bluuebunny/crossref_metadata_2025 huggingface dataset:
The 2Mass Redshift Survey
Authors: Huchra J. , Tollestrup E. , Schneider S. , Skrutski M. , Jarrett T. , Chester T. , Cutri R.
Published: June 2021

With the current convergence of determinations of the Hubble Constant (e.g. The Extragalactic Distance Scale, 1997, Livio, Donahue and Panagia, eds.) to values within ±25% rather than a factor of two, and the clear possibility of determining q0 using high redshift supernovae (Garnavich et al. 1998), the major remaining problem in observational cosmology is the determination of Ω — what is the dark matter, how much is there, and how is it distributed?

The most direct approach to the last two parts of the question has been to study galaxy dynamics, first through the motions of galaxies in binaries, groups and clusters, and in the last decade and a half, driven by the observation of our motion w.r.t. the Cosmic Microwave Background (CMB) and thenotion that DM must be clumped on larger scales than galaxy clusters if (Ω is to be unity, through the study of large scale galaxy flows.

The ratio of the mass density to the closure mass density, Ω, is thought by most observers to be ~0.1-0.3, primarily based on the results of dynamical measurements of galaxy clusters and, more recently, gravitational lensing studies of clusters. In contrast, most theoretical cosmologists opt for a high density universe, Ω = 1.0, based on the precepts of the inflation scenario, the difficulty of forming galaxies in low density models given the observed smoothness of the microwave background radiation, and the observational evidence from the matching of the available large scale flow measurements (and the absolute microwave background dipole velocity) to the local density field. However this last result is extremely controversial—matching the velocity field to the density field derived from IRAS (60μ) selected galaxy samples yields high Ω values (e.g., Dekel et al. 1993) but matching to optically selected samples yields low values (Hudson 1994; Lahav et al. 1994; Santiago et al. 1995). On small scales, the high Ω camp argues that the true matter distribution is much more extended than the distribution of galaxies, so the dynamical mass estimates are biased low.
The Virmos Project
Authors: MacCagni D. , Fèvre O. Le , Vettolani G. , Mancini D. , Picat J.P. , Cuby J.G. , Mellier Y. , Mazure A.
Published: June 2021

Large and deep spectroscopic samples of galaxies are essential to study galaxies and large scale structure evolution out to look-back times ~ 10% the current age of the vmiverse. Keeping this scientific and observational goal in mind, we designed and are presently building two wide-field imaging spectrographs to be installed at the Nasmyth foci of the ESO-VLT Unit Telescopes 3 and 4.
Archiving Electronic Publications - A Librarian’s Point of view
Authors: Grothkopf Uta
Published: June 2021

Archiving electronic journals is complex. There are many questions; Who archives? What is archived? How many copies should be archived. How can one ensure the integrity of electronic documents? How can access be maintained? Technology will provide some answers. Electronic archives will require periodic refreshing and migration to new technology. Many factors remain unknown at this time.
The Hipparcos Double and Multiple Star Solutions
Authors: Mignard F.
Published: June 2021

The Hipparcos Catalogue provides general astrometric and photometric information on double and multiple stars in specific fields of the main Catalogue and detailed data on the components in the various sections of a dedicated annex: the Double and Multiple Systems Annex (DMSA). Overall statistics of these solutions are presented for the 13211 entries of this annex and the different types of solutions are outlined.
New Ages For Old Clusters
Authors: Reid I.N.
Published: June 2021

A major result of the Hipparcos mission is the availability of accurate parallaxes for a much-increased sample of nearby subdwarfs. On the basis of those data, both Reid (1997-R97) and Gratton et al (1997-G97) have used main-sequence fitting techniques to obtain new estimates of globular cluster distances, deriving significantly larger moduli (by 0.15 to 0.3 mag) for extreme, metal-poor clusters such as M92 and M15. These re-calibrations are not solely the result of the revised parallax data - both D’Antona, Caloi & Mazzitelli (1997 - DCM) and Reid show that similar results can be derived from pre-Hipparcos subdwarf data if the calibrations are not tied exclusively to HD 103095. The longer distance scale leads to a brighter inferred turnoff, and, combined with the latest models (DCM), ages of only 11 to 13 Gyrs - substantially younger than the 16±2 Gyrs proposed by Bolte & Hogan (1992).

Recently, Pont et al (1997) have suggested that these revised distances reflect systematic bias in the calibration, notably underestimation of subdwarf abundances. Their distance modulus for M92 ( (m-M)0=14.68) is closer to the Bolte/Hogan value (14.65 mag) than those derived byG97 (14.82 mag) or Reid (14.93 mag). While we believe that Pont et al overestimate the bias, particularly, where high-resolution spectroscopic analyses are concerned (G97, Reid, preprint), there is no question that significant uncertainties remain in the cluster distance calibration. Colours,rather than luminosities, are particularly vulnerable, and a mismatch of 0.01 in (B-V) translates to δ(m — M)0 ~ 0.05 mag.
Astrometric Radial Velocities From Hipparcos
Authors: Dravins D. , Lindegren L. , Madsen S. , Holmberg J.
Published: June 2021

Space astrometry now permits accurate determinations of stellar radial motion, without using spectroscopy. Although the feasibility of deducing astrometric radial velocities from geometric projection effects was realized already by Schlesinger (1917), only with Hipparcos has it become practical. Such a program has now been carried out for the moving clusters of Ursa Major, Hyades, and Coma Berenices. Realized inaccuracies reach about 300 m/s (Dravins et al. 1997).

