bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alteration of CTCF-associated chromatin neighborhood inhibits TAL1-driven oncogenic transcription program and leukemogenesis
Authors: Li Ying , Liao Ziwei , Luo Huacheng , Benyoucef Aissa , Kang Yuanyuan , Lai Qian , Dovat Sinisa , Miller Barbara , Chepelev Iouri , Li Yangqiu , Zhao Keji , Brand Marjorie , Huang Suming 
Published: February 2020

Abstract
Aberrant activation of the TAL1 is associated with up to 60% of T-ALL cases and is involved in CTCF-mediated genome organization within the TAL1 locus, suggesting that CTCF boundary plays a pathogenic role in T-ALL. Here, we show that −31-Kb CTCF binding site (−31CBS) serves as chromatin boundary that defines topologically associating domain (TAD) and enhancer/promoter interaction required for TAL1 activation. Deleted or inverted −31CBS impairs TAL1 expression in a context-dependent manner. Deletion of −31CBS reduces chromatin accessibility and blocks long-range interaction between the +51 erythroid enhancer and TAL1 promoter-1 leading to inhibition of TAL1 expression in erythroid cells, but not T-ALL cells. However, in TAL1-expressing T-ALL cells, the leukemia-prone TAL1 promoter-IV specifically interacts with the +19 stem cell enhancer located 19 Kb downstream of TAL1 and this interaction is disrupted by the −31CBS inversion in T-ALL cells. Inversion of −31CBS in Jurkat cells alters chromatin accessibility, histone modifications and CTCF-mediated TAD leading to inhibition of TAL1 expression and TAL1-driven leukemogenesis. Thus, our data reveal that −31CBS acts as critical regulator to define +19-enhancer and the leukemic prone promoter IV interaction for TAL1 activation in T-ALL. Manipulation of CTCF boundary can alter TAL1 TAD and oncogenic transcription networks in leukemogenesis.
High density of unrepaired genomic ribonucleotides leads to Topoisomerase 1-mediated severe growth defects in absence of ribonucleotide reductase
Authors: Cerritelli Susana M , Iranzo Jaime , Sharma Sushma , Chabes Andrei , Crouch Robert J , Tollervey David , El Hage Aziz 
Published: February 2020

AbstractCellular levels of ribonucleoside triphosphates (rNTPs) are much higher than those of deoxyribonucleoside triphosphates (dNTPs), thereby influencing the frequency of incorporation of ribonucleoside monophosphates (rNMPs) by DNA polymerases (Pol) into DNA. RNase H2-initiated ribonucleotide excision repair (RER) efficiently removes single rNMPs in genomic DNA. However, processing of rNMPs by Topoisomerase 1 (Top1) in absence of RER induces mutations and genome instability. Here, we greatly increased the abundance of genomic rNMPs in Saccharomyces cerevisiae by depleting Rnr1, the major subunit of ribonucleotide reductase, which converts ribonucleotides to deoxyribonucleotides. We found that in strains that are depleted of Rnr1, RER-deficient, and harbor an rNTP-permissive replicative Pol mutant, excessive accumulation of single genomic rNMPs severely compromised growth, but this was reversed in absence of Top1. Thus, under Rnr1 depletion, limited dNTP pools slow DNA synthesis by replicative Pols and provoke the incorporation of high levels of rNMPs in genomic DNA. If a threshold of single genomic rNMPs is exceeded in absence of RER and presence of limited dNTP pools, Top1-mediated genome instability leads to severe growth defects. Finally, we provide evidence showing that accumulation of RNA/DNA hybrids in absence of RNase H1 and RNase H2 leads to cell lethality under Rnr1 depletion.
Cognitive impairment, endothelial biomarkers and mortality in maintenance haemodialysis patients: a prospective cohort study
Authors: Freire de Medeiros Camilla Maroni Marques , Diógenes da Silva Bruna Rafaele , Costa Bruno Gabriele , Sartori Vinicius Farina , Meneses Gdayllon Cavalcante , Bezerra Gabriela Freire , Martins Alice Maria Costa , Libório Alexandre Braga 
Published: February 2020

Abstract

Background
Haemodialysis (HD) patients have a high prevalence of cardiovascular disease risk factors as well as cognitive impairment. The objective of the present study was to evaluate the interrelationship between cognitive impairment, endothelium-related biomarkers and cardiovascular/non-cardiovascular mortality.

