bluuebunny/crossref_metadata_2025 huggingface dataset:
A Preliminary Study on The Improvement of Proper Motions For HipparcosStars by Using Photographic Plates
Authors: Jin W. , Tang Z. , Li J. , Wang S.
Published: June 2021

The 3435 photographic plates, which were obtained by using the 40cm astrograph at Zô-Sè station of Shanghai Observatory during 1901-1993, have been accumulated for observing open clusters, extragalatic nebulas, radio stars and variable stars etc. These plates cover 764 unoverlapping regions (2°.3 * 1°.7) on the sky. Most of the plates distribute along the ecliptic, about 10 000 Hipparcos stars, 27 000 PPM stars and 500 FK5 stars are included in these regions. Among these plates, there are 2718 plates having two observing epochs, and they cover 359 different regions; there are 142 and 92 regions where the intervals of two epochs are about 50 and 70 years, and the numbers of plates in these regions are about1494 and 1023 respectively. About 372 plates were photographed before 1949,which play an important action for improvement of proper motions of Hipparcos stars. Four methods used to improve the proper motions for Hipparcos stars were designed. If the 2718 plates mentioned above having two epochs were used for improvement of the proper motions of Hipparcos stars, the stellar number of 299, 1378, 377 and 1664 corresponding to the four methods will be obtained with final precision 0.7 mas/yr. If supplementary observations are made in 1997, the stellar number of 494, 2431, 1534 and 2899 will be obtained with the same precision.
Check on JPL DExxx Using Hipparcos and Tycho Observations
Authors: Morrison L.V. , Hestroffer D. , Taylor D.B. , Van Leeuwen F.
Published: June 2021

Obervations of the positions of Europa (J2) and Titan (S6) by Hipparcos, and Ganymede (J3) and Callisto (J4) by Tycho are analysed to give checks on the latest JPL ephemerides of the planets Jupiter and Saturn.

The observed positions of the satellites are compared with DExxx, using the G5 theory of the Galilean satellites and D.B. Taylor’s theory ofTitan to calculate their offsets from the barycentres of the two systems.

Each Tycho observation can be resolved into RA and Dec because the slitsare inclined to the scan direction. Hipparcos, on the other hand, which hasa uni-directional scan, requires a minimum of two (preferably orthogonal) scans to resolve the offsets into RA and Dec. We have subdivided the Hipparcos observations in time and solved for corrections to DExxx at several epochs over the period of the mission.

The Hipparcos observations of J2, and Tycho of J3 and J4, put tight constraints on the orbit of Jupiter, and agree closely with the series of ground-based observations made by the Carlsberg Meridian Telescope. In particular, they help to resolve a problem in the declination of Jupiter associated with larger than expected errors in the tracking of Voyager II and radio positions from the VLA.
Helium, [Fe/H] Abundances and the HR (Log TEFF, MBol) Diagram With Hipparcos Data of The Four Nearest Open Clusters: Hyades, Coma Berenices, The Pleiades and Praesepe
Authors: de Strobel G. Cayrel , Cayrel R. , Lebreton Y.
Published: June 2021

After having studied in great detail the observational HR diagram (log Teff, Mbol) composed by 40 main sequence stars of the Hyades (Perryman et al.,1997, A&A., in press), we have tried to apply the same method to the observational main sequences of the three next nearest open clusters: Coma Berenices, the Pleiades, and Praesepe. This method consists in comparing the observational main sequence of the clusters with a grid of theoretical ZAMSs. The stars composing the observational main sequences had to have reliable absolute bolometric magnitudes, coming all from individual Hipparcos parallaxes, precise bolometric corrections, effective temperatures and metal abundances from high resolution detailed spectroscopic analyses. If we assume, following the work by Fernandez et al. (1996, A&A,311,127), that the mixing-lenth parameter is solar, the position of a theoretical ZAMS, in the (log Teff, Mbol) plane, computed with given input physics, only depends on two free parameters: the He content Y by mass, and the metallicity Z by mass. If effective temperature and metallicity of the constituting stars of the 4 clusters are previously known by means of detailed analyses, one can deduce their helium abundances by means of an appropriate grid of theoretical ZAMS’s. The comparison between the empirical (log Teff, Mbol) main sequence of the Hyades and the computed ZAMS corresponding to the observed metallicity Z of the Hyades (Z= 0.0240 ± 0.0085) gives a He abundance for the Hyades, Y= 0.26 ± 0.02. Our interpretation, concerning the
observational position of the main sequence of the three nearest clusters after the Hyades, is still under way and appears to be greatly more difficult than for the Hyades. For the moment we can say that:

‒ The 15 dwarfs analysed in detailed in Coma have a solar metallicity: [Fe/H] = -0.05 ± 0.06. However, their observational main sequence fit better with the Hyades ZAMS.

‒ The mean metallicity of 13 Pleiades dwarfs analysed in detail is solar. A metal deficient and He normal ZAMS would fit better. But, a warning for absorption in the Pleiades has to be recalled.

‒ The upper main sequence of Praesepe, (the more distant cluster: 180 pc) composed by 11 stars, analysed in detail, is the one which has the best fit with the Hyades ZAMS. The deduced ‘turnoff age’ of the cluster is slightly higher than that of the Hyades: 0.8 Gyr instead of 0.63 Gyr.
The Contribution of Hipparcos to the Study of the Stellar Metal-Rich Population in the Solar Neighbourhood
Authors: de Strobel G. Cayrel , Soubiran C. , Lebreton Y.
Published: June 2021

The ‘1996 Edition’ of the Catalogue of [Fe/H] determinations by Cayrel de Strobel et al. (1997, A&A S 124,1) and two recent papers by Castro et al. (1997, AJ Vol.114, N.1) and by Feltzing and Gustafsson (A&A in press) have made possible to increase in the theoretical HR diagram (log Teff, Mbol the number of SMR stars.

