bluuebunny/crossref_metadata_2025 huggingface dataset:
Unique genomic traits for cold adaptation inNaganishia vishniacii, a polyextremophile yeast isolated from Antarctica
Authors: Nizovoy Paula , Bellora Nicolás , Haridas Sajeet , Sun Hui , Daum Chris , Barry Kerrie , Grigoriev Igor V , Libkind Diego , Connell Laurie B , Moliné Martín
Published: October 2020

Cold environments impose challenges to organisms. Polyextremophile microorganisms can survive in these conditions thanks to an array of counteracting mechanisms. Naganishia vishniacii, a yeast species hitherto only isolated from McMurdo Dry Valleys, Antarctica, is an example of a polyextremophile. Here we present the first draft genomic sequence of N. vishniacii. Using comparative genomics, we unraveled unique characteristics of cold associated adaptations. 336 putative genes (total: 6183) encoding solute transfers and chaperones, among others, were absent in sister species. Among genes shared by N. vishniacii and its closest related species we found orthologs encompassing possible evidence of positive selection (dN/dS > 1). Genes associated with photoprotection were found in agreement with high solar irradiation exposure. Also genes coding for desaturases and genomic features associated with cold tolerance (i.e. trehalose synthesis and lipid metabolism) were explored. Finally, biases in amino acid usage (namely an enrichment of glutamine and a trend in proline reduction) were observed, possibly conferring increased protein flexibility. To the best of our knowledge, such a combination of mechanisms for cold tolerance has not been previously reported in fungi, making N. vishniacii a unique model for the study of the genetic basis and evolution of cold adaptation strategies.
The C2 domain of the ubiquitin ligase Rsp5 is required for ubiquitination of the endocytic protein Rvs167 upon change of nitrogen source
Authors: Tanahashi Ryoya , Afiah Tira Siti Nur , Nishimura Akira , Watanabe Daisuke , Takagi Hiroshi
Published: October 2020

Ubiquitination is a key signal for endocytosis of proteins on the plasma membrane. The ubiquitin ligase Rsp5 of Saccharomyces cerevisiae, which contains an amino-terminal membrane-binding C2 domain, three substrate-recognizing tryptophan-tryptophan (WW) domains and a carboxyl-terminal catalytic homologous to the E6-AP carboxyl terminus (HECT) domain, can ubiquitinate plasma membrane proteins directing them for endocytosis. Here, we examined the roles of the C2 domain in endocytosis for the downregulation of the general amino acid permease Gap1, which is one of nitrogen-regulated permeases in S. cerevisiae. First, we constructed several rsp5 mutants producing Rsp5 variants without the C2 domain or with amino acid changes of membrane-binding lysine residues. These mutants showed defects in endocytosis of Gap1 in response to a preferred nitrogen source. Intriguingly, we found that ubiquitination of Gap1 in these mutant cells was highly similar to that in wild-type cells during endocytosis. These results indicate that the C2 domain is essential for endocytosis but not for ubiquitination of substrates such as Gap1. Moreover, genetic and biochemical analyses showed that the endocytic protein Rvs167 was ubiquitinated via Rsp5 and the C2 domain was required for efficient ubiquitination in response to a preferred nitrogen source. Here, we propose a mechanism for the C2 domain-mediated endocytosis of plasma membrane permeases.
Systematic recovery of instrumental timing and phase errors using interferometric surface-waves retrieved from large-N seismic arrays
Authors: Weemstra Cornelis , de Laat Janneke I , Verdel Arie , Smets Pieter
Published: October 2020

Instrumental timing and phase errors are a notorious problem in seismic data acquisition and processing. These can be frequency independent, for example due to clock drift, but may also be frequency dependent, for example due to imperfectly known instrument responses. A technique is presented that allows both types of errors to be recovered in a systematic fashion. The methodology relies on the time-symmetry usually inherent in time-averaged cross-correlations of ambient seismic noise: the difference between the arrival time of the direct surface-wave at positive time and the arrival time of the direct surface-wave at negative time is quantified. Doing this for all eligible receiver–receiver pairs of a large-N seismic array, including one or more receivers devoid of instrumental timing errors, the instrumental timing errors of all incorrectly timed receivers can be determined uniquely. Most notably, this is accomplished by means of a weighted least-squares inversion. The weights are based on the receiver–receiver distances and decrease the adverse effect of inhomogeneities in the noise illumination pattern on the recovered instrumental timing errors. Inversion results are furthermore optimized by limiting the inversion to receiver couples that (i) exceed a specific receiver–receiver distance threshold and (ii) whose time-averaged cross-correlations exceed a specific signal-to-noise ratio threshold. Potential frequency dependence of the timing errors is incorporated by means of an iterative, frequency-dependent approach. The proposed methodology is validated using synthetic recordings of ambient seismic surface-wave noise due to an arbitrary non-uniform illumination pattern. The methodology is successfully applied to time-averaged cross-correlations of field recordings of ambient seismic noise on and around the Reykjanes peninsula, SW Iceland.
Disclaimers in European Patent Applications
Authors: Barycki Michał
Published: October 2020

