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The effective detection and management of muscle-invasive bladder Transition Cell Carcinoma (TCC) continues to be an urgent clinical challenge. While some differences of gene expression and function in papillary (Ta), superficial (T1) and muscle-invasive (≥T2) bladder cancers have been investigated, the understanding of mechanisms involved in the progression of bladder tumors remains incomplete. Statistical methods of pathway-enrichment, cluster analysis and text-mining can extract and help interpret functional information about gene expression patterns in large sets of genomic data. The public availability of patient-derived expression microarray data allows open access and analysis of large amounts of clinical data. Using these resources, we investigated gene expression differences associated with tumor progression and muscle-invasive TCC. Gene expression was calculated relative to Ta tumors to assess progression-associated differences, revealing a network of genes related to Ras/MAPK and PI3K signaling pathways with increased expression. Further, we identified genes within this network that are similarly expressed in superficial Ta and T1 stages but altered in muscle-invasive T2 tumors, finding 7 genes (COL3A1, COL5A1, COL11A1, FN1, ErbB3, MAPK10 and CDC25C) whose expression patterns in muscle-invasive tumors are consistent in 5 to 7 independent outside microarray studies. Further, we found increased expression of the fibrillar collagen proteins COL3A1 and COL5A1 in muscle-invasive tumor samples and metastatic T24 cells. Our results suggest that increased expression of genes involved in mitogenic signaling may support the progression of muscle-invasive bladder tumors that generally lack activating mutations in these pathways, while expression changes of fibrillar collagens, fibronectin and specific signaling proteins are associated with muscle-invasive disease. These results identify potential biomarkers and targets for TCC treatments, and provide an integrated systems-level perspective of TCC pathobiology to inform future studies.
Citation: Ewald JA, Downs TM, Cetnar JP, Ricke WA (2013) Expression Microarray Meta-Analysis Identifies Genes Associated with Ras/MAPK and Related Pathways in Progression of Muscle-Invasive Bladder Transition Cell Carcinoma. PLoS ONE 8(2): e55414. https://doi.org/10.1371/journal.pone.0055414
Editor: Natasha Kyprianou, University of Kentucky College of Medicine, United States of America
Received: August 28, 2012; Accepted: December 22, 2012; Published: February 1, 2013
Copyright: © 2013 Ewald et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by the National Institutes of Health [grant numbers: CA123199,DK093690, RC2ES018764 to WAR]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Bladder cancer is a disease receiving growing attention within the cancer biology community. Transition Cell Carcinoma (TCC) occurs as papillary tumors (Ta stage), superficial tumors (T1 stage), and muscle-invasive tumors of increasing severity (T2, T3 and T4 stage). Approximately 20% of primary bladder cancers are muscle-invasive at presentation and are associated with a poor prognosis, with 5 year survival estimates for muscle-invasive TCC approaching the low survival rates for advanced metastatic pancreatic cancers, small cell lung cancers, liver and bile-duct cancers, stomach and non-small cell lung carcinomas [1], [2]. Although papillary and superficial tumors recur in 70% of patients after surgical removal, non-invasive tumors have a more favorable outcome than muscle-invasive tumors as only 10–20% of these recurrences progress to muscle-invasive disease [2]. The regulatory mechanisms that are altered and disrupted in muscle-invasive bladder cancer may represent a barrier to progression in superficial tumors, and are candidate targets for therapeutic intervention.
Accumulating evidence suggests that superficial and muscle-invasive tumors are pathobiologically distinct [3], [4]. Superficial tumors frequently overexpress or express constitutively active mutants of HRAS and FGFR3 leading to hyperactivated Ras/MAPK signaling activity [3], [4]. Muscle-invasive tumors demonstrate disrupted activity of p53 and Rb and other tumor suppressors, overexpress EGFR and ErbB2, MMP2 and MMP9, and other pro-angiogenic factors, while having deleted cyclin-dependent kinase inhibitor genes CDKN2A (p16Ink4a) and CDKN2B (p15Ink4b) [4]. However, there is evidence that suggests that Ta tumors in some patients may progress and become muscle-invasive. In addition to observations that 10–20% of patients who initially have Ta tumors later develop muscle-invasive disease, tumors ≥T1 share common chromosomal deletions, gains and amplifications that are distinct from those found in Ta stage tumors, suggesting that accumulated chromosomal aberrations may be involved in the progression from papillary to muscle-invasive tumors [1], [2]. Moreover, while activating mutations in FGFR3, ras isoforms, and PI3K are more common in papillary tumors, most high grade superficial tumors lack these mutations and are similar to invasive tumors, suggesting that these may be predisposed to progress to muscle-invasive disease [5]. At the same time, some tumor recurrences lose the activating mutations that are present in earlier tumors, which may also potentially drive progression [5]. In all, the relationship of superficial and muscle-invasive bladder cancer remains controversial and largely unresolved.
There are few effective systemic treatments for muscle-invasive bladder cancer, and an improved understanding of the molecular pathogenesis and progression of TCC is urgently needed. Analysis mRNA expression in different stages of bladder cancer could illustrate differences that exist which may promote progression from Ta and T1 tumors to higher stage recurrences, while similarities in expression patterns could clarify the relationship of tumor stages in progression of the disease. Insights into these molecular mechanisms of bladder tumor progression can provide targets for preventative and therapeutic interventions while providing biomarkers that reliably predict progression into muscle-invasive disease.
Microarray technology provides a powerful tool to measure mRNA expression across the entire genome of biological samples, allowing detailed analysis of large numbers of experimental and clinical samples in relatively little time. Typically in studies of various cancers, clinical samples are analyzed to identify genes expressed at relatively high or low amounts in common patterns that correlate with tumor stage and patient survival [6]. While this approach may be appropriate for identifying potentially useful diagnostic and prognostic biomarkers, it is often difficult to determine whether signature genes in advanced cancers are functionally relevant to tumor progression. Strategies to derive functional information from gene-expression datasets include expression clustering to identify genes with similar patterns of expression [7]and pathway enrichment programs including WebGestalt [8] that query Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and other databases to identify processes in which gene expression changes are focused. Another strategy is to analyze the published literature using automated text-mining programs such as PubGene and Chilibot to identify functional associations between genes, phenotypes and diseases within publications indexed in PubMed [9]–[12]. Such resources have made computational informatic tools available to scientists who need to analyze and interpret microarray data, yet few studies have taken advantage of this information.
Studies of whole-genome expression using microarray technology require resources that may not be widely available to all researchers. Reliable microarray studies require large numbers of samples to provide for an adequate analysis and can be prohibitively expensive and time consuming. Access to human tissues required for relevant analyses is often not available to researchers outside of the medical field. The establishment of public microarray data archives, including the Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/), has allowed free-access to a wealth of clinical and experimental data that can be analyzed and re-purposed by any investigator with the interest and the means to do so. The development of open-access analytical programs, including Oncomine (https://www.oncomine.org) [13] and Mayday [14], provide a means to investigate gene expression in data across multiple microarray studies. These advances allow researchers to pursue genome-scale investigations in clinically-derived human tissues without the time, expense, and administrative efforts associated with generating primary genomic data.
Here, we use public data to identify genes that are associated with TCC tumor progression and muscle-invasive disease in male patients without metastases. We find that the differential expression of a network of genes related to the mitogenic Ras/MAPK and related signaling pathways are associated with progression beyond Ta stage. Additionally, we identified a subset of 7 genes within this network whose expression is associated with muscle-invasive TCC.
Materials and Methods
Microarray Dataset
The Gene Expression Omnibus (GEO) website (http://www.ncbi.nlm.nih.gov/geo/) was used to search publicly available datasets for recent studies of bladder cancers with at least 3 samples representing all tumor grades and performed using up-to-date whole-genome microarray chips. We chose a dataset (GEO# GSE 31684; accessed 2/29/2012) which was originally used to develop predictive models of bladder cancer outcome [15], as it fulfilled these requirements and provided detailed patient data. Data was further selected from male TCC patients without associated metastases, carcinoma in situ or sarcoma to reduce potential variation in data, resulting in a total of 36 patient datasets (Table 1).
Data selection, calculations and statistics
The meta-analysis of public data was performed according to PRISMA guidelines (Table S1, Table S2). Microarray expression data was organized, managed, and calculated using Microsoft Excel (Redmond, WA). The microarray expression data of all 36 sample datasets were expressed in log2 scale, and the average expression values were calculated for samples of each pathological tumor grade. To identify general expression changes associated with progression of TCC, the gene probe expression values of tumor stage T1, T2, T3 and T4 samples were individually normalized to Ta by subtracting their log2 averages. Gene probes were selected based on both an increase or decrease in expression by a factor of 2 (log21/−1) and statistical significance (p<0.05) in at least one tumor stage based on Student's t-test as a more stringent method of selection than either criterion alone. To identify expression changes associated with muscle-invasive disease, genes were selected that did not significantly change from Ta to T1 but are significantly different by a factor of 2 in T2 tumors in addition to significance based on Student's t-test. Further, the average expression values of selected gene probes in each tumor grade were compiled, and 3×3 matrix self-organizing map-based clustering analysis of relative gene expression across tumor stages was performed with 10,000 iterations using Mayday [14]. Clusters of gene probes with minimal expression changes, representing apparent false-positives, were arbitrarily omitted from subsequent analysis.
Statistical pathway enrichment analysis of differentially expressed genes
To perform pathway enrichment analysis on selected genes, gene probe IDs were annotated with Entrez gene symbols (Affymetrix Human Genome U133 Plus 2.0 [HG-U133_Plus_2]; GEO# GPL570) and analyzed using the WebGestalt website (http://bioinfo.vanderbilt.edu/webgestalt/) to identify defined KEGG pathways that are significantly over-represented in the dataset [8], using default settings and the Fisher's Exact test, selecting pathways where p<0.01. These results produced lists of the genes included in the enriched pathways, and provided a connectivity map of each pathway. A model network based on these pathways was generated using the Visual Understanding Environment (http://vue.tufts.edu/). Gene expression heatmaps were generated using Mayday (http://www-ps.informatik.uni-tuebingen.de/mayday/wp/) [14].
Statistical validation of muscle-invasive tumor gene signature using outside datasets
To determine whether muscle-invasive-specific expression changes identified in our initial dataset are typical across an expanded number of samples and studies, we obtained expression data for each gene compiled within the Oncomine database [13]. This included 8 datasets from 7 studies in which gene expression is measured in superficial and muscle-invasive bladder tumors [16]–[22]. The median expression of each gene in superficial and muscle-invasive tumors from each dataset was recorded and the averaged difference was calculated. A Mann-Whitney Rank-Sum test was performed to determine the significance of expression changes across datasets.
Bibliomic text-mining for functional gene association
To obtain published results that link functional interactions of genes and phenotypes, selected genes were analyzed using PubGene [10], while genes and keywords "bladder cancer", "metastasis", "angiogenesis", "invasive" were analyzed using Chilibot [11]. An association network based on co-occurrances and implied functional relationships determined by each program was constructed based on these results.
Immunohistochemistry of Bladder Tumors
