms that are only further enhanced by the pandemic-induced social environment of fear, isolation, and socioeconomic pressure. Finally, we evaluate several FDA-approved therapeutics in the context of COVID-19–induced psychoneuroendocrine disorders.
Correlation of antimicrobial fraction unbound and sieving coefficient in critically ill patients on continuous renal replacement therapy: a systematic review
Authors: Farrar Julie E. , Mueller Scott W. , Stevens Victoria , Kiser Tyree H. , Taleb Sim , Reynolds Paul M.
Published: October 2021

Background

Fraction unbound has been used as a surrogate for antimicrobial sieving coefficient (SC) to predict extracorporeal clearance in critically ill patients on continuous renal replacement therapy (CRRT), but this is based largely on expert opinion.

Objectives

To examine relationships between package insert-derived fraction unbound (Fu-P), study-specific fraction unbound (Fu-S), and SC in critically ill patients receiving CRRT.

Methods

English-language studies containing patient-specific in vivo pharmacokinetic parameters for antimicrobials in critically ill patients requiring CRRT were included. The primary outcome included correlations between Fu-S, Fu-P, and SC. Secondary outcomes included correlations across protein binding quartiles, serum albumin, and predicted in-hospital mortality, and identification of predictors for SC through multivariable analysis.

Results

Eighty-nine studies including 32 antimicrobials were included for analysis. SC was moderately correlated to Fu-S (R2 = 0.55, P < 0.001) and Fu-P (R2 = 0.41, P < 0.001). SC was best correlated to Fu-S in first (<69%) and fourth (>92%) quartiles of fraction unbound and above median albumin concentrations of 24.5 g/L (R2 = 0.71, P = 0.07). Conversely, correlation was weaker in patients with mortality estimates greater than the median of 55% (R2 = 0.06, P = 0.84). SC and Fu-P were also best correlated in the first quartile of antimicrobial fraction unbound (R2 = 0.66, P < 0.001). Increasing Fu-P, flow rate, membrane surface area, and serum albumin, and decreasing physiologic charge significantly predicted increasing SC.

Conclusions

Fu-S and Fu-P were both reasonably correlated to SC. Caution should be taken when using Fu-S to calculate extracorporeal clearance in antimicrobials with 69%–92% fraction unbound or with >55% estimated in-hospital patient mortality. Fu-P may serve as a rudimentary surrogate for SC when Fu-S is unavailable.
Strategies for building robust prediction models using data unavailable at prediction time
Authors: Yang Haoyu , Tourani Roshan , Zhu Ying , Kumar Vipin , Melton Genevieve B , Steinbach Michael , Simon Gyorgy
Published: October 2021

Objective

Hospital-acquired infections (HAIs) are associated with significant morbidity, mortality, and prolonged hospital length of stay. Risk prediction models based on pre- and intraoperative data have been proposed to assess the risk of HAIs at the end of the surgery, but the performance of these models lag behind HAI detection models based on postoperative data. Postoperative data are more predictive than pre- or interoperative data since it is closer to the outcomes in time, but it is unavailable when the risk models are applied (end of surgery). The objective is to study whether such data, which is temporally unavailable at prediction time (TUP) (and thus cannot directly enter the model), can be used to improve the performance of the risk model.

Materials and Methods

An extensive array of 12 methods based on logistic/linear regression and deep learning were used to incorporate the TUP data using a variety of intermediate representations of the data. Due to the hierarchical structure of different HAI outcomes, a comparison of single and multi-task learning frameworks is also presented.

Results and Discussion

The use of TUP data was always advantageous as baseline methods, which cannot utilize TUP data, never achieved the top performance. The relative performances of the different models vary across the different outcomes. Regarding the intermediate representation, we found that its complexity was key and that incorporating label information was helpful.

