text:
- Research article
- Open Access
- Open Peer Review
Co-expressed immune and metabolic genes in visceral and subcutaneous adipose tissue from severely obese individuals are associated with plasma HDL and glucose levels: a microarray study
- Marcel GM Wolfs†1,
- Sander S Rensen†2,
- Elinda J Bruin-Van Dijk1,
- Froukje J Verdam2,
- Jan-Willem Greve2,
- Bahram Sanjabi3,
- Marcel Bruinenberg3,
- Cisca Wijmenga3,
- Timon W van Haeften1, 4,
- Wim A Buurman2,
- Lude Franke†3, 5 and
- Marten H Hofker†1Email author
© Wolfs et al; licensee BioMed Central Ltd. 2010
- Received: 28 January 2010
- Accepted: 5 August 2010
- Published: 5 August 2010
Excessive accumulation of body fat, in particular in the visceral fat depot, is a major risk factor to develop a variety of diseases such as type 2 diabetes. The mechanisms underlying the increased risk of obese individuals to develop co-morbid diseases are largely unclear.
We aimed to identify genes expressed in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) that are related to blood parameters involved in obesity co-morbidity, such as plasma lipid and glucose levels, and to compare gene expression between the fat depots.
Whole-transcriptome SAT and VAT gene expression levels were determined in 75 individuals with a BMI >35 kg/m2. Modules of co-expressed genes likely to be functionally related were identified and correlated with BMI, plasma levels of glucose, insulin, HbA1c, triglycerides, non-esterified fatty acids, ALAT, ASAT, C-reactive protein, and LDL- and HDL cholesterol.
Of the approximately 70 modules identified in SAT and VAT, three SAT modules were inversely associated with plasma HDL-cholesterol levels, and a fourth module was inversely associated with both plasma glucose and plasma triglyceride levels (p < 5.33 × 10-5). These modules were markedly enriched in immune and metabolic genes. In VAT, one module was associated with both BMI and insulin, and another with plasma glucose (p < 4.64 × 10-5). This module was also enriched in inflammatory genes and showed a marked overlap in gene content with the SAT modules related to HDL. Several genes differentially expressed in SAT and VAT were identified.
In obese subjects, groups of co-expressed genes were identified that correlated with lipid and glucose metabolism parameters; they were enriched with immune genes. A number of genes were identified of which the expression in SAT correlated with plasma HDL cholesterol, while their expression in VAT correlated with plasma glucose. This underlines both the singular importance of these genes for lipid and glucose metabolism and the specific roles of these two fat depots in this respect.
- Visceral Adipose Tissue
- Subcutaneous Adipose Tissue
- Plasma Insulin Level
- Metabolic Trait
- Glucose Metabolism Parameter
It has been proposed that obesity-induced chronic inflammation in adipose tissue precedes the development of insulin resistance and type 2 diabetes. Many inflammatory mediators have been found to be present at increased levels in obese subjects, including Tumor Necrosis Factor (TNF), C-reactive protein (CRP), interleukin-6 (IL-6), and the neutrophil products myeloperoxidase and calprotectin [1–4]. It was also shown that chronic inflammation in obesity is associated with the influx of macrophages into visceral adipose tissue [5–8]. Visceral adipose tissue (VAT) appears to have a larger effect on metabolism than subcutaneous fat (SAT). For example, individuals with a larger visceral fat mass show increased triglyceride levels and an increased risk of developing obesity co-morbidities such as type 2 diabetes and atherosclerosis. Evidence for this has been found by epidemiological studies relating waist-to-hip ratio or waist circumference with obesity-related co-morbidity [1, 9, 10]. However, the biological processes that underlie this differential impact of the two fat depots on metabolic disease are still obscure.
Although genome-wide association studies have identified many obesity and type 2 diabetes susceptibility genes, most of the individual differences in disease susceptibility among obese subjects are still unclear. A second hypothesis-free and potentially powerful approach to investigate biological processes in obese individuals is genome-wide expression profiling. The potential of this method is underscored by recent studies that have identified numerous genes differentially expressed after weight loss [11–13]. These genes are candidates to play a role in obesity-related co-morbidities, since weight loss improves the metabolic and inflammatory parameters associated with obesity co-morbidities [14, 15]. However, to our knowledge, no studies have reported direct investigation of relationships between obesity-related metabolic traits and genome-wide expression levels in both subcutaneous and visceral adipose tissue within obese individuals.
We determined genome-wide transcription levels in both subcutaneous adipose tissue and visceral adipose tissue obtained from a large group of severely obese patients some of whom had type 2 diabetes and/or non-alcoholic steatohepatitis (NASH). From these data we extracted groups of highly co-expressed genes. Subsequent correlation of these genes with metabolic parameters such as plasma glucose, insulin, cholesterol, triglycerides, and non-esterified free fatty acids revealed genes expressed in adipose tissue that are related to these parameters.
