cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.1378832
title: Soft Null Hypotheses: A Case Study of Image Enhancement Detection in Brain Lesions

description: This work is motivated by a study of a population of multiple sclerosis (MS) patients using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to identify active brain lesions. At each visit, a contrast agent is administered intravenously to a subject and a series of images are acquired to reveal the location and activity of MS lesions within the brain. Our goal is to identify the enhancing lesion locations at the subject level and lesion enhancement patterns at the population level. We analyze a total of 20 subjects scanned at 63 visits (∼30Gb), the largest population of such clinical brain images. After addressing the computational challenges, we propose possible solutions to the difficult problem of transforming a qualitative scientific null hypothesis, such as “this voxel does not enhance”, to a well-defined and numerically testable null hypothesis based on the existing data. We call such procedure “soft null” hypothesis testing as opposed to the standard “hard null” hypothesis testing. This problem is fundamentally different from: 1) finding testing statistics when a quantitative null hypothesis is given; 2) clustering using a mixture distribution; or 3) setting a reasonable threshold with a parametric null assumption.
DOI: 10.6084/m9.figshare.1378832.v1
title: Soft Null Hypotheses: A Case Study of Image Enhancement Detection in Brain Lesions

description: This work is motivated by a study of a population of multiple sclerosis (MS) patients using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to identify active brain lesions. At each visit, a contrast agent is administered intravenously to a subject and a series of images are acquired to reveal the location and activity of MS lesions within the brain. Our goal is to identify the enhancing lesion locations at the subject level and lesion enhancement patterns at the population level. We analyze a total of 20 subjects scanned at 63 visits (∼30Gb), the largest population of such clinical brain images. After addressing the computational challenges, we propose possible solutions to the difficult problem of transforming a qualitative scientific null hypothesis, such as “this voxel does not enhance”, to a well-defined and numerically testable null hypothesis based on the existing data. We call such procedure “soft null” hypothesis testing as opposed to the standard “hard null” hypothesis testing. This problem is fundamentally different from: 1) finding testing statistics when a quantitative null hypothesis is given; 2) clustering using a mixture distribution; or 3) setting a reasonable threshold with a parametric null assumption.
DOI: 10.6084/m9.figshare.1378852
title: AU4S: A novel synthetic peptide to measure the activity of ATG4 in living cells

description: ATG4 plays a key role in autophagy induction, but the methods for monitoring ATG4 activity in living cells are limited. Here we designed a novel fluorescent peptide named AU4S for noninvasive detection of ATG4 activity in living cells, which consists of the cell-penetrating peptide (CPP), ATG4-recognized sequence “GTFG,” and the fluorophore FITC. Additionally, an ATG4-resistant peptide AG4R was used as a control. CPP can help AU4S or AG4R to penetrate cell membrane efficiently. AU4S but not AG4R can be recognized and cleaved by ATG4, leading to the change of fluorescence intensity. Therefore, the difference between AU4S- and AG4R-measured fluorescence values in the same sample, defined as “F-D value,” can reflect ATG4 activity. By detecting the F-D values, we found that ATG4 activity paralleled LC3B-II levels in rapamycin-treated cells, but neither paralleled LC3B-II levels in starved cells nor presented a correlation with LC3B-II accumulation in WBCs from healthy donors or leukemia patients. However, when DTT was added to the system, ATG4 activity not only paralleled LC3B-II levels in starved cells in the presence or absence of autophagy inhibitors, but also presented a positive correlation with LC3B-II accumulation in WBCs from leukemia patients (<i>R<sup>2</sup></i> = 0.5288). In conclusion, this study provides a convenient, rapid, and quantitative method to monitor ATG4 activity in living cells, which may be beneficial to basic and clinical research on autophagy.
DOI: 10.6084/m9.figshare.1378852.v1
title: AU4S: A novel synthetic peptide to measure the activity of ATG4 in living cells