Discrepancies between astrometric and spectroscopic radial velocities reveal effects (other than stellar motion) that affect wavelength positions of spectral lines. Such are caused by stellar surface convection, and by gravitational redshifts. A parallel program (Gullberg & Dravins 1997) is analyzing high-precision spectroscopic radial velocities for different spectral lines in these stars, using the ELODIE radial-velocity instrument atHaute-Provence.
The Absolute Magnitude of the Early-Type MK Standards From Hipparcos Parallaxes
Authors: Jaschek C. , Gómez A.E.
Published: June 2021

We have analysed the standards of the MK system in the B0-F5 spectral region with the help of Hipparcos parallaxes, using only stars for which the error on the absolute magnitude is ≤ 0.3 mag. The sample stars (about one hundred) were scrutinized for companions and for interstellar extinction. We find that the main sequence is a wide band and that, although in general giants and dwarfs have different absolute magnitudes, the separation between luminosity class V and III is not clear. We conclude that there is no strict relation between luminosity class and absolute magnitude. The relation is only a statistical one and has a large intrinsic dispersion.

We have analysed similarly the system of standards defined by Garrison and Gray (1994) separating low and high rotational velocity standards. We find similar effects as in the original MK system.
The Distances and Absolute Magnitudes of Some Well-Known Red Variables
Authors: Wing Robert F.
Published: June 2021

Distances and absolute magnitudes have been obtained from an early distribution of Hipparcos data for a number of well-known late-type variables. These data were requested in 1981 in order to ensure that these important stars were not excluded from the Input Catalogue on account of their variability or very red color.

Measurements were requested for 20 Mira variables, and 14 of these were successfully observed. Of these, the nearest to the Sun were found to be R Leo (at 102 pc), χ Cyg (106), R Cas (107), R Car (128), T Cep (210),and R Aql (211), with formal errors ranging from ±12 to ±57 pc. Mira itself was not considered because the presence of a companion causes an 11-month wobble in its photocenter which is likely to lead to a spurious parallax. The absolute visual magnitudes of Miras at mean maximum range approximately from -2.5 to +2.0 with a clear dependence on spectral type (cooler stars being fainter). This trend is reversed for absolute magnitudes in the near infrared.

Results are also given for 10 small-amplitude variables of late type. The nearest of these are L2 Pup (M5 III, 61 pc) and R Dor (M8e, 62pc). The symbiotic star CH Cyg lies at a rather uncertain distance of 268 ± 65 pc.

Data were obtained for 23 carbon stars, including the brightest representatives of each of several subgroups. The nearest of these was found to be the SRb variable U Hya, at 162 ± 20 pc. The stars 19 Psc, Y CVn, W Ori, and HD 201626 were all found to be somewhat more than 200 pc away.
On The Mass-Luminosity Relation
Authors: Lampens P. , Kovalevsky J. , Froeschlé M. , Ruymaekers G.
Published: June 2021

The new Hipparcos parallaxes and photometry are used to determine individual masses and absolute (bolometric) magnitudes for the components of nearby visual binaries with good to very good orbits. The impact on the mass-luminosity relation (MLR) in the range 0 < MBol< +7.5 mag is then evaluated.

We selected 335 visual binaries within 50 pc (σπ/π < 10%) for a full error analysis of their orbits by computing the covariance matrix of the orbital elements with Pourbaix’(1994) algorithm. Using ΔHp and π, we estimated fractional and component masses as well as absolute magnitudes with theirrespective errors: 52 binary systems have relative mass errors smaller than 15%. Lutz and Kelker (1973) corrections have been applied to both datatypes. A new relation BC(Hp) as a function of Teff was obtained for the conversion to bolometric magnitudes. A doubly weighted linear regression model was applied next (Babu and Feigelson, 1996): we derived a ”mean” slope 3.82 ± 0.07 and zero point 4.94 ± 0.03 for the MLR, assuming a linear relationship.

Conclusions: a) the improvement of the data on masses by Hipparcos is largely quantitative; b) not all systems agree: small fluctuations from a ”mean” MLR are found as expected from evolutionary or abundance effects; c) the break in the slope of the MLR near MBol = +7 cannot be assessed due to a lack of low-mass binaries in our sample.
Towards an Improved Model of the Galaxy
Authors: Holmberg Johan , Lindegren Lennart , Flynn Chris
Published: June 2021

We use the Hipparcos survey to derive an improved model of the local galactic structure. The availability of parallaxes for all the stars permits direct determination of stellar distributions, eliminating the basic indeterminacy of classical methods based on star counts. Hipparcos gives for the
first time a truly three-dimensional view of the solar vicinity, and a complete, homogeneous and highly accurate set of magnitudes and colours. This means that new techniques can be applied in the treatment of the data which place strong constraints on a model that tries to describe the local Galactic structure. Here we investigate how well a static model of low complexitycan describe the Hipparcos observations.

The interpretation of the Hipparcos data is complicated by various observational errors and selection effects that are hard to treat correctly. We do not try to correct the data, but instead use a model and subject this model to the same observational errors and selection effects. A model catalogue is created that can be compared with the observed catalogue directly in the observational domain, thereby eliminating the effects from various biases.

