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The cox-filter method identifies respective subtype-specific lncRNA prognostic signatures for two human cancers
Suyan Tian ORCID: orcid.org/0000-0002-5942-15421,
Chi Wang2,3,
Jing Zhang4 &
Dan Yu5
The most common histological subtypes of esophageal cancer are squamous cell carcinoma (ESCC) and adenocarcinoma (EAC). It has been demonstrated that non-marginal differences in gene expression and somatic alternation exist between these two subtypes; consequently, biomarkers that have prognostic values for them are expected to be distinct. In contrast, laryngeal squamous cell cancer (LSCC) has a better prognosis than hypopharyngeal squamous cell carcinoma (HSCC). Likewise, subtype-specific prognostic signatures may exist for LSCC and HSCC. Long non-coding RNAs (lncRNAs) hold promise for identifying prognostic signatures for a variety of cancers including esophageal cancer and head and neck squamous cell carcinoma (HNSCC).
In this study, we applied a novel feature selection method capable of identifying specific prognostic signatures uniquely for each subtype – the Cox-filter method – to The Cancer Genome Atlas esophageal cancer and HSNCC RNA-Seq data, with the objectives of constructing subtype-specific prognostic lncRNA expression signatures for esophageal cancer and HNSCC.
By incorporating biological relevancy information, the lncRNA lists identified by the Cox-filter method were further refined. The resulting signatures include genes that are highly related to cancer, such as H19 and NEAT1, which possess perfect prognostic values for esophageal cancer and HNSCC, respectively.
The Cox-filter method is indeed a handy tool to identify subtype-specific prognostic lncRNA signatures. We anticipate the method will gain wider applications.
Esophageal cancer is a cancer of the esophagus, the hollow tube that carries foods and liquids from throat to stomach. The causes of esophageal cancer are unclear, but it is commonly believed that both environmental and genetic factors play roles in its initiation and progression [1]. For instance, smoking, heavy alcohol consumption, obesity, and damage to the esophagus from acid reflux (Barrett esophagus) are thought to increase the risk of developing esophageal cancer, while, the tendency of familial aggregation for esophageal cancer suggests that genetic components are of crucial importance. The most common histological subtypes of esophageal cancer are squamous cell carcinoma (ESCC) and adenocarcinoma (EAC). As far as prognosis is concerned, no evidence suggests any substantial difference between these two subtypes. Nevertheless, a study by The Cancer Genome Atlas research group [2] has demonstrated that non-marginal differences with regard to gene expression and somatic alteration exist between ESCC and EAC. Consequently, biomarkers that hold prognostic value for these two subtypes are expected to be distinct, at least to some extent.
Head and neck squamous cell carcinoma (HNSCC) develops in mucous membranes of the mouth, nose and throat. Hypopharyngeal squamous cell carcinoma (HSCC), which originates in mucosa of the hypopharynx and accounts for approximately 3% of HNSCC cases, has one of the poorest prognoses among HNSCC patients [3]. Laryngeal squamous cell cancer (LSCC) accounts for relatively more HNSCC cases and has a better prognosis compared to HSCC even though the initial sites of these two diseases are anatomically very close. LSCC originates in the larynx, whereas HSCC originates in the lower part of the throat near the larynx (i.e., the hypopharynx). Therefore, finding molecular markers that can distinguish between the two subtypes is crucial for survival prediction.
Long non-coding RNAs (lncRNAs) are a class of RNA molecules that have a length of more than 200 nucleotides and are without protein-coding capacity [4]. Therefore, lncRNAs have previously been regarded as transcriptional "junk." Nowadays, paramount investigations have demonstrated that lncRNAs can serve as novel biomarkers and therapeutic targets in complex diseases such as cancer. Identification of lncRNA signatures is in demand and usually requires the help of a feature selection method. The primary aims of feature selection are to reduce the number of features (e.g., genes or metabolites) under consideration to a manageable size, thus speeding up the learning process and facilitating biological interpretation and experimental validation [5].
Applying feature selection to lncRNA (vs mRNA) data might achieve better model parsimony because mRNA-based studies obtain signatures with a limited number of genes, and because the expression levels of lncRNAs are usually lower than those of mRNAs (thus less differentially expressed lncRNAs can be identified). Studies that aim to identify lncRNA signatures for esophageal cancers and HNSCC have increased dramatically. For example, studies by Cao et al. [6], Wang et al. [7] and Yao et al. [8] specifically aimed to identify lncRNA expression signatures with prognostic value for HNSCC patients, while several studies [9,10,11,12] identified relevant lncRNA signatures for esophageal cancer. Nevertheless, those studies usually considered HNSCC or esophageal cancer as a whole or only focused on one specific subtype.
In this study, we applied a novel feature selection method – the Cox-filter method [13] – to the cancer genome atlas (TCGA) esophageal cancer and HNSCC RNA-Seq data, with the objectives of constructing subtype-specific prognostic lncRNA expression signatures for EC and HNSCC. Precision medicine for those patients will only be possible once subtype-specific prognostic signatures become available.
Experimental data
The lncRNA expression values, namely, FPKM (fragments per kilo-bases per million) for HNSCC were retrieved from the TANRIC (The Atlas of ncRNA in Cancer) database [14], version 1.0.6 (https://www.tanric.org/), which was last updated on 07/29/2015. Then the corresponding clinical information was retrieved from the the Genomic Data Commons (https://gdc.cancer.gov) by matching the barcode IDs of samples in the TANRIC database [14] with those in the TCGA database. Patients without information on overall survival (OS), age, gender, pathological tumor stage and histological subtype were discarded. Only patients with LSCC and HSCC were retained for analysis. If the sum of FPKM values of lncRNA expression across all samples (LSCC and HSCC patients combined) was < 4, they were deleted. Finally, log 2 transformations on (FPKM counts + 1) were carried out, providing a better approximation to a normal distribution.
For the esophageal cancer study, both the expression profiles (RNA-Seq data) of TCGA ESCA cohort and clinical information such as overall survival time were downloaded from the Genomic Data Commons. Subsequently, the lncRNAs were collected by mapping the Ensemble IDs of RNA-Seq data to those in the TANRIC database [14] (given that the ESCA cohort is not included in the TANRIC database) so that expression profiles of lncRNAs were obtained.
The ratio of LSCC and HSCC is extremely high (89:6) while that for ESCC to EAC is very close to 1 (81:83), which represents the two extreme cases (huge imbalance of sample ratios versus perfect balance of sample ratios). Hence, using these two datasets, it is possible to examine the influence of subgroup size imbalance on the performance of a feature selection algorithm. The demographical characteristics of these two datasets are presented in Table 1.
Table 1 Characteristics of head and neck squamous cell carcinoma and esophageal cancer data
The Cox-filter method proposed by Tian et al. [13] screens genes one by one according to the significance level of the corresponding coefficients in a Cox model. Under the two-class cases (the model can easily be extended to multiple-class cases), the corresponding Cox model may be written as,
$$ {\lambda}_{\mathrm{i}\mathrm{jg}}\left(\mathrm{t}\right)={\lambda}_{0\mathrm{g}}\left(\mathrm{t}\right)\exp \Big({\upbeta}_{1\mathrm{g}}{\mathrm{I}}_{\mathrm{i}}\left(\mathrm{j}={\mathrm{c}}_2\right)+{\upbeta}_{2\mathrm{g}}{\mathrm{X}}_{\mathrm{i}\mathrm{jg}}+\left({\upbeta}_{1\mathrm{g}}{\mathrm{I}}_{\mathrm{i}}\left(\mathrm{j}={\mathrm{c}}_2\right)\times {\mathrm{X}}_{\mathrm{i}\mathrm{jg}}\right) $$
Tian et al. [13] provided a detailed description of the definitions of parameters (i.e., βs and λs) and a graphical illustration of all possible scenarios; those details are not presented here. For the current study, the features under consideration are lncRNAs, subtype-specific prognostic lncRNAs were those for which either β2g or (β2g + β3g) is significantly different from zero. More specifically, β2g ≠ 0 implies that lncRNA g has a prognostic value for subgroup c1 while (β2g + β3g) ≠ 0 implies lncRNA g has a prognostic value for subgroup c2. Therefore, β2g and β3g are the parameters of interest and their significance levels determine if subtype-specific lncRNAs exist.
Statistical language and packages
All statistical analyses were carried out in the R language, version 3.5 (www.r-project.org).
By applying the Cox-filter model to esophageal cancer data and setting the cutoff of adjusted p-values for these linear coefficients at 0.05, we identified 200 lncRNAs that have prognostic values for EAC and 96 for ESCC. Among them, there were 46 overlaps. We searched the GeneCards database for their biological relevance. For EAC, after removing 19 genes that are not be recognized by the GeneCards database (www.genecards.org), 58 lncRNAs were indicated to be directly related to cancers. For ESCC, 19 lncRNAs are unrecognizable as well. Among the remaining 77 lncRNAs, 27 of them were directly related to cancers. A Venn-diagram (Fig. 1) was made and the gene symbols were given, stratified by EAC-specific lncRNAs, ESCC-specific lncRNAs and overlapped lncRNAs between two subtypes. Among these unique 74 lncRNAs, 44 were regarded as being differentially expressed between cancer tissues and normal tissues.
Venn-diagram illustrating EAC- and ESCC-specific prognostic lncRNAs. Gene symbols of microRNAs that were misclassified as lncRNAs are crossed out. EAC: esophageal adenocarcinoma; ESCC: esophageal squamous cell carcinoma
For HNSCC, using a cutoff of 0.05 for adjusted p-values the Cox-filter method identified 126 LSCC lncRNAs (20 non-identifiable in the GeneCards database) and 89 HSCC lncRNAs (30 of which are non-identifiable in the GeneCards database). Fifty-six were directly related to cancers for LSCC and 16 for HSCC. Among these lncRNAs, 6 lncRNAs were shared by these two subtypes, and 44 lncRNAs were regarded as being differentially expressed between cancer tissues and normal tissues. Figure 2 presents gene symbols of those lncRNAs. From the gene symbols given in Figs. 1 and 2, we observed several microRNAs (e.g., MIR146A and MIR 296) that were mistakenly recognized as lncRNAs by the TANRIC database. Since TANRIC has not been updated since its initiation, it is natural to expect such errors. In the following results, those microRNAs were removed manually.
Venn-diagram illustrating LSCC-specific prognostic lncRNAs and HSCC-specific prognostic lncRNAs. Gene symbols of microRNAs that were misclassified as lncRNAs are crossed out. LSCC: laryngeal squamous cell cancer; HSCC: hypopharyngeal squamous cell cancer
In this study, Pvt1 oncogene (PVT1) with a confidence score of 25.4 is ranked on the second place for the EAC-specific prognostic lncRNAs. Based on the strategy of competitive endogenous RNA (ceRNA) networks [15], overexpression of PVT1 correlates with a poor prognosis [16] or a fast tumor progression [17] in esophageal cancer patients or in ESCC [18] In this study, PVT1 was indicated as an EAC-specific lncRNA since it does not belong to the intersection set between lncRNAs for these two subtypes.
CDKN2B antisense RNA 1 (CDKN2B-AS1), also known as ANRIL, was on the top of this list (i.e., cancer related EAC-specific prognostic lncRNAs), however, only three studies [19,20,21] have addressed its association with esophageal cancer. While the first two studies explored the association between CDKN2B-AS1 and esophageal cancer by way of genetic mutations, the third did so from the prospective of expression level. Other than esophageal cancer, CDKN2B-AS1 had been linked to a variety of cancer types such as acute lymphoblastic leukemia [22], gastric cancer [20, 23] and hepatocellular carcinoma (HCC) [24]. For other top-ranked lncRNAs, Yoon et al. [25] have demonstrated that LUCAT1 was over-expressed in tumor issues compared to paired normal tissues and may promote carcinogenesis of ESCC. Another recent study [26] has shown that up-regulation of CBR3-AS1 promoted cell proliferation and was positively correlated with pathologic stages of ESCC. Lastly, despite the absence of literature suggesting that TP53TG plays any role in the development and progression of esophageal cancer, this lncRNA can suppress tumor growth and is of importance for the correct response of P53 to DNA damage [27]. In addition, the association of TP53TG with other cancer types such as glioma and lung caner has been reported in previous studies.
Besides the lower prevalence of lncRNA studies on EAC, another possible explanation for the links of top-5-ranked lncRNAs with ESCC instead of EAC is that racial disparities of ESCC between Asian and Caucasian populations existed at the molecular level [28]. Then, it is natural to observe a link between PVT1 and ESCC during the literature mining considering those studies were all carried out in East Asia. In contrast, our work is based on the TCGA RNA-Seq data in which most patients are Whites.
On the other hand, for the top 5 directly-related-to-cancer lncRNAs for the ESCC, only two studies provided experimental supports on the association of HULC [29] and EGOT [30] with esophageal cancer. For the remaining three lncRNAs – LINC01089, TUSC8 and CAHM — the LncRNADisease2 database [31] used computational methods and predicted they are associated with gastric cancer. Even though the identified lncRNAs are related to a variety of cancers, more focus on their correlations with ESCC and EAC are in demand. The expression levels of those 10 lncRNAs were compared between ESCC and EAC, between esophageal cancer tissues and normal tissues using Wilcoxon tests. Among them, 6 (4 were specific for EAC, 1 for ESCC and 1 shared by both subtypes) had a corresponding p-value < 0.05 and may be considered as the differentially expressed lncRNAs between EAC and ESCC (Fig. 3). All these 6 lncRNAs except CAHM had corresponding Wilcoxon test p-values < 0.05 in the comparison of tumor tissues and normal tissues as well (Fig. 3). Nevertheless, as shown in Fig. 4a, these 10 lncRNAs hold very limited discriminative capacity to separate EAC from ESCC. In contrast, they can predict the prognosis status perfectly. In Fig. 4b, Kaplan-Meier curves were plotted for high-risk and low-risk groups (stratified according to the estimated risk scores of the multivariate Cox-regression model with these 10 lncRNAs as covariates), and then a log-rank test was performed to compare these survival curves. From Fig. 4b, we observed that within each subtype, the difference between the high-risk and low-risk groups was significant while within each risk group (between subtype), the difference was less or not significant. This result is expectable given that the outcomes (i.e., dependent variables) considered in the segmentation of subtypes and prognosis prediction are distinct.