The SMR Stars of this new enlarged sample had to have reliable absolute magnitudes, coming all from Hipparcos parallaxes, precise bolometric corrections, effective temperatures and metal abundances from high resolution detailed spectroscopic analyses.

With the help of an appropriate grid of isochrones computed by Lebreton (1997, Perryman et al. A&A, in press), ‘turn-off ages’could then be attributed to the slightly evolved stars (subgiants) of the sample. The (log Teff, Mbol) diagram constituted by the new sample of SMR stars, shows that the conclusions in a former paper by Cayrel de Strobel (1987, A&AJ 8,141) remain valid: the SMR stars areold stars in spite of their higher than solar metallicity. The result, that metal-rich stars were in the mean old stars, was interpreted in the 1987 paper as due to a more chemical uniformity of the nowadays interstellar medium of the Galaxy with respect of the older much more active interstellar medium.
Astrometric and Photometric Utilization of Dispersed Fringes From a Space Interferometry Mission
Authors: Scholz R.-D. , Hirte S. , Bastian U. , RÖser S.
Published: June 2021

Dispersed interferometer fringes as a new type of signal are currently under discussion for several space interferometry mission projects (GAIA, FAME, DIVA). The dispersed fringes are directly recorded by CCD mosaics whichare operated in drift-scan mode on board a continuously rotating satellite. They allow combined astrometric (perpendicular to the fringes, i.e. in the direction of the drift scan) and spectro-photometric measurements (in the direction of the dispersion of the fringes, i.e. perpendicular to the drift scan). We have simulated polychromatic dispersed fringe patterns of stars with known spectra. The specific instrument parameters used for the simulation are those envisaged for the DIVA instrument, with realistic assumptions on various noise contributions. The results can be scaled to GAIA and FAME instrument parameters. We have investigated simple algorithms which can be implemented in an on-board data reduction and used for the real-time attitude determination with bright and single stars. On the preliminary basis of 100 simulations per star of a given magnitude and spectral type, we have obtained first estimates of the achievable accuracy of the astrometric measurements and of the location of the photometric zero point λo.
Historical national accounting and dating the Great Divergence
Authors: Broadberry Stephen
Published: June 2021

By offering a particular interpretation of the new evidence on historical national accounting, Goldstone argues for a return to the Pomeranz (2000) version of the Great Divergence, beginning only after 1800. However, he fails to distinguish between two very different patterns of pre-industrial growth: (1) alternating episodes of growing and shrinking without any long-term trend in per capita income and (2) episodes of growing interspersed by per capita incomes remaining on a plateau, so that per capita GDP trends upwards over the long run. The latter dynamic pattern occurred in Britain and Holland from the mid-fourteenth century, so that Northwest Europe first edged ahead of the Yangzi delta region of China in the eighteenth century.
Contribution of New Particle Formation to Cloud Condensation Nuclei Activity and its Controlling Factors in a Mountain Region of Inland China
Authors: Cai M. F. , Liang B. L. , Sun Q. B. , Zhou S. Z. , Yuan B. , Shao M. , Tan H. B. , Xu Y. S. , Ren L. H. , Zhao J.
Published: June 2021

A 1‐month field campaign (May 29–June 29, 2018) was conducted at a mountain site (862 m above sea level) on the Wudang Mountains in China. The particle number size distribution (3–400 nm), size‐resolved cloud condensation nuclei (CCN, at 0.2% and 0.8% SS), and nonrefractory PM1 chemical composition were measured, respectively. The occurrence of the three chosen new particle formation (NPF) events (June 4, 7, and 11) was facilitated by southwest or west winds with a speed of about 3–4 m s−1. The hygroscopicity parameter () value of newly grown particles varied in a wide range (0.25–0.8) during the events, leading to large uncertainties (−98% to 38%) on the NCCN prediction compared to the campaign. During growth of the newly formed particles for the three events, condensation of sulfuric acid vapor accounts for 14%–42%, 2%–8%, and 3%–9%, respectively, indicating that organic vapors may play an important role in particle growth. For plume‐type events with rapid growth, the observed high CCN activity (i.e., June 7 event) may be explained by the contribution of amines and depression of surface tension in the presence of organic surfactants during particle growth. Our study demonstrates that the contribution of NPF to CCN concentration is modulated by many key factors including growth rate, hygroscopicity, concentrations of new particles and preexisting particles, and variation of those factors from one event to another leads to large uncertainties on the CCN prediction.
The Wildfire One-Two: First the Burn, Then the Landslides
Authors: Sidder Aaron
Published: June 2021

Severe wildfires strip away plant cover and reduce the soil’s ability to hold water. A new study develops a model to better understand landslide risk following a burn.
Reducing Planetary Health Risks Through Short‐Lived Climate Forcer Mitigation
Authors: Zheng Yiqi , Unger Nadine
Published: June 2021