Samples (n = 5 each) of normal bladder and T1, T2 and T3 bladder tumors were purchased from Biomax.us (Rockville, MD). Samples were processed and stained by the TRIP Laboratory facility (Depatment of Pathology, University of Wisconsin School of Medince and Public Health) using standard immunostaining procedures. Antibodies to COL3A1 and COL5A1 were purchased from Santa Cruz Biotechnology (Santa Cruz, CA) and visualized using DAB and Warp Red stains. Nuclei were visualized using hematoxylin staining. Microscopy and image processing was performed as previously described [23].
Western Immunoblotting
T24 bladder cancer cells and E6-immortalized human urothelial cells (HUCs) were the kind gift of Dr. Dale Bjorling, University of Wisconsin. T24 cells were cultured in DMEM media +10% FBS, while HUCs were cultured in Ham's F12 media +10% FBS. Cells were cultured to 70% confluence, scraped from plates, collected, solubilized and processed, analyzed by western immunoblotting, and quantified using Image J, as previously described [23]. Antibodies to COL3A1 and COL5A1 are described above. Antibodies recognizing β-actin were used as a loading control.
TCC progression is associated with differential expression of Ras/MAPK and related pathway genes
Our hypothesis was that gene expression differences exist between papillary/superficial and muscle-invasive bladder TCC tumors that define the regulation of tumor invasion, progression and metastasis. We developed an intuitive method, summarized in Figure 1, to select, analyze and interpret public microarray data using open access computational resources. We found a suitable dataset from the GEO database (GSE31684) containing expression data from 93 patient bladder tumors that were removed prior to any chemical treatment and used to identify gene expression signatures that predict outcome of high-risk bladder cancer [15]. To limit potential variation in sample expression data, sample data were selected from male patients with TCC of the bladder, without metastatic tumors, CIS or sarcoma, producing 36 total datasets that represented at least three patients per stage for all stages of TCC tumors (Table 1).
First, we calculated expression differences between Ta and T1–T4 bladder tumors to identify changes broadly associated with bladder cancer progression beyond papillary tumor stages. Data were processed, averaged, normalized to the expression of Ta tumors, and selected based on a greater than 2-fold threshold difference in expression at any stage beyond Ta, and p<0.05 using Student's t-test. This produced a list of 8110 gene-associated probes. Expression data was retrieved for those selected probes and analyzed using the self-organizing map cluster analysis within Mayday [14] to arbitrarily remove probes that reflect little change in expression, selecting 5509 total probes.
As receptor tyrosine kinases, mitogenic signaling pathways and tumor suppressors are each involved in superficial and muscle-invasive bladder cancer, our aim was to identify changes in gene expression that could compliment the activities of these pathways. The list of selected probes was analyzed with WebGestalt [8] to identify defined pathways that are significantly represented in the microarray data (p<0.05). Whether the selected genes were analyzed as a single group or separated based on increased or decreased expression, many of the pathways reliably associated with these genes are related to cancer-related signal transduction and similar pathways (Table 2, Table S3). The ten best supported pathways associated with the entire set of genes include "Cell Cycle", "Pathways in Cancer", and "Focal Adhesion". Beyond these ten, "MAPK signaling", "ErbB signaling" and "Bladder Cancer" pathways were also well supported. Likewise, when this list was separated into separate lists of 4816 increasing and 693 decreasing genes, many similar cancer-related signal transduction pathways were found to be represented in these genes. While other pathways represented in the data could also be associated with cancer progression and metastasis, such as "Metabolism" and "DNA Repair", the relationship of these pathways to current models of bladder progression is less direct. These results suggest that bladder cancer progression from Ta to T1+ stage tumors involves the increased expression of genes in mitogenic, cancer-associated pathways related to FGFR3 and ErbB family signaling.
KEGG pathways and other related ontologies and annotations are highly redundant, with individual genes associated with many multiple limited and interconnecting pathways. For this and other reasons, pathway enrichment analysis alone often does not adequately represent the global scope and relationships within the data. To better understand the relationships of these genes and how they may function in bladder cancer progression, we built an integrated pathway network model based on the KEGG maps of selected signaling pathways represented in the data (Table 2; Table S3). These results reveal that gene expression differences between Ta and T1 stage tumors largely occur within a signaling network related to Ras/MAPK signaling pathways, with increased expression of a majority of these genes (Figure 2).
The stimulatory and inhibitory interactions of gene products differentially expressed in T1–T4 versus Ta tumors were mapped based on KEGG pathway maps. Node color denotes relative expression: Yellow = Increased expression in muscle-invasive tumors; Blue = Decreased expression in muscle-invasive tumors. Green and red arrows represent stimulatory and inhibitory interactions, respectively. The names of genes with supported associations with muscle-invasive tumors are highlighted in bold italics.
Muscle-invasive TCC is associated with specific expression changes in ECM and signaling proteins
We further hypothesized that the expression of a subset of the genes within this signaling network model is specifically altered in muscle-invasive versus superficial tumors. Returning to the complete dataset, we selected genes that are expressed at similar levels within a 2 fold difference between Ta and T1 tumors, and are changed greater than 2 fold in T2 stage tumors with Student's t-test p<0.05 (Figure 1). After performing expression clustering analysis and arbitrarily removing clusters with minimal expression changes, as above, 496 total gene probes were selected for pathway enrichment analysis using WebGestalt. As before, these results show that the selected genes are associated with many signal transduction and cancer-related pathways that involve 23 of the selected genes (Table 3, Table S4, Figure 3). These genes were not focused in any single pathway, but instead were distributed across the network of pathways (Figure 2). Visualizing gene expression data relative to Ta tumors in a heatmap, the expression changes of selected genes are consistent in T2, T3 and T4 tumors (Figure 3). These results suggest that the differences of selected gene expression are distinct fundamental molecular characteristics of muscle-invasive tumors.
Yellow and blue indicate increased and decreased expression in candidate muscle-invasive genes, respectively, relative to the average expression in Ta tumors.
We then determined whether the relative expression of the selected genes could be observed in outside microarray datasets of superficial and muscle-invasive bladder tumors. Using Oncomine [24], we identified archived datasets containing expression data for each of the 23 selected candidate genes. The median gene expression of non-invasive and invasive tumors in each dataset was recorded, and the average change in expression of each gene was calculated across all datasets (Table 4). The Mann-Whitney Rank-Sum test was performed to determine the significance of the changes in median gene expression across datasets. These results show that expression of extracellular matrix genes COL3A1, COL5A1, COL11A1 and FN1 are significantly increased in muscle-invasive bladder tumors relative to Ta/T1 (p<0.05), while changes in CDC25C, MAPK10 and ErbB3 expression approached significance (p≤0.08) (Table 4). These final selected genes represent a sub-network of consistently-observed differences in gene expression of muscle-invasive and non-invasive bladder tumors that are associated with the activity of Ras/MAPK, PI3K and other signaling pathways (Figure 4).
Node color represents change in expression. Edges represent functional associations identified in the literature by text-mining programs PubGene and Chilibot. Selected genes separate into two functional groups of extracellular matrix and signal transduction genes. Black arrows represent generalized groups of outside genes with functional relationships to selected genes in the literature.
While the consistent expression changes of the 7 selected genes are well supported by expression data from human clinical samples, the functional relationships of these genes were not immediate. With the expectation that functional relationships of selected genes would be reflected in the literature, we used the text-mining programs Chilibot and PubGeneto identify and visualize these relationships [10], [11]. The results show that the genes can be placed in two functional groups of extracellular matrix proteins and signal transduction proteins (Figure 4). Outside genes that are functionally related to the selected genes showed little overlap between associated groups, suggesting that seven selected genes are critical nodes of regulation that coordinate the activities of outside gene pathway networks (Figure 4, and Data Not Shown). Further, the relationships of selected genes characteristics associated with advanced metastatic cancer were assessed using Chilibot. The CDC25C, ErbB3 and FN1 are previously associated with bladder cancer: The activity of CDC25C promotes proliferation and is a target for developing cancer therapies, including bladder cancer [25]; Decreased ErbB3 expression in bladder cancer is associated with poor prognosis [26]; and FN1 is a potential urine biomarker for bladder cancer [27]. All of the selected genes are associated with cancer and metastasis (Table 5). Interestingly, MAPK10 and FN1 were related to angiogenesis, COL5A1 and COL11A1 were associated only with invasion, while COL3A1, CDC25C and ErbB3 are associated with both. In all, the selected genes are associated with terms in published reports describe characteristics of muscle-invasive and metastatic tumors, and are relevant to mechanisms regulating the progression of advanced stage bladder cancer.
Increased COL3A1 and COL5A1 protein expression in muscle-invasive tumors and metastatic T24 cells
Because the expression changes of COL3A1 and COL5A1 are well supported statistically, the novelty of these genes' association with muscle-invasive bladder cancer, and the availability of validated antibodies recognizing these proteins, we investigated whether their protein expression is increased in samples of muscle-invasive bladder tumors removed from patients. While the intensity and extent of staining results were variable, we found that COL3A1 and COL5A1 was detected in epithelial and stromal cells of T2 and T3 tumors, while little to no staining was detected in normal bladder tissue and T1 tumors (Figure 5A). Additionally, we found that T24 cells, which are metastatic in an in vivo xenograft model, show increased expression of these proteins compared to E6-immortalized HUCs derived from normal tissue (Figure 5B, Data Not Shown). These results validate the novel association of COL3A1 and COL5A1 expression with muscle-invasive bladder tumors.
A. Immunohistochemistry of bladder tumors. DAB (brown) staining represents COL3A1 protein expression, while Warp Red staining represents COL5A1. Results are representative of five independent sample tissues per grade. B. Immunoblot analysis in immortalized non-cancer HUC cells and T24 bladder cancer cells. Expression of COL3A1 and COL5A1 was standardized to that of β-actin, and normalized to expression in HUC cells. These results are representative of 2 independent experiments.
The outcome of bladder cancer treatment is largely dependent upon the pathobiology of individual bladder tumors [2]. Previous microarray-based gene expression studies of various stage bladder cancers have recognized the distinct behaviors and genetic nature of superficial and muscle-invasive tumors, suggesting the possibility that the two are discrete pathobiological entities [4]. However, no biomarkers have proven able to predict progression to muscle-invasive disease, and the physiological mechanisms that drive bladder tumor progression and invasive behavior are not well understood.
We have analyzed a large collection of expression microarray-derived data to develop a functional picture of bladder cancer progression to muscle-invasive disease. We achieved this by using only publicly available microarray data and open-access computational resources. This avoids the need to generate custom tools to perform specific analyses to analyze large amounts of multi-dimensional data. Moreover, this strategy avoided the need to invest the time and resources to acquire appropriate clinical samples in large enough numbers to allow a meaningful analysis, as well as the time and resources to perform a large number of microarrays analyses. This is especially important given that a large amount of data already exists and is available to the biomedical research community. By re-purposing public data to address our specific interests, we have not only avoided significant expenses but we also help to increase the value drawn from existing data. This has resulted in a novel systems-level model of TCC progression and muscle-invasive disease that integrates gene expression data with functional information and relationships from previous experimental observations.