Methods
A total of 216 outpatients were recruited from three centres in a dialysis network in Brazil between June 2016 and June 2019. Sociodemographic and clinical data were obtained by applying a patient questionnaire, reviewing medical records data and conducting patient interviews. Cognitive function was assessed using the Cambridge Cognitive Examination. Plasma endothelium-related biomarkers [syndecan-1, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion protein-1 (VCAM-1) and angiopoietin-2 (AGPT2)] were measured. Patients were followed for 30 months. Cox proportional hazards regression models were used to assess the associations of the cognitive function scores and each endothelium-related biomarker with cardiovascular/non-cardiovascular mortality.

Results
Cognitive function was associated with cardiovascular mortality {each standard deviation [SD] better cognitive score was associated with a 69% lower risk for cardiovascular mortality [hazard ratio (HR) 0.31 [95% confidence interval (CI) 0.17–0.58]} but not with non-cardiovascular mortality. Moreover, cognitive function was also correlated with all endothelial-related biomarkers, except VCAM-1. ICAM-1, AGPT2 and syndecan-1 were also associated with cardiovascular mortality. The association between cognitive function and cardiovascular mortality remained significant with no HR value attenuation [fully adjusted HR 0.32 (95% CI 0.16–0.59)] after individually including each endothelial-related biomarker in the Cox model.

Conclusions
In conclusion, cognitive impairment was associated with several endothelium-related biomarkers. Moreover, cognitive impairment was associated with cardiovascular mortality but not with non-cardiovascular mortality, and the association between cognitive impairment and cardiovascular mortality in HD patients was not explained by any of the endothelial-related biomarkers.
ALMA band 8 observations of DLA 2233+131 at z = 3.150
Authors: Ogura Kazuyuki , Umehata Hideki , Taniguchi Yoshiaki , Matsuda Yuichi , Kashikawa Nobunari , Sheth Kartik , Murata Katsuhiro , Kajisawa Masaru , Kobayashi Masakazu A R , Murayama Takashi , Nagao Tohru 
Published: February 2020

Abstract
We present our ALMA Band 8 observations of a damped Ly$\alpha$ absorption (DLA) system at $z = 3.150$ observed in the spectrum of the quasar Q2233+131 at $z = 3.295$. The optical counterpart of this DLA has been identified and it shows a double-peaked Ly$\alpha$ emission line. Since one possible origin of DLAs at high redshift is an outflowing gas from star-forming galaxies, DLA 2233+131 provides a good laboratory to investigate the nature of high-z DLAs. Motivated by this, we have carried out ALMA band 8 observations to study the [C ii] line in this system. However, we do not detect any significant emission line in the observed pass bands. Instead, we have serendipitously found three submm continuum sources in the observed sky area. One appears to be the quasar Q2233+131 itself while the other two sources are newly identified submm galaxies (SMGs), called SMG1 and SMG2 in this paper. They are located at a separation of ${4{^{\prime \prime }_{.}}7}$ and ${8{^{\prime \prime }_{.}}1}$ from Q2233+131, respectively. Their 646 μm fluxes are $6.35\:$mJy and $6.43\:$mJy, respectively, being higher than that of Q2233+131, $3.62\:$mJy. Since these two SMGs are not detected in the optical images obtained with the Hubble Space Telescope and the Subaru Telescope, they have a very red spectral energy distribution. It is, therefore, suggested that they are high-redshift galaxies or very dusty galaxies at intermediate redshift, although we cannot rule out the possibility that they are optically very faint SMG analogs at low redshift. Follow-up observations will be necessary to explore the nature of this interesting region.
A Preliminary Model for the Migration of Sulfide Droplets in a Magmatic Conduit and the Significance of Volatiles
Authors: Yao Zhuosen , Mungall James E , Qin Kezhang 
Published: February 2020

