bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiwavelength study of different flaring and low-activity states of blazar 4C+21.35
Authors: Bhattacharya Debbijoy , Mohana A Krishna , Bhattacharyya Subir , Bhatt Nilay , Stalin C S 
Published: September 2020

ABSTRACT
Blazars, a class of active galactic nuclei, emit over the entire accessible electromagnetic spectrum and modelling of their broad-band spectral energy distribution (SED) is the key to constrain the underlying emission mechanisms. Here we report the results on the one-zone leptonic emission modelling carried out on the blazar 4C+21.35 using multiwavelength data spanning over the period 2008–2018. Broad-band SED modelling using γ-ray data from Fermi-Large Area Telescope, X-ray data from Swift-XRT and AstroSat, and UV–optical data from Swift-UVOT, AstroSat, and Catalina Real-Time Transient Survey was carried out at seven different epochs, including three γ-ray flaring episodes and four quiescent periods (three long-term averaged ones and one during AstroSat observing period). Our SED modelling suggests that two compact emission regions originating at a different time outside the broad-line region and moving away from the core with variation primarily in the jet electron spectra can explain the emission from the high-, moderate-, and low-activity periods. The emissions from high- and first low-activity states are likely to have originated in the first region. The moderate- and second low-activity states are likely due to the second emission region with fresh particle acceleration/injection at a later time.
Resolved star formation in the metal-poor star-forming region Magellanic Bridge C
Authors: Kalari Venu M , Rubio Monica , Saldaño Hugo P , Bolatto Alberto D 
Published: September 2020

ABSTRACT
Magellanic Bridge C (MB-C) is a metal-poor (∼1/5 Z⊙) low-density star-forming region located 59 kpc away in the Magellanic Bridge, offering a resolved view of the star formation process in conditions different to the Galaxy. From Atacama Large Millimetre Array CO (1–0) observations, we detect molecular clumps associated with candidate young stellar objects (YSOs), pre-main sequence (PMS) stars, and filamentary structure identified in far-infrared imaging. YSOs and PMS stars form in molecular gas having densities between 17 and 200 M⊙ pc−2, and have ages between ≲0.1 and 3 Myr. YSO candidates in MB -C have lower extinction than their Galactic counterparts. Otherwise, our results suggest that the properties and morphologies of molecular clumps, YSOs, and PMS stars in MB -C present no patent differences with respect to their Galactic counterparts, tentatively alluding that the bottleneck to forming stars in regions similar to MB-C is the conversion of atomic gas to molecular.
Tracing the 107 K warm–hot intergalactic medium with UV absorption lines
Authors: Fresco A Y , Péroux C , Merloni A , Hamanowicz A , Szakacs R 
Published: September 2020

ABSTRACT
Today, the majority of the cosmic baryons in the Universe are not observed directly, leading to an issue of ‘missing baryons’ at low redshift. Cosmological hydrodynamical simulations have indicated that a significant portion of them will be converted into the so-called warm–hot intergalactic medium (WHIM), with gas temperature ranging between 105 and 107 K. While the cooler phase of this gas has been observed using O vi and Ne viii absorbers at ultraviolet (UV) wavelengths, the hotter fraction detection relies mostly on observations of O vii and O viii at X-ray wavelengths. Here, we target the forbidden line of [Fe xxi] λ 1354 Å which traces 107 K gas at UV wavelengths, using more than 100 high-spectral resolution ($R\sim 49\, 000$) and high signal to noise VLT/UVES quasar spectra, corresponding to over 600 h of VLT time observations. A stack of these at the position of known Ly α absorbers lead to a 5σ limit of $\log [N\mathrm{([Fe\,{\small XXI}])]\lt }$17.4 (EWrest &lt; 22 mÅ), three orders of magnitude higher than the expected column density of the WHIM $\log [N\mathrm{([Fe\,{\small XXI}])]\lt }$14.5. This work proposes an alternative to X-ray detected 107 K WHIM tracers, by targeting faint lines at UV wavelengths from the ground benefiting from higher instrumental throughput, enhanced spectral resolution, longer exposure times, and increased number of targets. The number of quasar spectra required to reach this theoretical column density with future facilities including 4MOST, ELT/HIRES, MSE, and the Spectroscopic Telescope appears challenging at present. Probing the missing baryons is essential to constrain the accretion and feedback processes that are fundamental to galaxy formation.
Ejection of supermassive black holes and implications for merger rates in fuzzy dark matter haloes
Authors: El-Zant Amr A , Roupas Zacharias , Silk Joseph 
Published: September 2020