In the present study, we identified specific expression differences that occur with bladder cancer progression and muscle-invasive tumors. Our results show that progression from papillary Ta to more advanced stage tumors is associated with a general increase in expression of a network of genes involved in Ras/MAPK and associated signaling pathways (Figure 2). These pathways are closely associated with proliferation and are frequently disregulated in cancers, including bladder cancer. Interestingly, these pathways are downstream of the EGFR and ErbB2 family proteins whose expression and activity are related to bladder cancer progression, as well as ErbB3, FGFR3 and HRAS that are active in superficial tumors [4]. The increased expression of genes in Ras/MAPK and PI3K pathways may be related to the disregulation of p53, Rb and other tumor suppressors in muscle-invasive bladder tumors [3], [4]. The increased expression of components of this large pathway network may act to promote and enhance the effects of EGFR and ErbB2 activity, but the dependence of muscle-invasive tumors on the activities of these pathways in concert has not been investigated. Conversely, the relatively low expression of Ras/MAPK and PI3K pathways in superficial tumors may compensate for the elevated activity of ErbB3, FGFR3 and RAS isoforms, possibly a factor that limits the progression to muscle-invasive disease. These and other issues will be further addressed through the course of developing a systems-level understanding of bladder cancer progression.
We also used a similar approach to identify gene expression changes specifically associated with muscle-invasive tumors (Figure 2, Figure 3, Figure 4). We found that these initially selected genes occur sporadically across the initial network rather than focused on a particular pathway within the network, but the expression of these genes is consistent and distinct in superficial and muscle-invasive tumor samples (Figure 3). We then tested whether the expression differences of selected genes in our initial dataset were consistent with data from outside studies by using Oncomine to measure the median expression of each genes in 3 to 8 independent studies that include superficial and muscle-invasive bladder tumors, selecting a final set of 7 genes (Figure 4) [16]–[22]. Taking into account the number of samples within each study, these results ultimately represent the gene expression data of hundreds of individual tumors, supporting the statistical validity of our observations.
The selected 7 genes can be separated into extracellular matrix proteins (COL3A1, COL5A1, COL11A1, FN1) and kinase signaling proteins (CDC25C, MAPK10, ErbB3). While the variation in expression data does not support the use of any of these genes as biomarkers individually (Data Not Shown), their expression may support a more specific means to identify muscle-invasive bladder tumors in the future. FN1 itself is a potential urine biomarker for bladder cancer detection [27]. While well supported, their functional relationships and relevance to muscle-invasive bladder cancer were not immediately apparent. To aid in our interpretation, the data were analyzed using text-mining programs that identify instances where gene names occur in potentially interactive contexts within abstracts and full texts of published reports in PubMed [10], [11]. We found that these genes have been associated with cancer, bladder cancer, metastasis, angiogenesis, and invasion, suggesting that their involvement in cancer progression and/or muscle-invasive behaviors have been previously observed in various systems (Table 5).
The reported functions and interactions of the selected genes suggest a novel model of muscle-invasive disease in bladder cancer (Figure 6). COL3A1, COL5A1 and COL11A1 are fibrillar collagens, which act as "tracks" for metastatic invasion of breast tumors into secondary organs [28]. Formation of these fibrils is initiated by interactions between COL5A1 and COL11A1 proteins [29]. Tumor-secreted proteases diffuse along collagen fibrils and modify existing matrix to allow tumor cells a path of least-resistance along fibrils [30]. Collagens and FN1 are among many ligands for integrins, a class of surface receptor proteins that are functional heterodimers of 8 α and 18 β subunits that each bind specific ligands [31]. COL3A1 and COL5A1 are functionally related in connective tissue disorders [32], and expression of different collagens are associated with various cancers. FN1 "decorates" collagen fibrils and affects integrin binding specificity [31], [33]. Integrin signaling stimulates RAS/MAPK signaling and modifies the activity of receptor tyrosine kinases, including EGFR/ErbB proteins, which are also upstream of Ras/MAPK [31], [34]. Interestingly, FN1 has been reported to preferentially induce the activity of EGFR, ErbB2 and ErbB4 but not ErbB3 activity [34]. Our identification of decreased ErbB3 expression in muscle-invasive tumors is well supported by previous studies [26]. Formation of ErbB3/ErbB2 is kinetically preferred among ErbB family receptors, and ErbB3 is the only ErbB receptor that directly associates with and activates the PI3K signaling pathway [35]. In all, this evidence suggests a "class-switch" from ErbB3 to EGFR/ErbB2 mediated ErbB signaling, mediated in part by collagen and fibronectin-stimulated integrin signaling, is a key mechanism promoting muscle-invasion of bladder tumors. This may affect trafficking of active receptor proteins and impact the intensity and duration of downstream signaling [36], as well as alter the pathways that stimulate PI3K signaling.
Arrows represent positive interactions. Black "X"s on arrows represent antagonistic interactions. Red "X"s represent disrupted or decreased activity.
Importantly, the effects of these gene expression differences in muscle-invasive tumors are likely augmented by increased expression of genes in mitogenic pathways that we find associated with general bladder cancer progression in the absence of activation mutations in RAS and PI3K pathways that are prevalent in superficial tumors. The ErbB and collagen-activated integrin proteins are upstream activators of Ras/MAPK signaling, which is associated with proliferative and tumorigenic activity and which our above expression data shows is generally increased in muscle-invasive bladder cancer (Figure 2). Changes in how Ras/MAPK and PI3K signaling are regulated by upstream receptors may fundamentally alter the nature of the responses to those signaling pathways. The MAPK family protein MAPK10/JNK3 is generally involved in stress signaling and acts counter to Erk MAPK and PI3K signaling [37]. The decreased expression of antagonistic signaling proteins such as MAPK10 would further promote Ras/Erk MAPK signaling activity. Ultimately these activities modulate the expression and activities of proteins that affect proliferative, pro-metastatic and invasive behavior, including the CDC25C phosphatase which stimulates cyclin/CDK activity and mitosis. Metastasis and progression are further promoted by the disruption of tumor suppressors in muscle-invasive bladder cancer, including p53, Rb, myc and others that would act to limit proliferative and metastatic behavior [2]–[4]. As well as providing a basis for future systems-level studies of TCC, this model will inform efforts to identify and develop the therapeutic targets and predictive biomarkers that will guide the clinical treatment of muscle-invasive bladder cancer.
In summary, we have analyzed public expression microarray data of bladder tumors across stages, identifying the increased expression of the proliferative and pro-survival Ras/MAPK and PI3K pathways as a potential regulatory hallmark of tumor progression, while related genes, including fibrillar collagens are associated specifically with muscle-invasive bladder cancer. Translation of this information into clinical treatment may potentially improve the identification, treatment and outcome of bladder cancer in patients as well as in the treatment of other cancers.
Supporting Information
Table S1.
Prefered Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines Checklist.
Table S2.
Prefered Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines Checklist (Continued).
Table S3.
Genes differentially expressed, both increased and decreased, in T1–T4 staged bladder tumors versus Ta-stage tumors and associated with KEGG pathways, including Top 10 pathways listed in Table 2. Pathways selected based on Fisher's Exact Scores ≤0.01.
Table S4.
Genes differentially expressed, both increased and decreased, in Ta/T1-staged bladder tumors vs T2 tumors, and associated with KEGG pathways, including Top 10 pathways listen in Table 3. Pathways selected based on Fisher's Exact Scores ≤0.01.
The authors thank Glen Leverson Ph.D. and Chee Paul Lin of UW Department of Surgery for providing statistical analysis and support, and Sally A. Drew of The UW TRIP Lab for her expertise in immunohistochemistry. We thank Tihomir Miralem, Pamela Kreeger and Chad Vezina for their critical reviews and assistance in the writing of this manuscript.
Author Contributions
Conceived and designed the experiments: JAE TMD WAR. Performed the experiments: JAE WAR. Analyzed the data: JAE WAR TMD. Contributed reagents/materials/analysis tools: JAE. Wrote the paper: JAE TMD JPC WAR.
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- 16. Blaveri E, Simko JP, Korkola JE, Brewer JL, Baehner F, et al. (2005) Bladder cancer outcome and subtype classification by gene expression. Clin Cancer Res 11: 4044–4055.
- 17. Dyrskjot L, Kruhoffer M, Thykjaer T, Marcussen N, Jensen JL, et al. (2004) Gene expression in the urinary bladder: a common carcinoma in situ gene expression signature exists disregarding histopathological classification. Cancer Res 64: 4040–4048.
- 18. Dyrskjot L, Thykjaer T, Kruhoffer M, Jensen JL, Marcussen N, et al. (2003) Identifying distinct classes of bladder carcinoma using microarrays. Nat Genet 33: 90–96.
- 19. Dyrskjot L, Zieger K, Real FX, Malats N, Carrato A, et al. (2007) Gene expression signatures predict outcome in non-muscle-invasive bladder carcinoma: a multicenter validation study. Clin Cancer Res 13: 3545–3551.
- 20. Modlich O, Prisack HB, Pitschke G, Ramp U, Ackermann R, et al. (2004) Identifying superficial, muscle-invasive, and metastasizing transitional cell carcinoma of the bladder: use of cDNA array analysis of gene expression profiles. Clin Cancer Res 10: 3410–3421.
- 21. Sanchez-Carbayo M, Socci ND, Lozano J, Saint F, Cordon-Cardo C (2006) Defining molecular profiles of poor outcome in patients with invasive bladder cancer using oligonucleotide microarrays. J Clin Oncol 24: 778–789.
- 22. Stransky N, Vallot C, Reyal F, Bernard-Pierrot I, de Medina SG, et al. (2006) Regional copy number-independent deregulation of transcription in cancer. Nat Genet 38: 1386–1396.
- 23. Ewald JA, Jarrard DF (2012) Decreased skp2 expression is necessary but not sufficient for therapy-induced senescence in prostate cancer. Transl Oncol 5: 278–287.
- 24. Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, et al. (2004) ONCOMINE: a cancer microarray database and integrated data-mining platform. Neoplasia 6: 1–6.
- 25. Aressy B, Ducommun B (2008) Cell cycle control by the CDC25 phosphatases. Anticancer Agents Med Chem 8: 818–824.
- 26. Memon AA, Sorensen BS, Meldgaard P, Fokdal L, Thykjaer T, et al. (2006) The relation between survival and expression of HER1 and HER2 depends on the expression of HER3 and HER4: a study in bladder cancer patients. Br J Cancer 94: 1703–1709.
- 27. Eissa S, Zohny SF, Zekri AR, El-Zayat TM, Maher AM (2010) Diagnostic value of fibronectin and mutant p53 in the urine of patients with bladder cancer: impact on clinicopathological features and disease recurrence. Med Oncol 27: 1286–1294.
- 28. Gritsenko PG, Ilina O, Friedl P (2012) Interstitial guidance of cancer invasion. J Pathol 226: 185–199.
- 29. Wenstrup RJ, Smith SM, Florer JB, Zhang G, Beason DP, et al. (2011) Regulation of collagen fibril nucleation and initial fibril assembly involves coordinate interactions with collagens V and XI in developing tendon. J Biol Chem 286: 20455–20465.
- 30. Collier IE, Legant W, Marmer B, Lubman O, Saffarian S, et al. (2011) Diffusion of MMPs on the surface of collagen fibrils: the mobile cell surface-collagen substratum interface. PLoS One 6: e24029.
- 31. Juliano RL, Reddig P, Alahari S, Edin M, Howe A, et al. (2004) Integrin regulation of cell signalling and motility. Biochem Soc Trans 32: 443–446.
- 32. Zoppi N, Gardella R, De Paepe A, Barlati S, Colombi M (2004) Human fibroblasts with mutations in COL5A1 and COL3A1 genes do not organize collagens and fibronectin in the extracellular matrix, down-regulate alpha2beta1 integrin, and recruit alphavbeta3 Instead of alpha5beta1 integrin. J Biol Chem 279: 18157–18168.
- 33. Exposito JY, Valcourt U, Cluzel C, Lethias C (2011) The fibrillar collagen family. Int J Mol Sci 11: 407–426.
- 34. Cabodi S, Moro L, Bergatto E, Boeri Erba E, Di Stefano P, et al. (2004) Integrin regulation of epidermal growth factor (EGF) receptor and of EGF-dependent responses. Biochem Soc Trans 32: 438–442.
- 35. Citri A, Yarden Y (2006) EGF-ERBB signalling: towards the systems level. Nat Rev Mol Cell Biol 7: 505–516.
- 36. Resat H, Ewald JA, Dixon DA, Wiley HS (2003) An integrated model of epidermal growth factor receptor trafficking and signal transduction. Biophys J 85: 730–743.
- 37. Turjanski AG, Vaque JP, Gutkind JS (2007) MAP kinases and the control of nuclear events. Oncogene 26: 3240–3253.