description: ATG4 plays a key role in autophagy induction, but the methods for monitoring ATG4 activity in living cells are limited. Here we designed a novel fluorescent peptide named AU4S for noninvasive detection of ATG4 activity in living cells, which consists of the cell-penetrating peptide (CPP), ATG4-recognized sequence “GTFG,” and the fluorophore FITC. Additionally, an ATG4-resistant peptide AG4R was used as a control. CPP can help AU4S or AG4R to penetrate cell membrane efficiently. AU4S but not AG4R can be recognized and cleaved by ATG4, leading to the change of fluorescence intensity. Therefore, the difference between AU4S- and AG4R-measured fluorescence values in the same sample, defined as “F-D value,” can reflect ATG4 activity. By detecting the F-D values, we found that ATG4 activity paralleled LC3B-II levels in rapamycin-treated cells, but neither paralleled LC3B-II levels in starved cells nor presented a correlation with LC3B-II accumulation in WBCs from healthy donors or leukemia patients. However, when DTT was added to the system, ATG4 activity not only paralleled LC3B-II levels in starved cells in the presence or absence of autophagy inhibitors, but also presented a positive correlation with LC3B-II accumulation in WBCs from leukemia patients (<i>R<sup>2</sup></i> = 0.5288). In conclusion, this study provides a convenient, rapid, and quantitative method to monitor ATG4 activity in living cells, which may be beneficial to basic and clinical research on autophagy.
DOI: 10.6084/m9.figshare.1378877
title: Zircon U–Pb geochronology and Hf isotopic constraints on the petrogenesis of Early Triassic granites in the Wulonggou area of the Eastern Kunlun Orogen, Northwest China

description: Widespread granitic intrusions in the northeast part of the Wulonggou area were previously thought to be emplaced into the Palaeoproterozoic Jinshuikou Group during the Neoproterozoic. This contribution presents detailed LA-ICP-MS zircon U–Pb geochronology, major and trace element geochemistry, and zircon Hf isotope systematic on the Wulonggou Granodiorite and Xiaoyakou Granite from the Wulonggou area. Three granodiorite samples yielded U–Pb zircon ages of 247 ± 2, 248 ± 1, and 249 ± 1 Ma, and one granite sample yielded U–Pb zircon age of 246 ± 3 Ma. The granodiorite samples are metaluminous with an alumina saturation index of 0.90–0.96, as well as intermediate- to high-alkali contents of 5.49–6.14 wt.%, and low Zr+Nb+Ce+Y contents, and low Fe<sub>2</sub>O<sub>3T</sub>/MgO ratios, which suggest an I-type classical island arc magmatic source. The granite samples are peraluminous with an alumina saturation index of 1.02–1.03, Sr content of 305.00–374.00 ppm, Sr/Y ratios of between 17.68 and 28.77, (La/Yb)<sub>N</sub> values of 16.98–25.07, low HREEs (Yb = 1.10–2.00 ppm), and low Y (13.00–21.10 ppm), which suggest adakite-like rocks. All granodiorite samples have zircons <i>ε</i><sub>Hf</sub>(<i>t</i>) values ranging from −2.9 to +3.9, and granite samples have zircon <i>ε</i><sub>Hf</sub>(<i>t</i>) values ranging from −7.8 to +3.2. These Hf isotopic data suggest that the Early Triassic granites were derived from the partial melting of a mafic Mesoproterozoic lower crust, although the degree of ancient crustal assimilation may be higher for the Xiaoyakou Granite. It is suggested here that the ca. 246–248 Ma magma was generated during the northward subduction of the Palaeo-Tethys oceanic plate.
DOI: 10.6084/m9.figshare.1378877.v3
title: Zircon U–Pb geochronology and Hf isotopic constraints on the petrogenesis of Early Triassic granites in the Wulonggou area of the Eastern Kunlun Orogen, Northwest China