ABSTRACT
Fuzzy dark matter (FDM) consisting of ultralight axions has been invoked to alleviate galactic-scale problems in the cold dark matter scenario. FDM fluctuations, created via the superposition of waves, can impact the motion of a central supermassive black hole (SMBH) immersed in an FDM halo. The SMBH will undergo a random walk, induced by FDM fluctuations, that can result in its ejection from the central region. This effect is strongest in dwarf galaxies, accounting for wandering SMBHs and the low detection rate of active galactic nuclei in dwarf spheroidal galaxies. In addition, a lower bound on the allowed axion masses is inferred both for Sagitarius A* and heavier SMBH; to avoid ejection from the galactic centres, axion masses of the order of 10−22 eV or lighter are excluded. Stronger limits are inferred for merging galaxies. We find that the event rate of SMBH mergers in FDM haloes and the associated SMBH growth rates can be reduced by at least an order of magnitude.
NGTS-12b: A sub-Saturn mass transiting exoplanet in a 7.53 day orbit
Authors: Bryant Edward M , Bayliss Daniel , Nielsen Louise D , Veras Dimitri , Acton Jack S , Anderson David R , Armstrong David J , Bouchy François , Briegal Joshua T , Burleigh Matthew R , Cabrera Juan , Casewell Sarah L , Chaushev Alexander , Cooke Benjamin F , Csizmadia Szilárd , Eigmüller Philipp , Erikson Anders , Gill Samuel , Gillen Edward , Goad Michael R , Grieves Nolan , Günther Maximilian N , Henderson Beth , Hogan Aleisha , Jenkins James S , Lendl Monika , McCormac James , Moyano Maximiliano , Queloz Didier , Rauer Heike , Raynard Liam , Smith Alexis M S , Tilbrook Rosanna H , Udry Stéphane , Vines Jose I , Watson Christopher A , West Richard G , Wheatley Peter J 
Published: September 2020

ABSTRACT
We report the discovery of the transiting exoplanet NGTS-12b by the Next Generation Transit Survey (NGTS). The host star, NGTS-12, is a V = 12.38 mag star with an effective temperature of Teff = 5690 ± 130 K. NGTS-12b orbits with a period of P = 7.53 d, making it the longest period planet discovered to date by the main NGTS survey. We verify the NGTS transit signal with data extracted from the Transiting Exoplanet Survey Satellite (TESS) full-frame images, and combining the photometry with radial velocity measurements from HARPS and FEROS we determine NGTS-12b to have a mass of 0.208 ± 0.022 MJ and a radius of 1.048 ± 0.032 RJ. NGTS-12b sits on the edge of the Neptunian desert when we take the stellar properties into account, highlighting the importance of considering both the planet and star when studying the desert. The long period of NGTS-12b combined with its low density of just 0.223 ± 0.029 g cm−3 make it an attractive target for atmospheric characterization through transmission spectroscopy with a Transmission Spectroscopy Metric of 89.4.
Seed magnetic fields in turbulent small-scale dynamos
Authors: Seta Amit , Federrath Christoph 
Published: September 2020

ABSTRACTMagnetic fields in galaxies and galaxy clusters are amplified from a very weak seed value to the observed $\mu$G strengths by the turbulent dynamo. The seed magnetic field can be of primordial or astrophysical origin. The strength and structure of the seed field, on the galaxy or galaxy cluster scale, can be very different, depending on the seed-field generation mechanism. The seed field first encounters the small-scale dynamo, thus we investigate the effects of the strength and structure of the seed field on the small-scale dynamo action. Using numerical simulations of driven turbulence and considering three different seed-field configurations: (1) uniform field, (2) random field with a power-law spectrum, and (3) random field with a parabolic spectrum, we show that the strength and statistical properties of the dynamo-generated magnetic fields are independent of the details of the seed field. We demonstrate that, even when the small-scale dynamo is not active, small-scale magnetic fields can be generated and amplified linearly due to the tangling of the large-scale field. In the presence of the small-scale dynamo action, we find that any memory of the seed field for the non-linear small-scale dynamo generated magnetic fields is lost and thus, it is not possible to trace back seed-field information from the evolved magnetic fields in a turbulent medium.
Systematic use of synthetic 5′-UTR RNA structures to tune protein translation improves yield and quality of complex proteins in mammalian cell factories
Authors: Eisenhut Peter , Mebrahtu Aman , Moradi Barzadd Mona , Thalén Niklas , Klanert Gerald , Weinguny Marcus , Sandegren Anna , Su Chao , Hatton Diane , Borth Nicole , Rockberg Johan 
Published: September 2020