A European patent application may be amended by, among others, deleting a part of the claimed subject matter under established conditions or by the incorporation of an undisclosed or disclosed disclaimer. Disclaimers are a useful tool in order to maintain the balance between the practical needs of applicants and the interests of third parties in legal clarity and completeness. The incorporation of disclaimers may not extend beyond the content of the European patent application as filed and the protection it confers. The purpose of this paper is to illustrate how an applicant can introduce a negative technical feature into the patent application in the light of the extensive judicial practice of the Technical and Enlarged Boards of Appeal of the European Patent Office. The author has analysed the criteria for disclaimers set out in decisions G 1/03, G 2/10 and G 1/16 in accordance with the general notion of patent law and requirements of patentability. Additionally, this problem was also characterized in the light of the judicial practice of national courts and legislations of the EU Member States.
Surgical treatment of pleural empyema in Coronavirus disease 19 patients: the Southern Switzerland experience
Authors: Tessitore Adele , Patella Miriam , Giuliani Mauro , Theologou Thomas , Freguia Stefania , Minerva Eleonora Maddalena , Rugel Gregor , Cafarotti Stefano
Published: October 2020

We report the first surgical series of patients developing pleural empyema after severe bilateral interstitial lung disease in confirmed severe acute respiratory syndrome coronavirus 2 infection. The empyema results in a complex medical challenge that requires combination of medical therapies, mechanical ventilation and surgery. The chest drainage approach was not successful to relieve the symptomatology and to drain the excess fluid. After multidisciplinary discussion, a surgical approach was recommended. Even though decortication and pleurectomy are high-risk procedures, they must be considered as an option for pleural effusion in Coronavirus disease-positive patients. This is a life-treating condition, which can worsen the coronavirus disease manifestation and should be treated immediately to improve patient’s status and chance of recovery.
Causal effects of physical activity and sedentary behaviour on health deficits accumulation in older adults
Authors: García-Esquinas Esther , Ortolá Rosario , Martínez-Gómez David , Damián Javier , Prina Matthew , Rodríguez-Artalejo Fernando , Pastor-Barriuso Roberto
Published: October 2020

Background

Increasing physical activity (PA) and reducing sedentary behaviour (SB) have been associated with healthy ageing, but their effects when adjusted for reverse causation and selection bias remain unclear.

Methods

A deficits accumulation (DA) index based on the number and severity of 51 health deficits (0–100%) was calculated at baseline and three biannual follow-up visits, in a representative cohort of 3 228 community-dwelling older adults in Spain. Average differences in DA index by previous recreational PA, household PA, mentally-active SB and passive SB were estimated using marginal structural models with inverse probability of exposure and censoring weights.

Results

Compared with participants with previous recreational PA of 10–19.9 metabolic equivalent hours/week (MET-hours/week), average differences in DA index (95% confidence intervals) were 0.19 (−1.09, 1.48), 0.69 (−0.23, 1.61), −0.66 (−1.34, 0.02), −0.87 (−1.59, −0.13) and −0.55 (−1.37, 0.28) for 0, 0.1–9.9, 20–29.9, 30–39.9 and ≥40 MET-hours/week, respectively (P for trend = 0.006). Household PA showed no effect on subsequent DA after adjusting for reverse causation. Women, but not men, who spent 7–14.9, 15–20.9 and ≥21 h/week on mentally active SB had DA decreases of 0.09 (−1.00, 1.19), 1.08 (−0.28, 2.45) and 2.17 (0.58, 3.75), respectively, compared with 1–6.9 h/week (P for trend = 0.005); whereas women who spent 3–3.9, 4–4.9 and ≥5 h/day on passive SB showed DA increases of 0.41 (−0.52, 1.35), 1.35 (0.13, 2.57) and 2.13 (0.78, 3.47), respectively, compared with 2–2.9 h/day (P for trend = 0.001).

Conclusions

The proposed methodology allows estimation of the causal effects of PA and SB on ageing, by simulating a random assignment in which all subjects have the same probability of exposure.
The effect of angiotensin-converting enzyme levels on COVID-19 susceptibility and severity: a Mendelian randomization study
Authors: Butler-Laporte Guillaume , Nakanishi Tomoko , Mooser Vincent , Renieri Alessandra , Amitrano Sara , Zhou Sirui , Chen Yiheng , Forgetta Vincenzo , Richards J Brent
Published: October 2020

Background

There has been uncertainty about the safety or benefit of angiotensin-converting enzyme (ACE) inhibitors during the COVID-19 pandemic. We used Mendelian randomization using genetic determinants of serum-ACE levels to test whether decreased ACE levels increase susceptibility to SARS-CoV-2 infection or COVID-19 severity, while reducing potential bias from confounding and reverse causation in observational studies.

Methods

Genetic variants strongly associated with ACE levels, which were nearby the ACE gene, were identified from the ORIGIN trial and a separate genome-wide association study (GWAS) of ACE levels from the AGES cohort. The ORIGIN trial included 4147 individuals of European and Latino ancestries. Sensitivity analyses were performed using a study of 3200 Icelanders. Cohorts from the COVID-19 Host Genetics Initiative GWAS of up to 960 186 individuals of European ancestry were used for COVID-19 susceptibility, hospitalization and severe-disease outcome.