Study population
From April 2006 to January 2009, we recruited 75 severely obese subjects with a BMI between 35 and 70 who underwent elective bariatric surgery at the Department of General Surgery, Maastricht University Medical Centre (Maastricht, the Netherlands). Patients with acute or chronic inflammatory diseases (e.g. auto-immune diseases), degenerative diseases, reported alcohol consumption (>10 g/day), or who used anti-inflammatory drugs were excluded. This study was approved by the Medical Ethics Board of Maastricht University Medical Centre, in line with the ethical guidelines of the 1975 Declaration of Helsinki. Informed consent was obtained in writing from each individual.
Tissue sampling and RNA isolation
Venous blood samples were obtained after 8 hours fasting on the morning of surgery. All blood samples were collected in pre-chilled tubes and processed for analysis of various metabolic traits (shown in table 1) by routine clinical chemistry. Wedge biopsies of visceral adipose tissue (omentum majus), and subcutaneous adipose tissue (abdominal) were taken during surgery. Type 2 diabetes was defined according to the WHO criteria and NASH was diagnosed according to Brunt's criteria [16]. RNA was isolated using the Qiagen Lipid Tissue Mini Kit (Qiagen, Hilden, Germany, 74804) and RNA quality and concentration was assessed with an Agilent Bioanalyzer (Agilent Technologies, Waldbronn, Germany, 5067-1521).
RNA pre-hybridization processing and hybridization
Starting with 200 ng of RNA, the Ambion Illumina TotalPrep Amplification Kit was used for anti-sense RNA synthesis, amplification, and purification, according to the manufacturer's protocol (Applied Biosystems/Ambion, Austin, TX, USA). 750 ng of complementary RNA was hybridized to Illumina HumanHT12 BeadChips (Illumina, San Diego, CA, USA) and scanned on the Illumina BeadArray Reader. These micro arrays contain 48,813 different probes targeting 37,812 different genes; some genes are targeted by more than one probe.
Data normalization and quality control
Data were quantile-quantile normalized per tissue using Genespring GX software (Agilent technologies). Only samples were included that passed quality control filtering, which was based on the median probe intensity, the correlation with all other samples for the same tissue, general behaviour of known housekeeping genes, and principal component analysis over the samples. All expression data has been made freely available by submission to GEO under GSE22070.
Whole-transcriptome microarray data analysis
To find direct associations between gene expression levels and patient characteristics, Spearman rank correlation coefficients were determined between all available quantile-quantile normalized probe expression values and values of the measured traits. To identify differentially expressed genes in SAT and VAT a Wilcoxon Mann-Whitney U-test was used (as implemented in Genespring GX, Agilent technologies).
Next, for SAT and VAT separately, modules of highly co-expressed genes were constructed using pair wise average-linkage cluster analysis as described earlier [17]. First, Pearson correlation coefficients were determined between all the probes on the microarray. Probes with low expression values were not excluded because it is hard to determine a justified cut-off for exclusion of such probes. In addition, noise signals can be considered to be random and are thus not expected to show any co-expression across patients. We used Pearson correlation coefficients because we applied quantile-quantile normalization to the data and using these coefficients is a generally accepted method to construct co-expression networks. We did not take into account negative correlations between probes because this could lead to clustering of genes that are involved in mutually exclusive processes. After determination of correlation correlations between all possible probe pairs, the strongest correlated probe-pair was selected, and grouped together in a module that was assigned the average expression value of the two probes that constitute this module. After addition of this newly created module to the dataset, the two individual probes were removed from the data and the strongest correlation (either between probe-pairs, module-pairs or probe-module-pairs) in the dataset was again selected. This resulted in either the expansion of a module already created (when the strongest correlation was between a probe and a module or between two modules) or in the creation of a new module (when the strongest correlation was between two probe-pairs). We kept repeating this as an iterative process until the most significantly correlated pair was r < 0.65. To visualize the correlations between probes within the modules we constructed coloured heatmaps by plotting pair-wise correlation values of expression of all the probes within the modules. To calculate significance of overlap in gene content between modules and between different datasets we performed Fisher's exact tests using: http://research.microsoft.com/en-us/um/redmond/projects/mscompbio/fisherexacttest.