Abstract
Predictably regulating protein expression levels to improve recombinant protein production has become an important tool, but is still rarely applied to engineer mammalian cells. We therefore sought to set-up an easy-to-implement toolbox to facilitate fast and reliable regulation of protein expression in mammalian cells by introducing defined RNA hairpins, termed ‘regulation elements (RgE)’, in the 5′-untranslated region (UTR) to impact translation efficiency. RgEs varying in thermodynamic stability, GC-content and position were added to the 5′-UTR of a fluorescent reporter gene. Predictable translation dosage over two orders of magnitude in mammalian cell lines of hamster and human origin was confirmed by flow cytometry. Tuning heavy chain expression of an IgG with the RgEs to various levels eventually resulted in up to 3.5-fold increased titers and fewer IgG aggregates and fragments in CHO cells. Co-expression of a therapeutic Arylsulfatase-A with RgE-tuned levels of the required helper factor SUMF1 demonstrated that the maximum specific sulfatase activity was already attained at lower SUMF1 expression levels, while specific production rates steadily decreased with increasing helper expression. In summary, we show that defined 5′-UTR RNA-structures represent a valid tool to systematically tune protein expression levels in mammalian cells and eventually help to optimize recombinant protein expression.
Inhibition ofPlasmodium falciparumLysyl-tRNA synthetase via an anaplastic lymphoma kinase inhibitor
Authors: Zhou Jintong , Huang Zhenghui , Zheng Li , Hei Zhoufei , Wang Zhiyong , Yu Biao , Jiang Lubin , Wang Jing , Fang Pengfei 
Published: September 2020

AbstractAminoacyl-tRNA synthetases are attractive targets for the development of antibacterial, antifungal, antiparasitic agents and for the treatment of other human diseases. Lysyl-tRNA synthetase (LysRS) from this family has been validated as a promising target for the development of antimalarial drugs. Here, we developed a high-throughput compatible assay and screened 1215 bioactive compounds to identify Plasmodium falciparum cytoplasmic LysRS (PfLysRS) inhibitor. ASP3026, an anaplastic lymphoma kinase inhibitor that was used in clinical trials for the treatment of B-cell lymphoma and solid tumors, was identified as a novel PfLysRS inhibitor. ASP3026 suppresses the enzymatic activity of PfLysRS at nanomolar potency, which is &gt;380-fold more effective than inhibition of the human counterpart. In addition, the compound suppressed blood-stage P. falciparum growth. To understand the molecular mechanism of inhibition by ASP3026, we further solved the cocrystal structure of PfLysRS-ASP3026 at a resolution of 2.49 Å, providing clues for further optimization of the compound. Finally, primary structure-activity relationship analyses indicated that the inhibition of PfLysRS by ASP3026 is highly structure specific. This work not only provides a new chemical scaffold with good druggability for antimalarial development but also highlights the potential for repurposing kinase-inhibiting drugs to tRNA synthetase inhibitors to treat human diseases.
Structural analysis of SARS-CoV-2 genome and predictions of the human interactome
Authors: Vandelli Andrea , Monti Michele , Milanetti Edoardo , Armaos Alexandros , Rupert Jakob , Zacco Elsa , Bechara Elias , Delli Ponti Riccardo , Tartaglia Gian Gaetano 
Published: September 2020

AbstractSpecific elements of viral genomes regulate interactions within host cells. Here, we calculated the secondary structure content of &gt;2000 coronaviruses and computed &gt;100 000 human protein interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The genomic regions display different degrees of conservation. SARS-CoV-2 domain encompassing nucleotides 22 500–23 000 is conserved both at the sequence and structural level. The regions upstream and downstream, however, vary significantly. This part of the viral sequence codes for the Spike S protein that interacts with the human receptor angiotensin-converting enzyme 2 (ACE2). Thus, variability of Spike S is connected to different levels of viral entry in human cells within the population. Our predictions indicate that the 5′ end of SARS-CoV-2 is highly structured and interacts with several human proteins. The binding proteins are involved in viral RNA processing, include double-stranded RNA specific editases and ATP-dependent RNA-helicases and have strong propensity to form stress granules and phase-separated assemblies. We propose that these proteins, also implicated in viral infections such as HIV, are selectively recruited by SARS-CoV-2 genome to alter transcriptional and post-transcriptional regulation of host cells and to promote viral replication.
CovalentInDB: a comprehensive database facilitating the discovery of covalent inhibitors
Authors: Du Hongyan , Gao Junbo , Weng Gaoqi , Ding Junjie , Chai Xin , Pang Jinping , Kang Yu , Li Dan , Cao Dongsheng , Hou Tingjun 
Published: September 2020

