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  • 1
    Publication Date: 2013-07-23
    Description: Background Previous results from our trial showed that adding oxaliplatin to radiotherapy (RT) increased survival in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) at 2 years. Here, we present the data of long-term efficacy and late toxic effects. Patients and methods Between January 2001 and January 2003, 115 Patients with nonkeratinizing/undifferentiated locoregionally advanced NPC were randomly to receive either RT alone ( n = 56) or plus concurrent oxaliplatin 70 mg/m 2 weekly for six cycles ( n = 59). Results After a median follow-up of 114 months (range 18–139 months), the 5-year overall survival (OS) and metastasis-free survival (MFS) rates in the concurrent chemoradiotherapy (CCRT) group were significantly higher than those observed in the RT-alone group (OS, 73.2% versus 60.2%, P = 0.028; MFS, 74.7% versus 63.0%, P = 0.027). However, CCRT did not improve locoregional failure-free survival significantly. Subgroup analyses showed that the superiorities of CCRT mainly existed in the T3-4N0-1 stage subgroup (OS: HR = 0.394, P = 0.034). The grade 3/4 late toxic effects were similar in the two groups. Conclusion(s) The long-term follow-up data confirms the role of CCRT as a treatment of locoregionally advanced NPC. Oxaliplatin can be considered as an alternative optional therapeutic regimen for these patients due to its high efficiency and low toxic effect.
    Print ISSN: 0923-7534
    Electronic ISSN: 1569-8041
    Topics: Medicine
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  • 2
    Publication Date: 2014-08-01
    Description: Triantennary N -acetyl galactosamine (GalNAc, GN3 ), a high-affinity ligand for the hepatocyte-specific asialoglycoprotein receptor (ASGPR), enhances the potency of second-generation gapmer antisense oligonucleotides (ASOs) 6–10-fold in mouse liver. When combined with next-generation ASO designs comprised of short S -cEt ( S -2'- O -Et-2',4'-bridged nucleic acid) gapmer ASOs, ~60-fold enhancement in potency relative to the parent MOE (2'- O -methoxyethyl RNA) ASO was observed. GN3 -conjugated ASOs showed high affinity for mouse ASGPR, which results in enhanced ASO delivery to hepatocytes versus non-parenchymal cells. After internalization into cells, the GN3 -ASO conjugate is metabolized to liberate the parent ASO in the liver. No metabolism of the GN3 -ASO conjugate was detected in plasma suggesting that GN3 acts as a hepatocyte targeting prodrug that is detached from the ASO by metabolism after internalization into the liver. GalNAc conjugation also enhanced potency and duration of the effect of two ASOs targeting human apolipoprotein C-III and human transthyretin (TTR) in transgenic mice. The unconjugated ASOs are currently in late stage clinical trials for the treatment of familial chylomicronemia and TTR-mediated polyneuropathy. The ability to translate these observations in humans offers the potential to improve therapeutic index, reduce cost of therapy and support a monthly dosing schedule for therapeutic suppression of gene expression in the liver using ASOs.
    Keywords: Targeted inhibition of gene function
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 3
    Publication Date: 2015-07-15
    Description: Protein–protein interaction is of primary importance to understand protein functions. In recent years, the high-throughput AP-MS experiments have generated a large amount of bait–prey data, posing great challenges on the computational analysis of such data for inferring true interactions and protein complexes. To date, many research efforts have been devoted to developing novel computational methods to analyze these AP-MS data sets. In this article, we review and classify the key computational methods developed for the inference of protein–protein interactions and the detection of protein complexes from the AP-MS experiments. We hope that our review as well as the challenges highlighted in the article will provide valuable insights into driving future research for further advancing the state-of-the-art technologies in computational prediction, characterization and analysis of protein–protein interactions and protein complexes from the AP-MS data.