Conclusions

Using TUP data significantly helped predictive performance irrespective of the model complexity.
Transgender and nonbinary individuals and ICT-driven information practices in response to transexclusionary healthcare systems: a qualitative study
Authors: Wagner Travis L , Kitzie Vanessa L , Lookingbill Valerie
Published: October 2021

Objective

This qualitative research examines how transgender and gender nonbinary (T/GNB) persons from South Carolina navigate informational barriers within healthcare systems. This navigation can be described through the lens of information practices, or how T/GNB participants create, seek, use, and share information to achieve desired healthcare outcomes. Special focus is given to the roles of Information and Communication Technologies (ICTs) in shaping these practices.

Materials and Methods

The research utilizes participant data from semistructured interviews and focus groups conducted with 26 T/GNB individuals focusing on their health information practices. Data analysis utilized emic/etic coding and the constant comparative method to identify themes describing transexclusionary information barriers and respondent ICT-led information practices.

Results

Findings note healthcare systems producing cisnormativity by design resulting in T/GNB individuals viewing healthcare spaces as exclusionary. Exclusionary barriers included over reliance on medical, expert authority ignoring T/GNB embodiment, and a lack of contextual perspective to identities. In response, T/GNB seek, create, use, and share information via ICTs to challenge exclusionary practices.

Discussion

T/GNB ICT use addresses systemic barriers within healthcare systems suggesting a need to reframe healthcare systems through the lens of design justice, one that values T/GNB agency in understanding and producing health knowledge.

Conclusion

While many healthcare providers are not intentionally being transexclusionary, the design of healthcare information systems rely on cisnormative values, thus excluding many T/GNB from accessing healthcare in comfortable and safe ways. Shifting toward the values and practices of T/GNB as informed by ICT use will afford healthcare providers ways to undo barriers to care.
Promoting health equity for deaf patients through the electronic health record
Authors: James Tyler G , Sullivan Meagan K , Butler Joshua D , McKee Michael M
Published: October 2021

Language status can be conceptualized as an equity-relevant variable, particularly for non-English-speaking populations. Deaf and hard-of-hearing (DHH) individuals who use American Sign Language (ASL) to communicate comprise one such group and are understudied in health services research. DHH individuals are at high-risk of receiving lower-quality care due to ineffective patient–provider communication. This perspective outlines barriers to health equity research serving DHH ASL-users due to systems developed by large-scale informatics networks (eg, the Patient-Centered Clinical Outcomes Research Network), and institutional policies on self-serve cohort discovery tools. We list potential to help adequate capture of language status of DHH ASL-users to promote health equity for this population.
Organising Competition for the Market
Authors: Iossa Elisabetta , Rey Patrick , Waterson Michael
Published: October 2021

We study competition for the market in a setting where incumbents (and, to a lesser extent, neighbouring incumbents) benefit from a cost or information advantage. We first compare the outcome of staggered and synchronous tenders, before drawing the implications for market design. We find the timing of tenders interrelates with the likelihood of monopolisation. For high incumbency advantages and/or discount factors, monopolisation is expected, in which case synchronous tendering is preferable as it strengthens the pressure that entrants exercise on the monopolist. For low incumbency advantages and/or discount factors, other firms remain active, in which case staggered tendering is preferable as it maximises competitive pressure coming from the other firms. We use bus tendering in London to illustrate our insights and draw policy implications.
Relativistic scattering of a fast spinning neutron star by a massive black hole
Authors: Li Kaye Jiale , Wu Kinwah , Leung Po Kin , Singh Dinesh
Published: October 2021

The orbital dynamics of fast spinning neutron stars encountering a massive black hole (BH) with unbounded orbits are investigated using the quadratic-in-spin Mathisson–Papapetrou–Dixon (MPD) formulation. We consider the motion of the spinning neutron stars with astrophysically relevant speed in the gravity field of the BH. For such slow-speed scattering, the hyperbolic orbits followed by these neutron stars all have near the e = 1 eccentricity, and have distinct properties compared with those of e ≫ 1. We have found that, compared with geodesic motion, the spin–orbit and spin–spin coupling will lead to a variation of scattering angles at spatial infinity, and this variation is more prominent for slow-speed scattering than fast-speed scattering. Such a variation leads to an observable difference in pulse-arrival-time within a few hours of observation, and up to a few days or months for larger BH masses or longer spinning periods. Such a relativistic pulsar-BH system also emits a burst of gravitational waves (GWs) in the sensitivity band of Laser Interferometric Space Antenna, and for optimal settings, can be seen up to $100\, {\rm Mpc}$ away. A radio follow up of such a GW burst with SKA or FAST will allow for measuring the orbital parameters with high accuracy and testing the predictions of general relativity.
The application of ridgelines in extended radio source cross-identification
Authors: Barkus B , Croston J H , Piotrowska J , Mingo B , Best P N , Hardcastle M J , Mostert R I J , Röttgering H J A , Sabater J , Webster B , Williams W L
Published: October 2021