Results

Genetic variants were identified that explain between 18% and 37% of variance in ACE levels. Using genetic variants from the ORIGIN trial, a standard-deviation decrease in ACE levels was not associated with an increase in COVID-19 susceptibility [odds ratio (OR): 1.02, 95% confidence interval (CI): 0.90, 1.15], hospitalization (OR: 0.86, 95% CI: 0.68, 1.08) or severe disease (OR: 0.74, 95% CI: 0.51, 1.06). Using genetic variants from the AGES cohort, the result was similar for susceptibility (OR: 0.98, 95% CI: 0.89, 1.09), hospitalization (OR: 0.86, 95% CI: 0.66, 1.11) and severity (OR: 0.75, 95% CI: 0.50, 1.14). Multiple-sensitivity analyses led to similar results.

Conclusion

Genetically decreased serum ACE levels were not associated with susceptibility to, or severity of, COVID-19 disease. These data suggest that individuals taking ACE inhibitors should not discontinue therapy during the COVID-19 pandemic.
Impact of Immune Reconstitution-Induced Hepatic Flare on Hepatitis B Surface Antigen Loss in Hepatitis B Virus/Human Immunodeficiency Virus-1 Coinfected Patients
Authors: Yoshikawa Shiori , Yoshio Sachiyo , Yoshida Yuichi , Tsutsui Yuriko , Kawai Hironari , Yamazoe Taiji , Mori Taizo , Osawa Yosuke , Sugiyama Masaya , Iwamoto Masashi , Watashi Koichi , Kawaguchi Takumi , Akita Tomoyuki , Tanaka Junko , Kikuchi Yoshimi , Mizokami Masashi , Oka Shinichi , Kanto Tatsuya , Gatanaga Hiroyuki
Published: October 2020

Background

Hepatitis B surface antigen (HBsAg) loss is an ideal goal for chronic hepatitis B patients. Antiretroviral therapy (ART) in hepatitis B virus/human immunodeficiency virus-1 (HBV/HIV-1)–coinfected patients can lead to hepatic flare (HF) caused by immune reconstitution-induced inflammatory syndrome (IRIS). Here, we investigated the impact of IRIS-HF on HBsAg loss.

Methods

This was a retrospective study of 58 HBV/HIV-1–coinfected subjects HBsAg-positive for ≥6 months before ART initiation and followed for ≥1 year (median 9.9 years) after ART initiation. We examined humoral factors in sera from healthy volunteers, HIV-monoinfected patients, and HBV/HIV-1–coinfected patients with IRIS-HF or acute hepatitis B infection.

Results

During ART, HBsAg loss was observed in 20 of 58 HBV/HIV-1–coinfected patients (34.5%). Of the 58 patients, 15 (25.9%) developed IRIS-HF within 12 months of ART initiation. HBsAg loss was more frequent among patients who developed IRIS-HF (11/15, 73.3%) than those who did not (9/43, 20.9%). Multivariate analysis showed IRIS-HF was an independent predictor of subsequent HBsAg loss. Younger age and higher baseline HBV DNA titer were associated with IRIS-HF. Elevation of sCD163, not CXCL9, CXC10, CXCXL11, or CXCL13, was observed at IRIS-HF.

Conclusions

IRIS-HF was associated with HBsAg loss in HBV/HIV-1–coinfected patients.
Prolonged Severe Acute Respiratory Syndrome Coronavirus 2 Replication in an Immunocompromised Patient
Authors: Baang Ji Hoon , Smith Christopher , Mirabelli Carmen , Valesano Andrew L , Manthei David M , Bachman Michael A , Wobus Christiane E , Adams Michael , Washer Laraine , Martin Emily T , Lauring Adam S
Published: October 2020

We describe a case of chronic coronavirus disease 2019 (COVID-19) in a patient with lymphoma and associated B-cell immunodeficiency. Viral cultures and sequence analysis demonstrate ongoing replication of infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for at least 119 days. The patient had 3 admissions related to COVID-19 over a 4-month period and was treated twice with remdesivir and convalescent plasma with resolution of symptoms. The patient’s lack of seroconversion and prolonged course illustrate the importance of humoral immunity in resolving SARS-CoV-2 infection. This case highlights challenges in managing immunocompromised hosts, who may act as persistent shedders and sources of transmission.
Impact of an antimicrobial stewardship programme on reducing broad-spectrum antibiotic use and its effect on carbapenem-resistantAcinetobacter baumannii(CRAb) in hospitals in Jordan
Authors: Yusef Dawood , Hayajneh Wail A , Bani Issa Ali , Haddad Rami , Al-Azzam Sayer , Lattyak Elizabeth A , Lattyak William J , Gould Ian , Conway Barbara R , Bond Stuart , Conlon-Bingham Geraldine , Aldeyab Mamoon A
Published: October 2020

Objectives

To evaluate the impact of an antimicrobial stewardship programme (ASP) on reducing broad-spectrum antibiotic use and its effect on carbapenem-resistant Acinetobacter baumannii (CRAb) in hospitalized patients.

Methods

The study was a retrospective, ecological assessment in a tertiary teaching hospital over 6 years (January 2014 to December 2019). The intervention involved the implementation of an ASP in February 2018, which remains in effect today. This ASP consists of several components, including education, antibiotic guidelines, antibiotic restriction policy with prior approval, audit of compliance to the restriction policy and feedback. Restricted antibiotics were imipenem/cilastatin, ertapenem, meropenem, vancomycin, teicoplanin, tigecycline, colistin, amikacin, piperacillin/tazobactam, levofloxacin and ciprofloxacin. The intervention was evaluated by time-series methods.