description: Widespread granitic intrusions in the northeast part of the Wulonggou area were previously thought to be emplaced into the Palaeoproterozoic Jinshuikou Group during the Neoproterozoic. This contribution presents detailed LA-ICP-MS zircon U–Pb geochronology, major and trace element geochemistry, and zircon Hf isotope systematic on the Wulonggou Granodiorite and Xiaoyakou Granite from the Wulonggou area. Three granodiorite samples yielded U–Pb zircon ages of 247 ± 2, 248 ± 1, and 249 ± 1 Ma, and one granite sample yielded U–Pb zircon age of 246 ± 3 Ma. The granodiorite samples are metaluminous with an alumina saturation index of 0.90–0.96, as well as intermediate- to high-alkali contents of 5.49–6.14 wt.%, and low Zr+Nb+Ce+Y contents, and low Fe<sub>2</sub>O<sub>3T</sub>/MgO ratios, which suggest an I-type classical island arc magmatic source. The granite samples are peraluminous with an alumina saturation index of 1.02–1.03, Sr content of 305.00–374.00 ppm, Sr/Y ratios of between 17.68 and 28.77, (La/Yb)<sub>N</sub> values of 16.98–25.07, low HREEs (Yb = 1.10–2.00 ppm), and low Y (13.00–21.10 ppm), which suggest adakite-like rocks. All granodiorite samples have zircons <i>ε</i><sub>Hf</sub>(<i>t</i>) values ranging from −2.9 to +3.9, and granite samples have zircon <i>ε</i><sub>Hf</sub>(<i>t</i>) values ranging from −7.8 to +3.2. These Hf isotopic data suggest that the Early Triassic granites were derived from the partial melting of a mafic Mesoproterozoic lower crust, although the degree of ancient crustal assimilation may be higher for the Xiaoyakou Granite. It is suggested here that the ca. 246–248 Ma magma was generated during the northward subduction of the Palaeo-Tethys oceanic plate.
DOI: 10.6084/m9.figshare.1378877.v2
title: Zircon U–Pb geochronology and Hf isotopic constraints on the petrogenesis of Early Triassic granites in the Wulonggou area of the Eastern Kunlun Orogen, Northwest China

description: Widespread granitic intrusions in the northeast part of the Wulonggou area were previously thought to be emplaced into the Palaeoproterozoic Jinshuikou Group during the Neoproterozoic. This contribution presents detailed LA-ICP-MS zircon U–Pb geochronology, major and trace element geochemistry, and zircon Hf isotope systematic on the Wulonggou Granodiorite and Xiaoyakou Granite from the Wulonggou area. Three granodiorite samples yielded U–Pb zircon ages of 247 ± 2, 248 ± 1, and 249 ± 1 Ma, and one granite sample yielded U–Pb zircon age of 246 ± 3 Ma. The granodiorite samples are metaluminous with an alumina saturation index of 0.90–0.96, as well as intermediate- to high-alkali contents of 5.49–6.14 wt.%, and low Zr+Nb+Ce+Y contents, and low Fe<sub>2</sub>O<sub>3T</sub>/MgO ratios, which suggest an I-type classical island arc magmatic source. The granite samples are peraluminous with an alumina saturation index of 1.02–1.03, Sr content of 305.00–374.00 ppm, Sr/Y ratios of between 17.68 and 28.77, (La/Yb)<sub>N</sub> values of 16.98–25.07, low HREEs (Yb = 1.10–2.00 ppm), and low Y (13.00–21.10 ppm), which suggest adakite-like rocks. All granodiorite samples have zircons <i>ε</i><sub>Hf</sub>(<i>t</i>) values ranging from −2.9 to +3.9, and granite samples have zircon <i>ε</i><sub>Hf</sub>(<i>t</i>) values ranging from −7.8 to +3.2. These Hf isotopic data suggest that the Early Triassic granites were derived from the partial melting of a mafic Mesoproterozoic lower crust, although the degree of ancient crustal assimilation may be higher for the Xiaoyakou Granite. It is suggested here that the ca. 246–248 Ma magma was generated during the northward subduction of the Palaeo-Tethys oceanic plate.
DOI: 10.6084/m9.figshare.1378905
title: Geochronology and geochemistry of the Dabure basalts, central Qiangtang, Tibet: evidence for ~550 Ma rifting of Gondwana

description: Newly discovered basalts in the Dabure area (central Qiangtang block, northern Tibet) were subjected to laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) U–Pb zircon dating, geochemical analyses, and zircon Hf isotope analyses. Dating of magmatic zircons from three basalt samples indicates that the Dabure basalts formed during the late Ediacaran (~550 Ma). Xenocrystic zircons yield ages of 700–1150 Ma, providing evidence of the Cryogenian crust in the Tibet block. The Dabure basalts are alkaline, rich in Ti and Fe, and are strongly enriched in light rare earth elements without Eu anomalies. The basalts are geochemically similar to within-plate basalts but are relatively depleted in Nb and Ta. Although the analysed zircons show differences in their Hf isotope compositions, the geochemical data suggest that the Dabure basalts were derived from enriched mantle and that the source magmas were contaminated by the continental crust. The basalts may have erupted during rifting at ~550 Ma (from the dating of magmatic zircons), and may have been a product of the initial breakup of Gondwanaland.
DOI: 10.6084/m9.figshare.1378905.v1
title: Geochronology and geochemistry of the Dabure basalts, central Qiangtang, Tibet: evidence for ~550 Ma rifting of Gondwana

