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  • 1
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    Balkema
    In:  Professional Paper, The Effects of Surface Geology on Seismic Motion (Vol. 1), Rotterdam, Balkema, vol. 14, no. 16, pp. 121-133, (ISBN 0080419208)
    Publication Date: 1998
    Keywords: Modelling ; Synthetic seismograms ; Strong motions ; Three dimensional ; Finite Element Method
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  • 2
    Publication Date: 2012-11-11
    Description: Motivation: It becomes widely accepted that human cancer is a disease involving dynamic changes in the genome and that the missense mutations constitute the bulk of human genetic variations. A multitude of computational algorithms, especially the machine learning-based ones, has consequently been proposed to distinguish missense changes that contribute to the cancer progression (‘driver’ mutation) from those that do not (‘passenger’ mutation). However, the existing methods have multifaceted shortcomings, in the sense that they either adopt incomplete feature space or depend on protein structural databases which are usually far from integrated. Results: In this article, we investigated multiple aspects of a missense mutation and identified a novel feature space that well distinguishes cancer-associated driver mutations from passenger ones. An index (DX score) was proposed to evaluate the discriminating capability of each feature, and a subset of these features which ranks top was selected to build the SVM classifier. Cross-validation showed that the classifier trained on our selected features significantly outperforms the existing ones both in precision and robustness. We applied our method to several datasets of missense mutations culled from published database and literature and obtained more reasonable results than previous studies. Availability : The software is available online at http://www.methodisthealth.com/software and https://sites.google.com/site/drivermutationidentification/ . Contact : xzhou@tmhs.org Supplementary information : Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 3
    Publication Date: 2012-04-15
    Description: Exome sequencing strategy is promising for finding novel mutations of human monogenic disorders. However, pinpointing the casual mutation in a small number of samples is still a big challenge. Here, we propose a three-level filtration and prioritization framework to identify the casual mutation(s) in exome sequencing studies. This efficient and comprehensive framework successfully narrowed down whole exome variants to very small numbers of candidate variants in the proof-of-concept examples. The proposed framework, implemented in a user-friendly software package, named KGGSeq ( http://statgenpro.psychiatry.hku.hk/kggseq ), will play a very useful role in exome sequencing-based discovery of human Mendelian disease genes.
    Keywords: Computational Methods, Massively Parallel (Deep) Sequencing, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 4
    Publication Date: 2019
    Description: 〈p〉The zigzag-edged triangular graphene molecules (ZTGMs) have been predicted to host ferromagnetically coupled edge states with the net spin scaling with the molecular size, which affords large spin tunability crucial for next-generation molecular spintronics. However, the scalable synthesis of large ZTGMs and the direct observation of their edge states have been long-standing challenges because of the molecules’ high chemical instability. Here, we report the bottom-up synthesis of -extended [5]triangulene with atomic precision via surface-assisted cyclodehydrogenation of a rationally designed molecular precursor on metallic surfaces. Atomic force microscopy measurements unambiguously resolve its ZTGM-like skeleton consisting of 15 fused benzene rings, while scanning tunneling spectroscopy measurements reveal edge-localized electronic states. Bolstered by density functional theory calculations, our results show that [5]triangulenes synthesized on Au(111) retain the open-shell -conjugated character with magnetic ground states.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 5
    Publication Date: 2013-10-09