Extended radio sources are an important minority population in modern deep radio surveys, because they enable detailed investigation of the physics governing radio-emitting regions such as active galaxies and their environments. Cross-identification of radio sources with optical host galaxies is challenging for this extended population, due to their morphological complexity and multiple potential counterparts. In the first data release of the Low-Frequency Array (LOFAR) Two-metre Sky Survey (LoTSS DR1), the automated likelihood ratio for compact sources was supplemented by a citizen science visual identification process for extended sources. In this paper, we present a novel method for automating the host identification of extended sources by using ridgelines, which trace the assumed direction of fluid flow through the points of highest flux density. Applying a new code, RL-Xid, to LoTSS DR1, we demonstrate that ridgelines are versatile; by providing information about spatial structure and brightness distributions, they can be used both for optical host identification and morphological studies in radio surveys. RL-Xid draws ridgelines for 85 per cent of sources brighter than 10 mJy and larger than 15 arcsec, with an improved performance of 96 per cent for the subset >30 mJy and >60 arcsec. Using a sample of sources with known hosts from LoTSS DR1, we demonstrate that RL-Xid successfully identifies the host for 98 per cent of the sources with successfully drawn ridgelines, and performs at a comparable level to visual identification via citizen science. We also demonstrate that ridgeline brightness profiles provide a promising automated technique for morphological classification.
Constraining cosmology with a new all-sky Compton parameter map from the Planck PR4 data
Authors: Tanimura Hideki , Douspis Marian , Aghanim Nabila , Salvati Laura
Published: October 2021

We constructed a new all-sky Compton parameter map (y-map) of the thermal Sunyaev-Zel’dovich (tSZ) effect from the 100–857 GHz frequency channel maps delivered within the Planck data release 4. The improvements in terms of noise and systematic effects translated into a y-map with a noise level smaller by ∼7 per cent compared to the maps released in 2015, and with significantly reduced survey stripes. The produced 2020 y-map is also characterized by residual foreground contamination, mainly due to thermal dust emission at large angular scales and to cosmic infrared background and extragalactic point sources at small angular scales. Using the new Planck data, we computed the tSZ angular power spectrum and found that the tSZ signal dominates the y-map in the multipole range, 60 < ℓ < 600. We performed the cosmological analysis with the tSZ angular power spectrum and found $S_8 = 0.764 \, _{-0.018}^{+0.015} \, (stat) \, _{-0.016}^{+0.031} \, (sys)$, including systematic uncertainties from a hydrostatic mass bias and pressure profile model. The S8 value may differ by ±0.016 depending on the hydrostatic mass bias model and by +0.021 depending on the pressure profile model used for the analysis. The obtained value is fully consistent with recent Kilo-Degree Survey and Dark Energy Survey weak-lensing observations. While our result is slightly lower than the Planck CMB one, it is consistent with the latter within 2σ.
Resonant interactions of magneto-Poincaré and magneto-Rossby waves in quasi-two-dimensional rotating astrophysical plasma
Authors: Fedotova Maria , Klimachkov Dmitry , Petrosyan Arakel
Published: October 2021