Results

Statistically significant decreases in the level of antibiotic use, after the introduction of the ASP, were observed for the following antibiotics: imipenem/cilastatin (P = 0.0008), all carbapenems (P = 0.0001), vancomycin (P = 0.0006), colistin (P = 0.0016) and third-generation cephalosporins (P = 0.0004). A statistically significant decrease in the slope, after the introduction of the ASP, for ertapenem (P = 0.0044) and ciprofloxacin (P = 0.0117) was observed. For piperacillin/tazobactam, there was a significant increasing trend (P = 0.0208) before the introduction of the ASP. However, this increased trend was halted post-introduction of the ASP (P = 0.4574). The introduction of the ASP was associated with a significant impact on reducing the levels of CRAb (P = 0.0237).

Conclusions

The introduced antimicrobial stewardship interventions contributed to a reduction in the use of several broad-spectrum antibiotics, reversed the trends of increasing use of other antibiotics and were associated with a significant reduction in CRAb.
Electronic health records and clinician burnout: A story of three eras
Authors: Johnson Kevin B , Neuss Michael J , Detmer Don Eugene
Published: October 2020

Objective

The study sought to provide physicians, informaticians, and institutional policymakers with an introductory tutorial about the history of medical documentation, sources of clinician burnout, and opportunities to improve electronic health records (EHRs). We now have unprecedented opportunities in health care, with the promise of new cures, improved equity, greater sensitivity to social and behavioral determinants of health, and data-driven precision medicine all on the horizon. EHRs have succeeded in making many aspects of care safer and more reliable. Unfortunately, current limitations in EHR usability and problems with clinician burnout distract from these successes. A complex interplay of technology, policy, and healthcare delivery has contributed to our current frustrations with EHRs. Fortunately, there are opportunities to improve the EHR and health system. A stronger emphasis on improving the clinician’s experience through close collaboration by informaticians, clinicians, and vendors can combine with specific policy changes to address the causes of burnout.

Target audience

This tutorial is intended for clinicians, informaticians, policymakers, and regulators, who are essential participants in discussions focused on improving clinician burnout. Learners in biomedicine, regardless of clinical discipline, also may benefit from this primer and review.

Scope

We include (1) an overview of medical documentation from a historical perspective; (2) a summary of the forces converging over the past 20 years to develop and disseminate the modern EHR; and (3) future opportunities to improve EHR structure, function, user base, and time required to collect and extract information.
First Evidence of Western Bean Cutworm (Lepidoptera: Noctuidae) Overwintering in the Province of Québec (Canada)
Authors: Saguez Julien , Neau Mathieu , Rieux Christine , Vallières-Murray Maryse , Petrauskas Priscila , Mathieu Stéphanie , Duval Brigitte , Auger Yves , Fréchette Isabelle
Published: October 2020

The western bean cutworm, Striacosta albicosta (Smith), is considered a major corn pest in North America. In 2009, it started invading the province of Québec (northeastern Canada). To our knowledge, there has been no evidence that this pest could overwinter in this province. In the falls of 2017 and 2018, storage totes containing mature western bean cutworm larvae were placed in the soil in three agricultural regions, in Québec, where western bean cutworm invasions are frequent and crop damage is often significant. The goal was to evaluate if western bean cutworm could resist the province’s winter conditions. The storage totes were removed from the soil at different dates to estimate winter survival. Emergence cages were installed over the totes in the spring of the following year to determine whether western bean cutworm could complete its life cycle. In the spring of 2019, car shelters were also installed at two different sites to evaluate natural moth emergences in fields in which numerous mature western bean cutworm larvae and damage were reported in 2018. Western bean cutworm moth emergences occurred in both cases. These experiments constitute the first documented evidence that western bean cutworm can overwinter and complete its life cycle in Québec’s cold climate. It also represents the northernmost overwintering survival for this species ever documented in North America. The western bean cutworm’s ability to overwinter in Québec will have important implications for corn producers. Pest monitoring and management programs in the province of Québec will need to be adapted accordingly.
Postmarketing observational study of pazopanib in patients with metastatic soft tissue sarcoma in Japan
Authors: Teshima Yasutomo , Nomura Satoshi , Fukasawa Nobuaki
Published: October 2020

Background

This study evaluated the safety and efficacy of pazopanib in patients with metastatic soft tissue sarcoma in routine clinical use in Japan.

Methods

It was a multicentre, centrally registered and uncontrolled observational study in patients who received pazopanib for metastatic soft tissue sarcoma, with an observation period of 1 year after the start of drug administration. The study was conducted at 378 investigational sites in Japan from September 2012 to September 2019. Progression-free survival (PFS) and overall survival (OS) were the efficacy endpoints of the study.

Results

A total of 1970 patients were enrolled. Of these, 680 with finalized study forms were included in the analysis. Overall, 649 patients were included in the safety analysis set, and 569 were included in the efficacy analysis set. Most of the patients (81.97%) experienced at least one adverse drug reaction (ADR); 22.34% of patients reported serious ADRs and 34.98% of patients experienced grade ≥ 3 ADRs in the safety set. Hypertension (40.37%) and hepatic dysfunction (26.50%) were the two most common ADRs. A total of 262 deaths were reported, of which 12 were due to ADRs. The median PFS was 3.09 months, whereas the median OS was not reached at the end of the 1-year observation period.