Box-plots illustrating the expression levels of 6 differentially expressed lncRNAs between EAC and ESCC (which have a Wilcoxon test p-value < 0.05). Among them, 5 lncRNAs may be regarded as differentially expressed lncRNAs between esophageal cancer and normal controls (which have a corresponding Wilcoxon test p-value < 0.05 as well). EAC: esophageal adenocarcinoma; ESCC: esophageal squamous cell carcinoma
Discriminative value and prognostic value of the top 10 directly-related-to-cancer lncRNAs identified by the Cox-filter method for the esophageal cancer application. a Heat-map. b Kaplan-Meier curves. Based on the risk scores calculated using a multivariate Cox regression model, the samples were divided into a high- and low-risk of death groups. From these two plots, it was observed that while the lncRNAs possessed little information for segmentation of EAC and ESCC, they can distinguish the high- and low-risk groups perfectly well. In the Kaplan-Meier plot the log-rank p-value was also given. EAC: esophageal adenocarcinoma; ESCC: esophageal squamous cell carcinoma; LR: low-risk group; HR: high-risk group
Among the overlapped 11 lncRNAs, in addition to that CAHM was experimentally validated to be associated with colorectal cancer by a qPCR study [32] and astrocytoma [33] by a microarray study, TMEM51-AS1 was with chromophobe renal cell carcinoma [34] and liver cancer [35] by qPCR studies, RAD51-AS1 was with only ovarian epithelial cancer [36], RNF139-AS1 was with only astrocytoma [37] and LINC01089 with breast cancer [38] by qPCR and astrocytoma [33] by a microarray study, all except DSE and SPPL2B (which is not recorded on LncRNADisease2 database) were predicted to be correlated with a variety of cancers such as gastric cancer by the LncRNADisease2 database. Further studies are warranted to investigate the roles that the identified lncRNAs (including overlapped ones and unique-to-subtype ones by integrating the Cox-filter method and biological relevancy) may play during the development and progression of esophageal cancer.
For LSCC prognostic lncRNAs, H19, MALAT1, NEAT1, CYTOR and SNHG12 were ranked as the first five of this directly-related-to-cancer list. For HSCC, TERC, PCAT1, CYTOR, LINC01234 and LINC00958 made to the list. H19 is a well-known oncogene and acts as a driving force in a variety of cancers. For HNSCC specifically, a study by Guan et al. [39] demonstrated that overexpression of H19 is associated with tumor recurrence and poor prognosis by performing an experiment including 62 HNSCC patients (46 with LSCC and 14 with HSCC). A very recent study [40] also showed that the expression level of H19 was higher in patients with metastasized (vs non-metastasized) tongue squamous cell carcinoma, and was higher in tumor cells than normal squamous cells.
MALAT1 was found to be overexpressed in tumor tissues of oral squamous cell carcinoma (OSCC) patients by a real-time PCR experiment carried out by Zhou et al. [41]. Chang et al. [42] showed that inhibition of MALAT1 can prevent OSCC proliferation whereas its overexpression can promote OSCC. According to the ceRNA network, MALAT1 is a microRNA sponge of miR-125b of which STAT3 is predicted as a binding target. In addition, two studies [43, 44] provided experimental supports for the association of MALAT1 and tongue squamous cell carcinoma. Using qRT-PCR, Wang et al. [45] examined and compared the expression level of NEAT1 in LSCC and adjacent non-neoplastic tissues and showed that NEAT1 was significantly over-expressed in LSCC. Hence, they concluded that "NEAT1 plays an oncogenic role in the tumorigenesis of LSCC."
CYTOR, also known as LINC00152, was proved experimentally to be associated with progression and prognosis of tongue squamous cell carcinoma [46] and HNSCC [47]. Using TCGA RNA-Seq data and some bioinformatics tools, Guo et al. [48] identified CYTOR as an HNSCC-associated lncRNA and determined that its expression is positively correlated with lymph node metastasis and risk of death. Subsequently, its function was explored by cell-based experiments which suggested that CYTOR inhibited cell apoptosis after the treatment with chemotherapeutic drug diamminedichloroplatinum (DDP). Furthermore, acting as the microRNA sponge of miR-19-5p that combines with the 3'UTR region of WWP1, overexpression of SNHG12 may promote proliferation and invasion of LSCC [49]. In our analysis, CYTOR was shared by both LSCC and HSCC subtypes.
Even though no experimental evidence or computational prediction links TERC with HNSCC in the LncRNADisease2.0 database [31], literature mining in the PubMed database identified several studies to support their association. For LSCC specifically, Liu et al. [50] detected TERC gene amplification in precancerous and cancerous tissues using fluorescent in situ hybridization. In a recent study [51], the expression values of PCAT1 in paired HNSCC tissues and adjacent non-tumor tissues were measured using qRT-PCR. The results showed that PCAT1 was over-expressed in the tumor tissues, which consisted with the results given by the online bioinformatics tool, GEPIA (http://gepia.cancer-pku.cn). In addition, that study also proved that after the knockdown of PCAT1, p38 MAPK and apoptosis signal-regulating kinase 1 which induced Caspase 9 and PART mediated apoptosis were activated.
For the last two HSCC-specific lncRNAs, namely, LINC01234 and LINC00958, no evidence has been found to link them with HNSCC in either the LncRNADisease2 database (experimentally or computationally) or the PubMed literature search. Both of these genes overlapped the HSCC and LSCC subtypes. Likewise, for the final 3 overlapped lncRNAs, no support for a link with HNSCC can be found. Further studies are warranted.
Among these 9 unique directly-related-to-cancer lncRNAs, only CYTOR and SNHG12 have Wilcoxon test p-values < 0.05 (Fig. 5) and may be loosely regarded as differentially expressed genes between LSCC and HSCC subtypes, and between cancer tissues and normal tissues. The small sample size of HSCC in this analysis may explain the results to some degree. Similar to the results of esophageal cancer application, while these 9 lncRNAs cannot distinguish LSCC and HSCC, they do have prognostic value for predicting the risk of death for HNSCC patients (here, LSCC and HSCC were examined together given there were only 6 HSCC patients in this study). Corresponding heat-map and Kaplan-Meier curves are presented in Fig. 6. Lastly, the regulated mRNAs by the identified lncRNAs were retrieved from the lncRNADisease 2.0 database [31] and the pathway enrichment analysis was carried out using the String database [52]. The enriched GO terms and KEGG pathways for these four subtypes are presented in Table 2, from which we observe that no overlaps among these four subtypes occur.
Box-plots illustrating the expression levels of 2 differentially expressed lncRNAs between LSCC and HSCC (which have a Wilcoxon test p-value < 0.05). Because the sample size of HSCC is very small, only two lncRNAs barely made the significance level of 0.05, which were differentially expressed lncRNAs between cancer tissues and normal tissues as well. LSCC: laryngeal squamous cell cancer; HSCC: hypopharyngeal squamous cell cancer
Discriminative value and prognostic value of 9 top directly-related-to-cancer lncRNAs identified by the Cox-filter method for the head and neck cancer. a Heat-map of these lncRNAs. b Kaplan-Meier curves of these lncRNAs. While these lncRNAs possessed little information for segmentation of HSCC and LSCC, they can distinguish the high- and low-risk of death groups perfectly well. In the Kaplan-Meier plot the log-rank p-value is also given. Since the number of HSCC patients included in this study is very small, the log-rank test was based on two groups instead of four groups. LSCC: laryngeal squamous cell cancer; HSCC: hypopharyngeal squamous cell cancer; LR: low-risk group; HR: high-risk group
Table 2 Enriched pathway analysis for the mRNAs regulated by selected lncRNAs
The Cox-filter method is among the first efforts to develop feature selection algorithms capable of identifying prognostic genes specifically for different subtypes. When applied to gene expression profiles, it achieved satisfactory performance. In this study, we show that this method is applicable to lncRNA expression profiles, as illustrated by the two real-world applications in which the Cox-filter method identified many lncRNAs with meaningful implication with cancer. The ratio of the two distinct subtypes in these applications represent extreme cases: one with good balance case and one with bad balance. The Cox-filter method can easily deal with the first case. In the second case, it can still estimate the significance level of lncRNAs in minor subtypes by borrowing some information from the dominant subtype. Therefore, the Cox-filter method is a handy tool to construct subtype-specific prognostic lncRNA signatures, indeed.
The big drawback of the Cox-filter method is inclusion of many false positives in the final models. To address this drawback, several extensions that incorporate biological information and prioritize genes with high connectivity levels have been proposed [53, 54]. When applying to lncRNA profiles, the issue is still apparent and thus needs to be addressed as well. However, those extensions cannot be adopted to the lncRNA expression profiles directly because the biological pathway information was retrieved from a knowledgebase such as String [52] or HPRD [55], which focus on mRNAs (protein coding genes). A statistical model (e.g., the WGCNA method [56] with the capacity of constructing co-expression networks/modules is needed before implementing such Cox-filter extensions. Nevertheless, by combining biological relevancy information from the GeneCards database, we further refined the lncRNA lists identified by the Cox-filter method, and the resulting lncRNA signatures have been demonstrated to possess perfect prognostic value.
Data for head and neck squamous cell carcinoma (the HNSC cohort) were downloaded from The Atlas of ncRNA in Cancer (TANRIC) database (https://www.tanric.org/), and data for esophageal cancer (the ESCA cohort) were downloaded from the Genomic Data Commons of The Cancer Genome Atlas (https://gdc.cancer.gov).
ceRNA:
Competitive endogenous RNA
EAC:
Esophageal adenocarcinoma
ESCC:
Esophageal squamous cell carcinoma
FPKM:
Fragments per kilo-bases per million
HCC:
HNSCC:
Head and neck squamous cell carcinoma
HSCC:
Hypopharyngeal squamous cell carcinoma
lncRNA:
Long non-coding RNAs
LSCC:
Laryngeal squamous cell
TANRIC:
The atlas of ncRNA in cancer
TCGA:
The cancer genome atlas
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Villalba M, Lopez L, Redrado M, Ruiz T, de Aberasturi AL, de la Roja N, et al. Development of biological tools to assess the role of TMPRSS4 and identification of novel tumor types with high expression of this prometastatic protein. Histol Histopathol. 2017;32:929–40.
Kou N, Liu S, Li X, Li W, Zhong W, Gui L, et al. H19 facilitates tongue squamous cell carcinoma migration and invasion via sponging miR-let-7. Oncol Res. 2019;27:173–82.
Zhou X, Liu S, Cai G, Kong L, Zhang T, Ren Y, et al. Long non coding RNA MALAT1 promotes tumor growth and metastasis by inducing epithelial-Mesenchymal transition in Oral squamous cell carcinoma. Sci Rep. 2015;5:15972.
Chang S-M, Hu W-W. Long non-coding RNA MALAT1 promotes oral squamous cell carcinoma development via microRNA-125b/STAT3 axis. J Cell Physiol. 2018;233:3384–96.
Liang J, Liang L, Ouyang K, Li Z, Yi X. MALAT1 induces tongue cancer cells' EMT and inhibits apoptosis through Wnt/β-catenin signaling pathway. J Oral Pathol Med. 2017;46:98–105.
Su Y, Xiong J, Hu J, Wei X, Zhang X, Rao L. MicroRNA-140-5p targets insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) to suppress cervical cancer growth and metastasis. Oncotarget. 2016;7:68397–411.
Wang P, Wu T, Zhou H, Jin Q, He G, Yu H, et al. Long noncoding RNA NEAT1 promotes laryngeal squamous cell cancer through regulating miR-107/CDK6 pathway. J Exp Clin Cancer Res. 2016;35:22.
Rehmani A, Judkins C, Whelan A, Nguyen M, Schultz C. Comparison of safety and efficacy of unfractionated heparin versus Bivalirudin in patients undergoing percutaneous coronary intervention. Heart Lung Circ. 2017;26:1277–81.
Haque S-U, Niu L, Kuhnell D, Hendershot J, Biesiada J, Niu W, et al. Differential expression and prognostic value of long non-coding RNA in HPV-negative head and neck squamous cell carcinoma. Head Neck. 2018;40:1555–64.
Guo Y-Z, Sun H-H, Wang X-T, Wang M-T. Transcriptomic analysis reveals key lncRNAs associated with ribosomal biogenesis and epidermis differentiation in head and neck squamous cell carcinoma. J Zhejiang Univ Sci B. 2018;19:674–88.
Li J, Sun S, Chen W, Yuan K. Small Nucleolar RNA host gene 12 (SNHG12) promotes proliferation and invasion of laryngeal Cancer cells via sponging miR-129-5p and potentiating WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) expression. Med Sci Monit. 2019;25:5552–60.
Liu Y, Dong X, Tian C, Liu H. Human telomerase RNA component (hTERC) gene amplification detected by FISH in precancerous lesions and carcinoma of the larynx. Diagn Pathol. 2012;7:34.
Sur S, Nakanishi H, Steele R, Ray RB. Depletion of PCAT-1 in head and neck cancer cells inhibits tumor growth and induces apoptosis by modulating c-Myc-AKT1-p38 MAPK signalling pathways. BMC Cancer. 2019;19:354.
Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, et al. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2015;43:D447–52.
Tian S. Identification of subtype-specific prognostic signatures using cox models with redundant gene elimination. Oncol Lett. 2018;15:8545–55.
Tian S, Wang C, Chang HH, Sun J. Identification of prognostic genes and gene sets for early-stage non-small cell lung cancer using bi-level selection methods. Sci Rep. 2017;7:46164. https://doi.org/10.1038/srep46164.
Keshava Prasad TS, Goel R, Kandasamy K, Keerthikumar S, Kumar S, Mathivanan S, et al. Human protein reference database--2009 update. Nucleic Acids Res. 2009;37(SUPPL.1):D767–72.
Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008;9:559.
The Markey Cancer Center's Research Communications Office assisted with preparation of the manuscript.
This study was supported by the Education Department of Jilin Province (grant No. JJKH20190032KJ) and the Natural Science Foundation of China (grant No. 31401123).
Division of Clinical Research, The First Hospital of Jilin University, 1Xinmin Street, Changchun, Jilin, 130021, People's Republic of China
Suyan Tian
Department of Biostatistics, College of Public Health, University of Kentucky, 800 Rose St, Lexington, KY, 40536, USA
Chi Wang
Markey Cancer Center, University of Kentucky, 800 Rose St, Lexington, KY, 40536, USA
School of Life Science, 2699 Qianjin Street, Changchun, Jilin, 130012, People's Republic of China
Jing Zhang
Department of Otolaryngology Head and Neck Surgery, The Second Hospital of Jilin University, 218 Ziqiang Road, Changchun, Jilin, 130041, People's Republic of China
Dan Yu
Conceived and designed the study: ST DY. Analyzed the data: ST CW JZ. Interpreted data analysis and results: ST DY. Wrote the paper: ST JZ CW DY. All authors reviewed and approved the final manuscript.
Correspondence to Suyan Tian or Dan Yu.
Tian, S., Wang, C., Zhang, J. et al. The cox-filter method identifies respective subtype-specific lncRNA prognostic signatures for two human cancers. BMC Med Genomics 13, 18 (2020). https://doi.org/10.1186/s12920-020-0691-4
Long non-coding RNA (lncRNA)
Prognostic signature
Head and neck squamous cell carcinoma (HNSCC)
Cox regression model