The module expression - reflecting the average expression value of the probes constituting that module - was correlated with metabolic traits using a non-parametric Spearman rank correlation coefficient, which we chose because it is the most conservative method. For those modules that correlated with a trait, additional conditional analyses were performed, taking into account the possible confounders: menopausal status, hormone treatment and treatment for diabetes, hypertension, dyslipidemia, along with all the other traits we measured - thus gender, age, BMI, plasma levels of glucose, insulin, HbA1c, triglycerides, non-esterified fatty acids, HDL cholesterol, LDL cholesterol, total cholesterol, CRP, ALAT, and ASAT. To gain insight what these modules represent, the Panther classification system [18, 19] was used to find over- or underrepresented biological themes in the different modules. To visualize the relevant modules, graphs were created by connecting those genes within the modules that were strongly co-expressed (r > 0.65). Genes residing in modules specific to VAT or SAT or modules correlated to a metabolic trait were functionally annotated by manually inspecting KEGG pathways [20], and Pubmed and OMIM gene descriptions.
Quantitative RT-PCR
In order to estimate the technical quality of the micro array data we performed a validation experiment using quantitative RT-PCR (qRT-PCR). By using random stratified selection, as proposed in [21], we picked 10 genes that were upregulated in SAT, and 10 genes that were upregulated in VAT (Additional file 1, Table S1). Random stratified selection implies that all the genes upregulated in one fat depot were sorted on fold change values, and divided in 10 bins with an equal amount of genes. Next, from each bin one gene was randomly selected (Additional file 1, Table S1). We also measured expression levels of a gene that showed no difference in expression between the two fat depots in the micro array data ("house keeping gene" HKG; Additional file 1, Table S1). We used the same mRNA as was used for the micro arrays from 5 individuals. We performed triplicate measurements and we used a standard curve to be able to compare absolute transcript quantities. We calculated the fold change values between SAT and VAT relative to the HKG and compared these with the fold changes values we observed in the micro array experiment. Primers to perform the experiment were designed using http://www.autoprime.de[22] and obtained from Biolegio (Nijmegen, The Netherlands). Primer sequences are shown in Additional file 1, Table S1. To perform the qRT-PCR we used SYBR green (Biorad, Veenendaal, The Netherlands) on a 7900HT Fast Real-Time PCR System (Applied Biosystems, Nieuwerkerk aan de IJssel, The Netherlands).
Highly variable metabolic disturbances in severely obese subjects
Clinical and plasma parameters of the study population
All individuals
Individuals without type 2 diabetes and NASH
Type 2 diabetes patients
NASH patients
Individuals with type 2 diabetes and NASH
No. of individuals/Mean (SD)
Minimal/maximal values
No. of individuals/Mean (SD)
Minimal/maximal values
No. of individuals/Mean (SD)
Minimal/maximal values
No. of individuals/Mean (SD)
Minimal/maximal values
No. of individuals/Mean (SD)
Minimal/maximal values
Number of individuals
Age (years)
44.4 (9.9)
17 - 67
40.3 (9.2)
17 - 54
48.2 (9.4)
28 - 67
45.8 (8.9)
28 - 65
46.5 (8.1)
28 - 65
BMI (kg/m2)
46.5 (9.6)
34.6 - 73.6
42.6 (6.5)
34.6 - 56.8
49.4 (11.4)
34.8 - 73.6
48.7 (10.8)
34.8 - 73.6
49.6 (12.1)
34.8 - 73.6
Glucose (mmol/l)
6.60 (2.1)
4.3 - 14.5
5.53 (0.49)
4.3 - 6.5
8.73 (2.5)
4.3 - 14.5
7.16 (2.56)
4.3 - 14.5
8.8 (2.72)
4.3 - 14.5
Insulin (mU/l)
19.3 (10.9)
3.8 - 53
16.7 (8.8)
5.6 - 37
20.6 (13.1)
5.5 - 53
20.9 (11.1)
3.8 - 49
20.4 (10.9)
3.8 - 49
6.58 (1.39)
5.1 - 12.1
6 (0.54)
5.1 - 7.2
7.9 (1.78)
5.3 - 12.1
6.88 (1.65)
5.2 - 12.1
7.85 (1.88)
5.2 - 12.1
Total cholesterol (mmol/l)
5.08 (1.1)
3 - 9.8
4.93 (0.65)
3.5 - 6.1
5.15 (1.43)
3.5 - 9.8
5.08 (1.23)
3 - 9.8
5.2 (1.5)
3 - 9.8
HDL cholesterol (mmol/l)
0.98 (0.38)
0.5 - 2.8
1.05 (0.3)
0.6 - 1.9
0.8 (0.23)
0.5 - 1.3
0.93 (0.44)
0.5 - 2.8
0.78 (0.22)
0.5 - 2.8
LDL cholesterol (mmol/l)