Conclusions

The safety and efficacy profiles in this postmarketing observational study were consistent with prior data and registration clinical trials. No new safety signals were observed while treating patients with metastatic soft tissue sarcoma with pazopanib.
A multi-institutional survey of the quality of life after treatment for uterine cervical cancer: a comparison between radical radiotherapy and surgery in Japan
Authors: Kaneyasu Yuko , Fujiwara Hisaya , Nishimura Tetsuo , Sakurai Hideyuki , Kazumoto Tomoko , Ikushima Hitoshi , Uno Takashi , Tokumaru Sunao , Harima Yoko , Gomi Hiromichi , Toita Takafumi , Kita Midori , Noda Shin-ei , Takahashi Takeo , Kato Shingo , Ohkawa Ayako , Tozawa-Ono Akiko , Ushijima Hiroki , Hasumi Yoko , Hirashima Yasuyuki , Niibe Yuzuru , Nakagawa Tomio , Akita Tomoyuki , Tanaka Junko , Ohno Tatsuya ,   the Working Group of the Gynecological Tumor Committee of the Japanese Radiation Oncology Study Group (JROSG)
Published: October 2020

This study aimed to research the post-treatment quality of life (QOL) between radiotherapy (RT)- and operation (OP)-treated early cervical cancer survivors, using separate questionnaires for physicians and patients. We administered an observational questionnaire to patients aged 20–70 years old with Stages IB1–IIB cervical cancer who had undergone RT or OP and without recurrence as outpatients for ≥6 months after treatment. We divided 100 registered patients equally into two treatment groups (n = 50 each). The average age was 53 and 44 years in the RT and OP groups, respectively. The RT group included 34 and 66% Stage I and II patients, respectively, whereas the OP group included 66 and 34% Stage I and II patients, respectively. The OP group included 58% of patients with postoperative RT. Combination chemotherapy was performed in 84 and 48% of patients in the RT and OP groups, respectively. On the physicians’ questionnaire, we observed significant differences in bone marrow suppression (RT) and leg edema (OP). On the patients’ questionnaire, significantly more patients had dysuria and leg edema in the OP group than in the RT group, and severe (Score 4–5) leg edema was significantly higher in the post-operative RT group than in the OP only group. The frequency of sexual intercourse decreased after treatment in both groups. On the patients’ questionnaire, there were no significant differences between the two groups regarding sexual activity. These findings are useful to patients and physicians for shared decision-making in treatment choices. The guidance of everyday life and health information including sexual life after treatment is important.
Core-collapse supernova neutrino emission and detection informed by state-of-the-art three-dimensional numerical models
Authors: Nagakura Hiroki , Burrows Adam , Vartanyan David , Radice David
Published: October 2020

Based on our recent three-dimensional core-collapse supernova (CCSN) simulations including both exploding and non-exploding models, we study the detailed neutrino signals in representative terrestrial neutrino observatories, namely Super-Kamiokande (Hyper-Kamiokande), DUNE, JUNO, and IceCube. We find that the physical origin of difference in the neutrino signals between 1D and 3D is mainly proto-neutron-star convection. We study the temporal and angular variations of the neutrino signals and discuss the detectability of the time variations driven by the spiral standing accretion shock instability (spiral SASI) when it emerges for non-exploding models. In addition, we determine that there can be a large angular asymmetry in the event rate (${\gtrsim} 50 {{\ \rm per\ cent}}$), but the time-integrated signal has a relatively modest asymmetry (${\lesssim} 20 {{\ \rm per\ cent}}$). Both features are associated with the lepton-number emission self-sustained asymmetry and the spiral SASI. Moreover, our analysis suggests that there is an interesting correlation between the total neutrino energy (TONE) and the cumulative number of neutrino events in each detector, a correlation that can facilitate data analyses of real observations. We demonstrate the retrieval of neutrino energy spectra for all flavours of neutrino by applying a novel spectrum reconstruction technique to the data from multiple detectors. We find that this new method is capable of estimating the TONE within the error of ∼20 per cent if the distance to the CCSN is ≲6 kpc.
Double-peaked Lyman α emission at z = 6.803: a reionization-era galaxy self-ionizing its local H ii bubble
Authors: Meyer Romain A , Laporte Nicolas , Ellis Richard S , Verhamme Anne , Garel Thibault
Published: October 2020

We report the discovery of a double-peaked Lyman α profile in a galaxy at z = 6.803, A370p_z1, in the parallel Frontier Field of Abell 370. The velocity separation between the blue and red peaks of the Lyman α profile ($\Delta v=101_{-19}^{+38} (\pm 48)\, \rm km\, \rm s^{-1}$) suggests an extremely high escape fraction of ionizing photons $\gt 59(51){{\ \rm per\ cent}} (2\sigma)$. The spectral energy distribution indicates a young (50 Myr), star-forming ($12\pm 6 \, \rm {M}_\odot \rm {yr}^{-1}$) galaxy with an IRAC excess implying strong [O iii] + H β emission. On the basis of the high escape fraction measured, we demonstrate that A370p_z1 was solely capable of creating an ionized bubble sufficiently large to account for the blue component of its Lyman α profile. We discuss whether A370p_z1 may be representative of a larger population of luminous z ≃ 7 double-peaked Lyman α emitting sources with high escape fractions that self-ionized their surroundings without contributions from associated ultraviolet-fainter sources.
Calibration schemes with O(N log N) scaling for large-N radio interferometers built on a regular grid
Authors: Gorthi Deepthi B , Parsons Aaron R , Dillon Joshua S
Published: October 2020

