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Jean Collins
Jean Collins

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After applying your upgrade keys and verify your license is as expected, it is then time to download and install it on your UTM. Installing the new license file will replace the existing one running on your UTM. If you need to retain the old license for any reason make a UTM backup before installing. This is almost never necessary but you might be a special snowflake and have a good reason to do that.

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All rights for the fonts given on this website reserved by their owners (authors, designers). The license given on the font page only represents received data. For detailed information, please, read the files (e.g., readme.txt) from archive or visit the website given by an author (designer) or contact with him if you have any doubt. If there is no reported author (designer) or license, it means that there is no information on the given font, but it does not mean that the font is free.

I believe this is working as designed. AIUI, the issue here is that for a page loaded from a file:// URI, only files in (or below) the same directory of the filesystem are considered to be "same origin", and so putting the font in a different subtree (../font/) means it will be blocked by security policy restrictions.

You can relax this by setting security.fileuri.strict_origin_policy to false in about:config, but as this gives the page access to your entire local filesystem, it's something to be used with caution.

Note: the origin policy is calculated based on the html, NOT the css file! So a font file right besides an css file might not work, which is very confusing. (At least this is what I thought was the case with Firefox!)

@CharlesGoodwin @eradman Actually, both statements about the origin seem true except that they probably talk about two different things: same-origin check is based on the originating HTML file, while relative URLs for font faces are resolved relative to the CSS file containing the @font-face rule.

However, lncRNA profiles in most human cancers remain largely unknown, mainly due to the lack of such arrays. Previous studies have demonstrated that lncRNA profiling could be achieved by mining previously published gene expression microarray data because a large amount of lncRNA-specific probes were fortuitously represented on the commonly used microarray platforms [28, 29]. In the present study, we applied this method to conduct gene expressions of lncRNAs profiling on a cohort of 300 patients from GSE62254 as well as another independent data set from GEO database. By using the sample-splitting method, random survival forests-variable hunting (RSF-VH) algorithm and Cox regression analysis, we identified a prognostic, 24-lncRNA signature from the GSE62254 test series patients, and validated it in the GSE62254 validation series and another independent GEO cohort (GSE15459).

The raw CEL files were downloaded from GEO database and background adjusted using Robust Multichip Average (RMA) [30] which has been shown to be a solid measure tool for lncRNA profiling data [31]. The approach of lncRNA profile mining mainly referred to Xiaoqin Zhang et al [32]. Briefly, we mapped the Affymetrix HG-U133 Plus 2.0 probe set IDs to the NetAffx Annotation Files. Based on the Refseq transcript ID and/or Ensembl gene ID in NetAffx annotations, we only retained non-coding protein genes and further filtered them by eliminating pseudogenes including microRNAs, rRNAs and other short RNAs such as snoRNAs, snRNAs and tRNAs. Finally, 2448 annotated lncRNA transcripts with corresponding Affymetrix probe IDs were generated.

GC data sets and corresponding clinical data were downloaded from the publicly available GEO database. The following two cohorts of GC gene expression data were included in this study: GSE62254 [5] and GSE15459 [40]. After removal of the samples without survival status, a total of 492 GC patients analyzed in the present study (see Additional file 1). These included 300 GC patients from GSE62254 (180 patients from the test series and 120 patients from the validation series). And 192 GC patients from GSE15459 were included after 8 patients were removed due to absence of clinical outcome information.

To identify the prognostic lncRNA genes, we profiled lncRNA by mining the existing microarray gene expression data on a variety of commonly used commercial arrays. Of those, the Affymetrix Human Genome U133 array series is one of the most commonly used commercial microarrays in human cancer profiling [56]. As a public gene expression data repository, GEO has contained lots of gene expression data that could be used for further analysis. Based on this mining method, we additionally applied another method to select prognostic lncRNA genes. Predictors (genes) were selected by applying the random survival forest-variable hunting (RSF-VH) algorithm [36]. The random forests method is classified into a tree-based method which has an advantage in detecting interactions. This algorithm exploits maximal subtrees for effective variable selection, and the trees in a survival forest are grown randomly using a two-step randomization process [36]. Moreover, it has been developed for processing data with several variables larger than the number of samples. There is no denying that many published studies applied univariable and multivariable analyses on microarray data for screening where potential genes interacting with other genes may be dropped from the analyses. Actually, in this regard, the RSF-VH algorithm would be more powerful.

By applying the 24-lncRNA signature to the GSE62254 test series patients, a clear separation was observed in survival curves between patients with high- and low-risk signatures. Patients with a high-risk 24-lncRNA signature in their tumor specimens tended to have shortened survival, whereas patients with a low-risk 24-lncRNA signature tended to have prolonged survival. The association between the lncRNA signature and survival was significant no matter whether the former was evaluated as a continuous variable or category variable (divided by the median cutoff). The usefulness of this lncRNA signature could be internally validated in the non-overlapping GSE62254 patients (the validation series) and another independent cohort of GSE15459 that profiled through the same platform of GSE62254, indicating good reproducibility of this 24-lncRNA signature in GC. Taken together, our results suggest that the 24-lncRNA signature may be a significant determinant of survival in GC, rather than an accidental feature of the transcription noise.

The limitations should be acknowledged for our study. First, since the two GEO data sets involved in this study were profiled through Affymetrix Human Genome U133 Plus 2.0 chips which represents part but not all of the possible lncRNA presents, the lncRNAs candidates indentified here may not represent the complete lncRNA populations underlying GC biological behavior. Second, the DFS was regarded as the primary endpoint in the test and internal validation data set (GSE62254). Unfortunately, we could only use OS as the endpoint in external validation data set (GSE15459) because this data set did not contain the information about DFS. Despite this drawback, however, the significant and consistent correlation of the 24-lncRNA signature with OS in external validation data set indicates that it is a potential useful prognostic marker for GC. Finally, we have no experimental data and lack information on the mechanism behind the signature lncRNAs, and experimental studies on these lncRNAs are greatly needed to provide important information to further our understanding of their functional rolesin GC. 041b061a72


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