Increased interest in research of non-linear resonant interactions of waves in rotating astrophysical plasma has taken place in recent years. This is due to the discovering solar magneto-Rossby waves and the emergence of new data on the effect of three-wave interactions of magneto-Rossby waves on solar activity. In context of large-scale magnetohydrodynamic flows in presence of rotation, magneto-Poincaré waves and magneto-Rossby waves are highlighted. The β-plane approximation is developed to simplify the theory of spherical Rossby waves. Nevertheless, the representation of the Coriolis force in this approximation contains a latitude-independent term that ensures the existence of magneto-Poincaré waves on β-plane along with magneto-Rossby waves. In this paper, it is shown that they satisfy the phase matching condition, which leads to emergence of new non-linear interactions mechanisms of waves: two magneto-Poincaré waves and one magneto-Rossby wave; two magneto-Rossby waves and one magneto-Poincaré. Complete dispersion equations on β-plane in quasi-two-dimensional magnetohydrodynamic approximation is analysed both for homogeneous and stratified astrophysical plasma with vertical magnetic field. New dispersion relations for magneto-Poincaré waves on β-plane are obtained. Detailed qualitative analysis of the phase matching condition is carried out, and new types of three-wave interactions of magneto-Poincaré waves and magneto-Rossby waves are found. Three-wave interactions are studied and instabilities of the decay and amplification type are investigated.
Streaming instability with multiple dust species – II. Turbulence and dust–gas dynamics at non-linear saturation
Authors: Yang Chao-Chin , Zhu Zhaohuan
Published: October 2021

The streaming instability is a fundamental process that can drive dust–gas dynamics and ultimately planetesimal formation in protoplanetary discs. As a linear instability, it has been shown that its growth with a distribution of dust sizes can be classified into two distinct regimes, fast- and slow-growth, depending on the dust-size distribution and the total dust-to-gas density ratio ϵ. Using numerical simulations of an unstratified disc, we bring three cases in different regimes into non-linear saturation. We find that the saturation states of the two fast-growth cases are similar to its single-species counterparts. The one with maximum dimensionless stopping time τs,max = 0.1 and ϵ = 2 drives turbulent vertical dust–gas vortices, while the other with τs,max = 2 and ϵ = 0.2 leads to radial traffic jams and filamentary structures of dust particles. The dust density distribution for the former is flat in low densities, while the one for the latter has a low-end cut-off. By contrast, the one slow-growth case results in a virtually quiescent state. Moreover, we find that in the fast-growth regime, significant dust segregation by size occurs, with large particles moving towards dense regions while small particles remain in the diffuse regions, and the mean radial drift of each dust species is appreciably altered from the (initial) drag-force equilibrium. The former effect may skew the spectral index derived from multiwavelength observations and change the initial size distribution of a pebble cloud for planetesimal formation. The latter along with turbulent diffusion may influence the radial transport and mixing of solid materials in young protoplanetary discs.
Discovery of two bright high-redshift gravitationally lensed quasars revealed by Gaia
Authors: Desira Christopher , Shu Yiping , Auger Matthew W , McMahon Richard G , Lemon Cameron A , Anguita Timo , Neira Favio
Published: October 2021

We present the discovery and preliminary characterisation of two high-redshift gravitationally lensed quasar systems in Gaia Data Release 2 (DR2). Candidates with multiple close-separation Gaia detections and quasar-like colours in WISE, Pan-STARRS, and DES are selected for follow-up spectroscopy with the New Technology Telescope. We confirm DES J215028.71−465251.3 as a $z$ = 4.130 ± 0.006 asymmetric, doubly imaged lensed quasar system and model the lensing mass distribution as a singular isothermal sphere. The system has an Einstein radius of 1.202 ± 0.005 arcsec and a predicted time delay of ∼122.0 d between the quasar images, assuming a lensing galaxy redshift of $z$ = 0.5, making this a priority system for future optical monitoring. We confirm PS J042913.17+142840.9 as a $z$ = 3.866 ± 0.003 four-image quasar system in a cusp configuration, lensed by two foreground galaxies. The system is well modelled using a singular isothermal ellipsoid for the primary lens and a singular isothermal sphere for the secondary lens with Einstein radii 0.704 ± 0.006 and 0.241 ± 0.030 arcsec, respectively. A maximum predicted time delay of 9.6 d is calculated, assuming lensing galaxy redshifts of $z$ = 1.0. Furthermore, PS J042913.17+142840.9 exhibits a large flux ratio anomaly, up to a factor of 2.66 ± 0.37 in i band, that varies across optical and near-infrared wavelengths. We discuss LSST and its implications for future high-redshift lens searches and outline an extension to the search using supervised machine learning techniques.
Cosmic ray electrons released by supernova remnants
Authors: Morlino G , Celli S
Published: October 2021