Abstract
A close relationship between Ni–Cu–(PGE) sulfide deposits and magmatic conduit systems has been widely accepted, but our present understanding still rests on empirical inductions that sulfide liquids are entrained during magma ascent and aggregated at hydrodynamic traps such as the opening of a conduit into a larger magma body. In this contribution, a preliminary quantitative model for the dynamics of mm-scale sulfide droplets in a vertical magmatic conduit is developed, examining such limiting parameters as the size, transport velocity and the magmas’ maximum carrying capacity for sulfide droplets. Addition of numerous dense sulfide droplets significantly reduces magma buoyancy and rapidly increases the bulk viscosity, and the resulting pressure gradient in the propagating conduit dyke restricts the maximum volume fraction of droplets that can be carried by ascending magma. For sulfide droplets alone, the maximum carrying capacity is low, but it will be improved dramatically by the addition of volatiles which reduces the density and viscosity of silicate melt. Potential volatile degassing during decompression further facilitates sulfide entrainment by reducing bulk magma density, and the formation of buoyant compound vapour-sulfide liquid bubble drops also greatly enhances the carrying capacity. The breakdown of compound drops by detachment of parts of the vapour bubble or sulfide droplet may occur at low pressure, which liberates sulfide liquids from rising compound drops, potentially to collect in traps in the conduit system. When sulfide-laden magma flows through a widening conduit, many droplets can be captured by the re-circulation flow just downstream of the expanding section, followed by sulfide liquid accumulation and enhanced chemical interaction via diffusive exchange with the recirculating magma, potentially resulting in an economic, high-tonnage ore body. We apply our models to the emplacement of sulfide-rich magmatic suspensions at Noril’sk and show that the disseminated mineralization in intrusions could have formed when magmas carrying re-suspended sulfide liquid entrained from pre-existing sulfide accumulations in the conduit system reached their limiting sulfide carrying capacity as dictated by buoyancy and were deflected into blind sills flanking the principal conduit for flood basalt volcanism.
Formation of the Vergenoeg F–Fe–REE Deposit (South Africa) by Accumulation from a Ferroan Silicic Magma
Authors: Brandt S , Klemd R , Haase K M , Fassbender M L , Vennemann T 
Published: February 2020

AbstractSituated in the centre of the Paleoproterozoic Bushveld Large Igneous Province (LIP) of South Africa the Vergenoeg F–Fe–REE deposit is one of the largest, but at the same time most unusual, fluorite deposits on Earth. In situ major and trace element analyses of fayalite, magnetite, ilmenite, fluorapatite, fluorite and allanite from fayalite-rich rocks are combined with oxygen isotope data for fayalite, magnetite and ilmenite to unravel the complex evolution of the deposit. Textural and compositional characterization of the fayalite-rich rocks supports a magmatic formation as cumulates and an intense late hydrothermal overprint. Fayalite accumulated together with minor Ti-rich magnetite, ilmenite, fluorapatite and allanite from a highly evolved, H2O-poor felsic melt at low oxygen fugacity. Chondrite-normalized rare earth element (REE) patterns of fayalite and the recalculated parental melts, using fayalite–rhyolite partition coefficients, exhibit positive trends with strong enrichment of the heavy REE (HREE) relative to the light REE (LREE). Apart from the LREE depletion the patterns are similar to those of highly fractionated high-silica REE rhyolites that often occur in siliceous LIPs. We attribute the LREE depletion to crystallization of accessory allanite, the main host of the LREE in the cumulates. Chondrite-normalized REE patterns of the parental melt prior to fayalite accumulation, recalculated using allanite–rhyolite partition coefficients, resemble the composition of the rhyolites of the Rooiberg Group and therefore document a petrogenetic link to the Bushveld LIP. High δ18O values of fayalite (up to ≈7·4 ‰) are consistent with its crystallization in a rhyolitic melt that has formed by extensive fractionation from basic melts of the Rustenburg Layer Suite, the mafic member of the Bushveld LIP. Primary fluorite crystallized together with rare quartz, and a second generation of fayalite, magnetite and ilmenite from rare intercumulus melt in interstices between cumulate fayalite. Textural and mineral compositional data, as well as the generally negative δ18O values of magnetite (–2·9 to 0 ‰), are in agreement with the main magnetite–fluorite ore formation in Vergenoeg being related to a hydrothermal overprint, which was responsible for further F and Fe enrichments of the rocks. Fluorine-rich fluids, released from the crystallizing granites of the felsic member of the Bushveld LIP (Lebowa Granite Suite), caused the extensive alteration of fayalite to bowlingite and its replacement by Ti-poor magnetite and quartz. The hydrothermal overprint was associated with the widespread formation of secondary fluorite and minor fluorapatite. Our new petrogenetic model for the Vergenoeg deposit, as constrained from the primary fayalite cumulates, implies that the formation of the Vergenoeg deposit was directly linked to the evolution of the Bushveld LIP.
Dehydration of Glaucophane in the System Na2O–MgO–Al2O3–SiO2–H2O and the Effects of NaCl-, CO2- and Silicate-bearing Aqueous Fluids
Authors: Cheng Nanfei , Jenkins David M , Huang Fang 
Published: February 2020