Marguerite Therese Johnston Fury passed from this life to be with her Lord on Friday, November 23, 2018. It was the day of her 93rd Birthday.
She was the mother of six children. They were her life.
Born in Manhattan in 1925, to George T. and Anna (McGrath) Johnston, she grew up in the Bronx and graduated from St. Simon Stock High School.
She married the only man she ever loved, Michael H. Fury, in 1948 They had six children together, two born in the Bronx, and four more born in Rockland County after the young family moved to Pearl River in 1953.
Marguerite was a brilliant chemist, graduating at the top of her class with honors from Good Counsel College, White Plains, NY, in 1947. She graduated with a major and four minors. Interestingly, she was offered a promising career at Lederle Laboratories in Pearl River at graduation, but turned that offer aside to marry Michael and begin to raise a family in the Bronx — only to make Pearl River her home years later. She served as a High School teacher until the birth of her first child. Later life, she served as an active member of the Catholic Lay Women of Rockland County, President of the American Association of University Women (AAUW), the Delta Beta Phi Sorority, Catholic Family Movement, Christian One Person Organization, St. Margaret's School Auxiliary. She loved book study and Bible study, and was an avid member of numerous book and Bible study groups, including the Catholic Lay Women's Study Club of Rockland County.
She was a brilliant and accomplished woman, who chose for love to dedicate herself to her family. Her family was her life.
After her children, her second passion was her faith. Marguerite was a devout daughter of her spiritual Mother, the Roman Catholic Church, and gave her children and all who knew her the example of turning to her faith in good times, and in times of trial.
She was preceded in death by her parents, her cousin David Bravo, her Aunts Catherine V. McGrath, Mary C. "May" McGrath, Martha (McGrath) O'Dell and Patrick J. "Jack" McGrath. She is survived her precious daughters Marianne Burkhardt, Marguerite Engelbrektson and husband Jon, Maureen Simalchik, Madelyn Nealon; beloved sons Michael J. Fury and wife Donna, Mark Fury. Her grandchildren and their accomplishment brought her joy, including Brian Simalchik and wife Amanda Korman, Stephen Simalchik, Colin Fury, Kahyla Fury, Ian Fury, Megan Fury, Clayton Fury, Hallie Fury, Emily Nealon, Alyssa Nealon, step-grandchildren Jeanmarie Silverman, Christina Cartaya and husband Michael, Steven Silverman; great-grandson Mason Maynez; step-great-grandchildren Bobby Cartaya and Amelia Silverman.
She also leaves behind her beloved "sister" Anne Fury of Mamaroneck, NY, and her beloved "family" of Ken Mannix, Kimberly and Carrie.
Mass of Christian burial will take place Tuesday November 27th at 10:00 AM at St. Aedan's Church, 23 Reld Dr. Pearl River, NY 10965.
Burial to immediatly follow at Holy Cross Cemetery, 340 Ridge Rd. N. Arlington, NJ 07031.


