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  • 1
    Publication Date: 2016-05-05
    Description: On 2012 April 11, a great strike-slip earthquake (moment magnitude of M w 8.6) occurred off the west coast of northern Sumatra area followed by an M w 8.2 aftershock 2 hr later. Different geophysical data and methods have been used to investigate the mechanism, faulting, seismic radiation and slip propagation of this event, but frequency-dependent features of its rupture process have not been discussed much. In this study, we use a compressive sensing method based on sparsity inversion in the frequency domain to study the frequency-dependent seismic radiation and rupture process of this event. Our results indicate a very complex rupture process concerning at least three different rupture stages on multiple subfaults with nearly conjugate geometries. The main shock has triggered seismicity on a series of ridge-perpendicular or ridge-parallel conjugate strike-slip faults around the Nighty East Ridge. Obvious frequency-dependent rupture process has been presented and discussed. Combining results from slip inversion based on the finite-fault model, we observe that in the beginning stage of the rupture lower frequency radiation appears to originate from the areas with large slip, while the high-frequency radiation is located at the boundary of large-slip region or rupture front. Some radiation probably originates from the repeating slip on the main faults or triggered events on some nearby faults in the rupture area. The complex frequency-dependent seismic radiation patterns observed in this study provide important information for future investigation of rupture physics of this complex strike-slip event.
    Keywords: Seismology
    Print ISSN: 0956-540X
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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  • 2
    Publication Date: 2016-10-04
    Description: Motivation: Despite the widespread popularity of genome-wide association studies (GWAS) for genetic mapping of complex traits, most existing GWAS methodologies are still limited to the use of static phenotypes measured at a single time point. In this work, we propose a new method for association mapping that considers dynamic phenotypes measured at a sequence of time points. Our approach relies on the use of Time-Varying Group Sparse Additive Models (TV-GroupSpAM) for high-dimensional, functional regression. Results: This new model detects a sparse set of genomic loci that are associated with trait dynamics, and demonstrates increased statistical power over existing methods. We evaluate our method via experiments on synthetic data and perform a proof-of-concept analysis for detecting single nucleotide polymorphisms associated with two phenotypes used to assess asthma severity: forced vital capacity, a sensitive measure of airway obstruction and bronchodilator response, which measures lung response to bronchodilator drugs. Availability and Implementation: Source code for TV-GroupSpAM freely available for download at http://www.cs.cmu.edu/~mmarchet/projects/tv_group_spam , implemented in MATLAB. Contact: epxing@cs.cmu.edu 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: 2015-11-06
    Description: Congenital sodium diarrhea (CSD) refers to an intractable diarrhea of intrauterine onset with high fecal sodium loss. CSD is clinically and genetically heterogeneous. Syndromic CSD is caused by SPINT2 mutations. While we recently described four cases of the non-syndromic form of CSD that were caused by dominant activating mutations in intestinal receptor guanylate cyclase C (GC-C), the genetic cause for the majority of CSD is still unknown. Therefore, we aimed to determine the genetic cause for non-GC-C non-syndromic CSD in 18 patients from 16 unrelated families applying whole-exome sequencing and/or chromosomal microarray analyses and/or direct Sanger sequencing. SLC9A3 missense, splicing and truncation mutations, including an instance of uniparental disomy, and whole-gene deletion were identified in nine patients from eight families with CSD. Two of these nine patients developed inflammatory bowel disease (IBD) at 4 and 16 years of age. SLC9A3 encodes Na + /H + antiporter 3 (NHE3), which is the major intestinal brush-border Na + /H + exchanger. All mutations were in the NHE3 N-terminal transport domain, and all missense mutations were in the putative membrane-spanning domains. Identified SLC9A3 missense mutations were functionally characterized in plasma membrane NHE null fibroblasts. SLC9A3 missense mutations compromised NHE3 activity by reducing basal surface expression and/or loss of basal transport function of NHE3 molecules, whereas acute regulation was normal. This study identifies recessive mutations in NHE3, a downstream target of GC-C, as a cause of CSD and implies primary basal NHE3 malfunction as a predisposition for IBD in a subset of patients.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 4
    Publication Date: 2015-04-02
    Description: Precise and fluent genetic manipulation is still limited to only a few prokaryotes. Ideally the highly advanced technologies available in Escherichia coli could be broadly applied. Our efforts to apply lambda Red technology, widely termed ‘recombineering’, in Photorhabdus and Xenorhabdus yielded only limited success. Consequently we explored the properties of an endogenous Photorhabdus luminescens lambda Red-like operon, Plu2934/Plu2935/Plu2936. Bioinformatic and functional tests indicate that Plu2936 is a 5’-3’ exonuclease equivalent to Redα and Plu2935 is a single strand annealing protein equivalent to Redβ. Plu2934 dramatically enhanced recombineering efficiency. Results from bioinformatic analysis and recombineering assays suggest that Plu2934 may be functionally equivalent to Red, which inhibits the major endogenous E. coli nuclease, RecBCD. The recombineering utility of Plu2934/Plu2935/Plu2936 was demonstrated by engineering Photorhabdus and Xenorhabdus genomes, including the activation of the 49-kb non-ribosomal peptide synthase (NRPS) gene cluster plu2670 by insertion of a tetracycline inducible promoter. After tetracycline induction, novel secondary metabolites were identified. Our work unlocks the potential for bioprospecting and functional genomics in the Photorhabdus, Xenorhabdus and related genomes.
