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  • Oxford University Press  (24)
  • American Physical Society (APS)  (7)
  • American Institute of Physics (AIP)
  • 2010-2014  (31)
  • 2012  (31)
  • 1
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    Oxford University Press
    Publication Date: 2012-12-21
    Description: Motivation: Pathway or gene set analysis has been widely applied to genomic data. Many current pathway testing methods use univariate test statistics calculated from individual genomic markers, which ignores the correlations and interactions between candidate markers. Random forests-based pathway analysis is a promising approach for incorporating complex correlation and interaction patterns, but one limitation of previous approaches is that pathways have been considered separately, thus pathway cross-talk information was not considered. Results: In this article, we develop a new pathway hunting algorithm for survival outcomes using random survival forests, which prioritize important pathways by accounting for gene correlation and genomic interactions. We show that the proposed method performs favourably compared with five popular pathway testing methods using both synthetic and real data. We find that the proposed methodology provides an efficient and powerful pathway modelling framework for high-dimensional genomic data. Availability: The R code for the analysis used in this article is available upon request. Contact: xi.steven.chen@gmail.com 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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  • 2
    Publication Date: 2012-12-15
    Description: The heat pulse method is widely used to measure water flux through plants; it works by using the speed at which a heat pulse is propagated through the system to infer the velocity of water through a porous medium. No systematic, non-destructive calibration procedure exists to determine the site-specific parameters necessary for calculating sap velocity, e.g., wood thermal diffusivity and probe spacing. Such parameter calibration is crucial to obtain the correct transpiration flux density from the sap flow measurements at the plant scale and subsequently to upscale tree-level water fluxes to canopy and landscape scales. The purpose of this study is to present a statistical framework for sampling and simultaneously estimating the tree's thermal diffusivity and probe spacing from in situ heat response curves collected by the implanted probes of a heat ratio measurement device. Conditioned on the time traces of wood temperature following a heat pulse, the parameters are inferred using a Bayesian inversion technique, based on the Markov chain Monte Carlo sampling method. The primary advantage of the proposed methodology is that it does not require knowledge of probe spacing or any further intrusive sampling of sapwood. The Bayesian framework also enables direct quantification of uncertainty in estimated sap flow velocity. Experiments using synthetic data show that repeated tests using the same apparatus are essential for obtaining reliable and accurate solutions. When applied to field conditions, these tests can be obtained in different seasons and can be automated using the existing data logging system. Empirical factors are introduced to account for the influence of non-ideal probe geometry on the estimation of heat pulse velocity, and are estimated in this study as well. The proposed methodology may be tested for its applicability to realistic field conditions, with an ultimate goal of calibrating heat ratio sap flow systems in practical applications.
    Print ISSN: 0829-318X
    Electronic ISSN: 1758-4469
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
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  • 3
    Publication Date: 2012-08-08
    Description: : SORTALLER is an online allergen classifier based on allergen family featured peptide (AFFP) dataset and normalized BLAST E-values, which establish the featured vectors for support vector machine (SVM). AFFPs are allergen-specific peptides panned from irredundant allergens and harbor perfect information with noise fragments eliminated because of their similarity to non-allergens. SORTALLER performed significantly better than other existing software and reached a perfect balance with high specificity (98.4%) and sensitivity (98.6%) for discriminating allergenic proteins from several independent datasets of protein sequences of diverse sources, also highlighting with the Matthews correlation coefficient (MCC) as high as 0.970, fast running speed and rapidly predicting a batch of amino acid sequences with a single click. Availability and implementation: http://sortaller.gzhmc.edu.cn/ . Contact: taoailin@gzhmc.edu.cn 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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  • 4
    Publication Date: 2012-09-01
    Description: Background.  Syphilis has made a rapid resurgence in China, especially among high-risk groups including female sex workers (FSWs). Methods.  Two cities in each of 3 provinces in South China were chosen and allocated to intervention or control arms. The intervention consisted of enhancing community-based syphilis screening outreach intervention with comprehensive sexually transmitted infection services at designated clinics while the control maintained routine intervention activities. Generalized linear modeling was used to examine effect of the intervention on incident syphilis infection. Results.  A total of 8275 women were eligible, and 3597 women enrolled (n = 2011 in control arm, n = 1586 in intervention arm) in the study. The median follow-up duration was 375 days (interquartile range, 267–475). Syphilis incidence density in the intervention group was reduced by 70% (95% confidence interval, 53%–81%) compared with the incidence in the control arm. The syphilis prevention intervention benefits were robust among FSWs at low-tier venues, individuals with less than high school education, migrants, and women who did not report condom use during the last episode of sex. Conclusions.  Integrated sexually transmitted infection and human immunodeficiency virus prevention strategies substantially reduce syphilis incidence among FSWs, especially among those at low-tier venues. This intervention suggests the need for scaling up comprehensive FSW programs in China.