"Abell, M., Jung, E., & Taylor, M. (2011). Students' perceptions of cla" by Eunjoo Jung, V J. Molfese et al.
Abell, M., Jung, E., & Taylor, M. (2011). Students' perceptions of classroom instructional environments in the context of universal design for learning. Learning Environments Research, 14(2), 171-185.
Jung, Eunjoo; Molfese, V J.; and Larson, A E., "Abell, M., Jung, E., & Taylor, M. (2011). Students' perceptions of classroom instructional environments in the context of universal design for learning. Learning Environments Research, 14(2), 171-185." (2011). College Research Center. 23.


Sarah Belle started her professional life in the hospitality industry, working in some of the roughest hotels in Melbourne in the late Eighties, surrounded by drug dealers, prostitutes, pimps, and undercover police. Tiring of the inherent dangers of her working environment, Sarah completed a business degree and went on to work in the recruitment industry and the Department of Defence, where she met and married the man of her dreams: a dashing, Army Blackhawk pilot. They have four young sons and live on the beautiful Queensland coast, where Sarah's days are spent being a frazzled mum, writer, Bikram Yoga devotee and the only woman in a house of five males.
Let me ask you a question: what do you think of a new genre of Women's Fiction called 'Romagic Comedy'?
It's my own invention – probably not a very good one, but it is better than the Chakra underpants I came up with (so the wearer can have a dedicated Chakra colour, but not necessarily on show – great for those of us who can't wear Yellow or Orange). The were going to be called 'Chundies', so I think that Romagic is a vast improvement.
Like a lot of other writers, the hardest question for me to answer is, "What genre do you write?" There are gazillions of genres and cross-over genres now, so it can be quite daunting just to answer one simple question without babbling like a loon. Just where does HINDSIGHT fit in?
It's funny. It's sad. It involves the emotional growth of the protagonist. It's got romance in it. It involves time travel. It's set in both modern day and 1961. It could fit in to six different genres.
I am told that Chick Lit is dead – although I don't believe it. I don't write straight romance because, for me, the romantic element is secondary to the journey the protagonist takes. So, for all of us who write with a dash, a twist of something supernatural, what do we call our style?
Here's my answer: I write Romantic Comedy with a dash of magic – Romagic Comedy. What do you think? Is it growing on you yet?
Romantic comedies with a dash of magic captivate me because the entire premise is exceptional – whether it be past or future time travel, hypnosis, waking up dead or in another's body, being haunted, possessed, the subject of a spell or a wish that has gone wrong – it has me interested because automatically the protagonist is way out of her comfort zone. On top of that, she has to contend with all the conflict and emotional growth the author can throw at her!
I love coming up with a crazy situation, such as waking up in 1961, and then casting the character for whom this situation would create the most turmoil and conflict – a career maniac who is reliant on technology, designer wardrobes, a nanny and housekeeper and cafe lattes to help get her through the day. Enter Juliette Wilde, protagonist of HINDSIGHT. Thank goodness she still has her sense of humour to fall back on!
If you are after more authors of 'Romagic' ( I doubt it will ever be adopted by the Oxford Dictionary), you might like to look at the works of: Juliet Madison (fellow Escape Artist), Jenny Colgan, Marian Keyes, Melanie Rose and Kristy Greenwood.
To win a digital copy of Hindsight (Amazon or ITunes), just leave your name and email address in the comments sections below!


We're incredibly bummed to report today that Pilgrim guitarist and frontman Jon Rossi has passed away at the age of 26 years old. No cause of death has yet been revealed, but tributes and posts have begun pouring in from the metal community. Pilgrim released two highly influential doom albums in its career, 2012's Misery Wizard and 2014's II: Void Worship, as well as a demo, split, and live offering via Scion A/V.
Pilgrim just played in Providence with Cobalt and The Obsessed on October 25, and we had the pleasure of filming the band's live performance at Saint Vitus this March. You can watch Pilgrim's final performance below. Rest In Peace, Jon.