    Description: Previous genome-wide association studies (GWASs) identified multiple susceptibility loci that have highlighted the important role of TLR (Toll-like receptor) and CARD (caspase recruitment domain) genes in leprosy. A large three-stage candidate gene-based association study of 30 TLR and 47 CARD genes was performed in the leprosy samples of Chinese Han. Of 4363 SNPs investigated, eight SNPs showed suggestive association ( P 〈 0.01) in our previously published GWAS datasets (Stage 1). Of the eight SNPs, rs2735591 and rs4889841 showed significant association ( P 〈 0.001) in an independent series of 1504 cases and 1502 controls (Stage 2), but only rs2735591 (next to BCL10 ) showed significant association in the second independent series of 938 cases and 5827 controls (Stage 3). Rs2735591 showed consistent association across the three stages ( P 〉 0.05 for heterogeneity test), significant association in the combined validation samples (P corrected = 5.54 x 10 –4 after correction for 4363 SNPs tested) and genome-wide significance in the whole GWAS and validation samples ( P = 1.03 x 10 –9 , OR = 1.24). In addition, we demonstrated the lower expression of BCL10 in leprosy lesions than normal skins and a significant gene connection between BCL10 and the eight previously identified leprosy loci that are associated with NFB, a major regulator of downstream inflammatory responses, which provides further biological evidence for the association. We have discovered a novel susceptibility locus on 1p22, which implicates BCL10 as a new susceptibility gene for leprosy. Our finding highlights the important role of both innate and adaptive immune responses in leprosy.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 6
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-08-05
    Description: Mass-independent isotopic signatures for delta(33)S, delta(34)S, and delta(36)S from sulfide and sulfate in Precambrian rocks indicate that a change occurred in the sulfur cycle between 2090 and 2450 million years ago (Ma). Before 2450 Ma, the cycle was influenced by gas-phase atmospheric reactions. These atmospheric reactions also played a role in determining the oxidation state of sulfur, implying that atmospheric oxygen partial pressures were low and that the roles of oxidative weathering and of microbial oxidation and reduction of sulfur were minimal. Atmospheric fractionation processes should be considered in the use of sulfur isotopes to study the onset and consequences of microbial fractionation processes in Earth's early history.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Farquhar -- Bao -- Thiemens -- New York, N.Y. -- Science. 2000 Aug 4;289(5480):756-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA. E-mail: jfarquha@ucsd.edu (J.F. ); hbao@ucsd.edu (H.B.); and MHT@chem.ucsd.edu (M.T.).〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10926533" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2010-06-19
    Description: Volcanic eruptions release a large amount of sulphur dioxide (SO(2)) into the atmosphere. SO(2) is oxidized to sulphate and can subsequently form sulphate aerosol, which can affect the Earth's radiation balance, biologic productivity and high-altitude ozone concentrations, as is evident from recent volcanic eruptions. SO(2) oxidation can occur via several different pathways that depend on its flux and the atmospheric conditions. An investigation into how SO(2) is oxidized to sulphate-the oxidation product preserved in the rock record-can therefore shed light on past volcanic eruptions and atmospheric conditions. Here we use sulphur and triple oxygen isotope measurements of atmospheric sulphate extracted from tuffaceous deposits to investigate the specific oxidation pathways from which the sulphate was formed. We find that seven eruption-related sulphate aerosol deposition events have occurred during the mid-Cenozoic era (34 to 7 million years ago) in the northern High Plains, North America. Two extensively sampled ash beds display a similar sulphate mixing pattern that has two distinct atmospheric secondary sulphates. A three-dimensional atmospheric sulphur chemistry and transport model study reveals that the observed, isotopically discrete sulphates in sediments can be produced only in initially alkaline cloudwater that favours an ozone-dominated SO(2) oxidation pathway in the troposphere. Our finding suggests that, in contrast to the weakly acidic conditions today, cloudwater in the northern High Plains may frequently have been alkaline during the mid-Cenozoic era. We propose that atmospheric secondary sulphate preserved in continental deposits represents an unexploited geological archive for atmospheric SO(2) oxidation chemistry linked to volcanism and atmospheric conditions in the past.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bao, Huiming -- Yu, Shaocai -- Tong, Daniel Q -- England -- Nature. 2010 Jun 17;465(7300):909-12. doi: 10.1038/nature09100.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geology and Geophysics, Louisiana State University, Baton Rouge, Louisiana 70803-4101, USA. bao@lsu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20559384" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2008-05-24