Many features in the HR diagram are for the first time seen in field stars thanks to Hipparcos, such as the slanted red giant clump, previously seen in rich old open clusters such as Berkeley 18. This and other features ofthe observed HR diagram are well reproduced by the model thanks to the rather detailed modelling of the joint Mv/B — V distribution. Actually, separate distributions were derived for the three different components, disk, thick disk and halo, using the kinematic characteristics of the components to discriminate between them.
The Metallicity Distribution of Late Type Dwarfs
Authors: Haywood M. , Palasi J. , Gómez A. , Dasgal L. Meillon
Published: June 2021

The Hipparcos catalogue provides an accurate and extensive sampling of the solar neighbourhood HR diagram. The morphology of this diagram depends on selection criteria of the catalogue such as the limiting magnitude, angular separation and on the characteristics of the stellar populations near the sun (space density, metallicity, star formation rate, etc). Since the Hipparcos data are so accurate, one needs to model precisely the different selection bias and, at the same time, parametrize models of the galactic stellar populations with sufficient flexibility that as much information as possible can be grasped from the catalogue.

Comparisons between our model and the Hipparcos catalogue will be presented elsewhere. Since the quantity of information contained in the Hipparcoscatalogue is so important, models ought to be complex, and external contraints, obtained prior to any general comparison with the model, are welcome.

A major factor that influences the distribution of the stars in the HR diagram is the metallicity. For the late type stars, the metallicity distribution can be best studied by re-analysing a volume-limited sample of stars from the catalogue.
Hipparcos and Primary Distance Scale Indicators
Authors: Turon C.
Published: June 2021

The Hipparcos data are providing a dramatic increase, qualitatively and quantitatively, of the basic available distance information. For example, the numbers of stars for which a relative accuracy better than 10 % is available from Hipparcos data and from ground-based data are respectively 22 396and about 1000. Moreover, the range of spectral types and luminosity classes for which precise parallaxes are available is considerably enlarged, including many stars in open clusters and a small number of Cepheids and RR Lyrae. The bottom of the main sequence is populated down to absolute Hpmagnitude 14, including a number of subdwarf stars essential to derive globular clusters distances and ages (Pont et al, 1997a).

Finally, the Hipparcos data show how difficult are the calibration of photometric distances and the transformation of relative trigonometric parallaxes to absolute parallaxes. This is illustrated by the comparison of distances given in the last edition of the Catalogue of Nearby Stars (CNS3, Gliese & Jahreiß 1991), which is the best available compilation of stars said to be closer than 25 pc from ground-based data. About a third of them are found by Hipparcos to be (much) further than this limit (Perryman et ai, 1995). A second example is given by the study of (Binney et al, 1997).
The Hyades: Distance, Structure and Dynamics
Authors: Brown A.G.A. , Perryman M.A.C.
Published: June 2021

The Hipparcos parallaxes and proper motions together provide a consistent picture of the Hyades distance, structure and dynamics. They yield a cluster convergent point motion consistent with the individual trigonometric parallaxes, and together explain the large distance modulus derived from the most recent ground-based proper motion investigations as originating from differences in the space velocity and small systematic effects in the ground-based proper motions. Conversely, the smaller distance modulus generally derived from a variety of ground-based trigonometric parallax programmes originates from systematically larger values of the ground-based parallaxes. Although recent distance determinations to individual objects in the cluster, most notably the results of Torres et al. (1997a, b, c), are in excellent agreement with the Hipparcos trigonometric parallaxes, extrapolation to a mean cluster distance is again affected by systematic effects in the ground-based proper motion studies.

The combination of the Hipparcos astrometry with radial velocity measurements from ground-based programmes provides three-dimensional velocities allowing candidate membership selection to be based on 3-dimensional positional and kinematical criteria. A number of new cluster members have been found within 20 pc of the cluster centre. No evidence for systematic internal velocity structure is found; rather, the results are fully consistent with auniform cluster space motion with an internal velocity dispersion of about 0.3 km s-1. Spatial distribution, mass segregation, and binary distributions are consistent with N-body simulations.
Nearby Open Clusters and HR Diagram Calibration
Authors: Robichon N. , Arenou F. , Turon C. , Lebreton Y. , Mermilliod J.-C.
Published: June 2021

13 clusters have been analysed (Coma Ber, the Pleiades, IC 2602, IC 2391, Praesepe, Alpha Per, NGC 6475, Blanco 1, Stock 2, NGC 6633, IC 4756, NGC 2516 and NGC 3532). Cluster members have been selected using Hipparcos proper motions and parallaxes. The mean cluster parallaxes have been determined using Hipparcos intermediate data (abscissae on the Reference Great Circles) taking into account star to star correlations. Both selection of members and computation of cluster mean parallaxes are described in Mermilliod et al., 1997 and Robichon et al., 1997.

For each cluster, a selection of fainter stars in the ‘Base des Amas’ (Mermilliod, 1988), based on photometric data as well as radialvelocities and proper motions when available, has been done. From this selection and the computed mean parallaxes, the location of the 13 cluster sequences in the observational HR diagram is derived very accurately, at least for the closest clusters for which good photometry and small errors on the mean parallaxes are available. Relative positions of cluster sequences cannot only be explained by differences between cluster metallicities. For example, the Pleiades sequence is 0.5 magnitude bellow the Praesepe sequence whereas the adopted metallicities (obtained spectroscopically i.e. whithout any assumption on the helium content) are respectively -0.034 and +0.10.
Struve - Space Astrometry and Photometry Project
Authors: Ilin A.E. , Butkevich A.G. , Chubey M.S. , Gorshanov D.I. , Kanayev I.I. , Kirian T.R. , Kopylov I.M. , Yershov V.N.
Published: June 2021

The Space Astrometry and Photometry Project Struve is being designed at the Pulkovo Observatory in cooperation with other Russian space institutes. It is expected to be launched before 2010 with a duration of mission of at least 36 months.

The main objectives are to extend at milliarcsecond accuracy the Hipparcos satellite reference system to fainter objects including quasars and to get a second epoch for Hipparcos stars. The project Struve, along with the recently suggested project DIVA, will fill the intermediate place between Hipparcos and microarcsecond astrometry. Unlike DIVA, we propose far more extensive astrometric and photometric surveys.