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Symbolically, the roots of the tree of life dig deep, the trunk provides a foundation, the branches spread out for subsistence and nourishment, the leaves absorb and collect energy, and the fruit gives itself for the joy of others. The breath of life from the Tree of Life represents the spiritual nature of air and inspiration. The leaves of the tree have the properties to heal people not only physically, but also emotionally and spiritually.
There are various trees of life in folklore, mythology, religion and culture. In these references, the tree usually refers to immortality and fertility.
The nurturing aspects of life are embodied in the tree of life. The leaves of the tree represent nourishment by reaching out to the sun. Its leaves collect this nourishment and converts it to food that is eaten by others. It embraces the soil with its roots. The tree acknowledges the sun and Earth as the sources of the energy needed for survival.
The tree combines the four elements - fire, earth, water and air - to create its life-giving capability. Fire represents the light from the sun that gives the tree energy, earth represents the foundation and the support the tree receives from the soil, water represents the vital essence of the tree, and air represents the medium where it communicates with its surroundings.

subset: commoncrawl


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There are at least two reasons why we may find it hard to believe that being holy starts with being ourselves. First, before many of us can accept this truth, we may find ourselves trying to be someone who we are not, based on another person's interpretation of holiness. And second, once we finally set aside the notion that we're supposed to be someone else, it's a long process discovering who we really are.
At the heart of this understanding is accepting who you are before God. "For it was you who formed me in my inward parts, you knit me together in my mother's womb," says Psalm 139. "I praise you, for I am fearfully and wonderfully made." The beginning of sanctity is loving yourself as a creation of God. And that means all of yourself, even the parts of you that you wish weren't there, the parts of you that you wish God hadn't made, the parts of you that you lament. God loves us like a parent loves a child—often more for the parts of the child that are weaker or where the child struggles or falters. More often than not, those very weaknesses are the most important paths to holiness, because they remind you of your reliance on God.
Believing that God wants us to be ourselves has been a fantastically liberating idea for me. While I'm always called to grow, God asks only that I be myself, no matter what situation. So when I'm listening to a friend tell me his problems, or hearing someone's confession, or standing before a homeless man in the street, I don't have to say, "What would St. Peter or St. Francis of Assisi or St. Thérèse of Lisieux or Blessed John XXIII do?" Certainly they can be models of Christian action for me. But God has not placed them in this particular situation. God, in his mysterious wisdom, has placed me there, with my talents and skills, as well my weaknesses and limitations. Therefore, a better question is, "What should I do?"
As the Jesuit poet Gerard Manley Hopkins wrote,
"for Christ plays in ten thousand places,
lovely in eyes and lovely in limbs not his..."
In other words, my eyes and your limbs. Your eyes and limbs.
| from My Life with the Saints
James Martin, SJ, is associate editor of America magazine and a prolific author, writer, and editor.See More
An Off-Broadway cast has plenty of questions about life and faith - and Fr. James Martin, author of My Life with the Saints, is just the right person to offer some answers in A Jesuit Off-Broadway.Shop Now
En Mi vida con los Santos James Martin, SJ nos presenta una conmovedora experiencia respect a su relación con los Santos—desde María, la madre de Jesús, hasta San Francisco o la Madre Teresa—y la manera personal en la que ha side dirigido por los heroes de la Iglesia a lo largo de toda su vida.Shop Now
Let James Martin, SJ author of the bestselling book My Life with the Saints introduce you to his favorite Catholic saints in this exciting new saints DVD.Shop Now
Fr. Martin's illuminating and humorous account of seven busy and gratifying days at Lourdes is a vivid description of a place with a special, mysterious spiritual presence.Shop Now
This best-selling memoir of spiritual self-discovery is an homage to the Catholic saints who have accompanied Fr. Martin throughout his life. Click here to download the discussion guide for My Life with the Saints.Shop Now
Theater and theology share the stage in Fr. James Martin's A Jesuit Off-Broadway, the true story about the making of a celebrated play.Shop Now
A contemporary look at traditional devotions from well-known Catholic writers.Shop Now
Praying with America presents and celebrates the diversity of prayer over the past century and offers readers the wisdom and inspiration of leading Catholic thinkers on the practice of prayer.Shop Now


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Every fortnight, the Singapore Quiz Master leads quite the quiz night!
We'll have all the traditional quiz rounds like Current Affairs, General Knowledge, Picture Rounds, Geography etc so you can strut your mental stuff for the chance to win vouchers (and glory). Our quizzes are free to enter, and are run in teams of no more than 6, so feel free to assemble your own and register by emailing firstname.lastname@example.com or we can easily add you to a team on the night.