Future generations of radio interferometers targeting the 21 cm signal at cosmological distances with N ≫ 1000 antennas could face a significant computational challenge in building correlators with the traditional architecture, whose computational resource requirement scales as $\mathcal {O}(N^2)$ with array size. The fundamental output of such correlators is the cross-correlation products of all antenna pairs in the array. The FFT-correlator architecture reduces the computational resources scaling to $\mathcal {O}(N\log {N})$ by computing cross-correlation products through a spatial Fourier transform. However, the output of the FFT-correlator is meaningful only when the input antenna voltages are gain- and phase-calibrated. Traditionally, interferometric calibration has used the $\mathcal {O}(N^2)$ cross-correlations produced by a standard correlator. This paper proposes two real-time calibration schemes that could work in parallel with an FFT-correlator as a self-contained $\mathcal {O}(N\log {N})$ correlator system that can be scaled to large-N redundant arrays. We compare the performance and scalability of these two calibration schemes and find that they result in antenna gains whose variance decreases as 1/log N with increase in the size of the array.
AzTEC survey of the central molecular zone: increasing spectral index of dust with density
Authors: Tang Yuping , Wang Q Daniel , Wilson Grant W
Published: October 2020

The central molecular zone (CMZ) of our Galaxy hosts an extreme environment analogous to that found in typical starburst galaxies in the distant Universe. In order to understand dust properties in environments like our CMZ, we present results from a joint spectral energy distribution analysis of our AzTEC/Large Millimeter Telescope survey, together with existing Herschel far-IR data on the CMZ, from a wavelength range of 160 $\mu {\rm m}$ to 1.1 mm. We include global foreground and background contributions in a novel Bayesian modelling that incorporates the point spread functions of the different maps, which enables the full utilization of our high-resolution (10.5 arcsec) map at 1.1 mm and reveals unprecedentedly detailed information on the spatial distribution of dusty gas across the CMZ. There is a remarkable trend of increasing dust spectral index β, from 2.0 to 2.4, towards dense peaks in the CMZ, indicating a deficiency of large grains or a fundamental change in dust optical properties. This environmental dependence of β could have a significant impact on the determination of dust temperature in other studies. Depending on how the optical properties of dust deviate from the conventional model, dust temperatures could be underestimated by $10\!-\!50{{\ \rm per\ cent}}$ in particularly dense regions.
Constraining the cross-section of dark matter with giant radial arcs in galaxy clusters
Authors: Vega-Ferrero J , Dana J M , Diego J M , Yepes G , Cui W , Meneghetti M
Published: October 2020

We compare the statistics and morphology of giant arcs in galaxy clusters using N-body and non-radiative SPH simulations within the standard cold dark matter (CDM) model and simulations where dark matter (DM) has a non-negligible probability of interaction (parametrized by its cross-section), i.e self-interacting dark matter (SIDM). We use a ray-tracing technique to produce a statistically large number of arcs around six simulated galaxy clusters at different redshifts. Since DM is more likely to interact in colliding clusters than in relaxed clusters, and this probability of interaction is largest in denser regions, we focus our analysis on radial arcs (which trace the lensing potential in the central region better than tangential arcs) in galaxy clusters that underwent (or are undergoing) a major merger. We find that SIDM produces fewer radial arcs than standard CDM but they are on average more magnified. We also appreciate differences in the arc morphology that could be used to statistically favour one model versus the other.
Simulations of common envelope evolution in triple systems: circumstellar case
Authors: Glanz Hila , Perets Hagai B
Published: October 2020

The dynamical evolution of triple stellar systems could induce the formation of compact binaries and binary mergers. Common envelope (CE) evolution, which plays a major role in the evolution of compact binary systems, can similarly play a key role in the evolution of triples. Here, we use hydrodynamical simulations coupled with few-body dynamics to provide the first detailed models of the triple common envelope (TCE) evolution. We focus on the circumstellar case, where the envelope of an evolved giant engulfs a compact binary orbiting the giant, which then in-spirals into the core of the evolved star. Through our exploratory modelling, we find several possible outcomes of such TCE: the merger of the binary inside the third star’s envelope; the disruption of the in-spiralling binary following its plunge, leading to a chaotic triple dynamics of the stellar core and the two components of the former disrupted binary. The chaotic evolution typically leads to the in-spiral and merger of at least one of the former binary components with the core, and sometimes to the ejection of the second, or alternatively its further now-binary CE evolution. The in-spiral in TCE leads to overall slower in-spiral, larger mass ejection, and the production of more aspherical remnant, compared with a corresponding binary case of similar masses, due to the energy/momentum extraction from the inner-binary. We expect TCE to play a key role in producing various types of stellar-mergers and unique compact binary systems, and potentially induce transient electromagnetic and gravitational wave sources.
Self-modulation of fast radio bursts
Authors: Sobacchi Emanuele , Lyubarsky Yuri , Beloborodov Andrei M , Sironi Lorenzo
Published: October 2020