text:
Environmental fluctuations and the theory of the ecological niche
R.M. Nisbet, William Gurney, M.A. Pettipher
May and MacArthur proposed that a limit to the permissible degree of similarity between competing species might result from the resilience of any of the species to environmental fluctuations dropping dramatically as the differences between the competitors were reduced. For certain idealized models of species competing for a single type of resource this limit occurred when the ratio d/w was of order one (d being the spacing, assumed uniform, of the species along a resource spectrum and w the width, assumed constant for all species, of the resource utilization functions). Several authors have since suggested that this result might be rather fragile in the sense that it disappeared with only minor changes in the models. We have therefore studied a rather general model of a two-trophic-level system in order to identify the conditions under which this mechanism might produce a limit to niche overlap which is insensitive to the intensity of the environmental fluctuations. We call such a limit a hard limit, and we find that there is only a hard limit to niche overlap provided that all the following conditions are satisfied:
(a) there is little self-regulation of the consumer populations,
(b) the environmental fluctuation at the resource level is not too large, and
(c) the fluctuations in the specific growth rates of the consumers are not strongly positively correlated.
We illustrate these conditions by performing detailed calculations of the intensity of population fluctuations which arise from variation in various parameters in a competition model due to Schoener.
Journal of Theoretical Biology
environmental fluctuations
hard limit
Schoener
competing species
Nisbet, R. M., Gurney, W., & Pettipher, M. A. (1978). Environmental fluctuations and the theory of the ecological niche. Journal of Theoretical Biology, 75(2), 223-237. https://doi.org/10.1016/0022-5193(78)90232-1
Nisbet, R.M. ; Gurney, William ; Pettipher, M.A. / Environmental fluctuations and the theory of the ecological niche. In: Journal of Theoretical Biology. 1978 ; Vol. 75, No. 2. pp. 223-237.
@article{4d50de527faf462c83bb1a2ceed77706,
title = "Environmental fluctuations and the theory of the ecological niche",
abstract = "May and MacArthur proposed that a limit to the permissible degree of similarity between competing species might result from the resilience of any of the species to environmental fluctuations dropping dramatically as the differences between the competitors were reduced. For certain idealized models of species competing for a single type of resource this limit occurred when the ratio d/w was of order one (d being the spacing, assumed uniform, of the species along a resource spectrum and w the width, assumed constant for all species, of the resource utilization functions). Several authors have since suggested that this result might be rather fragile in the sense that it disappeared with only minor changes in the models. We have therefore studied a rather general model of a two-trophic-level system in order to identify the conditions under which this mechanism might produce a limit to niche overlap which is insensitive to the intensity of the environmental fluctuations. We call such a limit a hard limit, and we find that there is only a hard limit to niche overlap provided that all the following conditions are satisfied:1. (a) there is little self-regulation of the consumer populations,2. (b) the environmental fluctuation at the resource level is not too large, and3. (c) the fluctuations in the specific growth rates of the consumers are not strongly positively correlated.We illustrate these conditions by performing detailed calculations of the intensity of population fluctuations which arise from variation in various parameters in a competition model due to Schoener.",
keywords = "environmental fluctuations, hard limit, Schoener, competing species",
author = "R.M. Nisbet and William Gurney and M.A. Pettipher",
journal = "Journal of Theoretical Biology",
Nisbet, RM, Gurney, W & Pettipher, MA 1978, 'Environmental fluctuations and the theory of the ecological niche', Journal of Theoretical Biology, vol. 75, no. 2, pp. 223-237. https://doi.org/10.1016/0022-5193(78)90232-1
Environmental fluctuations and the theory of the ecological niche. / Nisbet, R.M.; Gurney, William; Pettipher, M.A.
In: Journal of Theoretical Biology, Vol. 75, No. 2, 21.11.1978, p. 223-237.
T1 - Environmental fluctuations and the theory of the ecological niche
AU - Nisbet, R.M.
AU - Gurney, William
AU - Pettipher, M.A.
N2 - May and MacArthur proposed that a limit to the permissible degree of similarity between competing species might result from the resilience of any of the species to environmental fluctuations dropping dramatically as the differences between the competitors were reduced. For certain idealized models of species competing for a single type of resource this limit occurred when the ratio d/w was of order one (d being the spacing, assumed uniform, of the species along a resource spectrum and w the width, assumed constant for all species, of the resource utilization functions). Several authors have since suggested that this result might be rather fragile in the sense that it disappeared with only minor changes in the models. We have therefore studied a rather general model of a two-trophic-level system in order to identify the conditions under which this mechanism might produce a limit to niche overlap which is insensitive to the intensity of the environmental fluctuations. We call such a limit a hard limit, and we find that there is only a hard limit to niche overlap provided that all the following conditions are satisfied:1. (a) there is little self-regulation of the consumer populations,2. (b) the environmental fluctuation at the resource level is not too large, and3. (c) the fluctuations in the specific growth rates of the consumers are not strongly positively correlated.We illustrate these conditions by performing detailed calculations of the intensity of population fluctuations which arise from variation in various parameters in a competition model due to Schoener.
AB - May and MacArthur proposed that a limit to the permissible degree of similarity between competing species might result from the resilience of any of the species to environmental fluctuations dropping dramatically as the differences between the competitors were reduced. For certain idealized models of species competing for a single type of resource this limit occurred when the ratio d/w was of order one (d being the spacing, assumed uniform, of the species along a resource spectrum and w the width, assumed constant for all species, of the resource utilization functions). Several authors have since suggested that this result might be rather fragile in the sense that it disappeared with only minor changes in the models. We have therefore studied a rather general model of a two-trophic-level system in order to identify the conditions under which this mechanism might produce a limit to niche overlap which is insensitive to the intensity of the environmental fluctuations. We call such a limit a hard limit, and we find that there is only a hard limit to niche overlap provided that all the following conditions are satisfied:1. (a) there is little self-regulation of the consumer populations,2. (b) the environmental fluctuation at the resource level is not too large, and3. (c) the fluctuations in the specific growth rates of the consumers are not strongly positively correlated.We illustrate these conditions by performing detailed calculations of the intensity of population fluctuations which arise from variation in various parameters in a competition model due to Schoener.
KW - environmental fluctuations
KW - hard limit
KW - Schoener
KW - competing species
JO - Journal of Theoretical Biology
JF - Journal of Theoretical Biology
Nisbet RM, Gurney W, Pettipher MA. Environmental fluctuations and the theory of the ecological niche. Journal of Theoretical Biology. 1978 Nov 21;75(2):223-237. https://doi.org/10.1016/0022-5193(78)90232-1

redpajama_set_name: RedPajamaCommonCrawl


Holdem Manager Forums > Holdem Manager 1.0 > Manager General > Duplicate hands just ignored?
View Full Version : Duplicate hands just ignored?
i wanted to make sure that if any hands that are considered duplicates when importing are simply ignored and there are now inserts or updates that occur to the DB at that moment.


text:
Q: ¿Como cambiar el formato de JSON.stringify()? al usar JSON.stringify(), obtengo todo el objeto en una sola linea, por ejemplo
const user = {
    'id': '1234',
    'nombre': 'Adam'
}

JSON.stringify(user)

Resulta en {"id":"1234","nombre":"Adam"}, pero en cambio, yo quiero que resulte algo como
{
    "id": "1234",
    "nombre": "Adam"
}

Que metodo podría utilizar para obtenerlo de la manera deseada?

A: Puedes hacer lo siguiente:

const user = {
    'id': '1234',
    'nombre': 'Adam'
}
console.log('Por defecto', JSON.stringify(user));
console.log('Con dos espacios') ;
console.log(JSON.stringify(user, null, 2));
console.log('Con 4 espacios');
console.log(JSON.stringify(user, null, 4));

Como ves, el método stringify acepta dos parámetros más, siendo el último el número de espacios para indentar el JSON resultante. Esto implica automáticamente usar nuevas líneas para cada valor.
El segundo parámetro es una función para tratar los datos de un modo "especial" cuando lo consideres necesario, pero se sale un poco del tema de la pregunta, así que simplemente pongo el enlace a la documentación de MDN por si quieres indagar más.

redpajama_set_name: RedPajamaStackExchange


Tough mattresses are too firm, they do not have bounce and convenience, there is absolutely nothing gentle about the surface and there is no convenience. Some individuals like the solidity but end up with chronic pain. Shoulder pain, back pain and different other musculoskeletal pains are typical when you sleep on a tough mattress. Soft mattress is not a much better option if it cannot evenly disperse the weight and does not supply appropriate back or lumbar assistance. The majority of soft mattresses tend to lose their firmness, no matter how firm they were at first. There is no pressure relief at tactical points of the body. In a brief span of time, the soft mattress totally gives up. Medium quality mattresses do not offer any break as they integrate the drawbacks of difficult and soft mattresses. They are just as bad for chronic pain like hard bed mattress as they can facilitate arthritis like soft bed mattress.
Purple has as many as fifteen patents entering into just one bed mattress. Some of the patents attend to press releasing comfort while some take care of the assistance, some take care of toughness while some attend to no feel motion transfer. Purple mattress will not cave in, it will not establish any indentation or impression of the body, it will not lose its firmness or softness, the upper layer or the base layer will not lose their main characteristics, the bed mattress will be versatile adequate to hold up against pressure thus offering relief at tactical points whenever required. It is better to be like lawn than a tree. Yard can stand up to a storm whereas a tree gets uprooted. Buckling of the surface is not a bad thing when one needs even circulation of weight or pressure. Purple bed mattress is nontoxic and allergen resistant or hypoallergenic. It is made from recyclable products. The mattress is CertiPUR-US ® licensed.
You may or may not have actually seen the ad video called the Purple bed mattress egg test. In the video, a sleep professional utilizes 4 eggs at 4 various locations, pasted onto a glass frame that she drops from a height on various bed mattress. The easy objective is to enjoy if the eggs break or they stay undamaged. The expectation is that if a bed mattress can evenly disperse weight and can take in the weight of a person or any load then there will be no particular force exerted onto any part of the item or individual sleeping on the bed mattress. All particular pressure points will have equivalent relief as the weight gets distributed uniformly throughout the mattress. For this reason, if a bed mattress is ideal then the eggs will not break. As one would anticipate, the eggs do break when they are allowed to fall from a height being pasted to a glass frame onto many bed mattress with the exception of Purple mattress.
Now, there has actually been criticism of the advertisement since Purple mattress has a grid life formation on its topmost layer so the eggs can suit those grids or box like structures without getting blasted due to the pressure of the glass frame onto the topmost surface area of the bed mattress. To be reasonable to Purple, it deserves to show its item's supremacy. It likewise has videos revealing a side sleeper test, back sleeper test and pressure mapping test. You can view them on the official website.
You can buy Purple bed mattress on Amazon or on the main website. You can use a Purple bed mattress voucher to obtain a discount rate. But you would perhaps consider Purple Mattress Vs Casper or Purple Mattress Vs GhostBed prior to you make a decision. You need to also think about Nectar mattress, which transcends to Purple, Casper and GhostBed among others. Let us quickly check out why.
Casper has four foam layers, GhostBed has 3 and Purple has 3. Nectar has 4. Casper and Purple are thinner than Nectar. Casper, GhostBed and Purple have firmness ranking of 6 to 7, six and a half to seven and six to 6 and a half out of ten respectively. Nectar has a lower firmness rating, therefore providing more convenience without compromising on stability and support. Nectar has the least motion transfer amongst the 4. It is also the most inexpensive. Queen Casper costs $950, Queen GhostBed costs $795 and Queen Purple costs $999. Queen Nectar mattress is tagged at $795 but you would get a $125 discount rate so you pay $670. Nectar has lifetime guarantee. Casper and Purple have 10 years. GhostBed has twenty years. Casper and Purple have a hundred nights trial while GhostBed has a hundred and one nights. Nectar has three hundred and sixty five nights of threat complimentary trial.