Global air pollution and climate change are major threats to planetary health. These threats are strongly linked through the short‐lived climate forcers (SLCFs); ozone (O3), aerosols, and methane (CH4). Understanding the impacts of ambitious SLCF mitigation in different source emission sectors on planetary health indicators can help prioritize international air pollution control strategies. A global Earth system model is applied to quantify the impacts of idealized 50% sustained reductions in year 2005 emissions in the eight largest global anthropogenic source sectors on the SLCFs and three indicators of planetary health: global mean surface air temperature change (∆GSAT), avoided PM2.5‐related premature mortalities and gross primary productivity (GPP). The model represents fully coupled atmospheric chemistry, aerosols, land ecosystems and climate, and includes dynamic CH4. Avoided global warming is modest, with largest impacts from 50% cuts in domestic (−0.085 K), agriculture (−0.034 K), and waste/landfill (−0.033 K). The 50% cuts in energy, domestic, and agriculture sector emissions offer the largest opportunities to mitigate global PM2.5‐related health risk at around 5%–7% each. Such small global impacts underline the challenges ahead in achieving the World Health Organization aspirational goal of a 2/3 reduction in the number of deaths from air pollution by 2030. Uncertainty due to natural climate variability in PM2.5 is an important underplayed dimension in global health risk assessment that can vastly exceed uncertainty due to the concentration‐response functions at the large regional scale. Globally, cuts to agriculture and domestic sector emissions are the most attractive targets to achieve climate and health co‐benefits through SLCF mitigation.
The Release of Inertial Instability Near an Idealized Zonal Jet
Authors: Thompson Callum F. , Schultz David M.
Published: June 2021

Inertial instability is a hydrodynamic instability that occurs in strong anticyclonic flow and is typically diagnosed by negative absolute vorticity in the Northern Hemisphere. As such, inertial instability is often observed on the anticyclonic‐shear side of jet streams, yet the release of the instability in this environment is still poorly understood. We construct an idealized midlatitude zonal jet and perform two experiments: one control simulation with no inertial instability and one experiment with inertial instability simulating its release. We find that the release of the instability results in meridional wind perturbations of up to 7 m s−1 over 200 km that persist for several days, in addition to radiating inertia–gravity waves several hundreds of kilometers away from the unstable region. Furthermore, these perturbations instigate light–moderate occurrences of clear‐air turbulence around the unstable region that persist for up to 12 h.
In‐Situ Measurements of Electron Temperature and Density in Mars' Dayside Ionosphere
Authors: Ergun R. E. , Andersson L. A. , Fowler C. M. , Thaller S. A. , Yelle R. V.
Published: June 2021

We present dayside electron temperature (Te) and density altitude profiles at Mars from MAVEN satellite deep‐dip orbits. The data are after recalibration of the Langmuir Probe and Waves instrument that results in reduced uncertainties to as low as ±82°K. At MAVEN's lowest altitudes, (∼120–∼135 km), the measured values of Te are, after uncertainties, higher than those predicted by several modeling efforts. To better understand this discrepancy, we perform a basic heat‐transfer analysis for two specific dayside deep dips. The analysis supports that CO2 excitation/de‐excitation of its lowest‐energy vibrational states dominates energy transfer to and from electrons. We hypothesize that the discrepancy between the measured and modeled Te is due to (a) the coupling of Te to CO2 vibrational temperatures combined with a non‐LTE (local thermal equilibrium) excess of excited CO2 and/or (b) a non‐Maxwellian electron distribution that moderates CO2 cooling.
Circular RNA hsa_circ_0110389 promotes gastric cancer progression through upregulating SORT1 via sponging miR-127-5p and miR-136-5p
Authors: Liang Min , Yao Wenxia , Shi Boyun , Zhu Xiongjie , Cai Rui , Yu Zhongjian , Guo Weihong , Wang Huaiming , Dong Zhijie , Lin Mingzhen , Zhou Xinke , Zheng Yanfang
Published: June 2021

Increasing studies have found that circular RNAs (circRNAs) are aberrantly expressed and play important roles in the occurrence and development of human cancers. However, the function of circRNAs on environmental carcinogen-induced gastric cancer (GC) progression remains poorly elucidated. In the present study, hsa_circ_0110389 was identified as a novel upregulated circRNA in malignant-transformed GC cells through RNA-seq, and subsequent quantitative real-time PCR verified that hsa_circ_0110389 was significantly increased in GC tissues and cells. High hsa_circ_0110389 expression associates with advanced stages of GC and predicts poor prognosis. Knockdown and overexpression assays demonstrated that hsa_circ_0110389 regulates proliferation, migration, and invasion of GC cells in vitro. In addition, hsa_circ_0110389 was identified to sponge both miR-127-5p and miR-136-5p and SORT1 was validated as a direct target of miR-127-5p and miR-136-5p through multiple mechanism assays; moreover, hsa_circ_0110389 sponged miR-127-5p/miR-136-5p to upregulate SORT1 expression and hsa_circ_0110389 promoted GC progression through the miR-127-5p/miR-136-5p–SORT1 pathway. Finally, hsa_circ_0110389 knockdown suppressed GC growth in vivo. Taken together, our findings firstly identify the role of hsa_circ_0110389 in GC progression, which is through miR-127-5p/miR-136-5p–SORT1 pathway, and our study provides novel insight for the identification of diagnostic/prognostic biomarkers and therapeutic targets for GC.
Inhibition of Polo-like kinase 4 induces mitotic defects and DNA damage in diffuse large B-cell lymphoma
Authors: Zhao Yi , Yang Juan , Liu Jiarui , Cai Yiqing , Han Yang , Hu Shunfeng , Ren Shuai , Zhou Xiangxiang , Wang Xin
Published: June 2021