Fast radio bursts (FRBs) are extreme astrophysical phenomena entering the realm of non-linear optics, a field developed in laser physics. A classical non-linear effect is self-modulation. We examine the propagation of FRBs through the circumburst environment using the idealized setup of a monochromatic linearly polarized GHz wave propagating through a uniform plasma slab of density N at distance R from the source. We find that self-modulation occurs if the slab is located within a critical radius Rcrit ∼ 1017(N/102 cm−3)(L/1042 erg s−1) cm, where L is the isotropic equivalent of the FRB luminosity. Self-modulation breaks the burst into pancakes transverse to the radial direction. When R ≲ Rcrit, the transverse size of the pancakes is smaller than the Fresnel scale. The pancakes are strongly diffracted as the burst exits the slab, and interference between the pancakes produces a frequency modulation of the observed intensity with a sub-GHz bandwidth. When R ∼ Rcrit, the transverse size of the pancakes becomes comparable with the Fresnel scale, and the effect of diffraction is weaker. The observed intensity is modulated on a time-scale of 10 µm, which corresponds to the radial width of the pancakes. Our results suggest that self-modulation may cause the temporal and frequency structure observed in FRBs.
Light and colour variations of Mira variables in the Small Magellanic Cloud
Authors: Ita Yoshifusa , Menzies John W , Whitelock Patricia A , Matsunaga Noriyuki , Takayama Masaki , Nakada Yoshikazu , Tanabé Toshihiko , Feast Michael W , Nagayama Takahiro
Published: October 2020

The goal of this paper is to characterize the light variation properties of Mira variables in the Small Magellanic Cloud. We have investigated a combined optical and near-infrared multi-epoch data set of Mira variables based on our monitoring data obtained over 15 yr. Bolometric correction relations are formulated for various near-infrared colours. We find that the same bolometric correction equation holds for both the bolometricly brightest and faintest pulsation phases. Period–bolometric magnitude relations and period–colour relations were derived using time-averaged values. Phase lags between bolometric phase and optical and near-infrared phases were detected from the O-rich (the surface C/O number ratio is below unity) Mira variables, while no significant systematic lags were observed in most of the C-rich (the C/O ratio is over unity) ones. Some Miras show colour phase inversions, e.g. H–Ks at its bluest while J–H and J–Ks are at their reddest values at about the bolometricly brightest phase. Their occurrence conditions were studied but no clear direct or indirect trigger was found. A large NIR colour change unassociated with stellar pulsation was observed in Miras with long secondary periods, and its possible explanation is described.
Radical Empiricism, Neutral Monism, and the Elements of Mind
Authors: Wishon Donovan
Published: October 2020

Neutral monism is the view that both ‘mind’ and ‘matter’ are grounded in a more fundamental form of reality that is intrinsically neither mental nor material. It has often been treated as an odd fringe theory deserving of at most a footnote in the broader philosophical debates. Yet such attitudes do a grave disservice to its sophistications and significance for late nineteenth and early twentieth-century philosophy of mind and psychology. This paper sheds light on this neglected view by situating it within broader historical monist debates about the mind and bringing attention to one of its central internal disputes regarding ‘mental chemistry’. By taking a closer look at how Ernst Mach, William James, and Bertrand Russell address the question of whether and how our mental episodes are composed of more basic elements, it highlights deep differences among their conceptions of the fundamental ‘neutral stuff’ and its relations to ‘mind’ and ‘matter’.
Epigenome engineering: new technologies for precision medicine
Authors: Sgro Agustin , Blancafort Pilar
Published: October 2020

Chromatin adopts different configurations that are regulated by reversible covalent modifications, referred to as epigenetic marks. Epigenetic inhibitors have been approved for clinical use to restore epigenetic aberrations that result in silencing of tumor-suppressor genes, oncogene addictions, and enhancement of immune responses. However, these drugs suffer from major limitations, such as a lack of locus selectivity and potential toxicities. Technological advances have opened a new era of precision molecular medicine to reprogram cellular physiology. The locus-specificity of CRISPR/dCas9/12a to manipulate the epigenome is rapidly becoming a highly promising strategy for personalized medicine. This review focuses on new state-of-the-art epigenome editing approaches to modify the epigenome of neoplasms and other disease models towards a more ‘normal-like state’, having characteristics of normal tissue counterparts. We highlight biomolecular engineering methodologies to assemble, regulate, and deliver multiple epigenetic effectors that maximize the longevity of the therapeutic effect, and we discuss limitations of the platforms such as targeting efficiency and intracellular delivery for future clinical applications.
The Transporter Classification Database (TCDB): 2021 update
Authors: Saier Milton H , Reddy Vamsee S , Moreno-Hagelsieb Gabriel , Hendargo Kevin J , Zhang Yichi , Iddamsetty Vasu , Lam Katie Jing Kay , Tian Nuo , Russum Steven , Wang Jianing , Medrano-Soto Arturo
Published: October 2020