description: Newly discovered basalts in the Dabure area (central Qiangtang block, northern Tibet) were subjected to laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) U–Pb zircon dating, geochemical analyses, and zircon Hf isotope analyses. Dating of magmatic zircons from three basalt samples indicates that the Dabure basalts formed during the late Ediacaran (~550 Ma). Xenocrystic zircons yield ages of 700–1150 Ma, providing evidence of the Cryogenian crust in the Tibet block. The Dabure basalts are alkaline, rich in Ti and Fe, and are strongly enriched in light rare earth elements without Eu anomalies. The basalts are geochemically similar to within-plate basalts but are relatively depleted in Nb and Ta. Although the analysed zircons show differences in their Hf isotope compositions, the geochemical data suggest that the Dabure basalts were derived from enriched mantle and that the source magmas were contaminated by the continental crust. The basalts may have erupted during rifting at ~550 Ma (from the dating of magmatic zircons), and may have been a product of the initial breakup of Gondwanaland.
DOI: 10.6084/m9.figshare.1378905.v3
title: Geochronology and geochemistry of the Dabure basalts, central Qiangtang, Tibet: evidence for ~550 Ma rifting of Gondwana

description: Newly discovered basalts in the Dabure area (central Qiangtang block, northern Tibet) were subjected to laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) U–Pb zircon dating, geochemical analyses, and zircon Hf isotope analyses. Dating of magmatic zircons from three basalt samples indicates that the Dabure basalts formed during the late Ediacaran (~550 Ma). Xenocrystic zircons yield ages of 700–1150 Ma, providing evidence of the Cryogenian crust in the Tibet block. The Dabure basalts are alkaline, rich in Ti and Fe, and are strongly enriched in light rare earth elements without Eu anomalies. The basalts are geochemically similar to within-plate basalts but are relatively depleted in Nb and Ta. Although the analysed zircons show differences in their Hf isotope compositions, the geochemical data suggest that the Dabure basalts were derived from enriched mantle and that the source magmas were contaminated by the continental crust. The basalts may have erupted during rifting at ~550 Ma (from the dating of magmatic zircons), and may have been a product of the initial breakup of Gondwanaland.
DOI: 10.6084/m9.figshare.1378905.v2
title: Geochronology and geochemistry of the Dabure basalts, central Qiangtang, Tibet: evidence for ~550 Ma rifting of Gondwana

description: Newly discovered basalts in the Dabure area (central Qiangtang block, northern Tibet) were subjected to laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) U–Pb zircon dating, geochemical analyses, and zircon Hf isotope analyses. Dating of magmatic zircons from three basalt samples indicates that the Dabure basalts formed during the late Ediacaran (~550 Ma). Xenocrystic zircons yield ages of 700–1150 Ma, providing evidence of the Cryogenian crust in the Tibet block. The Dabure basalts are alkaline, rich in Ti and Fe, and are strongly enriched in light rare earth elements without Eu anomalies. The basalts are geochemically similar to within-plate basalts but are relatively depleted in Nb and Ta. Although the analysed zircons show differences in their Hf isotope compositions, the geochemical data suggest that the Dabure basalts were derived from enriched mantle and that the source magmas were contaminated by the continental crust. The basalts may have erupted during rifting at ~550 Ma (from the dating of magmatic zircons), and may have been a product of the initial breakup of Gondwanaland.
DOI: 10.6084/m9.figshare.1381865
title: Molecular Dynamics Simulations of Sheet-like Replicators

description: This dataset contains 3D structures, MD trajectories and powder X-ray diffractograms (simulated and experimental) of tetrameric carboxynaphthalene disulfide. The MD simulations were performed in water with periodic boundary conditions. Either AMBER or GROMACS packages were used. For detailed description of the simulations see the linked paper (the link will appear upon acceptance). 
 