We expect an Output Catalogue of 20 million stars (density of about 500 stars per square degree). A sky survey will be complete down to V = 14 (about 15 million stars), and selected objects down to V = 19.5 will be observed within a special program. The proper motions of the Hipparcos stars will be determined with an accuracy of about 0.1 mas/yr. The mean accuracy of star positions in the output catalogue is expected to be 0.6 mas which could be achieved by proper design of the satellite (symmetry, smooth rotation etc.), optics and the micrometer. A properly designed micrometer (with CCD arrays, special processors for image processing and the compression of the data flux to the ground station) will give the possibility of observing all objects of the sky down to a definite limiting magnitude.
Two concerns about the interpretation of the estimates of historical national accounts before 1850
Authors: van Zanden Jan Luiten , Bolt Jutta
Published: June 2021

As contribution to the debate about the interpretation of the process of economic growth before the Industrial Revolution, we discuss two concerns about the currently available estimates of historical national accounts and the way in which these estimates should be interpreted. Firstly, we argue that estimates of the long-term trends of economic growth should make use of all information contained in time series of Gross Domestic Product (GDP henceforth), and therefore use standard regression analysis to establish those trends. Secondly, we point to the problem that the time series of historical GDP are based on very different estimation procedures, which probably affect the outcome in terms of the level of GDP per capita in the period before 1850. Both concerns imply that we do not entirely agree with Jack Goldstone’s views of pre-industrial growth. In particular, his conclusion that growth was cyclical before 1800 is inconsistent with the available GDP estimates, which point to sustained growth, albeit at a very low rate.
Late Cretaceous Crustal Shortening in the Northern Snake Range Metamorphic Core Complex: Constraints on the Structural Geometry and Magnitude of Pre‐Extensional Footwall Burial
Authors: Wrobel A. J. , Gans P. B. , Womer J. B.
Published: June 2021

Detailed geologic mapping and structural investigation of the footwall of the northern Snake Range (NSR) metamorphic core complex reveal km‐scale Late Cretaceous fold and thrust relationships of the northern Snake Range Fold and Thrust System (NSRFTS) that are broadly coeval with the deep burial and amphibolite facies metamorphism of Eocambrian strata. The O'Neill Peak Recumbent Syncline (OPRS) ‐ an NNW‐trending, non‐cylindrical, eastward‐opening, inclined to recumbent syncline and its overlying anticlinal closure, the O'Neill Peak Anticline, affect the entire Middle to Upper Cambrian stratigraphy, effectively doubling its structural thickness from ∼3.5 to ∼8 km. West of the OPRS, pervasive isoclinal folding in lower Cambrian schistose units and local thrust duplication of lower and middle Cambrian units of the Eightmile Thrust System record layer‐parallel shear and shortening. Detailed cross sections are used to create an interpretive pre‐extensional reconstruction of the NSR that integrates the NSRFTS with associated supracrustal shortening structures now exposed in the Confusion Range to the east. We conclude that the NSRFTS and overlying structures accommodated ≥10 km of horizontal shortening, resulting in ≥7 km of structural burial of the deepest structural levels in the NSR footwall, thus explaining the localized kyanite‐grade metamorphism and elevated thermobarometric P‐T estimates. This burial was apparently quite localized as evidenced by decreasing metamorphism to the north and south. The highest magnitude of subsequent extensional exhumation of the NSR footwall appears to coincides with the area of deepest burial, suggesting that Mesozoic crustal thickening influenced both the magnitudes and geometry of subsequent Cenozoic extensional exhumation.
Automated Technique for the Detection of Step‐Like Solar Wind Dynamic Pressure Changes: Application to the Response of the Transpolar Potential to Solar Wind Dynamic Pressure Fronts
Authors: Boudouridis A. , Zesta E.
Published: June 2021

The input from the solar wind (SW) and the accompanying Interplanetary Magnetic Field (IMF) is the defining feature of the solar wind‐magnetosphere interactions. One of the most important SW drivers is the solar wind dynamic pressure, and most significantly its sharp changes known as pressure fronts. Sudden enhancements in solar wind dynamic pressure, , have been shown to lead to intensification of the auroral electrojets (and Region 1 field‐aligned currents), increase in auroral emissions, and significant enhancement in ionospheric convection and the transpolar potential. Case studies of the interaction between pressure fronts and the terrestrial space environment shed great light on their importance to the structure and dynamics of the system. However, thorough understanding of the interaction requires fully statistical investigations. These statistical studies require a large number of suitable pressure front events. In the past these have been obtained through laborious manual inspection of solar wind data. We present an automated procedure that identifies sudden step enhancements in that satisfy a desired set of limiting step‐like characteristics, such as magnitude of the change, sign of the change (positive/negative), and rate of change. The procedure yields a list of suitable events, along with their step features within minutes. The technique is tested for missed events and false positives by direct comparison to manual inspection of the data. Its utility is illustrated by application to the statistical effect of pressure fronts to the transpolar potential as measured by the Assimilative Mapping of Ionospheric Electrodynamics (AMIE) technique.
A 22‐Year Evaluation of Convection Reaching the Stratosphere Over the United States
Authors: Homeyer Cameron R. , Bowman Kenneth P.
Published: June 2021