AbstractInhibitors that form covalent bonds with their targets have traditionally been considered highly adventurous due to their potential off-target effects and toxicity concerns. However, with the clinical validation and approval of many covalent inhibitors during the past decade, design and discovery of novel covalent inhibitors have attracted increasing attention. A large amount of scattered experimental data for covalent inhibitors have been reported, but a resource by integrating the experimental information for covalent inhibitor discovery is still lacking. In this study, we presented Covalent Inhibitor Database (CovalentInDB), the largest online database that provides the structural information and experimental data for covalent inhibitors. CovalentInDB contains 4511 covalent inhibitors (including 68 approved drugs) with 57 different reactive warheads for 280 protein targets. The crystal structures of some of the proteins bound with a covalent inhibitor are provided to visualize the protein–ligand interactions around the binding site. Each covalent inhibitor is annotated with the structure, warhead, experimental bioactivity, physicochemical properties, etc. Moreover, CovalentInDB provides the covalent reaction mechanism and the corresponding experimental verification methods for each inhibitor towards its target. High-quality datasets are downloadable for users to evaluate and develop computational methods for covalent drug design. CovalentInDB is freely accessible at http://cadd.zju.edu.cn/cidb/.
Regulation and pharmacological targeting of RAD51 in cancer
Authors: Grundy McKenzie K , Buckanovich Ronald J , Bernstein Kara A 
Published: September 2020

Abstract
Regulation of homologous recombination (HR) is central for cancer prevention. However, too little HR can increase cancer incidence, whereas too much HR can drive cancer resistance to therapy. Importantly, therapeutics targeting HR deficiency have demonstrated a profound efficacy in the clinic improving patient outcomes, particularly for breast and ovarian cancer. RAD51 is central to DNA damage repair in the HR pathway. As such, understanding the function and regulation of RAD51 is essential for cancer biology. This review will focus on the role of RAD51 in cancer and beyond and how modulation of its function can be exploited as a cancer therapeutic.
DDX5 resolves R-loops at DNA double-strand breaks to promote DNA repair and avoid chromosomal deletions
Authors: Yu Zhenbao , Mersaoui Sofiane Y , Guitton-Sert Laure , Coulombe Yan , Song Jingwen , Masson Jean-Yves , Richard Stéphane 
Published: September 2020

Abstract
R-loops are three-stranded structures consisting of a DNA/RNA hybrid and a displaced DNA strand. The regulatory factors required to process this fundamental genetic structure near double-strand DNA breaks (DSBs) are not well understood. We previously reported that cellular depletion of the ATP-dependent DEAD box RNA helicase DDX5 increases R-loops genome-wide causing genomic instability. In this study, we define a pivotal role for DDX5 in clearing R-loops at or near DSBs enabling proper DNA repair to avoid aberrations such as chromosomal deletions. Remarkably, using the non-homologous end joining reporter gene (EJ5-GFP), we show that DDX5-deficient U2OS cells exhibited asymmetric end deletions on the side of the DSBs where there is overlap with a transcribed gene. Cross-linking and immunoprecipitation showed that DDX5 bound RNA transcripts near DSBs and required its helicase domain and the presence of DDX5 near DSBs was also shown by chromatin immunoprecipitation. DDX5 was excluded from DSBs in a transcription- and ATM activation-dependent manner. Using DNA/RNA immunoprecipitation, we show DDX5-deficient cells had increased R-loops near DSBs. Finally, DDX5 deficiency led to delayed exonuclease 1 and replication protein A recruitment to laser irradiation-induced DNA damage sites, resulting in homologous recombination repair defects. Our findings define a role for DDX5 in facilitating the clearance of RNA transcripts overlapping DSBs to ensure proper DNA repair.
Influence of a low-dose tacrolimus protocol on the appearance of de novo donor-specific antibodies during 7 years of follow-up after renal transplantation
Authors: Unagami Kohei , Ishida Hideki , Furusawa Miyuki , Kitajima Kumiko , Hirai Toshihito , Kakuta Yoichi , Toki Daisuke , Shimizu Tomokazu , Omoto Kazuya , Okumi Masayoshi , Nitta Kosaku , Tanabe Kazunari 
Published: September 2020

Abstract

Background
Tacrolimus (TAC) is a key immunosuppressant drug for kidney transplantation (KTx). However, the optimal serum trough level of TAC for good long-term outcomes remains unclear. This study aimed to investigate the relationship between the maintenance TAC trough level and the appearance of de novo donor-specific anti-human leukocyte antigen (HLA) antibodies (dnDSAs).