    Print ISSN: 0022-1899
    Electronic ISSN: 1537-6613
    Topics: Medicine
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  • 5
    Publication Date: 2012-10-30
    Description: Polymorphisms in 3' untranslated region (UTR) of cancer-related genes might affect regulation by microRNA (miRNA) and contribute to carcinogenesis. In this study, we screened several single nucleotide polymorphisms (SNPs) in 3'UTR of cancer-related genes and investigated their effects on the risk of esophageal squamous cell carcinoma (ESCC). First, we used SNaPshot assay to genotype seven 3'UTR SNPs in 537 ESCC cases and 608 normal controls in a Chinese Han population and found that SNP rs6573 in 3'UTR of RAS-related proteins (RAP1A) was significantly associated with ESCC risk [ P = 0.02, odds ratio (OR) = 0.43; 95% confidence interval (CI): 0.21–0.91] and pathologic stage ( P = 0.03, OR = 1.89; 95% CI: 1.06–3.36). A putative binding site for miRNA-196a (miR-196a) exists in the 3'UTR of RAP1A, and the genetic variant, rs6573 A-〉C, is present in this binding region. We confirmed that miR-196a regulated the expression of RAP1A by luciferase reporter assay and that the regulation was affected by the RAP1A genotype. SNP rs6573 A to C change interfere in the interaction of miR-196a binding to RAP1A 3'UTR, resulting in higher constitutive expression of RAP1A. Moreover, we observed that RAP1A was overexpressed in the majority of ESCC tissues and correlated with RAP1A genotype and lymph node metastasis. In vitro study indicated RAP1A might function as a promoter for esophageal cancer cell migration and invasion through matrix metalloproteinase 2. Our study highlights RAP1A and SNP rs6573 functioning as potential personal diagnostic and prognosis markers for ESCC.
    Print ISSN: 0143-3334
    Electronic ISSN: 1460-2180
    Topics: Medicine
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  • 6
    Publication Date: 2012-12-20
    Description: In this article, we describe a long-non-coding RNA (lncRNA) and disease association database (LncRNADisease), which is publicly accessible at http://cmbi.bjmu.edu.cn/lncrnadisease . In recent years, a large number of lncRNAs have been identified and increasing evidence shows that lncRNAs play critical roles in various biological processes. Therefore, the dysfunctions of lncRNAs are associated with a wide range of diseases. It thus becomes important to understand lncRNAs’ roles in diseases and to identify candidate lncRNAs for disease diagnosis, treatment and prognosis. For this purpose, a high-quality lncRNA–disease association database would be extremely beneficial. Here, we describe the LncRNADisease database that collected and curated approximately 480 entries of experimentally supported lncRNA–disease associations, including 166 diseases. LncRNADisease also curated 478 entries of lncRNA interacting partners at various molecular levels, including protein, RNA, miRNA and DNA. Moreover, we annotated lncRNA–disease associations with genomic information, sequences, references and species. We normalized the disease name and the type of lncRNA dysfunction and provided a detailed description for each entry. Finally, we developed a bioinformatic method to predict novel lncRNA–disease associations and integrated the method and the predicted associated diseases of 1564 human lncRNAs into the database.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 7
    Publication Date: 2012-09-22
    Description: Progressive tumor-bearing patients deserve to benefit from more realistic approaches. Here, a study revealed the impact of modified periodic fasting and refeeding regimen on tumor progression or regression with little or no loss of food intake and body weight. Human A549 lung, HepG-2 liver, and SKOV-3 ovary progressive tumor-bearing mice were established and subjected to 4 wk of periodic fasting/refeeding cycles (PFRC), including periodic 1-d fasting/6-d refeeding weekly (protocol 1) and periodic 2-d fasting/5-d refeeding weekly (P2DF/5DR, protocol 2), with ad libitum ( AL )-fed hosts as controls. Afterwards, PFRC groups exhibited tumor growth arrest with some tendency towards regression; especially, complete regression of progressive tumors and metastases comprised between 43.75 and 56.25% of tumor-challenged hosts in P2DF/5DR group ( P 〈 0.05). AL controls, in contrast, showed continuous tumor progression and metastasis. Finally, 100% hosts in P2DF/5DR and 62.5–68.75% in periodic 1-d fasting/6-d refeeding weekly groups survived a 4-month study period vs . only 31.25–37.5% in AL control group. Immunological assays and Luminex microarray revealed that tumor growth remission is mainly via natural killer cell (NK) reactivity and cross-regulation of IGF-binding protein-3, IGF/IGF-receptor, and megakaryocyte growth and development factor autocrine and paracrine loops. In vivo cellular and humoral assays indicated that tumor-regressive induction by PFRC protocols could be partly terminated by NK cell and IGF-binding protein-3 blockade or replenishment of IGF-I/-II and megakaryocyte growth and development factor. These findings offer a better understanding of comprehensive modulation of periodic fasting/refeeding strategy on the balance between tumor progression and regression.