text:
The RNC is great for Cleveland business, but it's not the Cavaliers
Published Tue, Jul 19 2016 3:25 PM EDT
Donald Trump pins sold by vendor in Cleveland, Ohio during the Republican National Convention.
Fred Imbert | CNBC
CLEVELAND ― When this city was chosen as the host of the Republican National Convention, little did it know how much its fortune would change.
Just three days after Cleveland was named as the site of the RNC, hometown basketball hero LeBron James announced he'd return to the Cleveland Cavaliers in 2014 after four years with the Miami Heat.
An even bigger surprise, James would lead the Cavs to their first ever NBA title just two years later. And local businesses in Cleveland have had a big boom since.
After the Cavs' Game 7 win against the Golden State Warriors, the city celebrated with a big victory parade which was attended by about 1 million people. That said, the RNC's boost to business is not expected to be as large, with just 50,000 expected to be in the city.
"I do think it's going to be a little bit less," said Tanya Gunya, co-owner of The Chocolate Bar, a restaurant outside the Quicken Loans Arena ― where the convention is being held.
Cleveland Cavaliers Lebron James celebrates with the crowd during a parade to celebrate winning the 2016 NBA Championship in downtown Cleveland, Ohio, U.S. June 22, 2016.
Aaron Josefczyk | Reuters
Gunya said she "never anticipated" the amount of business she received after the Cavaliers won the championship, adding she expects a bump in business this week, but "not a spike."
Brendan Walton, owner of A.J. Rocco's, a restaurant and bar in downtown Cleveland, told CNBC on Monday "right now the basketball finals is surpassing, but it's only Day One."
"We were thinking it was going to be a little faster," he said. "Ultimately, I think folks over time, as they [go] to the more known areas, they start exploring more of Cleveland."
Michael Clark, district manager for Potbelly in Cleveland, said the company expects business to increase by at least 15 percent this week, however, "compared to the championship parade, we can't beat that. We were crushed that day."
The RNC will conclude Thursday, when Donald Trump is expected to officially become the Republican presidential nominee.


Habibi House is very much in the house! Abu Ashley works up another fresh tune that has a unique style and flavor.
Night Safari remixes Ed Sheerhan the only way he knows how, absolutely brilliantly.
This one is a little bit on the darker side, but it is some strong techno. Be careful with this tune, it is pretty damn hot, and you better know what you are doing when you handle this one.
Anytime you can give a solid original a dub rework, you should definitely do it. This Coyote Low Spirits Dub is everything a good song should be.
The question asked is clearly answered by the end of the song… After listening to this one, we all know you are feeling great.


text:
Flood generation and classification of a semi-arid intermittent flow watershed: Evrotas river
Ourania Tzoraki, David Cooper, Thomas Kjeldsen, Nikolaos P. Nikolaidis, Christos Gamvroudis, Jochen Froebrich, Erik Querner, Francesc Gallart, Nikolaos Karalemas
Hourly water level measurements were used to investigate the flood characteristics of a semi-arid river in Greece, the Evrotas. Flood events are analysed with respect to flood magnitude and occurrence and the performance of Curve Number approach over a period of 2007-2011. A distributed model, Soil and Water Assessment Tool, is used to simulate the historic floods (1970-2010) from the available rainfall data, and the performance of the model assessed. A new flood classification method was suggested the Peaks-Duration Over Threshold method that defines three flood types: 'usual', 'ecological' and 'hazardous'. We classify the basin according to the flood type for the most serious past simulated flood events. The proportion of hazardous floods in the main stream is estimated to be 5-7% with a lower figure in tributaries. Flood Status Frequency Graphs and radar plots are used to show the seasonality of simulated floods. In the Evrotas, the seasonality pattern of hazardous flood is in agreement with other studies in Greece and differs from other major European floods. The classification in terms of flood types in combination with flood type seasonality is identified as an important tool in flood management and restoration. © 2013 International Association for Hydro-Environment Engineering and Research.
International Journal of River Basin Management
Published - 1 Mar 2013
Fingerprint Dive into the research topics of 'Flood generation and classification of a semi-arid intermittent flow watershed: Evrotas river'. Together they form a unique fingerprint.
watershed Earth & Environmental Sciences
river Earth & Environmental Sciences
seasonality Earth & Environmental Sciences
soil and water assessment tool Earth & Environmental Sciences
tributary Earth & Environmental Sciences
water level Earth & Environmental Sciences
restoration Earth & Environmental Sciences
radar Earth & Environmental Sciences
Tzoraki, O., Cooper, D., Kjeldsen, T., Nikolaidis, N. P., Gamvroudis, C., Froebrich, J., Querner, E., Gallart, F., & Karalemas, N. (2013). Flood generation and classification of a semi-arid intermittent flow watershed: Evrotas river. International Journal of River Basin Management, 11(1), 77-92. https://doi.org/10.1080/15715124.2013.768623
Flood generation and classification of a semi-arid intermittent flow watershed : Evrotas river. / Tzoraki, Ourania; Cooper, David; Kjeldsen, Thomas; Nikolaidis, Nikolaos P.; Gamvroudis, Christos; Froebrich, Jochen; Querner, Erik; Gallart, Francesc; Karalemas, Nikolaos.
In: International Journal of River Basin Management, Vol. 11, No. 1, 01.03.2013, p. 77-92.
Tzoraki, O, Cooper, D, Kjeldsen, T, Nikolaidis, NP, Gamvroudis, C, Froebrich, J, Querner, E, Gallart, F & Karalemas, N 2013, 'Flood generation and classification of a semi-arid intermittent flow watershed: Evrotas river', International Journal of River Basin Management, vol. 11, no. 1, pp. 77-92. https://doi.org/10.1080/15715124.2013.768623
Tzoraki O, Cooper D, Kjeldsen T, Nikolaidis NP, Gamvroudis C, Froebrich J et al. Flood generation and classification of a semi-arid intermittent flow watershed: Evrotas river. International Journal of River Basin Management. 2013 Mar 1;11(1):77-92. https://doi.org/10.1080/15715124.2013.768623
Tzoraki, Ourania ; Cooper, David ; Kjeldsen, Thomas ; Nikolaidis, Nikolaos P. ; Gamvroudis, Christos ; Froebrich, Jochen ; Querner, Erik ; Gallart, Francesc ; Karalemas, Nikolaos. / Flood generation and classification of a semi-arid intermittent flow watershed : Evrotas river. In: International Journal of River Basin Management. 2013 ; Vol. 11, No. 1. pp. 77-92.
@article{b46a138af0024050a6417571ee443653,
title = "Flood generation and classification of a semi-arid intermittent flow watershed: Evrotas river",
abstract = "Hourly water level measurements were used to investigate the flood characteristics of a semi-arid river in Greece, the Evrotas. Flood events are analysed with respect to flood magnitude and occurrence and the performance of Curve Number approach over a period of 2007-2011. A distributed model, Soil and Water Assessment Tool, is used to simulate the historic floods (1970-2010) from the available rainfall data, and the performance of the model assessed. A new flood classification method was suggested the Peaks-Duration Over Threshold method that defines three flood types: 'usual', 'ecological' and 'hazardous'. We classify the basin according to the flood type for the most serious past simulated flood events. The proportion of hazardous floods in the main stream is estimated to be 5-7% with a lower figure in tributaries. Flood Status Frequency Graphs and radar plots are used to show the seasonality of simulated floods. In the Evrotas, the seasonality pattern of hazardous flood is in agreement with other studies in Greece and differs from other major European floods. The classification in terms of flood types in combination with flood type seasonality is identified as an important tool in flood management and restoration. {\textcopyright} 2013 International Association for Hydro-Environment Engineering and Research.",
author = "Ourania Tzoraki and David Cooper and Thomas Kjeldsen and Nikolaidis, {Nikolaos P.} and Christos Gamvroudis and Jochen Froebrich and Erik Querner and Francesc Gallart and Nikolaos Karalemas",
journal = "International Journal of River Basin Management",
publisher = "International Association of Hydraulic Engineering Research",
T1 - Flood generation and classification of a semi-arid intermittent flow watershed
T2 - Evrotas river
AU - Tzoraki, Ourania
AU - Cooper, David
AU - Kjeldsen, Thomas
AU - Nikolaidis, Nikolaos P.
AU - Gamvroudis, Christos
AU - Froebrich, Jochen
AU - Querner, Erik
AU - Gallart, Francesc
AU - Karalemas, Nikolaos
N2 - Hourly water level measurements were used to investigate the flood characteristics of a semi-arid river in Greece, the Evrotas. Flood events are analysed with respect to flood magnitude and occurrence and the performance of Curve Number approach over a period of 2007-2011. A distributed model, Soil and Water Assessment Tool, is used to simulate the historic floods (1970-2010) from the available rainfall data, and the performance of the model assessed. A new flood classification method was suggested the Peaks-Duration Over Threshold method that defines three flood types: 'usual', 'ecological' and 'hazardous'. We classify the basin according to the flood type for the most serious past simulated flood events. The proportion of hazardous floods in the main stream is estimated to be 5-7% with a lower figure in tributaries. Flood Status Frequency Graphs and radar plots are used to show the seasonality of simulated floods. In the Evrotas, the seasonality pattern of hazardous flood is in agreement with other studies in Greece and differs from other major European floods. The classification in terms of flood types in combination with flood type seasonality is identified as an important tool in flood management and restoration. © 2013 International Association for Hydro-Environment Engineering and Research.
AB - Hourly water level measurements were used to investigate the flood characteristics of a semi-arid river in Greece, the Evrotas. Flood events are analysed with respect to flood magnitude and occurrence and the performance of Curve Number approach over a period of 2007-2011. A distributed model, Soil and Water Assessment Tool, is used to simulate the historic floods (1970-2010) from the available rainfall data, and the performance of the model assessed. A new flood classification method was suggested the Peaks-Duration Over Threshold method that defines three flood types: 'usual', 'ecological' and 'hazardous'. We classify the basin according to the flood type for the most serious past simulated flood events. The proportion of hazardous floods in the main stream is estimated to be 5-7% with a lower figure in tributaries. Flood Status Frequency Graphs and radar plots are used to show the seasonality of simulated floods. In the Evrotas, the seasonality pattern of hazardous flood is in agreement with other studies in Greece and differs from other major European floods. The classification in terms of flood types in combination with flood type seasonality is identified as an important tool in flood management and restoration. © 2013 International Association for Hydro-Environment Engineering and Research.
UR - http://dx.doi.org/10.1080/15715124.2013.768623
JO - International Journal of River Basin Management
JF - International Journal of River Basin Management