Stratosphere‐reaching moist convection can significantly alter the dynamics, chemistry, and climate of the Earth system. This study seeks to add to the emerging understanding of the frequency, depth, and stratospheric impact of such events using 22 years (1996–2017) of ground‐based radar observations in the contiguous United States. While most prior studies identify such storms using the temperature lapse‐rate tropopause (LRT) as a troposphere‐stratosphere boundary, this study is the first to identify convection that reaches into stratospheric air below the LRT (tropopause depressions, excluding folds) as well. It is found that tropopause depression (TD) overshooting and LRT overshooting occur at similar frequency over the United States, with TD overshooting being more episodic in nature than LRT overshooting. TD overshooting is also found more often throughout the cooler months of the year, while LRT overshooting dominates all overshooting in the summer months. Stratospheric residence of overshoot material, as estimated using trajectory calculations driven by large‐scale winds, suggests that the vast majority of TD overshoot material does not remain in the stratosphere within 5 days downstream and rarely impacts altitudes more than 1 km above the LRT. Conversely, the majority of LRT overshoot material remains in the stratosphere downstream and routinely impacts altitudes >1 and >2 km above the tropopause.
MUC1-C activates the PBAF chromatin remodeling complex in integrating redox balance with progression of human prostate cancer stem cells
Authors: Hagiwara Masayuki , Fushimi Atsushi , Yamashita Nami , Bhattacharya Atrayee , Rajabi Hasan , Long Mark D. , Yasumizu Yota , Oya Mototsugu , Liu Song , Kufe Donald
Published: June 2021

The polybromo-associated PBAF (SWI/SNF) chromatin remodeling complex, which includes PBRM1, ARID2, and BRD7, regulates cell differentiation and genomic integrity. MUC1-C is an oncogenic protein that drives lineage plasticity in prostate cancer (PC) progression. The present work demonstrates that MUC1-C induces PBRM1, ARID2, and BRD7 expression by the previously unrecognized E2F1-mediated activation of their respective promoters. The functional significance of the MUC1-C→PBAF pathway is supported by demonstrating involvement of MUC1-C in associating with nuclear PBAF and driving the NRF2 antioxidant gene transcriptome in PC cells. Mechanistically, MUC1-C forms a complex with NRF2 and PBRM1 on the NRF2 target SLC7A11 gene that encodes the xCT cystine-glutamate antiporter, increases chromatin accessibility and induces SLC7A11/xCT expression. We also show that MUC1-C and PBRM1 are necessary for induction of other NRF2 target genes, including G6PD and PGD that regulate the pentose phosphate pathway. Our results further demonstrate that MUC1-C integrates activation of PBRM1 with the regulation of antioxidant genes, ROS levels, pluripotency factor expression and the cancer stem cell (CSC) state. These findings reveal a role for MUC1-C in regulating PBAF, redox balance and lineage plasticity of PC CSC progression. Our findings also uncover involvement of MUC1-C in integrating the PBAF and BAF pathways in cancer.
NF-κB-activated SPRY4-IT1 promotes cancer cell metastasis by downregulating TCEB1 mRNA via Staufen1-mediated mRNA decay
Authors: Zhao Lin , Jiang Longyang , Zhang Ming , Zhang Qiang , Guan Qiutong , Li Yalun , He Miao , Zhang Jingdong , Wei Minjie
Published: June 2021

Previous study demonstrated that most long non-coding RNAs (lncRNAs) function as competing endogenous RNAs or molecular sponges to negatively modulate miRNA and regulate tumor development. However, the molecular mechanisms of lncRNAs in cancer are not fully understood. Our study describes the role of the lncRNA SPRY4 intronic transcript 1 (SPRY4-IT1) in cancer metastasis by mechanisms related to Staufen1 (STAU1)-mediated mRNA decay (SMD). Briefly, we found that, high SPRY4-IT1 expression was associated with aggressiveness and poor outcome in human colorectal, breast and ovarian cancer tissues. In addition, functional assays revealed that SPRY4-IT1 significantly promoted colorectal, breast and ovarian cancer metastasis in vitro and in vivo. Mechanistically, microarray analyses identified several differentially-expressed genes upon SPRY4-IT1 overexpression in HCT 116 colorectal cancer cells. Among them, the 3′-UTR of transcription elongation factor B subunit 1 (TCEB1) mRNA can base-pair with the Alu element in the 3′-UTR of SPRY4-IT1. Moreover, SPRY4-IT1 was found to bind STAU1, promote STAU1 recruitment to the 3′-UTR of TCEB1 mRNA, and affect TCEB1 mRNA stability and expression, resulting in hypoxia-inducible factor 1α (HIF-1α) upregulation, and thereby affecting cancer cell metastasis. In addition, STAU1 depletion abrogated TCEB1 SMD and alleviated the pro-metastatic effect of SPRY4-IT1 overexpression. Significantly, we revealed that SPRY4-IT1 is also transactivated by NF-κB/p65, which activates SPRY4-IT1 to inhibit TCEB1 expression, and subsequently upregulate HIF-1α. In conclusion, our results highlight a novel mechanism of cytoplasmic lncRNA SPRY4-IT1 in which SPRY4-IT1 affecting TCEB1 mRNA stability via STAU1-mediated degradation during cancer metastasis.
AAV-mediated in vivo CAR gene therapy for targeting human T-cell leukemia
Authors: Nawaz Waqas , Huang Bilian , Xu Shijie , Li Yanlei , Zhu Linjing , Yiqiao Hu , Wu Zhiwei , Wu Xilin
Published: June 2021