The process that allows cosmic rays (CRs) to escape from their sources and be released into the Galaxy is still largely unknown. The comparison between CR electron and proton spectra measured at Earth suggests that electrons are released with a spectrum steeper than protons by Δsep ∼ 0.3 for energies above ∼10 GeV and by Δsep ∼ 1.2 above ∼1 TeV. Assuming that both species are accelerated at supernova remnant shocks, we here explore two possible scenarios that can in principle justify steeper electron spectra: (i) energy losses due to synchrotron radiation in an amplified magnetic field and (ii) time-dependent acceleration efficiency. We account for magnetic field amplification produced by either CR-induced instabilities or by magnetohydrodynamics instabilities my means of a parametric description. We show that both mechanisms are required to explain the electron spectrum. In particular, synchrotron losses can only produce a significant electron steepening above ∼1 TeV, while a time-dependent acceleration can explain the spectrum at lower energies if the electron injection into diffusive shock acceleration is inversely proportional to the shock speed. We discuss observational and theoretical evidences supporting such a behaviour. Furthermore, we predict two additional spectral features: a spectral break below ∼few GeV (as required by existing observations) due to the acceleration efficiency drop during the adiabatic phase, and a spectral hardening above ∼20 TeV (where no data are available yet) resulting from electrons escaping from the shock precursor.
Radio modelling of the brightest and most luminous non-thermal colliding-wind binary Apep
Authors: Bloot S , Callingham J R , Marcote B
Published: October 2021

Apep is the brightest and most luminous non-thermal colliding-wind binary by over an order of magnitude. It has been suggested from infrared observations that one of the Wolf–Rayet stars in Apep is launching an anisotropic wind. Here we present radio observations of Apep from 0.2 to 20 GHz taken over 33 yr. The spectrum reveals an extremely steep turnover in the flux density at low frequencies, where the flux density decreases by two orders of magnitude over only 325 MHz of bandwidth. This exponential decline is best described by free–free absorption, with a turnover frequency at 0.54 ± 0.01 GHz. Above the turnover, the spectrum is well described by a power-law and a high-frequency cut-off likely caused by inverse-Compton cooling. The light curve of Apep shows significant variation over the observing period, with Apep brightening by over 50 mJy in a span of 25 yr at 1.4 GHz. Models that assume spherical winds do not replicate all of the structure evident in the radio light curve. We derived a model that allows one of the winds in the system to be anisotropic. This anisotropic model recovers most of the structure of the light curve and is a significantly better statistical fit to the data than the spherical wind model. We suggest such a result is independent support that one of the Wolf–Rayet stars in Apep is launching an anisotropic wind. If the anisotropic wind model is correct, we predict a ∼25 per cent decrease of the 1.4 GHz flux density of Apep over the next 5 yr.
Upregulation of mNEIL3 inOgg1-null cells is a potential backup mechanism for 8-oxoG repair
Authors: Higgs Ellen B , Godschalk Roger , Langie Sabine A S , van Schooten Frederik-Jan , Hodges Nikolas J
Published: October 2021