3.22 (1.02)
1.1 - 7.4
3.16 (0.86)
1.1 - 4.3
3.29 (1.18)
1.5 - 7.4
3.17 (1.06)
1.5 - 7.4
3.32 (1.25)
1.5 - 7.4
TG (mmol/l)
2.26 (2.12)
0.63 - 16.4
1.67 (0.95)
0.63 - 4.2
3.31 (3.46)
0.88 - 16.4
2.73 (2.71)
0.88 - 16.4
3.56 (3.67)
0.88 - 16.4
NEFA (mmol/l)
0.64 (0.32)
0.12 - 1.66
0.52 (0.34)
0.12 - 1.66
0.72 (0.3)
0.16 - 1.33
0.71 (0.28)
0.21 - 1.33
0.76 (0.29)
0.21 - 1.33
ALAT (U/l)
25.7 (16.5)
6 - 124
19.8 (6.3)
7 - 37
32.3 (23.1)
10 - 124
27.7 (19.3)
6 - 124
32.4 (24.8)
6 - 124
ASAT (U/l)
25.3 (12.9)
7 - 72
21.1 (11.6)
7 - 50
28.9 (15.4)
8 - 72
28.4 (13)
8 - 72
30.7 (16)
8 - 72
CRP (mg/l)
10.2 (8.5)
1 - 37
9.9 (9.2)
1 - 37
13.1 (10)
1.7 - 35
10 (8.2)
1.7 - 35
12.8 (10.2)
1.7 - 35
Identification of genes overexpressed in subcutaneous and visceral adipose tissue
We determined genome-wide gene expression profiles of SAT and VAT to identify the gene expression differences in adipose tissue that could potentially underlie the variation described in metabolic traits. After quality control, 73 SAT samples and 69 VAT samples were retained for further analysis. RNA Integrity Numbers (RIN) of these samples ranged between 6.5 and 8.7 in SAT (average 7.6), and 6.2 and 9.4 in VAT (average 7.5). The qRT-PCR validation experiment showed that the 20 genes we tested showed very similar fold change values (correlation coefficient r = 0.88 between the microarray fold change and qRT-PCR fold change for the 20 genes) in the qRT-PCR and micro array experiments (Additional file 3, Table S3 and Additional file 4, Figure S1).
Preliminary analysis of the gene expression profiles revealed that 1,344 genes were significantly upregulated (p < 0.05 after Bonferroni correction) in SAT compared to VAT, with 609 genes showing a >1.5-fold change. In VAT, we identified 1,246 genes with a significantly higher expression compared to SAT (p < 0.05 after Bonferroni correction). Of these, 909 showed >1.5-fold increase (Additional file 5, Table S4A and S4B).
Remarkably, a large number of genes (138 genes) had a more than ten-fold higher expression in VAT than in SAT, whereas only 20 genes were upregulated by more than ten-fold in SAT (Additional file 5, Table S4A and S4B). Subsequent gene-set enrichment analysis of the 138 genes specifically expressed in VAT using Panther revealed that they are involved in signal transduction, cell adhesion, cell communication, and developmental processes (Bonferroni corrected p < 0.05). The 20 genes that showed >10-fold higher expression in SAT are highly enriched in homeobox transcription factors (HOXA9, HOXA10, HOXC8, HOXC9, IRX2, and IRX5). Additional file 6, Table S5A and S5B, shows the overrepresented biological processes in the groups of genes that are differentially expressed in VAT and SAT with different cut-offs based on fold change (fold change > 1, fold change > 1.5, and fold change > 10). Some biological Panther processes are overrepresented in the lists of genes with a fold change >1.5 in both VAT and SAT (p < 0.05 after Bonferroni correction). This might indicate that these processes - as defined by the Panther classification system - are important in both VAT and SAT, but that these processes are differently moderated in the distinct fat depots. Panther biological processes that are overrepresented amongst the genes upregulated >1.5-fold in both SAT and VAT are "lipid, fatty acid, and steroid metabolism", cell structure and motility, developmental processes, cell adhesion, neurogenesis, ectoderm development, immunity and defense, signal transduction, cell adhesion-mediated signalling, and cell communication. Biological processes specifically present in genes upregulated in SAT are cell structure and vitamin metabolism. In VAT such specific processes are "receptor protein tyrosine kinase pathway", cell surface receptor mediated signal transduction, mesoderm development, ligand-mediated signalling, complement mediated immunity, muscle contraction, cell proliferation and differentiation, extracellular matrix protein-mediated signalling, neuronal activities, cell cycle control, ion transport, protein modification, protein phosphorylation, other developmental process, oncogenesis, cation transport, and transport.