The Transporter Classification Database (TCDB; tcdb.org) is a freely accessible reference resource, which provides functional, structural, mechanistic, medical and biotechnological information about transporters from organisms of all types. TCDB is the only transport protein classification database adopted by the International Union of Biochemistry and Molecular Biology (IUBMB) and now (October 1, 2020) consists of 20 653 proteins classified in 15 528 non-redundant transport systems with 1567 tabulated 3D structures, 18 336 reference citations describing 1536 transporter families, of which 26% are members of 82 recognized superfamilies. Overall, this is an increase of over 50% since the last published update of the database in 2016. This comprehensive update of the database contents and features include (i) adoption of a chemical ontology for substrates of transporters, (ii) inclusion of new superfamilies, (iii) a domain-based characterization of transporter families for the identification of new members as well as functional and evolutionary relationships between families, (iv) development of novel software to facilitate curation and use of the database, (v) addition of new subclasses of transport systems including 11 novel types of channels and 3 types of group translocators and (vi) the inclusion of many man-made (artificial) transmembrane pores/channels and carriers.
TISCH: a comprehensive web resource enabling interactive single-cell transcriptome visualization of tumor microenvironment
Authors: Sun Dongqing , Wang Jin , Han Ya , Dong Xin , Ge Jun , Zheng Rongbin , Shi Xiaoying , Wang Binbin , Li Ziyi , Ren Pengfei , Sun Liangdong , Yan Yilv , Zhang Peng , Zhang Fan , Li Taiwen , Wang Chenfei
Published: October 2020

Cancer immunotherapy targeting co-inhibitory pathways by checkpoint blockade shows remarkable efficacy in a variety of cancer types. However, only a minority of patients respond to treatment due to the stochastic heterogeneity of tumor microenvironment (TME). Recent advances in single-cell RNA-seq technologies enabled comprehensive characterization of the immune system heterogeneity in tumors but posed computational challenges on integrating and utilizing the massive published datasets to inform immunotherapy. Here, we present Tumor Immune Single Cell Hub (TISCH, http://tisch.comp-genomics.org), a large-scale curated database that integrates single-cell transcriptomic profiles of nearly 2 million cells from 76 high-quality tumor datasets across 27 cancer types. All the data were uniformly processed with a standardized workflow, including quality control, batch effect removal, clustering, cell-type annotation, malignant cell classification, differential expression analysis and functional enrichment analysis. TISCH provides interactive gene expression visualization across multiple datasets at the single-cell level or cluster level, allowing systematic comparison between different cell-types, patients, tissue origins, treatment and response groups, and even different cancer-types. In summary, TISCH provides a user-friendly interface for systematically visualizing, searching and downloading gene expression atlas in the TME from multiple cancer types, enabling fast, flexible and comprehensive exploration of the TME.
Structural distinctions between NAD+ riboswitch domains 1 and 2 determine differential folding and ligand binding
Authors: Chen Hao , Egger Michaela , Xu Xiaochen , Flemmich Laurin , Krasheninina Olga , Sun Aiai , Micura Ronald , Ren Aiming
Published: October 2020

Riboswitches are important gene regulatory elements frequently encountered in bacterial mRNAs. The recently discovered nadA riboswitch contains two similar, tandemly arrayed aptamer domains, with the first domain possessing high affinity for nicotinamide adenine dinucleotide (NAD+). The second domain which comprises the ribosomal binding site in a putative regulatory helix, however, has withdrawn from detection of ligand-induced structural modulation thus far, and therefore, the identity of the cognate ligand and the regulation mechanism have remained unclear. Here, we report crystal structures of both riboswitch domains, each bound to NAD+. Furthermore, we demonstrate that ligand binding to domain 2 requires significantly higher concentrations of NAD+ (or ADP retaining analogs) compared to domain 1. Using a fluorescence spectroscopic approach, we further shed light on the structural features which are responsible for the different ligand affinities, and describe the Mg2+-dependent, distinct folding and pre-organization of their binding pockets. Finally, we speculate about possible scenarios for nadA RNA gene regulation as a putative two-concentration sensor module for a time-controlled signal that is primed and stalled by the gene regulation machinery at low ligand concentrations (domain 1), and finally triggers repression of translation as soon as high ligand concentrations are reached in the cell (domain 2).
OpenProt 2021: deeper functional annotation of the coding potential of eukaryotic genomes
Authors: Brunet Marie A , Lucier Jean-François , Levesque Maxime , Leblanc Sébastien , Jacques Jean-Francois , Al-Saedi Hassan R H , Guilloy Noé , Grenier Frederic , Avino Mariano , Fournier Isabelle , Salzet Michel , Ouangraoua Aïda , Scott Michelle S , Boisvert François-Michel , Roucou Xavier
Published: October 2020

OpenProt (www.openprot.org) is the first proteogenomic resource supporting a polycistronic annotation model for eukaryotic genomes. It provides a deeper annotation of open reading frames (ORFs) while mining experimental data for supporting evidence using cutting-edge algorithms. This update presents the major improvements since the initial release of OpenProt. All species support recent NCBI RefSeq and Ensembl annotations, with changes in annotations being reported in OpenProt. Using the 131 ribosome profiling datasets re-analysed by OpenProt to date, non-AUG initiation starts are reported alongside a confidence score of the initiating codon. From the 177 mass spectrometry datasets re-analysed by OpenProt to date, the unicity of the detected peptides is controlled at each implementation. Furthermore, to guide the users, detectability statistics and protein relationships (isoforms) are now reported for each protein. Finally, to foster access to deeper ORF annotation independently of one’s bioinformatics skills or computational resources, OpenProt now offers a data analysis platform. Users can submit their dataset for analysis and receive the results from the analysis by OpenProt. All data on OpenProt are freely available and downloadable for each species, the release-based format ensuring a continuous access to the data. Thus, OpenProt enables a more comprehensive annotation of eukaryotic genomes and fosters functional proteomic discoveries.