Polo-like kinase 4 (PLK4), a key regulator of centriole biogenesis, has recently been shown to play key roles in tumorigenesis. Blocking PLK4 expression by interference or targeted drugs exhibits attractive potential in improving the efficacy of chemotherapy. Nevertheless, the role of PLK4 in diffuse large B-cell lymphoma (DLBCL) is still undefined. In this study, we discover that PLK4 is a potential target for the treatment of DLBCL, and demonstrate the efficacy of a PLK4 inhibitor when used in combination with doxorubicin. Pharmaceutical inhibition of PLK4 with CFI-400945 inhibited DLBCL cell proliferation and induced apoptotic cell death. The anti-tumor effects were accompanied by mitotic defects, including polyploidy and cytokinesis failure. Activation of p53 and Hippo/YAP tumor suppressor signaling pathway was identified as the potential mechanisms driving CFI-400945 activity. Moreover, CFI-400945 treatment resulted in activation of DNA damage response. Combining CFI-400945 with doxorubicin markedly delayed tumor progression in DLBCL xenografts. Finally, PLK4 was increased in primary DLBCL tissues and cell lines. High levels of PLK4 expression were associated with poor survival in the patients receiving CHOP-based treatment, implicating PLK4 as a predictive biomarker of DLBCL chemosensitivity. These results provide the therapeutic potential of CFI-400945 both as monotherapy or in combination with doxorubicin for the treatment of DLBCL.
In-silico trial of intracranial flow diverters replicates and expands insights from conventional clinical trials
Authors: Sarrami-Foroushani Ali , Lassila Toni , MacRaild Michael , Asquith Joshua , Roes Kit C. B. , Byrne James V. , Frangi Alejandro F.
Published: June 2021

The cost of clinical trials is ever-increasing. In-silico trials rely on virtual populations and interventions simulated using patient-specific models and may offer a solution to lower these costs. We present the flow diverter performance assessment (FD-PASS) in-silico trial, which models the treatment of intracranial aneurysms in 164 virtual patients with 82 distinct anatomies with a flow-diverting stent, using computational fluid dynamics to quantify post-treatment flow reduction. The predicted FD-PASS flow-diversion success rates replicate the values previously reported in three clinical trials. The in-silico approach allows broader investigation of factors associated with insufficient flow reduction than feasible in a conventional trial. Our findings demonstrate that in-silico trials of endovascular medical devices can: (i) replicate findings of conventional clinical trials, and (ii) perform virtual experiments and sub-group analyses that are difficult or impossible in conventional trials to discover new insights on treatment failure, e.g. in the presence of side-branches or hypertension.
AsCas12a ultra nuclease facilitates the rapid generation of therapeutic cell medicines
Authors: Zhang Liyang , Zuris John A. , Viswanathan Ramya , Edelstein Jasmine N. , Turk Rolf , Thommandru Bernice , Rube H. Tomas , Glenn Steve E. , Collingwood Michael A. , Bode Nicole M. , Beaudoin Sarah F. , Lele Swarali , Scott Sean N. , Wasko Kevin M. , Sexton Steven , Borges Christopher M. , Schubert Mollie S. , Kurgan Gavin L. , McNeill Matthew S. , Fernandez Cecilia A. , Myer Vic E. , Morgan Richard A. , Behlke Mark A. , Vakulskas Christopher A.
Published: June 2021

Though AsCas12a fills a crucial gap in the current genome editing toolbox, it exhibits relatively poor editing efficiency, restricting its overall utility. Here we isolate an engineered variant, “AsCas12a Ultra”, that increased editing efficiency to nearly 100% at all sites examined in HSPCs, iPSCs, T cells, and NK cells. We show that AsCas12a Ultra maintains high on-target specificity thereby mitigating the risk for off-target editing and making it ideal for complex therapeutic genome editing applications. We achieved simultaneous targeting of three clinically relevant genes in T cells at >90% efficiency and demonstrated transgene knock-in efficiencies of up to 60%. We demonstrate site-specific knock-in of a CAR in NK cells, which afforded enhanced anti-tumor NK cell recognition, potentially enabling the next generation of allogeneic cell-based therapies in oncology. AsCas12a Ultra is an advanced CRISPR nuclease with significant advantages in basic research and in the production of gene edited cell medicines.
Transition-metal-free allylation of 2-azaallyls with allyl ethers through polar and radical mechanisms
Authors: Deng Guogang , Duan Shengzu , Wang Jing , Chen Zhuo , Liu Tongqi , Chen Wen , Zhang Hongbin , Yang Xiaodong , Walsh Patrick J.
Published: June 2021

Allylation of nucleophiles with highly reactive electrophiles like allyl halides can be conducted without metal catalysts. Less reactive electrophiles, such as allyl esters and carbonates, usually require a transition metal catalyst to facilitate the allylation. Herein, we report a unique transition-metal-free allylation strategy with allyl ether electrophiles. Reaction of a host of allyl ethers with 2-azaallyl anions delivers valuable homoallylic amine derivatives (up to 92%), which are significant in the pharmaceutical industry. Interestingly, no deprotonative isomerization or cyclization of the products were observed. The potential synthetic utility and ease of operation is demonstrated by a gram scale telescoped preparation of a homoallylic amine. In addition, mechanistic studies provide insight into these C(sp3)–C(sp3) bond-forming reactions.
Converting copper sulfide to copper with surface sulfur for electrocatalytic alkyne semi-hydrogenation with water
Authors: Wu Yongmeng , Liu Cuibo , Wang Changhong , Yu Yifu , Shi Yanmei , Zhang Bin
Published: June 2021