    Print ISSN: 1467-5463
    Electronic ISSN: 1477-4054
    Topics: Biology , Computer Science
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  • 4
    Publication Date: 2015-10-15
    Description: Background: This study aimed to establish an effective prognostic nomogram with or without plasma Epstein-Barr virus DNA (EBV DNA) for nondisseminated nasopharyngeal carcinoma (NPC). Methods: The nomogram was based on a retrospective study of 4630 patients who underwent radiotherapy with or without chemotherapy at Sun Yat-sen University Cancer Center from 2007 to 2009. The predictive accuracy and discriminative ability of the nomogram were determined by a concordance index (C-index) and calibration curve and were compared with EBV DNA and the current staging system. The results were validated using bootstrap resampling and a prospective cohort study on 1819 patients consecutively enrolled from 2011 to 2012 at the same institution. All statistical tests were two-sided. Results: Independent factors derived from multivariable analysis of the primary cohort to predict recurrence were age, sex, body mass index (BMI), T stage, N stage, plasma EBV DNA, pretreatment high sensitivity C-reactive protein (hs-CRP), lactate dehydrogenase (LDH), and hemoglobin level (HGB), which were all assembled into the nomogram with (nomogram B) or without EBV DNA (nomogram A). The calibration curve for the probability of recurrence showed that the nomogram-based predictions were in good agreement with actual observations. The C-index of nomogram B for predicting recurrence was 0.728 ( P 〈 .001), which was statistically higher than the C-index values for nomogram A (0.690), EBV DNA (0.680), and the current staging system (0.609). The C-index of nomogram B (0.730) and nomogram A (0.681) remained higher for predicting recurrence among patients treated with intensity-modulated radiotherapy ( P 〈 .001). The results were confirmed in the validation cohort. Conclusions: The proposed nomogram with or without plasma EBV DNA resulted in more accurate prognostic prediction for NPC patients.
    Electronic ISSN: 1460-2105
    Topics: Medicine
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  • 5
    Publication Date: 2014-09-30
    Description: N -α-Acetyltransferase 10 protein (Naa10p, also called arrest-defective 1), the catalytic subunit of N -acetyltransferase A, is a critical regulator of cell death and proliferation. Naa10p is also shown to regulate cancer metastasis by inhibiting cell motility; however, its role in cancer metastasis is not fully understood. In this study, we found that high expression of Naa10p is positively correlated with the survival of patients with breast cancer, whereas negatively correlated with lymph node metastasis. Naa10p inhibits breast cancer cell migration and invasion in vitro and decreases the xenograft growth and metastasis in nude mice. Microarray screening revealed that Naa10p downregulates inhibitors of differentiation 1 ( ID1 ) expression. Naa10p binds to signal transducer and activator of transcription 5a (STAT5a) and decreases STAT5a-stimulated ID1 expression in an acetyltransferase-independent manner. Moreover, Naa10p antagonizes Janus kinase 2-STAT5a signaling by lowering p65-activated interleukin-1β expression. Our results demonstrate a novel mechanism through which Naa10p inhibits the metastasis of breast cancer cells by targeting STAT5a.
    Print ISSN: 0143-3334
    Electronic ISSN: 1460-2180
    Topics: Medicine
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  • 6
    Publication Date: 2015-10-22
    Description: To investigate the coupling relationship between great earthquake and ionosphere, the GPS-derived total electron contents (TECs) by the Center for Orbit Determination in Europe and the foF2 data from the Space Weather Prediction Center were used to analyse the impending ionospheric anomalies before the Iquique Mw8.2 earthquake in Chile on 2014 April 1. Eliminating effects of the solar and geomagnetic activities on ionosphere by the sliding interquartile range with the 27-day window, the TEC analysis results represent that there were negative anomalies occurred on 15th day prior to the earthquake, and positive anomalies appeared in 5th day before the earthquake. The foF2 analysis results of ionosonde stations Jicamarca, Concepcion and Ramey show that the foF2 increased by 40, 50 and 45 per cent, respectively, on 5th day before the earthquake. The TEC anomalous distribution indicates that there was a widely TEC decrement over the epicentre with the duration of 6 hr on 15th day before the earthquake. On 5th day before the earthquake, the TEC over the epicentre increased with the amplitude of 15 TECu, and the duration exceeded 6 hr. The anomalies occurred on the side away from the equator. All TEC anomalies in these days were within the bounds of equatorial anomaly zone where should be the focal area to monitor ionospheric anomaly before strong earthquakes. The relationship between ionospheric anomalies and geomagnetic activity was detected by the cross wavelet analysis, which implied that the foF2 was not affected by the magnetic activities on 15th day and 5th day prior to the earthquake, but the TECs were partially affected by anomalous magnetic activity during some periods of 5th day prior to the earthquake.