Chimeric antigen receptor (CAR) T-cell therapy is the most active field in immuno-oncology and brings substantial benefit to patients with B cell malignancies. However, the complex procedure for CAR T-cell generation hampers its widespread applications. Here, we describe a novel approach in which human CAR T cells can be generated within the host upon injecting an Adeno-associated virus (AAV) vector carrying the CAR gene, which we call AAV delivering CAR gene therapy (ACG). Upon single infusion into a humanized NOD.Cg-Prkdcscid Il2rgem26/Nju tumor mouse model of human T-cell leukemia, AAV generates sufficient numbers of potent in vivo CAR cells, resulting in tumor regression; these in vivo-generated CAR cells produce antitumor immunological characteristics. This instantaneous generation of in vivo CAR T cells may bypass the need for patient lymphodepletion, as well as the β processes of traditional CAR T-cell production, which may make CAR therapy simpler and less expensive. It may allow the development of intricate, individualized treatments in the form of on-demand and diverse therapies.
Clinical stage drugs targeting inhibitor of apoptosis proteins purge episomal Hepatitis B viral genome in preclinical models
Authors: Clark Michelle P. , Huynh Thao , Rao Shringar , Mackiewicz Liana , Mason Hugh , Romal Shahla , Stutz Michael D. , Ahn Sang H. , Earnest Linda , Sozzi Vitina , Littlejohn Margaret , Tran Bang M. , Wiedemann Norbert , Vincan Elizabeth , Torresi Joseph , Netter Hans J. , Mahmoudi Tokameh , Revill Peter , Pellegrini Marc , Ebert Gregor
Published: June 2021

A major unmet clinical need is a therapeutic capable of removing hepatitis B virus (HBV) genome from the liver of infected individuals to reduce their risk of developing liver cancer. A strategy to deliver such a therapy could utilize the ability to target and promote apoptosis of infected hepatocytes. Presently there is no clinically relevant strategy that has been shown to effectively remove persistent episomal covalently closed circular HBV DNA (cccDNA) from the nucleus of hepatocytes. We used linearized single genome length HBV DNA of various genotypes to establish a cccDNA-like reservoir in immunocompetent mice and showed that clinical-stage orally administered drugs that antagonize the function of cellular inhibitor of apoptosis proteins can eliminate HBV replication and episomal HBV genome in the liver. Primary human liver organoid models were used to confirm the clinical relevance of these results. This study underscores a clinically tenable strategy for the potential elimination of chronic HBV reservoirs in patients.
Expression of CYP24A1 and other multiple sclerosis risk genes in peripheral blood indicates response to vitamin D in homeostatic and inflammatory conditions
Authors: Law Samantha P. L. , Gatt Prudence N. , Schibeci Stephen D. , McKay Fiona C. , Vucic Steve , Hart Prue , Byrne Scott N. , Brown David , Stewart Graeme J. , Liddle Christopher , Parnell Grant P. , Booth David R.
Published: June 2021

Although genetic and epidemiological evidence indicates vitamin D insufficiency contributes to multiple sclerosis (MS), and serum levels of vitamin D increase on treatment with cholecalciferol, recent metanalyses indicate that this vitamin D form does not ameliorate disease. Genetic variation in genes regulating vitamin D, and regulated by vitamin D, affect MS risk. We evaluated if the expression of vitamin D responsive MS risk genes could be used to assess vitamin D response in immune cells. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy controls and people with MS treated with dimethyl fumarate. We assayed changes in expression of vitamin D responsive MS risk (VDRMS) genes in response to treatment with 25 hydroxy vitamin D in the presence or absence of inflammatory stimuli. Expression of CYP24A1 and other VDRMS genes was significantly altered in PBMCs treated with vitamin D in the homeostatic and inflammatory models. Gene expression in MS samples had similar responses to controls, but lower initial expression of the risk genes. Vitamin D treatment abrogated these differences. Expression of CYP24A1 and other MS risk genes in blood immune cells indicate vitamin D response and could enable assessment of immunological response to vitamin D in clinical trials and on therapy.
Single cell derived mRNA signals across human kidney tumors
Authors: Young Matthew D. , Mitchell Thomas J. , Custers Lars , Margaritis Thanasis , Morales-Rodriguez Francisco , Kwakwa Kwasi , Khabirova Eleonora , Kildisiute Gerda , Oliver Thomas R. W. , de Krijger Ronald R. , van den Heuvel-Eibrink Marry M. , Comitani Federico , Piapi Alice , Bugallo-Blanco Eva , Thevanesan Christine , Burke Christina , Prigmore Elena , Ambridge Kirsty , Roberts Kenny , Braga Felipe A. Vieira , Coorens Tim H. H. , Del Valle Ignacio , Wilbrey-Clark Anna , Mamanova Lira , Stewart Grant D. , Gnanapragasam Vincent J. , Rampling Dyanne , Sebire Neil , Coleman Nicholas , Hook Liz , Warren Anne , Haniffa Muzlifah , Kool Marcel , Pfister Stefan M. , Achermann John C. , He Xiaoling , Barker Roger A. , Shlien Adam , Bayraktar Omer A. , Teichmann Sarah A. , Holstege Frank C. , Meyer Kerstin B. , Drost Jarno , Straathof Karin , Behjati Sam
Published: June 2021