    Keywords: Recombination
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 5
    Publication Date: 2015-10-18
    Description: Bone mineral density (BMD) is a highly heritable trait used both for the diagnosis of osteoporosis in adults and to assess bone health in children. Ethnic differences in BMD have been documented, with markedly higher levels in individuals of African descent, which partially explain disparity in osteoporosis risk across populations. To date, 63 independent genetic variants have been associated with BMD in adults of Northern-European ancestry. Here, we demonstrate that at least 61 of these variants are predictive of BMD early in life by studying their compound effect within two multiethnic pediatric cohorts. Furthermore, we show that within these cohorts and across populations worldwide the frequency of those alleles associated with increased BMD is systematically elevated in individuals of Sub-Saharan African ancestry. The amount of differentiation in the BMD genetic scores among Sub-Saharan and non-Sub-Saharan populations together with neutrality tests, suggest that these allelic differences are compatible with the hypothesis of selective pressures acting on the genetic determinants of BMD. These findings constitute an explorative contribution to the role of selection on ethnic BMD differences and likely a new example of polygenic adaptation acting on a human trait.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
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  • 6
    Publication Date: 2015-10-23
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 7
    Publication Date: 2019
    Description: 〈span〉〈div〉SUMMARY〈/div〉Backprojection (BP) of teleseismic 〈span〉P〈/span〉 waves is a powerful tool to study the evolution of seismic radiation of large earthquakes. The common interpretations on the BP results are qualitative comparisons with earthquake kinematic observations, such as the evolution of slip on the fault and rupture velocity. However, the direct relation between the BP images and physical properties of the earthquake rupture process remains unclear and is needed for further application of this technique. In this study, we start from a theoretical formulation of the BP images, which is linear in the frequency domain, and carry on a synthetic exercise with kinematic source representations and virtual receivers embedded in a homogeneous full-space. We find that the fundamental linear formulation of the BP method is most correlated with the true kinematic source properties: in frequency domain the BP images are proportional to the images of slip motion through a scaling matrix $\mathbf {F}(\omega )$ that accounts for radiation pattern and source–receiver geometry and that acts as a spatial smoothing operator. Overall, the synthetic BP images match relatively well the kinematic models and our exercise validates that the BP image can be directly used to track the spatiotemporal propagation of rupture front. However, because $\mathbf {F}(\omega )$ is not strictly an identity matrix due to limited station coverage in space (azimuth and distance) and to the limited frequency bands of the seismograms, it remains difficult to recover the details in the rupture fronts from BP images. We define a resolvability parameter ε〈sub〉〈span〉I〈/span〉〈/sub〉(ω) built from $\mathbf {F}(\omega )$ that incorporates fault geometry, radiation pattern and wave propagation (source–array geometry) to quantify the ability of the BP method to resolve details of the rupture on the fault. ε〈sub〉〈span〉I〈/span〉〈/sub〉(ω) successfully captures the similarity between BP images and kinematic source. We analyse the resolvability of most tectonically active regions and the most commonly used seismic arrays. Based on this global resolvability analysis, we propose an empirical relation between the seismic frequency, resolvable area and earthquake magnitude. It provides general guidelines to choose the lowest frequency in seismic waveform (e.g. about 0.3 Hz for 〈span〉M〈/span〉〈sub〉w〈/sub〉 8 and 1 Hz for 〈span〉M〈/span〉〈sub〉w〈/sub〉 7 earthquakes) and to interpret the BP image in terms of the source kinematics. In general, this work attempts to provide a clear interpretation of the BP images in light of the real earthquake rupture process and give a systematic evaluation of seismic data limitations.〈/span〉
    Print ISSN: 2051-1965
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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  • 8
    Publication Date: 2012-05-29
    Description: Differences in siphonophore communities between summer and winter in the northern South China Sea and the influence of environmental conditions on their variations were studied. Our results suggested that local coastal upwelling and surface ocean currents driven by the southwest monsoon enhanced the species number and abundance of siphonophores in summer, while the northeast monsoon forced the cold coastal current into the study area, resulting in low species richness and abundance in winter.