Methods
A total of 584 KTx recipients were enrolled in this study, of whom 164 developed dnDSAs during the follow-up period and 420 did not.

Results
We found no significant relationship between TAC trough level during the follow-up period and dnDSA incidence. Patients who developed dnDSAs had a significantly greater number of HLA-A/B/DR mismatches (3.4 ± 1.3 versus 2.8 ± 1.5; P &lt; 0.001), were more likely to have preformed DSAs (48.2% versus 27.1%; P &lt; 0.001) and showed poor allograft outcome.

Conclusions
There was no clear relationship between TAC trough level and dnDSA incidence for KTx recipients whose TAC trough levels were kept within the narrow range of 4–6 ng/mL during the immunosuppression maintenance period.
Brain tumors and COVID-19: the patient and caregiver experience*
Authors: Voisin Mathew R , Oliver Kathy , Farrimond Stuart , Chee Tess , Arzbaecher Jean , Kruchko Carol , Maher Mary Ellen , Tse Chris , Cashman Rosemary , Daniels Maureen , Mungoshi Christine , Lamb Sharon , Granero Anita , Lovely Mary , Baker Jenifer , Payne Sally , Zadeh Gelareh 
Published: September 2020

Abstract

Background
Since the COVID-19 pandemic began, thousands of medical procedures and appointments have been canceled or delayed. The long-term effects of these drastic measures on brain tumor patients and caregivers are unknown. The purpose of this study is to better understand how COVID-19 has affected this vulnerable population on a global scale.

Methods
An online 79-question survey was developed by the International Brain Tumour Alliance, in conjunction with the SNO COVID-19 Task Force. The survey was sent to more than 120 brain tumor charities and not-for-profits worldwide and disseminated to pediatric and adult brain tumor patients and caregivers. Responses were collected from April to May 2020 and subdivided by patient versus caregiver and by geographical region.

Results
In total, 1989 participants completed the survey from 33 countries, including 1459 patients and 530 caregivers. There were no significant differences in COVID-19 testing rates (P = .662) or positive cases for brain tumor patients between regions (P = .1068). Caregivers were significantly more anxious than patients (P ≤ .0001). Patients from the Americas were most likely to have lost their jobs due to the pandemic, practiced self-isolation, and received telehealth services (P ≤ .0001). Patients from Europe experienced the most treatment delays (P = .0031). Healthcare providers, brain tumor charities, and not-for-profits were ranked as the most trusted sources of information.

Conclusions
As a result of COVID-19, brain tumor patients and caregivers have experienced significant stress and anxiety. We must continue to provide accessible high-quality care, information, and support in the age of COVID-19.
Evolution of GA Metabolic Enzymes in Land Plants
Authors: Yoshida Hideki , Takehara Sayaka , Mori Masaki , Ordonio Reynante Lacsamana , Matsuoka Makoto 
Published: September 2020

Abstract
Gibberellins (GAs) play key roles in various developmental processes in land plants. We studied the evolutionary trends of GA metabolic enzymes through a comprehensive homology search and phylogenetic analyses from bryophytes to angiosperms. Our analyses suggest that, in the process of evolution, plants were able to acquire GA metabolic enzymes in a stepwise manner and that the enzymes had rapidly diversified in angiosperms. As a good example of their rapid diversification, we focused on the GA-deactivating enzyme, GA 2-oxidase (GA2ox). Although the establishment of a GA system first occurred in lycophytes, its inactivation system mediated by GA2oxs was established at a much later time: the rise of gymnosperms and the rise of angiosperms through C19-GA2ox and C20-GA2ox development, respectively, as supported by the results of our direct examination of their enzymatic activities in vitro. Based on these comprehensive studies of GA metabolic enzymes, we discuss here that angiosperms rapidly developed a sophisticated system to delicately control the level of active GAs by increasing their copy numbers for their survival under different challenging environments.