Gene modules based on co-expression can classify genes reliably
In SAT, we identified 67 modules containing 5 or more genes. These modules comprised 3,263 genes in total. In VAT, 4,509 genes could be grouped into 76 modules of 5 or more genes (Additional file 7, Table S6A and S6B). Additional files 8 and 9, Figure S2 and Figure S3 respectively, show coloured heat-maps of pair-wise correlations between genes residing in the modules identified in SAT and VAT. Bright red indicates a strong negative co-expression, whereas bright green indicates strong positive co-expression. Expression of genes within a single module are strongly correlated whereas genes that belong to different modules generally do not show strong co-expression. As expected, some genes residing in different modules are strongly negatively correlated to each other, as module construction was solely based on gene-pairs, showing strong positive co-expression.
Overlap between genes in the 10 largest modules identified in subcutaneous (SAT) and visceral adipose tissue (VAT)
*5 69
*6 29
*1 536
*2 307
*7 27
*4 56
*3 115
*9 58
*8 54
Modules of co-expressed adipose tissue genes associated with specific metabolic traits
Modules correlated with metabolic traits in subcutaneous (SAT) and visceral adipose tissue (VAT)
Module ID
Correlated trait
No. of genes in module
6.6 × 10-66
HDL cholesterol
2.5 × 10-7
7.0 × 10-6
1.8 × 10-5
HDL cholesterol
2.7 × 10-5
HDL cholesterol
3.0 × 10-5
8.2 × 10-60
4.3 × 10-6
2.8 × 10-5
2.1 × 10-5
Correlations between the modules, associated to a trait, and all the traits were recalculated taking into account various potential confounding factors. Such confounding factors might be women's menopausal status, the use of hormone therapy, and treatment for diabetes, hypertension, or dyslipidemia (Additional file 11, Table S8). Age, gender, menopausal status, hormone treatment, and treatment for diabetes, hypertension, and dyslipidemia did not influence the results of the uncorrected correlation analysis (Additional file 12, Table S9A and S9B). Correction for BMI showed that BMI is a confounder for the correlations between plasma insulin levels and module VAT 40, which is in line with the significant correlation between module VAT 40 and both BMI and plasma insulin levels. BMI also confounds the correlation between module SAT 8 and plasma HDL levels. However, since insulin and BMI are not correlated to this module if corrected for plasma HDL levels (p-values of 0.276 and 0.331 respectively) we conclude that plasma HDL levels, and not BMI or plasma insulin levels, drive module SAT 8.
These data suggest that genes co-expressed in SAT mainly modulate plasma HDL levels, while genes co-expressed in VAT may affect plasma glucose and insulin levels, thereby contributing to the development of type 2 diabetes.
Genes co-expressed in adipose tissue involved in immune and metabolic processes
Over-represented Panther biological processes in modules correlated to a metabolic trait in subcutaneous (SAT) and visceral adipose tissue (VAT)
SAT Module 4
SAT Module 8
VAT Module 9
No. of genes in module
No. of genes in module
No. of genes in module
Signal transduction
2.8 × 10-4
- Intracellular signalling cascade
2.0 × 10-3
Immunity and defense
3.5 × 10-9
4.1 × 10-17
8.2 × 10-7
- T-cell-mediated immunity
9.2 × 10-5
6.4 × 10-4
- MHCII-mediated immunity
2.5 × 10-5
- Macrophage-mediated immunity
7.5 × 10-5
3.3 × 10-2
- Endocytosis
6.2 × 10-3
- B-cell and antibody-mediated immunity
2.4 × 10-2
4.9 × 10-2
- Complement mediated immunity
2.4 × 10-3
2.8 × 10-7
1.2 × 10-3
- Ion transport
1.8 × 10-4
Cell adhesion
1.6 × 10-3
9.2 × 10-4
Lipid, fatty acid and steroid metabolism
9.7 × 10-3
Carbohydrate metabolism
2.5 × 10-3
Among those genes residing in both SAT 4 and SAT 8 involved in immune-related processes, several are members of well-described pathways. As an example, several members of Fcγ receptor-mediated signalling are present in SAT 4 and 8, including FCGR2A, FCGR2B, Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog (FGR) [23, 24], spleen tyrosine kinase (SYK) [25, 26], protein tyrosine phosphatase 6, non-receptor type 6 (PTPN6; also called SHP-1), TYRO protein tyrosine kinase binding protein (TYROBP; also called DAP12), and cytochrome b-245, alpha polypeptide (CYBA) [27, 28]. Another example of a pathway that is overrepresented amongst the genes present in modules SAT 4 and SAT 8 is the Toll-like receptor signalling pathway. Genes that belong to this pathway are Toll-like receptor 5, 7, and 8 (TLR5, TLR7, TLR8), CD14 molecule (CD14), lymphocyte antigen 96 (LY96; also known as MD-2), Bruton agammaglobulinemia tyrosine kinase (BTK) [29], and myeloid differentiation primary response gene (88) (Myd88). Our data thus suggest that some genes in SAT 4 and SAT 8 are involved in immune-related signalling pathways such as the Toll-like receptor signalling and the Fcγ receptor-mediated signalling pathways.