Reactive oxygen species formation and resultant oxidative damage to DNA are ubiquitous events in cells, the homeostasis of which can be dysregulated in a range of pathological conditions. Base excision repair (BER) is the primary repair mechanism for oxidative genomic DNA damage. One prevalent oxidised base modification, 8-oxoguanine (8-oxoG), is recognised by 8-oxoguanine glycosylase-1 (OGG1) initiating removal and repair via BER. Surprisingly, Ogg1 null mouse embryonic fibroblasts (mOgg1−/− MEFs) do not accumulate 8-oxoG in the genome to the extent expected. This suggests that there are backup repair mechanisms capable of repairing 8-oxoG in the absence of OGG1. In the current study, we identified components of NER (Ercc1, Ercc4, Ercc5), BER (Lig1, Tdg, Nthl1, Mpg, Mgmt, NEIL3), MMR (Mlh1, Msh2, Msh6) and DSB (Brip1, Rad51d, Prkdc) pathways that are transcriptionally elevated in mOgg1−/− MEFs. Interestingly, all three nucleotide excision repair genes identified: Ercc1 (2.5 ± 0.2-fold), Ercc4 (1.5 ± 0.1-fold) and Ercc5 (1.7 ± 0.2-fold) have incision activity. There was also a significant functional increase in NER activity (42.0 ± 7.9%) compared to WT MEFs. We also observed upregulation of both Neil3 mRNA (37.9 ± 1.6-fold) and protein in mOgg1−/− MEFs. This was associated with a 3.4 ± 0.4-fold increase in NEIL3 substrate sites in genomic DNA of cells treated with BSO, consistent with the ability of NEIL3 to remove 8-oxoG oxidation products from genomic DNA. In conclusion, we suggest that in Ogg1-null cells, upregulation of multiple DNA repair proteins including incision components of the NER pathway and Neil3 are important compensatory responses to prevent the accumulation of genomic 8-oxoG.
TRF2-mediated ORC recruitment underlies telomere stability upon DNA replication stress
Authors: Higa Mitsunori , Matsuda Yukihiro , Fujii Jumpei , Sugimoto Nozomi , Yoshida Kazumasa , Fujita Masatoshi
Published: October 2021

Telomeres are intrinsically difficult-to-replicate region of eukaryotic chromosomes. Telomeric repeat binding factor 2 (TRF2) binds to origin recognition complex (ORC) to facilitate the loading of ORC and the replicative helicase MCM complex onto DNA at telomeres. However, the biological significance of the TRF2–ORC interaction for telomere maintenance remains largely elusive. Here, we employed a TRF2 mutant with mutations in two acidic acid residues (E111A and E112A) that inhibited the TRF2–ORC interaction in human cells. The TRF2 mutant was impaired in ORC recruitment to telomeres and showed increased replication stress-associated telomeric DNA damage and telomere instability. Furthermore, overexpression of an ORC1 fragment (amino acids 244–511), which competitively inhibited the TRF2–ORC interaction, increased telomeric DNA damage under replication stress conditions. Taken together, these findings suggest that TRF2-mediated ORC recruitment contributes to the suppression of telomere instability.
VARIDT 2.0: structural variability of drug transporter
Authors: Fu Tingting , Li Fengcheng , Zhang Yang , Yin Jiayi , Qiu Wenqi , Li Xuedong , Liu Xingang , Xin Wenwen , Wang Chengzhao , Yu Lushan , Gao Jianqing , Zheng Qingchuan , Zeng Su , Zhu Feng
Published: October 2021

The structural variability data of drug transporter (DT) are key for research on precision medicine and rational drug use. However, these valuable data are not sufficiently covered by the available databases. In this study, a major update of VARIDT (a database previously constructed to provide DTs’ variability data) was thus described. First, the experimentally resolved structures of all DTs reported in the original VARIDT were discovered from PubMed and Protein Data Bank. Second, the structural variability data of each DT were collected by literature review, which included: (a) mutation-induced spatial variations in folded state, (b) difference among DT structures of human and model organisms, (c) outward/inward-facing DT conformations and (d) xenobiotics-driven alterations in the 3D complexes. Third, for those DTs without experimentally resolved structural variabilities, homology modeling was further applied as well-established protocol to enrich such valuable data. As a result, 145 mutation-induced spatial variations of 42 DTs, 1622 inter-species structures originating from 292 DTs, 118 outward/inward-facing conformations belonging to 59 DTs, and 822 xenobiotics-regulated structures in complex with 57 DTs were updated to VARIDT (https://idrblab.org/varidt/ and http://varidt.idrblab.net/). All in all, the newly collected structural variabilities will be indispensable for explaining drug sensitivity/selectivity, bridging preclinical research with clinical trial, revealing the mechanism underlying drug-drug interaction, and so on.
The human telomeric proteome during telomere replication
Authors: Lin Chih-Yi Gabriela , Näger Anna Christina , Lunardi Thomas , Vančevska Aleksandra , Lossaint Gérald , Lingner Joachim
Published: October 2021