Electrocatalytic alkyne semi-hydrogenation to alkenes with water as the hydrogen source using a low-cost noble-metal-free catalyst is highly desirable but challenging because of their over-hydrogenation to undesired alkanes. Here, we propose that an ideal catalyst should have the appropriate binding energy with active atomic hydrogen (H*) from water electrolysis and a weaker adsorption with an alkene, thus promoting alkyne semi-hydrogenation and avoiding over-hydrogenation. So, surface sulfur-doped and -adsorbed low-coordinated copper nanowire sponges are designedly synthesized via in situ electroreduction of copper sulfide and enable electrocatalytic alkyne semi-hydrogenation with over 99% selectivity using water as the hydrogen source, outperforming a copper counterpart without surface sulfur. Sulfur anion-hydrated cation (S2−-K+(H2O)n) networks between the surface adsorbed S2− and K+ in the KOH electrolyte boost the production of active H* from water electrolysis. And the trace doping of sulfur weakens the alkene adsorption, avoiding over-hydrogenation. Our catalyst also shows wide substrate scopes, up to 99% alkenes selectivity, good reducible groups compatibility, and easily synthesized deuterated alkenes, highlighting the promising potential of this method.
Optical force mapping at the single-nanometre scale
Authors: Yamanishi Junsuke , Yamane Hidemasa , Naitoh Yoshitaka , Li Yan Jun , Yokoshi Nobuhiko , Kameyama Tatsuya , Koyama Seiya , Torimoto Tsukasa , Ishihara Hajime , Sugawara Yasuhiro
Published: June 2021

Three-dimensional (3D) information of the optical response in the nanometre scale is important in the field of nanophotonics science. Using photoinduced force microscopy (PiFM), we can visualize the nano-scale optical field using the optical gradient force between the tip and sample. Here, we demonstrate 3D photoinduced force field visualization around a quantum dot in the single-nanometre spatial resolution with heterodyne frequency modulation technique, using which, the effect of the photothermal expansion of the tip and sample in the ultra-high vacuum condition can be avoided. The obtained 3D mapping shows the spatially localized photoinduced interaction potential and force field vectors in the single nano-scale for composite quantum dots with photocatalytic activity. Furthermore, the spatial resolution of PiFM imaging achieved is ~0.7 nm. The single-nanometer scale photoinduced field visualization is crucial for applications such as photo catalysts, optical functional devices, and optical manipulation.
Room-temperature oxygen vacancy migration induced reversible phase transformation during the anelastic deformation in CuO
Authors: Li Lei , Chen Guoxujia , Zheng He , Meng Weiwei , Jia Shuangfeng , Zhao Ligong , Zhao Peili , Zhang Ying , Huang Shuangshuang , Huang Tianlong , Wang Jianbo
Published: June 2021

From the mechanical perspectives, the influence of point defects is generally considered at high temperature, especially when the creep deformation dominates. Here, we show the stress-induced reversible oxygen vacancy migration in CuO nanowires at room temperature, causing the unanticipated anelastic deformation. The anelastic strain is associated with the nucleation of oxygen-deficient CuOx phase, which gradually transforms back to CuO after stress releasing, leading to the gradual recovery of the nanowire shape. Detailed analysis reveals an oxygen deficient metastable CuOx phase that has been overlooked in the literatures. Both theoretical and experimental investigations faithfully predict the oxygen vacancy diffusion pathways in CuO. Our finding facilitates a better understanding of the complicated mechanical behaviors in materials, which could also be relevant across multiple scientific disciplines, such as high-temperature superconductivity and solid-state chemistry in Cu-O compounds, etc.
A high-throughput screen for TMPRSS2 expression identifies FDA-approved compounds that can limit SARS-CoV-2 entry
Authors: Chen Yanwen , Lear Travis B. , Evankovich John W. , Larsen Mads B. , Lin Bo , Alfaras Irene , Kennerdell Jason R. , Salminen Laura , Camarco Daniel P. , Lockwood Karina C. , Tuncer Ferhan , Liu Jie , Myerburg Michael M. , McDyer John F. , Liu Yuan , Finkel Toren , Chen Bill B.
Published: June 2021

SARS-CoV-2 (2019-nCoV) is the pathogenic coronavirus responsible for the global pandemic of COVID-19 disease. The Spike (S) protein of SARS-CoV-2 attaches to host lung epithelial cells through the cell surface receptor ACE2, a process dependent on host proteases including TMPRSS2. Here, we identify small molecules that reduce surface expression of TMPRSS2 using a library of 2,560 FDA-approved or current clinical trial compounds. We identify homoharringtonine and halofuginone as the most attractive agents, reducing endogenous TMPRSS2 expression at sub-micromolar concentrations. These effects appear to be mediated by a drug-induced alteration in TMPRSS2 protein stability. We further demonstrate that halofuginone modulates TMPRSS2 levels through proteasomal-mediated degradation that involves the E3 ubiquitin ligase component DDB1- and CUL4-associated factor 1 (DCAF1). Finally, cells exposed to homoharringtonine and halofuginone, at concentrations of drug known to be achievable in human plasma, demonstrate marked resistance to SARS-CoV-2 infection in both live and pseudoviral in vitro models. Given the safety and pharmacokinetic data already available for the compounds identified in our screen, these results should help expedite the rational design of human clinical trials designed to combat active COVID-19 infection.
Oxoammonium salts are catalysing efficient and selective halogenation of olefins, alkynes and aromatics
Authors: Wang Weijin , Li Xinyao , Yang Xiaoxue , Ai Lingsheng , Gong Zhiwen , Jiao Ning , Song Song
Published: June 2021

Electrophilic halogenation reactions have been a reliable approach to accessing organohalides. During the past decades, various catalytic systems have been developed for the activation of haleniums. However, there is still a short of effective catalysts, which could cover various halogenation reactions and broad scope of unsaturated compounds. Herein, TEMPO (2,2,6,6-tetramethylpiperidine nitroxide) and its derivatives are disclosed as active catalysts for electrophilic halogenation of olefins, alkynes, and aromatics. These catalysts are stable, readily available, and reactive enough to activate haleniums including Br+, I+ and even Cl+ reagents. This catalytic system is applicable to various halogenations including haloarylation of olefins or dibromination of alkynes, which were rarely realized in previous Lewis base catalysis or Lewis acid catalysis. The high catalytic ability is attributed to a synergistic activation model of electrophilic halogenating reagents, where the carbonyl group and the halogen atom are both activated by present TEMPO catalysis.
A natural riboswitch scaffold with self-methylation activity
Authors: Flemmich Laurin , Heel Sarah , Moreno Sarah , Breuker Kathrin , Micura Ronald
Published: June 2021