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I added downloads for the full audio for lessons 6 through 11. This makes it easier to listen to while you are out and about. You can find them at the end of each lesson or on the downloads page.
- Home
- Background
- Lessons
- Dictionary
- Resources
- News
- About


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ZT3 Ingwe
|ZT3 Ingwe
An Ingwe with control fins extended
|Anti-tank guided missile
|Place of origin
|South Africa
|Service history
|In service
|Used by
|See Users
|South African Border War
|Production history
|Denel Dynamics
|Denel Dynamics
|1987 – present
|28.5 kilograms (63 lb)
|1,750 millimetres (69 in)
|127 millimetres (5.0 in)
|Tandem-charge HEAT warhead, Multi-Purpose Penetrator (MPP) warhead
|250 m – 5,000 metres (3.1 mi)
|0.200 kilometres per second (450 mph)
|Laser beam riding
The ZT3 Ingwe (Leopard) is a modern South African multi-role laser beam riding anti-tank guided missile (ATGM) manufactured by Denel Dynamics (formerly Kentron).
Design and development[edit]
The ZT3 and its launch system was developed under the codename "Project Raleigh" in the 1980s as a "long-range indigenous antitank guided missile". The missile was developed to provide the South African Army's mechanized infantry vehicles, such as the Ratel IFV, with anti-tank capabilities and to supplement the ageing MILAN missile system that was in service at the time. Pre-production models, mounted in a triple launcher on top of a Ratel IFV, saw service in Operation Moduler during the South African Border War with good effect.[1]
In the years since, Denel Dynamics have continually upgraded the system to improve its range, accuracy, reliability and warhead effectiveness. In May 2010, Denel Dynamics and Rheinmetall Denel Munitions were working on a new series of multi-purpose warheads for the missile system. Denel stated that due to changing trends in warfare in recent years, customers required a "generic precision land-attack missile" that can be used against a variety of targets such as buildings and bunkers.
Denel is also developing the missile system for use on the Badger Infantry Fighting Vehicle that will enter service with the South African Army as part of Project Hoefyster. The company has also collaborated with the French-South African company, ATE, to integrate the missile system for use on helicopter platforms such as the Eurocopter EC635, the MI-24 Mk III Super Hind and Eurocopter Fennec for use in various Air Forces around the world. Several missile systems in use with the South African Army were also modernised in 2005 as part of Project Adrift.[2]
In February 2013, Denel unveiled a new version of the system at the International Defence Exhibition held in Abu Dhabi. The new system, called the Portable Launch System (IPLS), is a portable, light-weight launch system that comprises a new missile launch unit designed for use on light vehicle mounts or tripods. It can fire both HEAT (High Explosive Anti-Tank) and Multi-Purpose Penetrator versions of the Ingwe.[3]
The system consists of a laser projection unit and guidance and control units. The system uses a laser beam riding missile that automatically determines its own position in the laser beam and manoeuvres onto its Line-of-sight (LOS). The sighting system varies from a non-stabilised optic system for light vehicles to a stabilised day/night system on helicopter launch systems. Automatic targeting modules can also be added to the missile system that can be added to ensure fully automatic post-lock on missile guidance by the operator. The missile can engage targets at ranges from 250 m to 5,000 metres (3.1 mi). It employs a tandem warhead to defeat up to 1,000 millimetres (39 in) of armour.[1] The missile is also designed to be stealthy (virtually hard to detect) and highly resistant to countermeasures.[3]
As of 2009, the ZT-3 was estimated to cost approximately $39,900.[4]
Launch platforms[edit]
Denel states that the Ingwe missile can be integrated on a wide variety of launch platforms, from Infantry-crewed stationary launchers to Helicopter-based launchers. The missile is known to be integrated for use on the following platforms:
- Ratel Infantry Fighting Vehicle
- DefTech AV8 armoured fighting vehicle[5]
- MI-24 Mk III Super Hind
- Eurocopter EC635
- Eurocopter Fennec
- Badger Infantry Fighting Vehicle
- Denel Rooivalk[3]
Current operators[edit]
- Algeria
- Algerian Air Force – 700 delivered between 2000 and 2001 for Mi-24 MKIII SuperHind helicopters.[6]
- Iraq
- Iraqi Air Force – 300 delivered between 2010 and 2012 for Eurocopter EC635 helicopters.[6]
- Malaysia
- Malaysian Army – 216 missiles ordered and 54 missile turrets for use on the DefTech AV8 armoured combat vehicles.[5]
- South Africa
- South African Army – used on the Ratel IFV and will be integrated onto the Badger Infantry Fighting Vehicle.[6]
Operational history[edit]
The weapon was first used on 10 September 1987 when a pre-production Ratel ZT3 destroyed several T-55 tanks at the Lomba River in Angola.[7]
See also[edit]
- Missiles of comparable design
- Missiles of comparable role
- ^ a b Engelbrecht, Leon. "Fact file: Denel ZT3 Ingwe precision guided missile". DefenceWeb. Retrieved 5 May 2014.
- ^ Engelbrecht, Leon. "Ingwe goes multi-purpose". Retrieved 5 May 2014.
- ^ a b c "Latest Ingwe missile debuts at IDEX". DefenceWeb. Retrieved 5 May 2014.
- ^ https://www.forecastinternational.com/samples/F656_CompleteSample.pdf
- ^ a b "Denel inks R3.5 billion deal with Malaysia". defenceweb.co.za. defenceweb. Retrieved 3 July 2014.
- ^ a b c "SIPRI Arms Transfers Database". SIPRI. Retrieved 3 May 2014.
- ^ Helmoed-Romer Heitman, Paul Hannon (1991). Modern African Wars: South-West Africa. Osprey. ISBN 978-1-85532-122-9. Retrieved 12 May 2008.
External links[edit]
- Media related to Ingwe missiles at Wikimedia Commons


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+27 11 403 4935 firstname.lastname@example.com
The Tipfuxeni Project was launched in Parktown in Johannesburg on Tuesday 23 September 2014.
The project, funded by the National Lottery Trust and a collaboration between government, the Southern African NGO Network (SANGONeT) and South African National NGO Coalition (SANGOCO) aims to provide South African non-governmental organisations (NGOs) with a "user-friendly 'one-stop' internet entry point to information on South African development funding issues".
The project allows funders to communicate with NGOs in South Africa (SA) and connects South African NGOs with each other to share 'up-to-date information and capacity- building resources to enhance their fundraising efforts'.
The project is in line with the government's National Development Plan and has been developed with the National Broadband Advisory Council, established to ensure that government, the private sector, academia and civil society work together to reach the SA Connect broadband policy targets.
The SA Connect policy aims to give every South African access to a broadband connection at a cost of 2.5 percent or less of the average monthly income.
Speaking at the launch deputy minister for national planning, performance monitoring and evaluation, Buti Manamela, said the National Broadband Policy [South Africa Connect] seeks to move the country away from over-reliance on mobile broadband and to achieve 100 percent broadband penetration by 2020.
"Minister Siyabonga Cwele [minister of telecommunications and postal services] has indicated that in the current financial year, R20-million has been allocated for the finalisation of the first phase of the Broadband Plan. In the medium term, government is looking to connect 580 clinics, 4 444 schools, 182 police stations, and 572 other government offices."
The Tipfuxeni Project
The first phase of the project is a web platform that allows NGOS to "share content, access funding opportunities, undertake online fundraising, profile their own work and share best practice models."
According to Manamela, "The Tipfuxeni Project recognises that information and communication technologies have a critical role to play in ensuring that NPOs embrace the vision outlined in the NDP's Vision 2030.
"The project is founded on the belief that access to ICT plays a crucial role in creating conditions for meaningful participation of people in society."
He said that the Xitsonga word Tipfuxeni, which means 'do it for yourself', is a critical underpinning of the national call to action: 'Together We Move South Africa Forward', and added that Tipfuxeni is being rolled out while government is focused on harnessing ICT more effectively to create an internationally competitive knowledge economy, improve productivity and expand access to new markets and social development. Manamela concluded saying that the Tipfuxeni Project would ultimately empower communities by strengthening NGOs.
Read more on www.southafrica.info/services/government/tipfuxeni-connects-ngos


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"Sounds like Pink Floyd meeting Mew at an ambient electronica night, before collaborating on an A-list indie movie soundtrack."
- Team Rock's Limelight Feature
"A universe of dreamy prog in keyboards and synths. On Their third Album, All Burn, brothers Casey and Jesse Cooper set complex, bright melodies and heartbeat-pulsing rhythms adrift. "Transit" sounds like a Pink Floyd Ballad sung with a Peter Gabriel-like coo, as synths tug and move the track forward."
- NPR Music, All Songs Considered
"A majestic, expansive record filled with electronic flourishes, soaring vocals and melody to spare."
- AllMusic, album premiere
"A brilliant array of shimmering sorrow and opaque optimism...few previous listeners could've anticipated how luscious, melodic, cohesive, and affective their third outing, all burn, would be."
- The Big Takeover Magazine
"A Beautiful, Surprisingly melodic dream-pop gem."
- New Noise Magazine


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- USTA Tennis On Campus Section Championships
- Eastern Championship
- Florida Championship
- Intermountain Championship
- Mid-Atlantic Championship
- Middle States Championship
- Midwest Championship
- Missouri Valley Championship
- New England Championship
- Northern Championship
- Northern California Championship
- Pacific Northwest Championship
- Southern Championship
- Southern California Championship
- Southwest Championship
- Texas Championship
- USTA Tennis On Campus Invitationals
- Other USTA Tennis On Campus Events
- Alumni Tennis Events and Young Adult Leagues - Calling All Players!
- USTA Tennis On Campus Section Championships
Play Tennis This Summer
Just because your Tennis On Campus season is drawing to a close doesn't mean that you can't spend more time on the courts! Check out these great summer tennis options - there's something for everyone:
USTA League Tennis
USTA League Tennis is the country's largest recreational tennis league, helping more than 325,000 players nationwide get on the court, have a good time, and step up their game. Many college players find that joining a league tennis team is a great way to continue playing and improving their tennis game during the summer. If several members of your team will be in the same area, you could also form a team of your own. Leagues are available for all ability levels across the entire country. For more information, please visit the USTA League Tennis homepage. You can also check out local flex leagues for singles, doubles and mixed play.
USTA Tournament Tennis
USTA Tournament Tennis is another way to compete during the summer months. Most tournaments take place over a weekend and are run as singles and/or doubles draws. Just like with USTA League Tennis, USTA Tournament Tennis is available across the country. The tournament calendar is always changing to include more events. For more information or to enter a tournament in your area, please visit the USTA Tournament Tennis homepage.
World TeamTennis Recreational League
The World TeamTennis Recreational League program features year-round leagues that have provided playing opportunities for players of all ages and abilities across the United States since 1985. The format is familiar to collegiate club tennis players; it is the same format used for the USTA Tennis On Campus National Championships. Teams may also have an opportunity to
qualify for WTT National Qualifiers and the National Championship. For more information or to join a local WTT league, please visit the World TeamTennis Recreational League homepage.