In this study, we have identified genes expressed in SAT and VAT that are related to lipid and glucose metabolism parameters in obesity. In particular, plasma levels of HDL cholesterol and glucose were found to be correlated to sets of co-expressed, and thus functionally related, genes (modules). Remarkably, several SAT modules were correlated to plasma HDL cholesterol levels and one VAT module was correlated to plasma glucose levels, although these SAT modules contained primarily the same genes as the VAT module. This difference highlights the fact that SAT and VAT have a distinct biological role. In silico classification of the co-expressed genes revealed that a significant number are involved in immunity and metabolism. This is in line with the concept that the immune and metabolic systems are tightly interconnected and that this interconnection is pivotal in the development of co-morbidities of obesity.
Several of the genes we have identified in this study play a role in pathways or processes that have already been linked to obesity co-morbidity, in particular HDL levels. These pathways or processes include immunity-related signalling pathways, the complement cascade, cholesterol metabolism and trafficking, lysosomal degradation and trafficking, and composition of the HDL particle [30–40]. A crucial finding of this study is the identification of novel genes that are correlated to HDL and glucose levels in severely obese individuals. The role of these genes in obesity co-morbidity is largely unknown, and further research is required to unravel the relationship between these genes and HDL and glucose levels. Possibly these genes may control plasma HDL cholesterol and glucose levels, or they might be involved in the response of adipose tissue to changed plasma HDL and glucose levels.
An earlier micro array study performed by Tchkonia et al [41] investigated differences in gene expression levels between differentiated and undifferentiated adipocytes derived from subcutaneous, visceral, and mesenteric adipose tissue. We observed an overlap between the results of this study and our own data that was higher than expected: In our study we identified 1344 genes to be upregulated in SAT and 1246 in VAT. Of these 1344 and 1246 genes, 103 and 87 respectively had also been identified in the study of Tchkonia et al, which identified 920 transcripts to be differently expressed across fat depots in either differentiated or undifferentiated cells (overrepresentation p-values: 2.5 × 10-7 for SAT and 8.7 × 10-5 for VAT, Fisher's exact test assuming that 20,000 unique genes were tested in total). Of the 87 genes differentially expressed in the study of Tchkonia et al that overlapped with genes upregulated in VAT in our study, 76 (87%) were differentially expressed in undifferentiated adipocytes that had been derived from distinct fat depots. 39 of these 76 genes (51%) were present in module VAT 4, which is substantially higher than expected (p-value: 2.5 × 10-11; Fisher's exact test, again assuming that 20,000 different genes were tested). These observations make it tempting to speculate that this module is related to processes in VAT-specific undifferentiated adipocytes. This is line with absence of a module in SAT that contains the same genes as module VAT 4.
Previous studies on the effects of obesity on genome-wide expression levels in SAT revealed several classes of genes to be regulated by obesity [12, 13]. Downregulated genes in obesity include lipolytic genes. Upregulated genes include genes controlling the structure and turnover of the extracellular matrix (ECM) and genes of infiltrating immune cells encoding cytokines and plasma membrane proteins. Another study investigating gene expression levels in whole SAT before and after weight loss [11] found similar sets of genes as found in the studies mentioned above [12, 13]. A subset of these genes was shown to be linked to glucose disposal rate, indicating that they may be involved in insulin resistance. Among the genes involved in immunity and the ECM, there was an overrepresentation of genes expressed in immune cells (e.g. macrophages), whereas genes involved in lipid metabolism were mostly genes expressed in adipocytes. Investigation of 31 genes specifically expressed in macrophages but not in adipocytes [11] revealed that these genes show significantly different gene expression profiles during weight loss induced by a stringent diet. 2 genes did not respond to this diet, whereas 7 genes responded strongly, 11 genes responded weakly, and another 11 genes showed an intermediate response [11].