Methylation is a prevalent post-transcriptional modification encountered in coding and non-coding RNA. For RNA methylation, cells use methyltransferases and small organic substances as methyl-group donors, such as S-adenosylmethionine (SAM). SAM and other nucleotide-derived cofactors are viewed as evolutionary leftovers from an RNA world, in which riboswitches have regulated, and ribozymes have catalyzed essential metabolic reactions. Here, we disclose the thus far unrecognized direct link between a present-day riboswitch and its inherent reactivity for site-specific methylation. The key is O6-methyl pre-queuosine (m6preQ1), a potentially prebiotic nucleobase which is recognized by the native aptamer of a preQ1 class I riboswitch. Upon binding, the transfer of the ligand’s methyl group to a specific cytidine occurs, installing 3-methylcytidine (m3C) in the RNA pocket under release of pre-queuosine (preQ1). Our finding suggests that nucleic acid-mediated methylation is an ancient mechanism that has offered an early path for RNA epigenetics prior to the evolution of protein methyltransferases. Furthermore, our findings may pave the way for the development of riboswitch-descending methylation tools based on rational design as a powerful alternative to in vitro selection approaches.
Electrochemical activation of C–H by electron-deficient W2C nanocrystals for simultaneous alkoxylation and hydrogen evolution
Authors: Lin Xiu , Zhang Shi-Nan , Xu Dong , Zhang Jun-Jun , Lin Yun-Xiao , Zhai Guang-Yao , Su Hui , Xue Zhong-Hua , Liu Xi , Antonietti Markus , Chen Jie-Sheng , Li Xin-Hao
Published: June 2021

The activation of C–H bonds is a central challenge in organic chemistry and usually a key step for the retro-synthesis of functional natural products due to the high chemical stability of C–H bonds. Electrochemical methods are a powerful alternative for C–H activation, but this approach usually requires high overpotential and homogeneous mediators. Here, we design electron-deficient W2C nanocrystal-based electrodes to boost the heterogeneous activation of C–H bonds under mild conditions via an additive-free, purely heterogeneous electrocatalytic strategy. The electron density of W2C nanocrystals is tuned by constructing Schottky heterojunctions with nitrogen-doped carbon support to facilitate the preadsorption and activation of benzylic C–H bonds of ethylbenzene on the W2C surface, enabling a high turnover frequency (18.8 h−1) at a comparably low work potential (2 V versus SCE). The pronounced electron deficiency of the W2C nanocatalysts substantially facilitates the direct deprotonation process to ensure electrode durability without self-oxidation. The efficient oxidation process also boosts the balancing hydrogen production from as-formed protons on the cathode by a factor of 10 compared to an inert reference electrode. The whole process meets the requirements of atomic economy and electric energy utilization in terms of sustainable chemical synthesis.
Co-benefits of protecting mangroves for biodiversity conservation and carbon storage
Authors: Rahman Md Mizanur , Zimmer Martin , Ahmed Imran , Donato Daniel , Kanzaki Mamoru , Xu Ming
Published: June 2021

The conservation of ecosystems and their biodiversity has numerous co-benefits, both for local societies and for humankind worldwide. While the co-benefit of climate change mitigation through so called blue carbon storage in coastal ecosystems has raised increasing interest in mangroves, the relevance of multifaceted biodiversity as a driver of carbon storage remains unclear. Sediment salinity, taxonomic diversity, functional diversity and functional distinctiveness together explain 69%, 69%, 27% and 61% of the variation in above- and belowground plant biomass carbon, sediment organic carbon and total ecosystem carbon storage, respectively, in the Sundarbans Reserved Forest. Functional distinctiveness had the strongest explanatory power for carbon storage, indicating that blue carbon in mangroves is driven by the functional composition of diverse tree assemblages. Protecting and restoring mangrove biodiversity with site-specific dominant species and other species of contrasting functional traits would have the co-benefit of maximizing their capacity for climate change mitigation through increased carbon storage.
A stochastic quantum program synthesis framework based on Bayesian optimization
Authors: Xiao Yao , Nazarian Shahin , Bogdan Paul
Published: June 2021

Quantum computers and algorithms can offer exponential performance improvement over some NP-complete programs which cannot be run efficiently through a Von Neumann computing approach. In this paper, we present BayeSyn, which utilizes an enhanced stochastic program synthesis and Bayesian optimization to automatically generate quantum programs from high-level languages subject to certain constraints. We find that stochastic synthesis can comparatively and efficiently generate a program with a lower cost from the high dimensional program space. We also realize that hyperparameters used in stochastic synthesis play a significant role in determining the optimal program. Therefore, BayeSyn utilizes Bayesian optimization to fine-tune such parameters to generate a suitable quantum program.
The study of differences by region and type of gambling on the degree of gambling addiction in Japan
Authors: Hayano Shingo , Dong Ran , Miyata Yoshie , Kasuga Sakutaro
Published: June 2021