    Print ISSN: 0013-7227
    Topics: Medicine
    Published by Oxford University Press on behalf of The Endocrine Society.
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  • 8
    Publication Date: 2012-10-10
    Description: Messenger ribonucleic acids (RNAs) contain a large number of cis -regulatory RNA elements that function in many types of post-transcriptional regulation. These cis -regulatory elements are often characterized by conserved structures and/or sequences. Although some classes are well known, given the wide range of RNA-interacting proteins in eukaryotes, it is likely that many new classes of cis -regulatory elements are yet to be discovered. An approach to this is to use computational methods that have the advantage of analysing genomic data, particularly comparative data on a large scale. In this study, a set of structural discovery algorithms was applied followed by support vector machine (SVM) classification. We trained a new classification model (CisRNA-SVM) on a set of known structured cis -regulatory elements from 3'-untranslated regions (UTRs) and successfully distinguished these and groups of cis -regulatory elements not been strained on from control genomic and shuffled sequences. The new method outperformed previous methods in classification of cis -regulatory RNA elements. This model was then used to predict new elements from cross-species conserved regions of human 3'-UTRs. Clustering of these elements identified new classes of potential cis -regulatory elements. The model, training and testing sets and novel human predictions are available at: http://mRNA.otago.ac.nz/CisRNA-SVM .
    Keywords: Computational Methods, Genomics, Transcriptome Mapping - Monitoring Gene Expression
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 9
    Publication Date: 2012-10-10
    Description: The Mmr multidrug efflux pump recognizes and actively extrudes a broad range of antimicrobial agents, and promotes the intrinsic resistance to these antimicrobials in Mycobacterium tuberculosis . The expression of Mmr is controlled by the TetR-like transcriptional regulator Rv3066, whose open reading frame is located downstream of the mmr operon. To understand the structural basis of Rv3066 regulation, we have determined the crystal structures of Rv3066, both in the absence and presence of bound ethidium, revealing an asymmetric homodimeric two-domain molecule with an entirely helical architecture. The structures underscore the flexibility and plasticity of the regulator essential for multidrug recognition. Comparison of the apo-Rv3066 and Rv3066–ethidium crystal structures suggests that the conformational changes leading to drug-mediated derepression is primarily due to a rigid body rotational motion within the dimer interface of the regulator. The Rv3066 regulator creates a multidrug-binding pocket, which contains five aromatic residues. The bound ethidium is found buried within the multidrug-binding site, where extensive aromatic stacking interactions seemingly govern the binding. In vitro studies reveal that the dimeric Rv3066 regulator binds to a 14-bp palindromic inverted repeat sequence in the nanomolar range. These findings provide new insight into the mechanisms of ligand binding and Rv3066 regulation.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 10
    Publication Date: 2012-12-01
    Description: Recent evidences show that genetic polymorphisms falling in miRNA binding sites can alter the strength of miRNA binding and disturb miRNA-mediated posttranscriptional regulation. Our study aimed to investigate the role of single-nucleotide polymorphisms (SNPs) in putative miRNA binding sites in gastric cancer (GC). Based on microarray and quantitative reverse transcription PCR analyses, we found that miR-181a was significantly upregulated in GC tissues. Bioinformatics survey was used to explore SNPs within miR-181a binding sites. Three SNPs were genotyped in a case–control study (500 cases and 502 controls). The T allele genotypes (rs12537CT and TT) of MTMR3 were found associated with significantly increased GC risk [adjusted odds ratio 1.72, 95% confidence interval (CI) 1.36–2.16, P = 3.99 x 10 –5 ] and poor overall survival [hazard ratio (HR) 1.38, 95% CI 1.03–1.83, P = 0.029], although they were not an independent prognostic factor in multivariate Cox regression analysis (HR 1.28, 95% CI 0.95–1.72, P = 0.11). We further demonstrated that the rs12537CT genotype carriers had lower MTMR3 mRNA expression levels than CC genotype carriers in GC tissues ( P = 0.013), whereas no significant difference in miR-181a expression levels was found ( P = 0.135). Luciferase assay revealed that miR-181a directly targeted MTMR3 , and its suppressive effect was enhanced when the rs12537C allele was substituted by T variant, although the difference was not significant ( P = 0.055). Our study suggested that rs12537 is associated with susceptibility and prognosis of GC in southern Han Chinese, and miR-181a and its target gene MTMR3 play important roles in GC.
    Print ISSN: 0143-3334
    Electronic ISSN: 1460-2180
    Topics: Medicine
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