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Britain Royal Baby
Broadcaster Natalie Morales, of NBC, broadcasts a live report, across from St. Mary's Hospital exclusive Lindo Wing in London, Monday, July 22, 2013. Buckingham Palace officials say Prince William's wife, Kate, has been admitted to the hospital in the early stages of labour. Royal officials said that Kate traveled by car to St. Mary's Hospital in central London. Kate _ also known as the Duchess of Cambridge _ is expected to give birth in the private Lindo Wing of the hospital, where Princess Diana gave birth to William and his younger brother, Prince Harry.The baby will be third in line for the British throne _ behind Prince Charles and William _ and is anticipated eventually to become king or queen. (AP Photo/Lefteris Pitarakis)


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Eureka Miniatures: 28mm Modern Armed Afghans
Eureka Miniatures' 28mm armed Afghans are probably the figures we have been asked about most in the past month. We now have them in stock, after a shipment from Eureka touched down this afternoon.
Fighting 15s currently stocks only the following items in the range:
100MOD70 Armed Afghans, 15-figure set
100MOD76 Type 63 Rocket Launcher with ammunition boxes and two Afghan crew
The set costs GBP24.75; the rocket launcher and crew GBP11.00. Prices include VAT and reflect the poor exchange rate we are currently getting against the Australian dollar.
Our initial stocks are limited. We have more on the way soon.
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Posting your comment.


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A River Falls woman was airlifted from a crash scene this week after the pickup truck she was driving struck a guardrail and landed in a Pierce County ditch.
The Pierce County Sheriff's Office said 22-year-old Janie Whitebear was transported by LifeLink III helicopter after the crash, reported at 3:33 a.m. Sunday, Dec. 23, in the town of River Falls.
Deputies said the crash occurred on Highway 65 near 820th Street, where it appeared Whitebear lost control of a 2015 Chevy Colorado and crashed into a guardrail before coming to rest in a ditch. Deputies did not disclose the extent of her injuries.
A Regions spokeswoman said Wednesday that the hospital had no information on Whitebear.
River Falls ambulance crews and firefighters, along with Ellsworth police, assisted deputies at the crash, which remains under investigation.


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Sunday, September 20, 2009
Wine Number One.
Trips to New York City with Spike usually mean one thing: a full-on total attack on food.
Never in my life have I ventured so deep into the heart of the restaurant beast than when traveling with Spike. No restaurant is too intimidating and no menu is too vast for a thorough vetting. In fact, it's never just one restaurant, on a typical evening, it hasn't been uncommon for Spike to lead the charge in hitting up to three restaurants for three complete meals, which usually leaves me unable to sleep and in various stages of discomfort. A learning experience for sure, but I pay in the end.
With Star Chefs in full swing, it was time to head down to The Bowery and check out Daniel Boulud's new joint, DBGB - a riff on the famous Bowery music venue CBGB's (now defunct).
Oddly enough, I'm old enough to have actually seen shows at CBGB's so going to DBGB was an interesting experience. The restaurant is more French brasserie and doesn't share the same location as the old club but it's pretty darn good. The fries were done right and generally the food is quite tasty.
But the true star of the menu are their sausages. The flavor and texture of the currywurst was just spot on. Creamy, smooth and with a little texture - sausage perfection. The Basque Boudin was just as good with the perfect balance of texture, spice and blood. I wanted more but there was so much to explore.
Soon Josh and ladyfriend Mo joined us and it was Game On. We went to town on the menu, and we hit it hard.
Octopus a la Plancha - eggplant, tomato, crispy panisse
Boudin Basque - blood and pigs head sausage, espelette pepper, scallion mashed potatoes.
Berliner - german currywurst, turnip confit.
Beef Bone Marrow - katz pastrami, watercress, pickled mustard seed, rye bread toast.
French Fries
Veal Tongue Sauce Gribiche - egg dressing, fingerling potatoes.
Tablier de Sapeur - lyonnais-style crispy tripe, mustard sauce, spicy tomato-tripe salad.
Pied de Cochon Pane - crispy pigs feet, romaine heart salad, sauce dijonnaise.
Red Curry Mussels - spicy coconut milk, tomato & thai herbs.
Handmade Strozzapreti Pasta - spring peas, zucchini & tomato.
Paleron Carbonnade - flat iron steak braised in dark beer, root vegetables & gingerbread croutons.
Wine Number Two
Fig Tart with vanilla ice cream
and a Sundae
A bit of fanboy-ism: Thomas Keller's copper pot.
DBGB Kitchen & Bar
299 Bowery Street
New York, New York 10003
Posted by onocoffee at 11:26 PM No comments: Links to this post
Labels: food, friends, restaurant, review, travel
Sausage Sunday Brunch at Jojo
Yours truly with Crucial and Chef John.
Spike ponders wine and the menu at Jojo.
Tuna - tartare, chive oil and gaufrette potatoes.
French fries for the steak.
Hanger Steak - gingered mushrooms, white asparagus, soy caramel sauce and a fried egg.
The Original - the molten chocolate cake that started it all.
160 East 64th Street
New York, New York 10065
Posted by onocoffee at 2:23 PM No comments: Links to this post
Labels: food, friends, restaurant, review, travel
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It's no secret that California is home to many beautiful hiking trails & spots. One recent discovery that had us mind blown was the plethora of hiking trails in the Bay Area's Marin County!
Not only is Marin County home to Muir Woods National Park & Mt. Tamalpais State Park, there's a bevy of cute little towns, beaches & trails that give you beautiful vista views, with minimal exertion. One such astounding trail we discovered recently on our Mojo quest was Dawn Falls.
Family friendly, relatively short & easy – this was an enchanting walk through moss-covered forests, littered with fall foliage & redwood trees. It's only towards the very end, that there is a small set of switchbacks, leading to the top of Dawn Falls – a mini 25 foot waterfall. Now, the water was all dried up once we reached the top – there was no waterfall to see! Locals shared that early spring (February-March) is a better time to see water & an actual waterfall.
In spite of this, we were pretty zenned out with Mojo, here are some reasons why:
Soaring Redwood Trees
Fantastic Fall Foliage
Enchanting Moss Covered Forest
Charming Bridges
As you can see, I'm pretty convinced this little gem of a walk/hike is Marin's best kept secret! So if you're in the area, and Muir Woods happens to have sold out parking, or there's far too much traffic heading that way…. here's another hassle-free, peaceful & equally alluring alternative to discovering scenic Mojo, in Dawn Falls.
What You Need To Know
How to Get There
Google Maps
Trail Info
2.2 miles round trip, 1-1.5 hours
Good For
Families, Dog-friendly, Winter Walks/Hikes
Watch Out For
Parking is street parking only & tends to fill up early, however you can park by the residential area adjacent to the trail. Waterfall might be dried during off season.
Best Time to go
November – March, preferably during Dawn or Morning hours
Nearby Places to Eat
Pin this for reference!
Also published on Medium.


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Ep. 251: Cock & Bull Feat. Amit, Priyanka and Navin/
This week on Cock & Bull, we have Amit, Priyanka and Navin covering the wide expanse of India to talk about morons down south and up north. They also discuss new films, Bhayander and also pick their favourite wild animals.
Follow Cyrus Says on Facebook: https://goo.gl/Ekg9Iy
You can listen to this show and other awesome shows on the IVM Podcast App on Android: https://goo.gl/tGYdU1 or iOS: https://goo.gl/sZSTU5
You can check out our website at http://www.ivmpodcasts.com/


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For all of my readers who aren't aware, I will be away on vacation starting August 29th to September 5th. There will be no new postings/updates during that week I run a one woman show with my website alongside my business partner Ryan and not only do I run my website full time but I also work full time in advertising. With that being said I need a vacation to rest, de-stress and to recharge.
Posts will resume full throttle on Tuesday, September 6th with lots of fab features as well as we have TIFF, the Emmy's and tons of Fashion Week updates to look forward too.
I will also post photos of my vacation when I come back.
I apologize for the inconvenience but I hope you all understand!
Vicky B.