We conducted an online national survey using the South Oaks Gambling Screen (SOGS) on 42,880 people in Japan to identify gambling addiction prevalence differences with regard to gambling type and region. This study included 14,780 individuals (valid responses) who engaged in gambling activities in the past year. There was a large difference in mean SOGS score by gambling type: public gambling and casinos score ≈ 4.0, whereas lotteries (including numbers, etc.) ≈ 1.43. SOGS scores were much higher for those who participated in more than one gambling type than for those who participated in only one type. Regional differences in SOGS scores were also confirmed, with more populous prefectures having lower and less populous having higher SOGS scores. Integrating SOGS scores with existing data concerning hobbies and recreational behaviors across regions indicated that regions characterized by lower SOGS scores were also characterized by greater activity for hobbies and recreational behaviors.
Influence of prokaryotic microorganisms on initial soil formation along a glacier forefield on King George Island, maritime Antarctica
Authors: Krauze Patryk , Wagner Dirk , Yang Sizhong , Spinola Diogo , Kühn Peter
Published: June 2021

Compared to the 1970s, the edge of the Ecology Glacier on King George Island, maritime Antarctica, is positioned more than 500 m inwards, exposing a large area of new terrain to soil-forming processes and periglacial climate for more than 40 years. To gain information on the state of soil formation and its interplay with microbial activity, three hyperskeletic Cryosols (vegetation cover of 0–80%) deglaciated after 1979 in the foreland of the Ecology Glacier and a Cambic Cryosol (vegetation cover of 100%) distal to the lateral moraine deglaciated before 1956 were investigated by combining soil chemical and microbiological methods. In the upper part of all soils, a decrease in soil pH was observed, but only the Cambic Cryosol showed a clear direction of pedogenic and weathering processes, such as initial silicate weathering indicated by a decreasing Chemical Index of Alteration with depth. Differences in the development of these initial soils could be related to different microbial community compositions and vegetation coverage, despite the short distance among them. We observed—decreasing with depth—the highest bacterial abundances and microbial diversity at vegetated sites. Multiple clusters of abundant amplicon sequence variants were found depending on the site-specific characteristics as well as a distinct shift in the microbial community structure towards more similar communities at soil depths > 10 cm. In the foreland of the Ecology Glacier, the main soil-forming processes on a decadal timescale are acidification and accumulation of soil organic carbon and nitrogen, accompanied by changes in microbial abundances, microbial community compositions, and plant coverage, whereas quantifiable silicate weathering and the formation of pedogenic oxides occur on a centennial to a millennial timescale after deglaciation.
Interaction of genetic and environmental factors for body fat mass control: observational study for lifestyle modification and genotyping
Authors: Kang Joon Ho , Kim Heewon , Kim Jinki , Seo Jong-Hwa , Cha Soyeon , Oh Hyunjung , Kim Kyunga , Park Seong-Jin , Kim Eunbin , Kong Sunga , Lee Jae-Hak , Bae Joon Seol , Won Hong-Hee , Joung Je-Gun , Yang Yoon Jung , Kim Jinho , Park Woong-Yang
Published: June 2021

Previous studies suggested that genetic, environmental factors and their interactions could affect body fat mass (BFM). However, studies describing these effects were performed at a single time point in a population. In this study, we investigated the interaction between genetic and environmental factors in affecting BFM and implicate the healthcare utilization of lifestyle modifications from a personalized and genomic perspective. We examined how nutritional intake or physical activity changes in the individuals affect BFM concerning the genetic composition. We conducted an observational study including 259 adult participants with single nucleotide polymorphism (SNP) genotyping and longitudinal lifestyle monitoring, including food consumption and physical activities, by following lifestyle modification guidance. The participants’ lifelog data on exercise and diet were collected through a wearable device for 3 months. Moreover, we measured anthropometric and serologic markers to monitor their potential changes through lifestyle modification. We examined the influence of genetic composition on body fat reduction induced by lifestyle changes using genetic risk scores (GRSs) of three phenotypes: GRS-carbohydrate (GRS-C), GRS-fat (GRS-F), and GRS-exercise (GRS-E). Our results showed that lifestyle modifications affected BFM more significantly in the high GRS class compared to the low GRS class, indicating the role of genetic factors affecting the efficiency of the lifestyle modification-induced BFM changes. Interestingly, the influence of exercise modification in the low GRS class with active lifestyle change was lower than that in the high GRS class with inactive lifestyle change (P = 0.022), suggesting the implication of genetic factors for efficient body fat control.
Electro-steric opening of the clc-2 chloride channel gate
Authors: De Jesús-Pérez José J. , Méndez-Maldonado G. Arlette , López-Romero Ana E. , Esparza-Jasso David , González-Hernández Irma L. , De la Rosa Víctor , Gastélum-Garibaldi Roberto , Sánchez-Rodríguez Jorge E. , Arreola Jorge
Published: June 2021

The widely expressed two-pore homodimeric inward rectifier CLC-2 chloride channel regulates transepithelial chloride transport, extracellular chloride homeostasis, and neuronal excitability. Each pore is independently gated at hyperpolarized voltages by a conserved pore glutamate. Presumably, exiting chloride ions push glutamate outwardly while external protonation stabilizes it. To understand the mechanism of mouse CLC-2 opening we used homology modelling-guided structure–function analysis. Structural modelling suggests that glutamate E213 interacts with tyrosine Y561 to close a pore. Accordingly, Y561A and E213D mutants are activated at less hyperpolarized voltages, re-opened at depolarized voltages, and fast and common gating components are reduced. The double mutant cycle analysis showed that E213 and Y561 are energetically coupled to alter CLC-2 gating. In agreement, the anomalous mole fraction behaviour of the voltage dependence, measured by the voltage to induce half-open probability, was strongly altered in these mutants. Finally, cytosolic acidification or high extracellular chloride concentration, conditions that have little or no effect on WT CLC-2, induced reopening of Y561 mutants at positive voltages presumably by the inward opening of E213. We concluded that the CLC-2 gate is formed by Y561-E213 and that outward permeant anions open the gate by electrostatic and steric interactions.
Association of glomerular filtration rate slope with timely creation of vascular access in incident hemodialysis
Authors: Lim Lee-Moay , Lin Ming-Yen , Hwang Shang-Jyh , Chen Hung-Chun , Chiu Yi-Wen
Published: June 2021