    Keywords: Geodynamics and Tectonics
    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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  • 7
    Publication Date: 2016-01-16
    Description: We reproduce the galaxy clustering catalogue from the SDSS-III Baryon Oscillation Spectroscopic Survey Final Data Release (BOSS DR11&DR12) with high fidelity on all relevant scales in order to allow a robust analysis of baryon acoustic oscillations and redshift space distortions. We have generated (6000) 12 288 MultiDark patchy BOSS (DR11) DR12 light cones corresponding to an effective volume of ~192 000 [ h –1 Gpc] 3 (the largest ever simulated volume), including cosmic evolution in the redshift range from 0.15 to 0.75. The mocks have been calibrated using a reference galaxy catalogue based on the halo abundance matching modelling of the BOSS DR11&DR12 galaxy clustering data and on the data themselves. The production follows three steps. First, we apply the patchy code to generate a dark matter field and an object distribution including non-linear stochastic galaxy bias. Secondly, we run the halo/stellar distribution reconstruction hadron code to assign masses to the various objects. This step uses the mass distribution as a function of local density and non-local indicators (i.e. tidal field tensor eigenvalues and relative halo exclusion separation for massive objects) from the reference simulation applied to the corresponding patchy dark matter and galaxy distribution. Finally, we apply the sugar code to build the light cones. The resulting MultiDark patchy mock light cones reproduce the number density, selection function, survey geometry, and in general within 1, for arbitrary stellar mass bins, the power spectrum up to k  = 0.3 h Mpc –1 , the two-point correlation functions down to a few Mpc scales, and the three-point statistics of the BOSS DR11&DR12 galaxy samples.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 8
    Publication Date: 2016-03-09
    Description: Future dark energy experiments will require accurate theoretical predictions for the baryon acoustic oscillations (BAOs). Here, we use large N -body simulations to study any systematic shifts and damping in BAO due to non-linear effects. The impact of cosmic variance is largely reduced by dividing the tracer power spectrum by that from a ‘BAO-free’ simulation starting with the same random amplitudes and phases. The accuracy of our simulations allows us to resolve well dark matter (sub)haloes, which permits us to study with high accuracy (better than 0.02 per cent for dark matter and 0.07 per cent for low-bias haloes) small BAO shifts α towards larger k , and non-linear damping nl of BAO in the power spectrum. For dark matter, we provide an accurate parametrization of the evolution of α as a function of the linear growth factor D ( z ). For halo samples, with bias from 1.2 to 2.8, we measure a typical BAO shift of 0.25 per cent, with no appreciable evolution with redshift. Moreover, we report a constant shift as a function of halo bias. We find a different evolution of the BAO damping in all halo samples as compared to dark matter with haloes suffering less damping, and also find some weak dependence on bias. Larger BAO shift and damping are measured in redshift-space, which can be explained by linear theory due to redshift-space distortions. A clear modulation in phase with the acoustic scale is observed in the scale-dependent halo bias due to the presence of BAOs. We compare our results with previous works.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 9
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    Oxford University Press
    Publication Date: 2015-09-22
    Description: Motivation: During the evolution, functional sites on the surface of the protein as well as the hydrophobic core maintaining the structural integrity are well-conserved. However, available protein structure alignment methods align protein structures based solely on the 3D geometric similarity, limiting their ability to detect functionally relevant correspondences between the residues of the proteins, especially for distantly related homologous proteins. Results: In this article, we propose a new protein pairwise structure alignment algorithm (UniAlign) that incorporates additional evolutionary information captured in the form of sequence similarity, sequence profiles and residue conservation. We define a per-residue score (UniScore) as a weighted sum of these and other features and develop an iterative optimization procedure to search for an alignment with the best overall UniScore. Our extensive experiments on CDD, HOMSTRAD and BAliBASE benchmark datasets show that UniAlign outperforms commonly used structure alignment methods. We further demonstrate UniAlign's ability to develop family-specific models to drastically improve the quality of the alignments. Availability and implementation: UniAlign is available as a web service at: http://sacan.biomed.drexel.edu/unialign Contact: ahmet.sacan@drexel.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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  • 10
    Publication Date: 2015-07-10
    Description: We present a comparison of major methodologies of fast generating mock halo or galaxy catalogues. The comparison is done for two-point (power spectrum and two-point correlation function in real and redshift space), and the three-point clustering statistics (bispectrum and three-point correlation function). The reference catalogues are drawn from the BigMultiDark N -body simulation. Both friend-of-friends (including distinct haloes only) and spherical overdensity (including distinct haloes and subhalos) catalogues have been used with the typical number density of a large volume galaxy surveys. We demonstrate that a proper biasing model is essential for reproducing the power spectrum at quasi-linear and even smaller scales. With respect to various clustering statistics, a methodology based on perturbation theory and a realistic biasing model leads to very good agreement with N -body simulations. However, for the quadrupole of the correlation function or the power spectrum, only the method based on semi- N -body simulation could reach high accuracy (1 per cent level) at small scales, i.e. r  〈 25 h –1 Mpc or k  〉 0.15 h Mpc –1 . Full N -body solutions will remain indispensable to produce reference catalogues. Nevertheless, we have demonstrated that the more efficient approximate solvers can reach a few per cent accuracy in terms of clustering statistics at the scales interesting for the large-scale structure analysis. This makes them useful for massive production aimed at covariance studies, to scan large parameter spaces, and to estimate uncertainties in data analysis techniques, such as baryon acoustic oscillation reconstruction, redshift distortion measurements, etc.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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