PDB files are snapshots from the MD simulations; they can be viewed using any 3D structure viewer (e.g. Avogadro). The trajectories (*.xtc - GROMACS, *.mdcrd - AMBER/NetCDF) can be visualized using e.g. VMD.
Partial charges for the naphthalene building blocks are provided within *.mol2 files (N-0 for the neutral and N-1 for the deprotonated subunit). 
The parameter/topology files have .top (GROMACS) and .prmtop (AMBER) extensions. 
Files labeled "sheet1" contain results of simulations of 16 repeats of tetramer IV showed in Figure 4 and S13 of the paper. The suffix "-exp_box" refers to structures which were constrained to the box determined experimentally ("min" - after energy minimization, "equil" - after equilibration).
Files labeled "sheet2" contain results of simulations of 12 repeats of tetramer IV showed in Figure S14 of the paper. 
Files labeled "sheet3" contain results of simulations of 16 repeats of tetramer IV showed in Figure S15 of the paper. The assembly was unstable, the initial structure started dissociating from the very beginning of the simulation. The trajectory is in NetCDF format.
Files labeled "tetramerIV-2" contain results of simulations of isolated, partially deprotonated tetramer IV in water (solvent was removed from the trajectory).
Link to the article will be added upon its acceptance.
DOI: 10.6084/m9.figshare.1381865.v1
title: Molecular Dynamics Simulations of Sheet-like Replicators

description: This dataset contains 3D structures, MD trajectories and powder X-ray diffractograms (simulated and experimental) of tetrameric carboxynaphthalene disulfide. The MD simulations were performed in water with periodic boundary conditions. Either AMBER or GROMACS packages were used. For detailed description of the simulations see the linked paper (the link will appear upon acceptance). 
 
PDB files are snapshots from the MD simulations; they can be viewed using any 3D structure viewer (e.g. Avogadro). The trajectories (*.xtc - GROMACS, *.mdcrd - AMBER/NetCDF) can be visualized using e.g. VMD.
Partial charges for the naphthalene building blocks are provided within *.mol2 files (N-0 for the neutral and N-1 for the deprotonated subunit). 
The parameter/topology files have .top (GROMACS) and .prmtop (AMBER) extensions. 
Files labeled "sheet1" contain results of simulations of 16 repeats of tetramer IV showed in Figure 4 and S13 of the paper. The suffix "-exp_box" refers to structures which were constrained to the box determined experimentally ("min" - after energy minimization, "equil" - after equilibration).
Files labeled "sheet2" contain results of simulations of 12 repeats of tetramer IV showed in Figure S14 of the paper. 
Files labeled "sheet3" contain results of simulations of 16 repeats of tetramer IV showed in Figure S15 of the paper. The assembly was unstable, the initial structure started dissociating from the very beginning of the simulation. The trajectory is in NetCDF format.
Files labeled "tetramerIV-2" contain results of simulations of isolated, partially deprotonated tetramer IV in water (solvent was removed from the trajectory).
Link to the article will be added upon its acceptance.
DOI: 10.6084/m9.figshare.1384844
title: Prenatal antidepressant exposure associated with <i>CYP2E1</i> DNA methylation change in neonates

description: Some but not all neonates are affected by prenatal exposure to serotonin reuptake inhibitor antidepressants (SRI) and maternal mood disturbances. Distinguishing the impact of these 2 exposures is challenging and raises critical questions about whether pharmacological, genetic, or epigenetic factors can explain the spectrum of reported outcomes. Using unbiased DNA methylation array measurements followed by a detailed candidate gene approach, we examined whether prenatal SRI exposure was associated with neonatal DNA methylation changes and whether such changes were associated with differences in birth outcomes. Prenatal SRI exposure was first associated with increased DNA methylation status primarily at <i>CYP2E1</i>(β<sub>Non-exposed</sub> = 0.06, β<sub>SRI-exposed</sub> = 0.30, FDR = 0); however, this finding could not be distinguished from the potential impact of prenatal maternal depressed mood. Then, using pyrosequencing of <i>CYP2E1</i> regulatory regions in an expanded cohort, higher DNA methylation status—both the mean across 16 CpG sites (<i>P</i> &lt; 0.01) and at each specific CpG site (<i>P</i> &lt; 0.05)—was associated with exposure to lower 3rd trimester maternal depressed mood symptoms only in the SRI-exposed neonates, indicating a maternal mood x SRI exposure interaction. In addition, higher DNA methylation levels at CpG2 (<i>P</i> = 0.04), CpG9 (<i>P</i> = 0.04) and CpG10 (<i>P</i> = 0.02), in the interrogated <i>CYP2E1</i> region, were associated with increased birth weight independently of prenatal maternal mood, SRI drug exposure, or gestational age at birth. Prenatal SRI antidepressant exposure and maternal depressed mood were associated with altered neonatal <i>CYP2E1</i> DNA methylation status, which, in turn, appeared to be associated with birth weight.