The factors associated with the timely creation of distal vascular access for hemodialysis initiation are unclear. We aimed to explore the association between the slope of estimated glomerular filtration rate (eGFR) and the successful usage of vascular access upon hemodialysis initiation. This single center retrospective cohort study enrolled chronic kidney disease patients who undertook a multidisciplinary care program from 2003 to 2016. Using eGFR slope as predictor, we evaluated the vascular access created timely upon hemodialysis initiation. Among the 987 patients, vascular access was created at a median eGFR of 5.8 min/ml/1.73 m2, with a median duration of 3.1 months before hemodialysis. The proportions of vascular access created timely, created not timely (vascular access immature), and not created were 68.5%, 8.8%, and 22.7%, respectively. There was a significant negative association of eGFR upon vascular access creation with eGFR slope (r = − 0.182, P < 0.001). The fastest eGFR slope patients (the first quartile or < − 10 min/ml/1.73 m2/year) had the lowest percentage of vascular access created timely. In the multivariable logistic regression analysis, only higher eGFR upon vascular access creation (P = 0.001) and eGFR slope (P = 0.009) were significantly associated with vascular access created timely. The adjusted odds ratios of each quartile of eGFR slopes for vascular access created timely were 0.46 (95% confidence interval 0.27–0.86), 1.30 (0.62, 2.72), 1.00 (reference), and 0.95 (0.48–1.87), respectively. eGFR slope is associated with the timely creation of vascular access for the initiation of hemodialysis in a reverse-J-shaped pattern and may help determine the time of vascular access creation.
Ischemic heart injury leads to HIF1-dependent differential splicing of CaMK2γ
Authors: Williams Allison Lesher , Walton Chad B. , Pinell Blake , Khadka Vedbar S. , Dunn Brandyn , Lee Katie , Anagaran M. C. Therese , Avelar Abigail , Shohet Ralph V.
Published: June 2021

Ischemic heart disease is a leading cause of heart failure and hypoxia inducible factor 1 (HIF1) is a key transcription factor in the response to hypoxic injury. Our lab has developed a mouse model in which a mutated, oxygen-stable form of HIF1α (HIF-PPN) can be inducibly expressed in cardiomyocytes. We observed rapid cardiac dilation and loss of contractility in these mice due to lower expression of excitation–contraction coupling genes and reduced calcium flux. As alternative splicing plays an underappreciated role in transcriptional regulation, we used RNA sequencing to search for splicing changes in calcium-handling genes of HIF-PPN hearts and compared them to previous sequencing data from a model of myocardial infarction (MI) to select for transcripts that are modified in a pathological setting. We found overlap between genes differentially expressed in HIF-PPN and post-MI mice (54/131 genes upregulated in HIF-PPN hearts at 1 day and/or 3 days post-MI, and 45/78 downregulated), as well as changes in alternative splicing. Interestingly, calcium/calmodulin dependent protein kinase II, gamma (CAMK2G) was alternatively spliced in both settings, with variant 1 (v1) substantially decreased compared to variants 2 (v2) and 3 (v3). These findings were also replicated in vitro when cells were transfected with HIF-PPN or exposed to hypoxia. Further analysis of CAMK2γ protein abundance revealed only v1 was detectable and substantially decreased up to 7 days post-MI. Rbfox1, a splicing factor of CAMK2G, was also decreased in HIF-PPN and post-MI hearts. Subcellular fractionation showed CAMK2γ v1 was found in the nuclear and cytoplasmic fractions, and abundance decreased in both fractions post-MI. Chromatin immunoprecipitation analysis of HIF1 in post-MI hearts also demonstrated direct HIF1 binding to CAMK2G. CaMK2 is a key transducer of calcium signals in both physiological and pathological settings. The predominantly expressed isoform in the heart, CaMK2δ, has been extensively studied in cardiac injury, but the specific role of CaMK2γ is not well defined. Our data suggest that loss of CaMK2γ after MI is HIF1-dependent and may play an important role in the heart’s calcium signaling and transcriptional response to hypoxia.
Automated parasitological diagnosis in clinical microbiology laboratories
Authors: Fernández-Rivas Gema , Rivaya Belén , Romaní Nona , Wang Jun Hao Wang , Alcaide Mireya , Matas Lurdes
Published: June 2021

Although there is a low prevalence of parasitological infections in Europe, the diagnosis of intestinal parasites is still difficult and laborious for microbiology laboratories. Currently, antigen detection assays and molecular biology allow a more accurate diagnosis, but these techniques have limitations as they cannot detect all the possible parasites present in the samples. The objective of the study was to evaluate the accuracy and the usefulness of automated microscopy SediMAX2 (77 Elektronika, Budapest, Hungary) in the detection of parasitic infections from feces. A total of 197 formol-fixed stool samples were processed in parallel by wet mount examination and by SediMAX2. Sensitivities, specificities and predictive values were analyzed, reaching a sensitivity of 89.51% and a specificity of 98.15% and a very good positive predictive value (99.22%). SediMAX2 is a good tool for a reliable diagnosis of intestinal parasitic infections. The rapid processing and the flexibilty of storage of images analyzed make its incorporation into the day to day laboratory routine recommendable.