text:
Free Enterprise Momentum Continues with Passage of Prevailing Wage Repeal and Right to Work Laws in Kentucky
Saturday, January 7, 2017 11:50 AM
Posted in News Releases 2017, Politics and Policy
Contact: Jeff Leieritz (202) 905-2104
leieritz@abc.org
WASHINGTON, D.C., Jan. 7– Associated Builders and Contractors (ABC) today commended the Kentucky Senate's passage of bills that would end forced unionization and repeal the state's wasteful prevailing wage law.
The Kentucky Senate today passed HB 3, which would repeal the state's costly and inefficient prevailing law by a vote of 25-12 after the Kentucky House of Representatives passed the bill by a vote of 60-35 on Jan. 5. The Senate also passed Right to Work legislation, HB 1, by a vote of 25-12, which would prevent workers from being required to join a labor union in order to accept or maintain a job. The Kentucky House of Representatives passed HB 1 by a vote of 61-34 on Jan. 5. Both bills now await Governor Bevin's (R-Ky.) signature.
"Associated Builders and Contractors applauds the Kentucky Legislature's decisive actions to promote free enterprise and fair and open competition and looks forward to other states following suit in embracing these merit shop principles," said ABC Vice President of Regulatory, Labor and State Affairs Ben Brubeck. "By creating new opportunities for all Kentucky contractors shut out by the archaic and costly prevailing wage law, and allowing workers to freely decide whether to join a labor union, the Kentucky legislature has enacted needed improvements to the state's business climate, ranked 32nd in the country by ABC's latest Merit Shop Scorecard."
"Associated Builders and Contractors of Indiana/Kentucky commends the leadership of Governor Bevin, Speaker Hoover, Chairman DeCesare, Representative Koenig, Chairman McDaniel, Senate President Stivers and Leader Thayer for their support of fair and efficient government policies that will benefit all Kentuckians," said ABC of Indiana/Kentucky President J.R. Gaylor. "These leaders articulated the need for a better business environment in Kentucky leading up to last November's election, were given free enterprise-supporting majorities in both chambers of the legislature by the voters of the commonwealth and have delivered these crucial policies that will help grow Kentucky's economy."
Should these bills be signed into law, Kentucky will become the 21st state not subject to prevailing wage requirements on public construction projects and the 27th Right to Work state (the fifth to reject forced unionization since 2012).
ABC released its latest Merit Shop Scorecard rankings in November 2016. The meritshopscorecard.org website reviews and grades state-specific policies and information significant to the success of the commercial and industrial construction industry. The scorecard grades states on their policies on prevailing wage and project labor agreement (PLA) mandates and Right to Work status, as well as their construction job growth rate, commitment to developing a well-trained workforce, career and technical education (CTE) opportunities and results, and use of public-private partnerships (P3s). Plagued in part by its prevailing wage and failure to adopt a Right to Work law to date, Kentucky's business environment ranks 32nd in the country.
ABC opposes wasteful prevailing wage laws because they contain outdated job restrictions that do not match the needs of today's competitive construction business environment. Prevailing wage requirements discourage many qualified small and minority-owned contractors from bidding on public projects. State governments' complex and inefficient wage rate determinations and work restrictions make it difficult for them to compete with better capitalized corporations. Studies have shown that state prevailing wage laws can needlessly inflate construction costs by as much as 38 percent.
ABC supports Right to Work laws because they guarantee workers can seek employment without fearing they will be required to join (or pay) a union if they are hired. These laws simply allow workers who do not want to participate in collective bargaining to opt out of joining the union or paying dues or fees. If all or most of the members of a bargaining unit believe union representation will advance their interests, then nothing in a Right to Work law prohibits them from exercising their federally protected right to organize a union and collectively bargain with their employer. U.S. Bureau of Labor Statistics reports that private sector employment grew 5.2 percent faster in Right to Work states than non-Right to Work states from 2003-2013. Additionally, U.S. Department of Commerce data show that per capita disposable income, adjusted for cost of living, was higher in Right to Work states than the national average in 2013.
Neighboring West Virginia also repealed its prevailing wage law and adopted Right to Work legislation in 2016. Despite rhetoric that both actions would have dire economic consequences, the state's monthly construction unemployment rate has consistently improved compared to its 2015 rate, and the state now ranks second in the country in year-over-year construction unemployment rate progress according to the latest report.
Right to Work law, right-to-work, Prevailing Wage
« Construction Lost Jobs in December
Overall Construction Input Prices Firm in December as Energy Prices Surge »
ABC Names the Top-performing Contractors in U.S. Commercial and Industrial Construction
October Construction Unemployment Rates Down in 45 States Year Over Year, Says ABC


I feel so lost and so alone right now. He was my world, and he was my everything. He was always there for me no matter what. I just cannot get a grip on this.
His millions of fans and thousands he influenced likely feel the same way. Along with Bill Monroe, Stanley and his brother Carter established bluegrass music in the 1940s. ABC News reports that the boys grew up being sung traditional songs by their father, and learning to play old-time clawhammer style banjo from their mother. They formed the Clinch Mountain Boys, but when Carter died in 1966, the music seemed to stop.
Not for long, however. Ralph would recover and reform the band once again. Jerry Garcia and Bob Dylan were amongst the more distinguished fans. During an eight-decade long career he'd become Dr. Ralph Stanley, join the Grand Ole Opry (2000) and the International Bluegrass Hall of Honor (1992), and become as important to the genre as Elvis Presley was to rock 'n' roll. In the early 2000s Stanley enjoyed a career resurgence when his songs on the O Brother, Where Art Thou? soundtrack earned him a Grammy. "O Death" became a modern day signature song, drawing a much younger audience to his live shows.
The "Living Legends" medal from the Library of Congress and a National Medal of Arts were among the other honors Stanley earned. He also played for two presidential inaugurations, but perhaps his greatest honor is his legacy. In addition to his music and a family known for bluegrass players, he mentored young artists like Keith Whitley and Rick Skaggs.
Earlier this month, Bluegrass Today shared that Dr. Stanley had retired. At the most recent Hills on the Home Festival, his son, Ralph Stanley II, announced he was taking over the Clinch Mountain Boys — a move many years in the making. Stanley did not attend this festival.


text:
Rublev Stays Hot, Overcomes Coric For St. Petersburg Title
by Staff | October 18th, 2020, 3:55 pm
Andrey Rublev continued his strong play since the restart capturing his home title in St. Petersburg beating Boric Coric 7-6(5), 6-4.
The title was Rublev's fourth of 2020 and sixth of his career. Rublev, who turns 23 on Tuesday, has won 14 of his last 15 matches.
"I feel happy. This one is really special for me," Rublev said after his first St. Petersburg final. "I think this one is the most special for me, for the moment, and will always be special.
"I am proud and I am happy with the way I am performing," he added. "I try not to think about it. I try to focus on the things I still need to improve, because there are so many things I can improve and I have to improve if I want to be at the same level or even better."
Rublev's recent run has put him into position for a year-end spot in the ATP Finals.
"I know I have a really good chance to qualify, but still it is not 100 per cent yet," Rublev said. "This year, I didn't expect that I would have a chance, so in the end nothing is going to change for me. Even if I don't make it, the season was really good for me anyway. If I make it, it is really good news. One chance to compete against the best players, to do my best."
While Rublev improves to 6-2 in ATP finals, Coric drops to 2-6 including a loss in this final last year to Daniil Medvedev. And he's now 0-4 against Rublev having never won a set.
"When I go back home I can train even more, I can train harder," Coric said. "Next year I will come back for sure and hopefully I can win."
Medvedev Keeps Winning, Takes St. Petersburg Title Over Coric
Bautista Agut, Tsonga, Popular Fognini Lead ATP St. Petersburg; Preview
Rublev Stays Hot, Extends Run Winning Rotterdam Title Over Fucsovics
Dzumhur Wins 1st ATP Title for Bosnia and Herzegovina at St. Petersburg
Humbert Holds Off Auger-Aliassime In Halle Thriller, Meets Rublev For Title
Read more stories about: 2020 Season, Fall Season
Tags: Andrey Rublev, Borna Coric