Tumor cells may share some patterns of gene expression with their cell of origin, providing clues into the differentiation state and origin of cancer. Here, we study the differentiation state and cellular origin of 1300 childhood and adult kidney tumors. Using single cell mRNA reference maps of normal tissues, we quantify reference “cellular signals” in each tumor. Quantifying global differentiation, we find that childhood tumors exhibit fetal cellular signals, replacing the presumption of “fetalness” with a quantitative measure of immaturity. By contrast, in adult cancers our assessment refutes the suggestion of dedifferentiation towards a fetal state in most cases. We find an intimate connection between developmental mesenchymal populations and childhood renal tumors. We demonstrate the diagnostic potential of our approach with a case study of a cryptic renal tumor. Our findings provide a cellular definition of human renal tumors through an approach that is broadly applicable to human cancer.
Correlator convolutional neural networks as an interpretable architecture for image-like quantum matter data
Authors: Miles Cole , Bohrdt Annabelle , Wu Ruihan , Chiu Christie , Xu Muqing , Ji Geoffrey , Greiner Markus , Weinberger Kilian Q. , Demler Eugene , Kim Eun-Ah
Published: June 2021

Image-like data from quantum systems promises to offer greater insight into the physics of correlated quantum matter. However, the traditional framework of condensed matter physics lacks principled approaches for analyzing such data. Machine learning models are a powerful theoretical tool for analyzing image-like data including many-body snapshots from quantum simulators. Recently, they have successfully distinguished between simulated snapshots that are indistinguishable from one and two point correlation functions. Thus far, the complexity of these models has inhibited new physical insights from such approaches. Here, we develop a set of nonlinearities for use in a neural network architecture that discovers features in the data which are directly interpretable in terms of physical observables. Applied to simulated snapshots produced by two candidate theories approximating the doped Fermi-Hubbard model, we uncover that the key distinguishing features are fourth-order spin-charge correlators. Our approach lends itself well to the construction of simple, versatile, end-to-end interpretable architectures, thus paving the way for new physical insights from machine learning studies of experimental and numerical data.
The perpetual fragility of creeping hillslopes
Authors: Deshpande Nakul S. , Furbish David J. , Arratia Paulo E. , Jerolmack Douglas J.
Published: June 2021

Soil creeps imperceptibly but relentlessly downhill, shaping landscapes and the human and ecological communities that live within them. What causes this granular material to ‘flow’ at angles well below repose? The unchallenged dogma is churning of soil by (bio)physical disturbances. Here we experimentally render slow creep dynamics down to micron scale, in a laboratory hillslope where disturbances can be tuned. Surprisingly, we find that even an undisturbed sandpile creeps indefinitely, with rates and styles comparable to natural hillslopes. Creep progressively slows as the initially fragile pile relaxes into a lower energy state. This slowing can be enhanced or reversed with different imposed disturbances. Our observations suggest a new model for soil as a creeping glass, wherein environmental disturbances maintain soil in a perpetually fragile state.
Tumor-associated hematopoietic stem and progenitor cells positively linked to glioblastoma progression
Authors: Lu I-Na , Dobersalske Celia , Rauschenbach Laurèl , Teuber-Hanselmann Sarah , Steinbach Anita , Ullrich Vivien , Prasad Shruthi , Blau Tobias , Kebir Sied , Siveke Jens T. , Becker Jürgen C. , Sure Ulrich , Glas Martin , Scheffler Björn , Cima Igor
Published: June 2021

Brain tumors are typically immunosuppressive and refractory to immunotherapies for reasons that remain poorly understood. The unbiased profiling of immune cell types in the tumor microenvironment may reveal immunologic networks affecting therapy and course of disease. Here we identify and validate the presence of hematopoietic stem and progenitor cells (HSPCs) within glioblastoma tissues. Furthermore, we demonstrate a positive link of tumor-associated HSPCs with malignant and immunosuppressive phenotypes. Compared to the medullary hematopoietic compartment, tumor-associated HSPCs contain a higher fraction of immunophenotypically and transcriptomically immature, CD38- cells, such as hematopoietic stem cells and multipotent progenitors, express genes related to glioblastoma progression and display signatures of active cell cycle phases. When cultured ex vivo, tumor-associated HSPCs form myeloid colonies, suggesting potential in situ myelopoiesis. In experimental models, HSPCs promote tumor cell proliferation, expression of the immune checkpoint PD-L1 and secretion of tumor promoting cytokines such as IL-6, IL-8 and CCL2, indicating concomitant support of both malignancy and immunosuppression. In patients, the amount of tumor-associated HSPCs in tumor tissues is prognostic for patient survival and correlates with immunosuppressive phenotypes. These findings identify an important element in the complex landscape of glioblastoma that may serve as a target for brain tumor immunotherapies.
Atomically-resolved interlayer charge ordering and its interplay with superconductivity in YBa2Cu3O6.81
Authors: Hsu Chun-Chih , Huang Bo-Chao , Schnedler Michael , Lai Ming-Yu , Wang Yuh-Lin , Dunin-Borkowski Rafal E. , Chang Chia-Seng , Lee Ting-Kuo , Ebert Philipp , Chiu Ya-Ping
Published: June 2021

High-temperature superconductive (SC) cuprates exhibit not only a SC phase, but also competing orders, suppressing superconductivity. Charge order (CO) has been recognized as an important competing order, but its microscopic spatial interplay with SC phase as well as the interlayer coupling in CO and SC phases remain elusive, despite being essential for understanding the physical mechanisms of competing orders and hence superconductivity. Here we report the achievement of direct real-space imaging with atomic-scale resolution of cryogenically cleaved YBa2Cu3O6.81 using cross-sectional scanning tunneling microscopy/spectroscopy. CO nanodomains are found embedded in the SC phase with a proximity-like boundary region characterized by mutual suppression of CO and superconductivity. Furthermore, SC coherence as well as CO occur on both CuO chain and plane layers, revealing carrier transport and density of states mixing between layers. The CO antiphase correlation along the c direction suggests a dominance of Coulomb repulsion over Josephson tunneling between adjacent layers.
CIB2 regulates mTORC1 signaling and is essential for autophagy and visual function
Authors: Sethna Saumil , Scott Patrick A. , Giese Arnaud P. J. , Duncan Todd , Jian Xiaoying , Riazuddin Sheikh , Randazzo Paul A. , Redmond T. Michael , Bernstein Steven L. , Riazuddin Saima , Ahmed Zubair M.
Published: June 2021