Abstract
Arc magmas are thought to be generated by partial melting of the mantle wedge above the subduction slab, which is triggered by the fluids from the dehydration of subducting oceanic crust. Among the dehydration reactions, those occurring at the depths of the blueschist-to-eclogite transition are considered to be very important. The sodium amphibole glaucophane (□Na2Mg3Al2Si8O22(OH)2, where □ represents a vacancy) is characteristic of blueschists, so that determining the higher-temperature stability of end-member glaucophane helps constrain the maximum temperature of the transition between blueschists and eclogites. A reversed determination of the dehydration reaction 2 glaucophane = 4 jadeite + 3 enstatite + 2 quartz + 2 H2O was done in the system Na2O–MgO–Al2O3–SiO2–H2O over the pressure-temperature (P–T) range of 2·5–3·3 GPa and 760–900 °C for durations of 24–96 hours, using synthetic phases as starting materials. The reaction was bracketed at 830–850 °C at 2·5 GPa and at 810–830 °C at 2·9 GPa in the presence of water. In addition to pure water, 5 molality H2O–NaCl (mole fraction XNaCl = 0·08) and 5 molality H2O–CO2 (XCO2 = 0·08) fluids were used to check the effects of NaCl and CO2, respectively, on the dehydration reaction. The H2O–NaCl fluid shifts the reaction boundary at 2·5 GPa from 840 °C to a lower T (800 °C), while the CO2–H2O fluid shifts the boundary to a higher T (860 °C). At these high P–T conditions, the fluid, even without any added NaCl or CO2, is a silicate-bearing aqueous fluid. The different effects of NaCl and CO2 are attributed to differences in their capabilities to inhibit the solubility of silicates, such as quartz in water, and in changing the activity of water at such P–T conditions. The difference can shift the depth of dehydration by 6 km for an average low dT/dP geothermal gradient of 325 °C/GPa. The shift in the boundary could be considerably larger for shallower dT/dP slab-top geothermal gradients. The experimental results show a good fit with those from thermodynamic modelling and aqueous geochemical calculation.
Polyphase Zircon Growth during Slow Cooling from Ultrahigh Temperature: an Example from the Archean Pikwitonei Granulite Domain
Authors: Guevara Victor E , MacLennan Scott A , Dragovic Besim , Caddick Mark J , Schoene Blair , Kylander-Clark Andrew R C , Couëslan Chris G 
Published: February 2020