    Description: Understanding the composition of the atmosphere over geological time is critical to understanding the history of the Earth system, as the atmosphere is closely linked to the lithosphere, hydrosphere and biosphere. Although much of the history of the lithosphere and hydrosphere is contained in rock and mineral records, corresponding information about the atmosphere is scarce and elusive owing to the lack of direct records. Geologists have used sedimentary minerals, fossils and geochemical models to place constraints on the concentrations of carbon dioxide, oxygen or methane in the past. Here we show that the triple oxygen isotope composition of sulphate from ancient evaporites and barites shows variable negative oxygen-17 isotope anomalies over the past 750 million years. We propose that these anomalies track those of atmospheric oxygen and in turn reflect the partial pressure of carbon dioxide (P(CO2)) in the past through a photochemical reaction network linking stratospheric ozone to carbon dioxide and to oxygen. Our results suggest that P(CO2) was much higher in the early Cambrian than in younger eras, agreeing with previous modelling results. We also find that the (17)O isotope anomalies of barites from Marinoan (approximately 635 million years ago) cap carbonates display a distinct negative spike (around -0.70 per thousand), suggesting that by the time barite was precipitating in the immediate aftermath of a Neoproterozoic global glaciation, the P(CO2) was at its highest level in the past 750 million years. Our finding is consistent with the 'snowball Earth' hypothesis and/or a massive methane release after the Marinoan glaciation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bao, Huiming -- Lyons, J R -- Zhou, Chuanming -- England -- Nature. 2008 May 22;453(7194):504-6. doi: 10.1038/nature06959.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geology and Geophysics, E235 Howe-Russell Geoscience Complex, Louisiana State University, Baton Rouge, Louisiana 70803, USA. bao@lsu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18497821" target="_blank"〉PubMed〈/a〉
    Keywords: Atmosphere/*chemistry ; Barium Sulfate/chemistry ; Carbon Dioxide/*analysis/metabolism ; Geologic Sediments/*chemistry ; History, Ancient ; *Ice Cover ; Oxygen Isotopes ; Ozone/analysis/chemistry ; Partial Pressure ; Photochemistry
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2009-01-03
    Description: The oxygen isotope composition of terrestrial sulfate is affected measurably by many Earth-surface processes. During the Neoproterozoic, severe "snowball" glaciations would have had an extreme impact on the biosphere and the atmosphere. Here, we report that sulfate extracted from carbonate lenses within a Neoproterozoic glacial diamictite suite from Svalbard, with an age of approximately 635 million years ago, falls well outside the currently known natural range of triple oxygen isotope compositions and indicates that the atmosphere had either an exceptionally high atmospheric carbon dioxide concentration or an utterly unfamiliar oxygen cycle during deposition of the diamictites.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bao, Huiming -- Fairchild, Ian J -- Wynn, Peter M -- Spotl, Christoph -- New York, N.Y. -- Science. 2009 Jan 2;323(5910):119-22. doi: 10.1126/science.1165373.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geology and Geophysics, E235 Howe-Russell Complex, Louisiana State University, Baton Rouge, LA 70803, USA. bao@lsu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19119231" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2019
    Description: 〈p〉Although Cas9-mediated genome editing has been widely used to engineer alleles in animal models of human inherited diseases, very few homology-directed repair (HDR)–based genetic editing systems have been established in postnatal mouse models for effective and lasting phenotypic rescue. Here, we developed an HDR-based Cas9/RecA system to precisely correct 〈i〉Pde6b〈/i〉 mutation with increased HDR efficiency in postnatal 〈i〉rodless〈/i〉 (〈i〉rd1〈/i〉) mice, a retinitis pigmentosa (RP) mutant model characterized by photoreceptor degeneration and loss of vision. The Cas9/RecA system incorporated Cas9 endonuclease enzyme to generate double-strand breaks (DSBs) and bacterial recombinase A (RecA) to increase homologous recombination. Our data revealed that Cas9/RecA treatment significantly promoted the survival of both rod and cone photoreceptors, restored the expression of PDE6B in rod photoreceptors, and enhanced the visual functions of 〈i〉rd1〈/i〉 mice. Thus, this study provides a precise therapeutic strategy for RP and other genetic diseases.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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