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The Rising Sun Dive Center
Welcome to Rising Sun Dive Centre. The only PADI 5* Gold Palm and National Geographic Dive Centre in Zanzibar. Located on the untouched South East coast of the island, our dive centre was the first to discover this unexplored region.
With over 19 years experience we offer you the highest levels of customer care and attention whilst encouraging you to conserve and explore the marine environment.
We take divers from complete beginners up to professional level and have a massive variety of diving guaranteeing something for everyone. With our small groups of a maximum of 6 divers per guide we are able to offer you the chance to escape the large crowds and get the most from your dives. If you would like more detailed information about the Scuba Diving facility please visit www.risingsun-zanzibar.com


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The Company is committed to complying with its continuous disclosure obligations pursuant to the Corporations Act and Listing Rules set by the Australian Stock Exchange. Specifically, the Company's policy is to ensure compliance with Listing Rules 3.1, 3.1A and 3.1B.
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The Board of Directors and CEO are responsible for the ongoing review of information which may be material, making disclosures to the ASX and issuing media releases on behalf of the Company.
To ensure clear, consistent and appropriate information, the Chairman and the CEO are the only Officers authorised to speak to the media.
The Board of Directors aims to ensure that the shareholders are informed of all major developments affecting the Company's state of affairs. Information is communicated to shareholders through:


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Discover what awaits you and your lover inside...
Intimacy in a healthy relationship should be fun, exciting and safe while always growing and evolving. An invigorating sex life provides vitality, health and happiness across all facets of an individual's being. YesNoMaybe helps lovers achieve these principles by providing a secure platform for couples to better understand each other and their mutual desires. Our exciting service fosters erotic communication by comparing lovers completed YesNoMaybe lists -- a catalog of various sexual activities a person may or may not be interested in. Each individual notes their inclination towards the activity and then submits the list to be shared with a partner. YesNoMaybe automatically scans the lists and shows mutual positive interests ranked by desirability. These results can be used as the foundation for intimate discussion, role-playing and sexual exploration.
In addition to our primary service, YesNoMaybe has a growing list of games and some very tantalizing features on the horizon. Upcoming releases will allow YesNoMaybe to be used by a wider audiance (called a Party) for more general fun and games. This will be a great lead-up to bachelor or bachelortte parties to get the group in the mood! Check back often as we'll be launching this and our flagship product -- something so spicy we're keeping it under the covers...for now!
Frequently Asked Questions
Honest communication is important in a physical relationship. It allows everyone to understand the boundaries of consent and safety while maximizing the satisfaction and pleasure of sex. We need to understand our partner's desires and what activities they do or do not have an interest in. At the same time, we must convey our own urges and hesitations we feel to our lovers. Such honest dialog is not easy to obtain as people may be scared to share their inner most thoughts and feelings. YesNoMaybe's service allows for personal exploration by presenting different actions and fosters candid conversation by displaying interests lovers have mutual desire for.
A YesNoMaybe list is a wide inventory of sexual acts - many will be interesting and enjoyable, some may not. Each YesNoMaybe member completes their list by identifying what turns them on (Yes), off (No) or is something they may consider (Maybe). These lists can be cross referenced in order to allow the couple to have a greater understanding on each others fantasies and desires. Lists such as ours have been around for a long time and are often used by sex therapists, marriage counselors or adventurous couples.
The mainstream acceptance of BDSM or related practices of dominance, submission, restraining and role-playing has provided new avenues of sexual growth for many couples. YesNoMaybe proudly supports these efforts given they are done safely under full consent by all individuals involved.
While we include erotic photography and suggestive themes designed to heighten a person's sense of arousal, YesNoMaybe is not a pornographic site and does not have any explicitly nude images. Given the nature of our content, YesNoMaybe is intended for adults only.
It is simple. Register for a free membership by clicking here. Be sure to answer profile questions honestly as we may use them to assist you in the future. Once you have activated your account you may log in to the 'Lounge' area of the site. Within this section, further instructions and advice will guide your journey.
Well aren't you just full of questions? While we like and appreciate those with a thorough attitude like yours, Master says you will just have to wait on this one. Be patient. Good things come to those who wait...


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Lumsden Activities
Steam Heritage
From its inception until the 1950s, steam locomotives were the main motive power on New Zealand's railways. The Kingston Branch was a major railway line in Southland, New Zealand. Its construction began in 1864 and it passed through Lumsden in 1876. A few remnants of this fabulous steam train heritage can still be seen in Lumsden.
The Lumsden Railway Station - now preserved as a tourist information centre
The original New Zealand railways water tower -which harks back to the days when puffing trains refilled tanks before continuing their journey. The tower is close to the Lumsden Station and is often photographed in winter dripping in frozen icicles.
A large Yard Crane built in 1908 by Applebys from Leicester.
A short wooden trestle bridge across Lumsden Creek built to carry both road and rail traffic. This small but attractive bridge can be seen near the northern town entry.
It is possible to enjoy a short stroll along the Oreti River while staying in Lumsden by walking along short gravel roads behind Lumsden. The river can be accessed from 2 main points in Lumsden.
Albion Street on the north side of Lumsden which passes the Lumsden Camping Ground and ends on the pebble banks of the river.
On the south side of Lumsden follow Pluto Road West which also ends on another section of the Oreti River.
Walking along the banks of the Oreti River looking at the birds, colourful pebbles and swirling water is a most pleasurable experience enjoyed by both tourists and locals.
Trout Fishing
The Southland of New Zealand is famous for its trophy trout, crystal clear waters and river access. Over 35 excellent trout fishing rivers, streams and lakes are within 1 hours drive of Lumsden such as the Aparima, Mataura, Nevis, Oreti, Upukerora, Von, Waiau, Waikaia and Waimea, Fishing novices and experts from all over the world regularly base their fly fishing trips from Lumsden.
The Oreti River is a braided glacial river that winds its way past Lumsden in split runs and deep pools. It is a picture perfect place for walking, fishing or sightseeing. The river can be accessed Albion Street and Pluto Road West. Another access point is behind the Lumsden Recycling Centre on the south side of town. Fishing licenses are available for sale at the Lumsden Pharmacy along with some fishing supplies.
Bird Watching
The Oreti River travels for over 171kms and slowly curves its way through the open plains of the lower South Island. It is home to large brown trout and flocks of gulls, ducks and other water birds. The Oreti River has been identified as an Important Bird Area because for much of its length it supports breeding colonies of endangered Black-billed Gulls.
Pairs of paradise-duck are commonly sighted as well as other wetland and water birds. The paradise shelducks are typically observed flying in pairs. They are very vocal birds, with males giving a characteristic 'zonk zonk', while females make a more shrill 'zeek zeek' while flying or as a warning to intruders.
Lumsden has its own long 9 - hole golf course which is maintained beautifully by the local members. During summer a competition is run on Wednesday evenings at 6.00pm and Saturday mornings. Visitors are made to feel very welcome. The club is about 5km out of town on Highway 6 to Invercargill. Drop in to the club to contact members to organise a round.
For further information about the activities available in Lumsden, please visit southlandnz.com


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After such a long hiatus between the bed crown post and the garden tour yesterday, I'm trying to be a little more organized, and get focused on some regular posts!
Yesterday I took this great cabinet down to Aunt Bee's.
I picked it up just a couple weekends ago, and it was the culmination of a fantastic junking weekend!
If you follow me on Instagram, you also saw a preview pic of a table I picked up at a barn sale....this was all in the same weekend.
Epic, I tell ya.
I love that kind of luck.
There are plenty of dud weekends, so it's nice to get a big stash of good stuff in a couple days.
This was from an estate sale, and the family was so fun.
Great sense of humor and super helpful.
There were a few other pieces I got at this one, and they were equally good!
This is a totally handmade piece.
I love that each individual drawer was put together and the patina on each handle is fabulous.
And if you've been reading my blog for any length of time, you know I have a love of aqua.
But did you know I also have a love of mint green??
It was almost too much for me to handle seeing this!
After a good cleaning, and a little touch up with some additional paint, she is available in my space!
And, for those of you who are not anywhere near me, I have a little bonus info for you.
Aunt Bee's House is now offering shipping! I'm so excited about this prospect!
Now if you see something I have and you just can't live without it, you can purchase and have it shipped to you through Aunt Bee's House and a shipping company they are working with.
If you want details on any of my pieces, just message me here or on my Facebook page, and I can give you the info and put you in touch with the shop.
Or, you can go directly to Aunt Bee's Facebook page, and the phone number to the shop is listed there.
Before I sign off for today, I have one more question for you, friends.
Do you prefer seeing more posts, or beautifully staged and set up posts, even if it means there might be a break between posts for a few days?
I've been thinking about this over the last week, and I'd love your input.
xo Denise
Let's Connect!