In our studies of a group of 75 severely obese individuals, the genes in SAT modules 4 and 8, and VAT module 9 showed significant overlap with the genes differentially expressed after weight loss [11], as well as with the genes differentially expressed between lean and obese individuals [12] (Additional file 13, Table S10A). In addition, genes in these modules overlap with macrophage genes differentially expressed during dietary intervention and with genes predictive of insulin sensitivity (Additional file 13, Table S10B and S10C). Strikingly, of the 31 genes specifically expressed in macrophages but not in adipocytes investigated by Capel et al. [11], 26 are present in SAT modules 4 and 8, which are correlated to HDL levels (p = 2.1 × 10-40; Fisher's exact test assuming that 20,000 different genes were tested). Moreover the grouping of these macrophage genes based on different expression patterns during dietary intervention closely resembles the grouping of the genes in SAT modules 4 and 8 generated in our study; 6 of 7 genes identified as high responders to energy restriction regarding their expression are present in module SAT 4, and 10 of 11 genes identified as low responders are present in module SAT 8 [11]. The overlap of genes found in these studies with different designs - comparing lean with obese individuals, studying the same individuals after weight loss, and studying quantitative metabolic traits in obese individuals - supports these approaches and strongly suggests that the genes identified are involved in obesity-related disease mechanisms.
It should be noted that the correlations between the modules and the metabolic traits identified in our study are not driven by BMI, since BMI itself was not correlated to the modules - except VAT 40. The correlation between module SAT 8 and plasma HDL levels was confounded by BMI and plasma insulin levels, but the absence of any correlation between this module and BMI or plasma insulin levels after correction for plasma HDL levels, indicates that HDL is the driver of this module. It can be speculated that module SAT 8 represents a BMI/plasma insulin driven effect of HDL whereas module SAT 4 represents an effect of HDL independent of BMI/plasma insulin.
A remaining question is what biological phenomena are driving the modules correlated to a metabolic trait. Here, we will mainly focus on SAT modules 4 and 8, because these two modules contain the largest number of genes, making it more valid to identify over-represented pathways in them. Capel et al. [11] investigated 31 genes specifically expressed in macrophages but not in adipocytes. Of these, 26 are present in SAT modules 4 and 8, which are correlated to HDL levels. The presence of genes within these modules that are specifically expressed in macrophages, might be a reflection of the relative number of macrophages in the whole adipose tissue and it is possible that SAT modules 4 and 8 are, at least in part, driven by the degree of macrophage infiltration. The presence of two different modules of macrophage genes, as confirmed by grouping of the macrophage genes by Capel et al., might be driven by differences between or within macrophages (e.g. macrophage infiltration or activation). Another possible biological mechanism that might underlie the appearance of SAT modules 4 and 8 are differences in adipocyte size, since with equal numbers of macrophages per m3 the relative amount of macrophage mRNA would increase if adipocytes get larger. Other mechanisms that may operate are the induction of adipocyte autophagy, ER-stress, or inflammasome activation. In order to get insight into these questions histology experiments are required to quantitate macrophage infiltration, adipocyte size, markers of autophagy, ER-stress, and inflammasome activation. Of note, 13 of the 31 macrophage-specific genes were also present in VAT module 9. This overlap is still highly significant, although less striking than in SAT (p = 1.6 × 10-22; Fisher's exact test assuming that 20,000 different genes were tested).
Importantly, VAT is the most metabolically active fat depot, and it has been proposed that complications of obesity correlate to an excess of visceral fat rather than to subcutaneous fat accumulation [9, 10]. However, many studies investigating gene expression in adipose tissue have only focused on SAT. In our study, we included samples from both fat depots and we identified numerous genes differentially expressed in VAT and SAT. In this regard our results are in line with a previous study in ten nondiabetic, normolipidemic obese men [42], but due to our larger sample size we were able to detect more genes differentially expressed in SAT and VAT.
Unexpectedly the module correlated to plasma glucose levels in VAT contained primarily the same genes as the modules correlated to plasma HDL cholesterol levels in SAT. Moreover the genes differentially expressed in SAT and VAT were not correlated to any of the parameters we tested, and expression levels of the genes that were correlated to plasma HDL levels in SAT and glucose levels in VAT were similar in both tissue types. This could indicate that although gene expression levels in VAT and SAT are associated with different plasma parameters - glucose and HDL levels, respectively - the molecular perturbations that underlie these associations are the same. Further, it might imply that gene expression in SAT is a reasonably good "model" for gene expression in VAT in regard to HDL and glucose metabolism.
In conclusion, our data confirm the genes and pathways that were associated to obesity in earlier studies; they are mainly related to immunity and metabolism and include immunity-related signalling pathways, the complement cascade, cholesterol metabolism and trafficking, lysosomal degradation and trafficking, and composition of the HDL particle. Our study also reveals large sets of novel genes differentially expressed across VAT and SAT and genes involved in HDL cholesterol and glucose metabolism parameters in obesity. Finally, we have shown that genes with expression levels correlated to plasma HDL cholesterol and glucose levels are the same in SAT and VAT, but whereas such genes correlate to plasma HDL levels in SAT, they correlate to plasma glucose levels in VAT.