Telomere shortening can cause detrimental diseases and contribute to aging. It occurs due to the end replication problem in cells lacking telomerase. Furthermore, recent studies revealed that telomere shortening can be attributed to difficulties of the semi-conservative DNA replication machinery to replicate the bulk of telomeric DNA repeats. To investigate telomere replication in a comprehensive manner, we develop QTIP-iPOND - Quantitative Telomeric chromatin Isolation Protocol followed by isolation of Proteins On Nascent DNA - which enables purification of proteins that associate with telomeres specifically during replication. In addition to the core replisome, we identify a large number of proteins that specifically associate with telomere replication forks. Depletion of several of these proteins induces telomere fragility validating their importance for telomere replication. We also find that at telomere replication forks the single strand telomere binding protein POT1 is depleted, whereas histone H1 is enriched. Our work reveals the dynamic changes of the telomeric proteome during replication, providing a valuable resource of telomere replication proteins. To our knowledge, this is the first study that examines the replisome at a specific region of the genome.
GMrepo v2: a curated human gut microbiome database with special focus on disease markers and cross-dataset comparison
Authors: Dai Die , Zhu Jiaying , Sun Chuqing , Li Min , Liu Jinxin , Wu Sicheng , Ning Kang , He Li-jie , Zhao Xing-Ming , Chen Wei-Hua
Published: October 2021

GMrepo (data repository for Gut Microbiota) is a database of curated and consistently annotated human gut metagenomes. Its main purposes are to increase the reusability and accessibility of human gut metagenomic data, and enable cross-project and phenotype comparisons. To achieve these goals, we performed manual curation on the meta-data and organized the datasets in a phenotype-centric manner. GMrepo v2 contains 353 projects and 71,642 runs/samples, which are significantly increased from the previous version. Among these runs/samples, 45,111 and 26,531 were obtained by 16S rRNA amplicon and whole-genome metagenomics sequencing, respectively. We also increased the number of phenotypes from 92 to 133. In addition, we introduced disease-marker identification and cross-project/phenotype comparison. We first identified disease markers between two phenotypes (e.g. health versus diseases) on a per-project basis for selected projects. We then compared the identified markers for each phenotype pair across datasets to facilitate the identification of consistent microbial markers across datasets. Finally, we provided a marker-centric view to allow users to check if a marker has different trends in different diseases. So far, GMrepo includes 592 marker taxa (350 species and 242 genera) for 47 phenotype pairs, identified from 83 selected projects. GMrepo v2 is freely available at: https://gmrepo.humangut.info.
Genome-wide analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine at single-nucleotide resolution unveils reduced occurrence of oxidative damage at G-quadruplex sites
Authors: An Jiao , Yin Mengdie , Yin Jiayong , Wu Sizhong , Selby Christopher P , Yang Yanyan , Sancar Aziz , Xu Guo-Liang , Qian Maoxiang , Hu Jinchuan
Published: October 2021

8-Oxo-7,8-dihydro-2′-deoxyguanosine (OG), one of the most common oxidative DNA damages, causes genome instability and is associated with cancer, neurological diseases and aging. In addition, OG and its repair intermediates can regulate gene transcription, and thus play a role in sensing cellular oxidative stress. However, the lack of methods to precisely map OG has hindered the study of its biological roles. Here, we developed a single-nucleotide resolution OG-sequencing method, named CLAPS-seq (Chemical Labeling And Polymerase Stalling Sequencing), to measure the genome-wide distribution of both exogenous and endogenous OGs with high specificity. Our data identified decreased OG occurrence at G-quadruplexes (G4s), in association with underrepresentation of OGs in promoters which have high GC content. Furthermore, we discovered that potential quadruplex sequences (PQSs) were hotspots of OGs, implying a role of non-G4-PQSs in OG-mediated oxidative stress response.