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Jul 6, 2009
SMALL FACES - FROM THE BEGINNING (DECCA 1967) Jap DSD mastering cardboard sleeve + 14 bonus
From The Beginning was released in 1967 as a spoiler by Decca, the Small Faces' old label, to coincide with the release of their new album on the Immediate label entitled Small Faces (confusingly, the only album they made for Decca was also self-titled). The Small Faces did not especially appreciate the gesture, and made a point of specifically discouraging people from buying From The Beginning in the advertising for their new album.
From The Beginning contained all the hits they had had with Decca (What'cha Gonna Do About It, Sha-La-La-La-Lee, Hey Girl, All Or Nothing and My Mind's Eye), available on any number of compilations, alongside a number of previously unreleased recordings. These and are now the chief attraction of this album.
The Small Faces had one line-up change while they were with Decca, when in October 1965 Jimmy Winston left and was replaced on keyboards by Ian McLagan. Although the Decca album Small Faces depicted Ian McLagan on the cover when it was released in May 1966, Jimmy Winston played on five or six of the tracks, recorded before his departure, and largely comprising their stage act of the time.
Unfortunately, it seems not to be known when these outtakes were recorded but the stage favourite Baby, Don't You Do It (a Marvin Gaye cover) has Jimmy Winston on lead vocals and guitar so some others may well have been recorded before October 1965, possibly the bizarre but interesting version of Runaway and the excellent takes on Don Covay's Take This Hurt Off Me and the Miracles' You've Really Got A Hold On Me. Both of these demonstrate what a fine band they were, and what a great vocalist Steve Marriott was. Indeed one wonders why space could not be found for some of these recordings on their first album. After Ian McLagan joined, they began to put Booker T-style instrumentals on their B-sides, so the cover of Plum Nellie here probably features him rather than Jimmy Winston on keyboards.
The album also included earlier versions of songs they re-recorded for Immediate, including My Way Of Giving, which they had handed over to Chris Farlowe for a single, and (Tell Me) Have You Ever Seen Me...
9 comments:
- Tarkus said...
Wonderful mod piece!
Thanx a lot.
- July 6, 2009 at 3:09 PM
- Gerard said...
Thank You!
- July 6, 2009 at 9:23 PM
all small faces´s stuff is a must, thanks for spreading it!!
- July 9, 2009 at 7:54 PM
Pelase, if you have Art of Lovin' non-LP 1968 single 'You've Got the Power' b/w 'Good Times' (Mainstream catalog number 687)!!!
- July 10, 2009 at 8:00 AM
Like ithe Immediate CDs, I also have these Decca releases in their remastered US counterparts, but figured there may be some hidden gems on these that I didn't have...and they did not disappoint. I thought I had pretty much everything from the Small Faces, but I apparently was still missing a couple of tracks, so thank for posting these Japanese versions. Don;t know why we can't put CDs like this out in America...the imports always seem to have a few extra things. And then they wonder why the music industry is falling apart.
- July 17, 2009 at 5:17 PM
I also thought I had all the songs on "From the Beginning" on my other Small Faces albums (mostly the two self-titles ones). I really appreciate these Japanese versions.
I remember in the 1990s that the record stores would have Japanese-import CD singles with B-sides not available on any American releases. Stupid record companies.
You have a nice blog that meets a cool niche.
- April 28, 2010 at 10:09 AM
- øשlqaeda said...
sweet spot you have here friend. i was about to post this very fine album but here it lives, in robust bits no lesscccc. just found you so i felt obligated to hute & letcha know i added ya to me own 'bloggy roll'. must harvest more treasures now. be seeing you :)
- July 31, 2010 at 2:06 AM
The Small Faces got screwed out of their deserved royalties for many decades.
It wasn't until around 2000 they started seeing the paycheques they deserved, which isn't a pleasant thought when you consider the cirmcumstances of Ronnie's passing.
It's great to see someone publicising the band, but for the aforementioned reason alone I personally don't feel comfortable seeing anyone providing links to free copies of their albums.
I would say to anyone that followed the download link and enjoyed what they heard, PLEASE consider buying a copy of the album and giving the last couple of remaining living band members a little payback in the way of thanks for their work.
It's the least they deserve for the financial shafting they suffered over the years, surely?
- August 9, 2010 at 10:37 PM
- KDNYfm said...
I still have a couple of these albums on vinyl purchased back in the day.
Thanx for sharing the updates/remasters.
- March 8, 2012 at 8:09 PM


text: Home > Bookshop > Health > Asperger's Syndrome « Back Your Special Friend: A Book for Peers of Children Diagnosed with Asperger Syndrome Santomauro, Josie Our Price Retail Price AUD$9.95 Your Price AUD$3.80 Minimum Order: 1 In Stock (2) Dispatch: 1 day Your Special Friend: A Book for Peers /Santomauro, Jo/Paper/1843106612/S036-E AUD$3.80 QTY Gift Wrapping Add Gift Wrapping (click checkbox) If you would like a gift wrapping message, please add it in the Notes section on the checkout page, thank you. AUD$2.95 Publisher: Jessica Kingsley Publishers ISBN-13: 9781843106616 Series: Asperger Syndrome: After the Diagnosis Binding: Paperback Year Published: 2009 Intended as a support tool in the initial period after diagnosis, Your Special Friend is varied and engaging, and addresses questions or concerns that the child might have, such as 'What are the characteristics of AS?', 'Why has my friend got Asperger?', and 'How can I help my friend?'. Also included are poems, stories, illustrations and activities to help them come to terms with and move forward from a friend's diagnosis of AS. Your Special Friend will be essential reading for children in the initial period after a friend's diagnosis of AS. ID: 183271 Code: FO000061


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One of our customers moved into a new location. They had existing CAT5 wiring and jacks in place, however the wiring went in a conduit going to the floor above which they have no access to. The previous tenant of this office space apparently had office space on multiple floors or offices within the building, and their network room was located elsewhere in the building.
Since there was a centralized location where all of the wiring in their office came together, which happened to be fairly closely to where the cable company installed their cable modem, the wires for the jacks that are going to be used by this customer were cut out, and punched down into a small 12 port patch panel.
|This is where the router and patch panel were placed, high up on the ceiling.
The black box on the left is a surge protector to connect power to the router.
|A close up of the newly mounted router, and new 12 port patch panel.


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September 8, 2017
HBN Law St. Maarten office temporarily closed due to Hurricane Irma
Due to the passing of hurricane Irma and the widespread damage caused to St. Maarten, our office in St. Maarten is temporarily closed. We expect to reopen in the week of September 18, 2017. Further updates will be posted on this website. If you need to contact our St. Maarten office, please contact firstname.lastname@example.com or email@example.com or call +5999 434-3300.


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Floral Care Testimonials
This photo of the gerberas reveal how they lasted after standing in solutions of water and various preservatives. After four days some of the gerberas in three different preservative brands and a plain water control begin to droop. There are dramatic differences after eleven days. The stems in the Vita Flora Preservative did best.
From FRESH FLOWERS
Identifying, Selecting, and Arranging
"There is no substitute for this product, it's as essential as the flowers we use!"
Reggie & Michael's Designs
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Floral Designs by Jo
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"I've been using Vita Flora for six months … My shrinkage and product loss have been almost nonexistent. My vase arrangement sales have doubled. My clients have noticed not only the longevity of the flowers, but an apparent increase in fragrance."
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Photos below by Dinhanian Floral Products – Portland, Oregon


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Pardon Our Dust: Year in review
It's been a robust year on the Pardon Our Dust Blog. Here's a taste of what we've shared:
Some excellent kitchen remodels . . .
A Westwood kitchen in a New York state of mind
Downey kitchen and dining room for $27,642
Where the money went: DIY luxury kitchen
See more kitchens
Some bath remodeling stuff . . .
Bathroom in Carlsbad has style and accessibility
Pedestal sinks: Faddish, fabulous or folly?
Rate This Remodel: Wide open spaces
See more on baths
Cool design ideas . . .
Grass cloth trompe l'oeil: It makes sense
A Craftsman comeback
Curbside Critic: low-cost, high-style gates
Looking for a pretty good architect or designer?
See more design ideas
Contractor stuff . . .
Contractor markups: How much is too much?
New service reveals contractors' credit histories
Looking for a pretty good contractor?
See more contractor stuff
Lots on green remodeling . . .
Does your green builder run a green business?
Upcoming talks on natural finishes
Jay Leno's bird-friendly wind turbines
See more green remodeling
Guest bloggers galore . . .
How Jeannie got new floors for her Cambria cottage
Peggy's impressive efforts to restore her vintage Burbank cottage
Designer to pedestal sink: Goodbye and good riddance!
See more guest bloggers
Your opinions in assorted polls . . .
Which new TV show would you watch?
Shower or bath most important?
Should wood-burning fireplaces be regulated?
When a couple remodels, whose opinion matters most?
See more polls
A bit about my remodel . . .
Loving my new solar-powered fountain
Getting started
Too much weird green?
See more about my remodel
And we've made a great start on . . .
Readers' best 100 remodeling tips
Coming next: Remodeling resolutions for 2008. Start thinking . . .


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We've made it to Christmas week!!!
Hadley has been enjoying a few new gifts, and so have I. We've had such a great time celebrating with our East coast family but we are ready to take off for Montana tomorrow morning! We'll be unwinding in the mountains so I can't promise you'll be hearing much from me on here. I'll definitely be posting on Instagram though if you want to follow along on our trip (@lnhudson28).
Someone wanted to bring along her jellies:)
I hope you all have such a wonderful holiday with your loved ones.
See you in 2015... EEEEK!!!!


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Playing Musical Scales on the Piano
In piano, perhaps more than any other instrument, you can use scales to do some great things — like play entire songs. Although not all scales are songs, all songs are created from scales, be it an entire scale or just a few notes from the scale. Remember the "Do-Re-Mi" song from The Sound of Music? The whole darn song is about scales, and those kids had fun!
Besides using scales to understand the notes in a song's melody, you can use scales to beef up your finger power on the piano. Plus, the more scales you know, the easier it becomes to play the piano.
Put simply, a musical scale is a series of notes in a specific, consecutive order. Major and minor scales are the two most common types, and they have the following attributes:
They're eight notes long.
The top and bottom notes are an octave apart, so they have the same name.
The series follows a stepwise pattern up and down, and the name of each note in the scale follows the alphabet up and down.
Each scale gets its own wacky-sounding name, like C major. A scale derives its name from the following two things:
The scale's bottom note, or the tonic. For example, a C major scale starts on C.
The stepwise pattern used to create the scale. Music has two kinds of steps, half-steps and whole-steps, which are the building blocks of scales. The "major" part of C major means the third note of the scale is a major third above the tonic.
Note that on a keyboard some white keys have a black key in between and some white keys are side by side. On a piano keyboard:
Two keys side by side (whether black or white) are one half-step apart.
Two keys separated by one other key (black or white) are a whole-step apart.
Two half-steps equal one whole-step.
Knowing some basic facts about scales, you can build any scale starting on any root note simply by applying the correct scale pattern (or combination of whole- and half-steps).


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Each week we record the sermon and upload it to the website.
Click on one of the years below to browse for sermons. Better, you may use the search feature and locate a sermon using the date, speaker's name, sermon's title or Bible passage.
2010 2011 2012 2013 2014 2015 2016 2017 2018 2019
You may search for sermons from 2005 to 2009 by downloading this Excel spreadsheet. Send an email to request a sermon and then it will be uploaded.