    Print ISSN: 0142-7873
    Electronic ISSN: 1464-3774
    Topics: Biology
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  • 9
    Publication Date: 2014-11-21
    Description: WRKY proteins are involved in various physiological processes in plants, especially in coping with diverse biotic and abiotic stresses. However, limited information is available on the roles of specific WRKY transcription factors in poplar defense. In this study, we reported the characterization of PtoWRKY60 , a Group IIa WRKY member, from Populus tomentosa Carr. The gene expression profile of PtoWRKY60 in various tissues showed that it significantly accumulated in old leaves. Phylogenetic analyses revealed that PtoWRKY60 had a close relationship with AtWRKY18, AtWRKY40 and AtWRKY60. PtoWRKY60 was induced mainly by salicylic acid (SA) and slightly by Dothiorella gregaria Sacc., jasmonic acid, wounding treatment, low temperature and salinity stresses. Overexpression of PtoWRKY60 in poplar resulted in increased resistance to D. gregaria . The defense-associated genes, such as PR5.1 , PR5.2 , PR5.4 , PR5.5 and C PR5 , were markedly up-regulated in transgenic plants overexpressing PtoWRKY60 . These results indicate that PtoWRKY60 might be partly involved in the signal transduction pathway initiated by SA in Populus .
    Print ISSN: 0829-318X
    Electronic ISSN: 1758-4469
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
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  • 10
    Publication Date: 2014-11-27
    Description: Previous studies have emphasized ethnically heterogeneous human leukocyte antigen (HLA) classical allele associations to rheumatoid arthritis (RA) risk. We fine-mapped RA risk alleles within the major histocompatibility complex (MHC) in 2782 seropositive RA cases and 4315 controls of Asian descent. We applied imputation to determine genotypes for eight class I and II HLA genes to Asian populations for the first time using a newly constructed pan-Asian reference panel. First, we empirically measured high imputation accuracy in Asian samples. Then we observed the most significant association in HLA-DRβ1 at amino acid position 13, located outside the classical shared epitope ( P omnibus = 6.9 x 10 –135 ). The individual residues at position 13 have relative effects that are consistent with published effects in European populations (His 〉 Phe 〉 Arg 〉 Tyr Gly 〉 Ser)—but the observed effects in Asians are generally smaller. Applying stepwise conditional analysis, we identified additional independent associations at positions 57 (conditional P omnibus = 2.2 x 10 –33 ) and 74 (conditional P omnibus = 1.1 x 10 –8 ). Outside of HLA-DRβ1, we observed independent effects for amino acid polymorphisms within HLA-B (Asp9, conditional P = 3.8 x 10 –6 ) and HLA-DPβ1 (Phe9, conditional P = 3.0 x 10 –5 ) concordant with European populations. Our trans-ethnic HLA fine-mapping study reveals that (i) a common set of amino acid residues confer shared effects in European and Asian populations and (ii) these same effects can explain ethnically heterogeneous classical allelic associations (e.g. HLA-DRB1*09:01 ) due to allele frequency differences between populations. Our study illustrates the value of high-resolution imputation for fine-mapping causal variants in the MHC.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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