AbstractQuantifying the timescales of Archean ultrahigh temperature (UHT) metamorphism is essential for constraining the style of plate tectonics on the early Earth. However, such timescales can be difficult to quantify, due to the antiquity of Archean rocks and the extreme thermal conditions of UHT metamorphism. We constrain the timescales of Archean UHT metamorphic processes recorded by a single rock sample from the Pikwitonei granulite domain (northwestern Superior Province), through the integration of two U–Pb zircon petrochronologic techniques. In this study we combine: (1) high-spatial resolution laser ablation split-stream inductively coupled mass spectrometry (LASS) on in situ zircon (in thin section) and hand-picked zircon; and (2) high-precision isotope dilution thermal ionization mass spectrometry (ID-TIMS) analyses on microsampled fragments from the same hand-picked zircon analysed by LASS. Phase equilibria modelling and Zr-in-rutile thermometry suggest the rock followed a P–T path characterized by decompression at &gt; 960 °C, followed by near-isobaric cooling at ∼0·8 GPa. In situ LASS zircon analyses could be interpreted to record zircon growth at broadly ∼2665 Ma, though the large uncertainties on isotopic dates make potentially distinct growth episodes difficult to distinguish. ID-TIMS U–Pb dates of zircon fragments reveal a polyphase zircon growth history over a 24 Ma duration, from 2673 to 2649 Ma. Zircon trace element compositions, textures, and microstructural relationships, as well as evaluation of zircon-garnet equilibrium, suggest zircon grew during melt crystallization, after UHT decompression and garnet resorption. Variable Ti concentrations within zircon domains indicate: (1) zircon crystallized through the temperature interval of ∼875 °C to ∼730 °C, potentially in isolated rock domains with variable zircon saturation temperature; and/or (2) zircon crystallized over a narrower temperature interval in isolated rock domains with variable aTiO2 and/or aSiO2. Collectively, the data suggest the west-central Pikwitonei granulite domain reached peak UHT conditions prior to 2673 Ma, after which suprasolidus conditions in the lower crust persisted for at least 24 Ma. Such an interpretation would be impossible if based on either the LASS or ID-TIMS zircon data alone, which highlights the utility of applying both techniques in tandem to constrain metamorphic timescales in ancient UHT terranes.
On Non-Eliminative Structuralism. Unlabeled Graphs as a Case Study, Part A†
Authors: Leitgeb Hannes 
Published: February 2020

Abstract
This is Part A of an article that defends non-eliminative structuralism about mathematics by means of a concrete case study: a theory of unlabeled graphs. Part A summarizes the general attractions of non-eliminative structuralism. Afterwards, it motivates an understanding of unlabeled graphs as structures sui generis and develops a corresponding axiomatic theory of unlabeled graphs. As the theory demonstrates, graph theory can be developed consistently without eliminating unlabeled graphs in favour of sets; and the usual structuralist criterion of identity can be applied successfully in graph-theoretic proofs. Part B will turn to the philosophical interpretation and assessment of the theory.
Listening Difficulties of Children With Cochlear Implants in Mainstream Secondary Education
Authors: Krijger Stefanie , Coene Martine , Govaerts Paul J. , Dhooge Ingeborg 
Published: February 2020

Objectives:
Previous research has shown that children with cochlear implants (CIs) encounter more communication difficulties than their normal-hearing (NH) peers in kindergarten and elementary schools. Yet, little is known about the potential listening difficulties that children with CIs may experience during secondary education. The aim of this study was to investigate the listening difficulties of children with a CI in mainstream secondary education and to compare these results to the difficulties of their NH peers and the difficulties observed by their teachers.

Design:
The Dutch version of the Listening Inventory for Education Revised (LIFE-R) was administered to 19 children (mean age = 13 years 9 months; SD = 9 months) who received a CI early in life, to their NH classmates (n = 239), and to their teachers (n = 18). All participants were enrolled in mainstream secondary education in Flanders (first to fourth grades). The Listening Inventory for Secondary Education consists of 15 typical listening situations as experienced by students (LIFEstudent) during class activities (LIFEclass) and during social activities at school (LIFEsocial). The teachers completed a separate version of the Listening Inventory for Secondary Education (LIFEteacher) and Screening Instrument for Targeting Educational Risk.

Results:
Participants with CIs reported significantly more listening difficulties than their NH peers. A regression model estimated that 75% of the participants with CIs were at risk of experiencing listening difficulties. The chances of experiencing listening difficulties were significantly higher in participants with CIs for 7 out of 15 listening situations. The 3 listening situations that had the highest chance of resulting in listening difficulties were (1) listening during group work, (2) listening to multimedia, and (3) listening in large-sized classrooms. Results of the teacher’s questionnaires (LIFEteacher and Screening Instrument for Targeting Educational Risk) did not show a similar significant difference in listening difficulties between participants with a CI and their NH peers. According to teachers, NH participants even obtained significantly lower scores for staying on task and for participation in class than participants with a CI.

Conclusions:
Although children with a CI seemingly fit in well in mainstream schools, they still experience significantly more listening difficulties than their NH peers. Low signal to noise ratios (SNRs), distortions of the speech signal (multimedia, reverberation), distance, lack of visual support, and directivity effects of the microphones were identified as difficulties for children with a CI in the classroom. As teachers may not always notice these listening difficulties, a list of practical recommendations was provided in this study, to raise awareness among teachers and to minimize the difficulties.