text:
Beautmuse, CDs, Music
Various Artists – Aretha Franklin & Otis Redding Together (Rhino/Warners) CD REVIEW
Written by Gary Steel on August 5, 2014
ME SO DUMB: when I saw this listed, I jumped at the chance to review it, thinking that it was a compilation of duets between two of the greatest soul singers that ever lived.
I don't know what planet I was on that morning. Clearly, Redding and Franklin could never have recorded an album's worth of duets, because poor Otis was dead and gone by the end of 1967, and Urethra (as my gay friends at school called her) didn't hit her stride until 1968.
So, what do we have here? It's simply a double CD, one of which is a 23-track Aretha Franklin 'best of', the other of which is a 27-track Otis Redding 'best of'.
In theory, slinging two such great soul singers together makes a lot of sense; the reality is somewhat flawed.
Redding was at an unassailable peak when that plane went down, creating a legend and forever preventing him from embarrassing himself further down the line by embarking on duets with Mariah Carey or doing half-assed '80s synth-pop projects.
While a lot of the songs here are covers of well-worn songs ('My Girl', 'Satisfaction'), he puts his inimitable big-lipped wet-kiss of a voice on every one of them. It's an unlovely instrument on the face of it, but there's a warmth and an unforced emotive quality that's always right there, in your face, along with terrific control and very tightly focused nuance of expression. There's no getting around the fact, though, that had he lived five or six more years he would probably have made music that put just about everything here in the shade. Everything, that is, except for 'Try A Little Tenderness' and 'I've Been Loving You Too Long', two songs that could wrench your heart out of your chest cavity, such is the sheer emotive impact.
While Redding's small discography will always remain without serious blemish, the queen of soul, Aretha Franklin, was able to commit heinous sins later in her career. It almost seemed as though each time she put on a few more pounds, her musical indiscretions had to get loaded with more saccharine sounds. They save the worst for last, so at least the careful listener can choose to omit her odious 1986 duet with George Michael, 'I Knew You Were Waiting (For Me)'.
Whoever compiled this 'best of' had our best interests at heart, however, because her best years (1967 through the mid-'70s) are well represented, and the '80s and onwards are blessedly present in only a few small doses.
But I admit that I do have something of a problem with Aretha Franklin. There's no doubt that she has one hell of a big, strong gospel hollerin' voice, and respect to that. (Speaking of her calling card, 'Respect', perhaps the 'together' concept of this double CD came from the fact that Redding contributes his own version of this song also). I just don't like it that much. One or two songs are great, but anything more and I need to leave the room: even when she sings a song demanding of sensitivity, like '(You Make Me Feel Like A) Natural Woman', there simply is none. Her voice is always the same, never pretty or pensive. Even Janis Joplin's shriek is a good deal more tolerable to these old ears.
That's just me. She is the queen of soul, after all, and there's a wealth of good stuff here, great performances all, in there own way. Audiences who have grown up in an era where pop singers have songs written for them, or write their own, may find it hard to comprehend that many of the songs are covers. They may wonder why she bothers with 'Son Of A Preacher Man' or 'Let It Be' or 'Bridge Over Troubled Water'. She does, however, wrap her tonsils around these tunes with authority, and give them her own soul twist.
So, then, two pretty damn fine selections by two of the best soul singers, on two CDs that you buy together. Well, that's still weird to me. Why would you have to have them Siamese twinned? I guess it comes down to whether the consumer wants a dose of both at the same time, and whether the price appeals.
One thing I was astonished by was the sound quality. I've become accustomed to '60s soul sounding piercingly thin on a decent hi-fi set-up and tend to avoid listening to it as a result on anything less than a crappy iPod dock. But the production values and mastering here are superb. While the recording quality obviously varies from track to track, and Franklin's disc sounds a bit better because most of the tracks were recorded a bit later, it's fair to say that in both cases the voices come at you with all the force and richness they did the first time round, while the instruments have the kind of transparency and separation in the mix that only the better studios could have allowed. They even have deep bass, and hallelujah to that! GARY STEEL
Sound = 4/5
Music = 3.5/5
Otis Redding – Try A Little Tenderness by bebepanda


Could you give precise measurements for the hand so that I can see where the print needs to be adjusted. I can't get the cylinder to rotate properly. the hand does not engage when the hammer is fully down in the slot, I have to rotate the cylinder manually about 1/4 inch before it will catch. I love it otherwise.
Sounds like the hand's leaf spring is too weak maybe? Not quite sure though.
I attached a screenshot of the main sketch but it mightbe a little chaotic.
How reliable would the mechanisms in this be with pla? Could this be made instead with alternative parts (springs, rubber bands ect) if pla isn't reliable?
Most types of PLA should work. My internals are made entirely from PLA and it still works. Only problem can be the leaf springs loosing some of their tension over time.
There simply is no space to fit in rubber bands or coil springs anywhere as the design is historically made for leaf springs.
Ehm imaginary .44 cal round ball and conical projectiles!?
This is a functional replica not a sharp gun. While technically possible, actually loading this thing with gunpowder, bullets and percussions caps is not advised (At least not for a polymer 3D print).
ich dachte, das ich laut Deinem Text endlich einmal eine funktionierende Waffe zum ausdrucken gefunden hätte.
Aber wieder einmal Fehlanzeige. Obwohl ich den "Hand" verlängert und verstärkt habe, ist der Trigger ohne Funktion und die Trommel wird auch nicht mitgenommen. Schade.
I thought that according to your text, I finally found a working weapon to print out.
But once again no indication. Although I extended and strengthened the "hand", the trigger has no function and the drum is not taken along. Too bad.
I'm sorry to hear you have problems with the make. But one thing is for sure, this design is working.
Mechanical especially kinematic 3D prints are a LOT harder to pull off than static figurines. It all comes down to proper tolerances, print quality and selection of materials. If any of the mechanical features does not work as intended, one of the requrements was not met.
Some parts of this thing, like the receiver, have very intricate geometry thus need to be printed seperate, slow and with a lot of support material in cavities (like the slot for the hand). All of this excess material has to be cleaned out thoroughly later on for parts to move with minimum friction.
But first off maybe we can do some troubleshooting here if you post more detail and/or pictures.
What do you mean by "trigger has no function"? It's only a lever, that locks into a groove of the hammer and releases it when pulled back. I don't see what could have gone wrong here.
The rotation of the cylinder is the most error-prone part, I'll give you that (and it was on the real thing too!). It is done by a tiny hand and requires a finely tuned leaf spring made from fairly elastic filament. But what do you mean by "extended and strengthened hand"? All parts were designed in situ and, provided good print quality, fit together as is. One cannot expect too alter the geometry of one single part and expect it to fit with the rest.
I really hope you have not yet given up on my design. I'm pretty proud of it and hope I can help you get your Colt working too!
Love that brass color, what filament did you use?
Filament is actually the same anthracite PLA as the receiver with a thin coat in matte gold spray paint. When the paint wears off, the silver/anthracite shows through giving a well aged brass look.


The Mexico's Secretariat of Tourism decided to embrace the beautiful cities throughout Mexico, and created the Pueblos Magicos (Magical Towns) programs in 2001. The program was designed to feature towns throughout Mexico that depicted history, culture, and the natural beauty of Mexico.
Currently, there are 83 villages in 31 Mexican states that are being promoted in the Magical Towns program, with new towns joining each year. When you visit any of these towns you can expect to see true Mexico. You will see a different view of Mexico other than the beaches and tourist towns that you are used to. Cancun, Los Cabos, and Puerto Vallarta are resort towns that tourists visit, but there are 83 other cities that you can enjoy too.
Bacalar in the Yucatan Peninsula, near Cancun, is one of those cities added to the Magical Towns program. It was added in 2006, because of its rich heritage and Mayan history. It is near Cancun, and is a seaside village that pirates often invaded, but the pirates are no longer here, and Bacalar is always an interesting city on the coast of Mexico.
Bacalar is also a wonderful water packed destination with many activities. An amazing lagoon is located in front of Bacalar, and the lagoon has seven different shades of blue, which is beautiful. The lagoon is the perfect spot for swimming, snorkeling, diving, and boating. Bacalar is a unique, but stunning town that offers visitors a glimpse into the culture of Mexico.
In 1729 the San Felipe Fort was built. This is where many battles were held. Bacalar is also known as the Cenote Azul Gateway, because of its submerged caverns, which are something that everyone should see when coming to Mexico.
The Magical Village of Bacalar is just a short drive from Cancun, as it only takes a couple of hours. If your next vacation is at the Villa del Palmar Cancun, then take one day to go to the Magical Town of Bacalar. You won't regret it, because Bacalar offers history, culture, and natural beauty.


Indium is a material added by GregTech 5 mod.
Indium is a LuV-tier material, it is required for the creation of the alloy Indium Gallium Phosphide, which is used in endgame circuity.
The methods of obtaining this material were artificially made very tricky and hard to find out to a normal player.
Indium Concentrate has to be created from 2 ore processing products and an acid.
Tiny Pile of Indium Dust is created by letting the Indium Concentrate react with Aluminium Dust.
The Lead-Zinc solution obtained as a byproduct has to be processed to retain the metals remaining in it.
Once the first full dust of this material is obtained, it is easier to create it from UU-Matter other than to keep the complicated processing factory to perform the operations above.
This page was last modified on 22 March 2018, at 22:58.


In a curiously delayed move, Apple has finally launched a customer support account on Twitter.
Apple now has an official Twitter account dedicated to helping customers with their iDevices.
The account, aptly named @AppleSupport, has only been live for one hour, but has already posted north of 100 tweets.
Most responses seem to be directing customers to Direct Messages or Apple support pages.
However, @AppleSupport's bio says the page will "provide tips, tricks and helpful information".
The page already has over 18,000 followers, and that figure is quickly rising.
It's worth noting that Apple still doesn't have an official account that spans its entire brand.
However, the company does operate a number of accounts for specific services like the App Store, Apple Music, and iTunes.
What's more, several company executives at Apple also have personal accounts, including CEO Tim Cook.
The @AppleSupport page's operational hours are 08:00 to 17:00 (PT), and currently only offers English-languge support.
What do you think of Apple's new Twitter account? Let us know in the comments.


West Deptford – Senate president Steve Sweeney, Deputy Speaker John Burzichelli and Assemblyman Adam Taliaferro announced the receipt of two important block grants totaling more than $276,000 for community service grants to organizations in the Third Legislative District.
The grants came from the Community Services Block Grants in the New Jersey Department of Community Affairs. The Tri-County Community Action Agency, Inc. which helps low- and moderate-income residents identify and overcome barriers to self-sufficiency, received $254,550. And the CATA Farmworkers Support Committee, which empowers and educates farmworkers through leadership development and capacity building programing, received $22,352.
The awards will provide funds for health, education, employment, housing and services for farmworkers in southern New Jersey.


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