Age-related macular degeneration (AMD) is a multifactorial neurodegenerative disorder. Although molecular mechanisms remain elusive, deficits in autophagy have been associated with AMD. Here we show that deficiency of calcium and integrin binding protein 2 (CIB2) in mice, leads to age-related pathologies, including sub-retinal pigment epithelium (RPE) deposits, marked accumulation of drusen markers APOE, C3, Aβ, and esterified cholesterol, and impaired visual function, which can be rescued using exogenous retinoids. Cib2 mutant mice exhibit reduced lysosomal capacity and autophagic clearance, and increased mTORC1 signaling—a negative regulator of autophagy. We observe concordant molecular deficits in dry-AMD RPE/choroid post-mortem human tissues. Mechanistically, CIB2 negatively regulates mTORC1 by preferentially binding to ‘nucleotide empty’ or inactive GDP-loaded Rheb. Upregulated mTORC1 signaling has been implicated in lymphangioleiomyomatosis (LAM) cancer. Over-expressing CIB2 in LAM patient-derived fibroblasts downregulates hyperactive mTORC1 signaling. Thus, our findings have significant implications for treatment of AMD and other mTORC1 hyperactivity-associated disorders.
COVseq is a cost-effective workflow for mass-scale SARS-CoV-2 genomic surveillance
Authors: Simonetti Michele , Zhang Ning , Harbers Luuk , Milia Maria Grazia , Brossa Silvia , Huong Nguyen Thi Thu , Cerutti Francesco , Berrino Enrico , Sapino Anna , Bienko Magda , Sottile Antonino , Ghisetti Valeria , Crosetto Nicola
Published: June 2021

While mass-scale vaccination campaigns are ongoing worldwide, genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to monitor the emergence and global spread of viral variants of concern (VOC). Here, we present a streamlined workflow—COVseq—which can be used to generate highly multiplexed sequencing libraries compatible with Illumina platforms from hundreds of SARS-CoV-2 samples in parallel, in a rapid and cost-effective manner. We benchmark COVseq against a standard library preparation method (NEBNext) on 29 SARS-CoV-2 positive samples, reaching 95.4% of concordance between single-nucleotide variants detected by both methods. Application of COVseq to 245 additional SARS-CoV-2 positive samples demonstrates the ability of the method to reliably detect emergent VOC as well as its compatibility with downstream phylogenetic analyses. A cost analysis shows that COVseq could be used to sequence thousands of samples at less than 15 USD per sample, including library preparation and sequencing costs. We conclude that COVseq is a versatile and scalable method that is immediately applicable for SARS-CoV-2 genomic surveillance and easily adaptable to other pathogens such as influenza viruses.
Climate change favours large seasonal loss of Arctic ozone
Authors: von der Gathen Peter , Kivi Rigel , Wohltmann Ingo , Salawitch Ross J. , Rex Markus
Published: June 2021

Chemical loss of Arctic ozone due to anthropogenic halogens is driven by temperature, with more loss occurring during cold winters favourable for formation of polar stratospheric clouds (PSCs). We show that a positive, statistically significant rise in the local maxima of PSC formation potential (PFPLM) for cold winters is apparent in meteorological data collected over the past half century. Output from numerous General Circulation Models (GCMs) also exhibits positive trends in PFPLMover 1950 to 2100, with highest values occurring at end of century, for simulations driven by a large rise in the radiative forcing of climate from greenhouse gases (GHGs). We combine projections of stratospheric halogen loading and humidity with GCM-based forecasts of temperature to suggest that conditions favourable for large, seasonal loss of Arctic column O3could persist or even worsen until the end of this century, if future abundances of GHGs continue to steeply rise.
Rapid proliferation due to better metabolic adaptation results in full virulence of a filament-deficient Candida albicans strain
Authors: Dunker Christine , Polke Melanie , Schulze-Richter Bianca , Schubert Katja , Rudolphi Sven , Gressler A. Elisabeth , Pawlik Tony , Prada Salcedo Juan P. , Niemiec M. Joanna , Slesiona-Künzel Silvia , Swidergall Marc , Martin Ronny , Dandekar Thomas , Jacobsen Ilse D.
Published: June 2021

The ability of the fungal pathogen Candida albicans to undergo a yeast-to-hypha transition is believed to be a key virulence factor, as filaments mediate tissue damage. Here, we show that virulence is not necessarily reduced in filament-deficient strains, and the results depend on the infection model used. We generate a filament-deficient strain by deletion or repression of EED1 (known to be required for maintenance of hyphal growth). Consistent with previous studies, the strain is attenuated in damaging epithelial cells and macrophages in vitro and in a mouse model of intraperitoneal infection. However, in a mouse model of systemic infection, the strain is as virulent as the wild type when mice are challenged with intermediate infectious doses, and even more virulent when using low infectious doses. Retained virulence is associated with rapid yeast proliferation, likely the result of metabolic adaptation and improved fitness, leading to high organ fungal loads. Analyses of cytokine responses in vitro and in vivo, as well as systemic infections in immunosuppressed mice, suggest that differences in immunopathology contribute to some extent to retained virulence of the filament-deficient mutant. Our findings challenge the long-standing hypothesis that hyphae are essential for pathogenesis of systemic candidiasis by C. albicans.