This work was financially supported by the Dutch Diabetes Foundation grant 2006.00.007, IOP genomics grant IGE05012A, and a Transnational University Limburg grant. LF received a Horizon Breakthrough grant from the Netherlands Genomics Initiative (93519031) and a VENI grant from NWO (ZonMW grant 916.10.135).
We are indebted to Yanti Slaats (NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht) for collecting tissue samples, to Pieter van der Vlies and Mark Kiestra (Department of Genetics, University Medical Center Groningen, The Netherlands) for technical expertise, and Jana van Vliet-Ostaptchouk (Department of Pathology and Medical Biology, Molecular Genetics, University Medical Center Groningen, The Netherlands) for critically reading the manuscript. We thank Jackie Senior for editing the manuscript.
Authors' Affiliations
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- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1755-8794/3/34/prepub
Pre-publication history
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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Something's afoot: investigating the names for shoes
Whether you're a shoe aficionado or somebody who regards footwear as merely something to help avoid standing on nails, you might be interested in the etymological backgrounds to the names of some common varieties of shoe. We've taken five of them, and traced their – perhaps surprising – linguistic histories…
You probably know that there are at least two common uses of the word clog: the noun 'a shoe with a thick wooden sole' and the verb 'to block or become blocked', or 'to fill up or crowd'. What you might not realize is that these definitions come from the same root: a Middle English word meaning a block of wood.
While the ultimate origin of clog is not known, two elements of this original sense branched out separately to give the two modern senses. It led to the shoe, because of its wooden sole (and clog may originally have referred solely (!) to the sole). The verb stems from a block of wood being attached to the leg or neck of a person or animal, to impede motion or prevent escape. The earliest sense of the verb clog means to fasten one of these clogs to a person or animal, and this later transferred to the broader sense of 'impede', and then to clog's current meaning.
Speaking of terms for shoes which seem to have unrelated homonyms, what connects the brogue which is 'a strong outdoor shoe with ornamental perforated patterns in the leather' or 'a rough shoe of untanned leather', and the brogue which is 'a marked accent, especially Irish or Scottish, when speaking English'?
I had fondly imagined that the two might be linked by the dual meanings of tongue (in the mouth and in the shoe), but a possible theory is a little more prosaic. The rough shoe of tanned leather was once chiefly worn in parts of Ireland and the Scottish Highlands, and it has been suggested that brogue (the accent) arose in the 18th century with an original sense 'the speech of those who wear brogues'.
You might have wondered what the connection was between the varieties of mule; what (that is) the backless woman's shoe could have to do with the offspring of a donkey and a horse. Well, etymologically at least, the answer is 'nothing'. The latter comes from the Latin mūlus (referring to the animal), while the former is from the Latin mulleī (red high-soled shoes worn by patricians). In English, the earliest use of mule with this etymological root (in the 14th century, according to current Oxford English Dictionary research) referred to a chilblain, especially one on the heel; only from the mid-16th century did mule refer to a slipper or shoe.
I had assumed that the sandal was so-named because it was made of sandalwood (which is also known as sandal). Again, I have jumped to conclusions: the two words actually have different etymological roots. Sandalwood (a 'tree which yields fragrant timber and oil', and also used of that timber and oil) comes from the medieval Latin sandalum, and ultimately from Sanskrit čandana. On the other hand, the sandal you're probably more familiar with – the ones on your feet that you're often advised not to combine with socks – comes via Latin from the Greek sandalion, the diminutive of sandalon meaning 'wooden shoe'.
Stiletto refers to 'a woman's shoe with a thin, high tapering heel', or specifically to the heel in question (also known as a stiletto heel). The word stiletto is Italian and is the diminutive of stilo (dagger), thus stiletto literally means 'a small dagger' – a sense that fans of weaponry will still be familiar with. The association between the heel and the dagger is self-evident, and arose in the early 20th century. Centuries earlier, stiletto was occasionally used to designate a pointed beard – a sense found in the work of the 17th-century playwright John Ford.

subset: commoncrawl


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We're in the process of organising the launch event for the new Internet Safety qualification. There will be two events - held on Friday, 1 September and Monday, 4 September, both at Cardonald College.
The events will be a combined launch and training event - with attendees having the opportunity to get their hands on some of the technologies that will be involved in the pilot (such as Moodle).
The events are for pilot centres (only)... of which there are 41. Contact Derek for more information about these events.
Monday, August 14, 2006
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Patatas Bravas - Potatoes for the Brave, Spanish Style!
from: Tart
There are many recipes for this famous Spanish tapas dish - this recipe was given to me by a Spanish friend from Madrid, and is the only recipe I use now..........I like the fact that the potatoes are baked in the oven, making it easier to prepare & socialise with a glass of Sangria or two! - however you choose to serve it, this is a "must" for your Tapas table!
(Serves 10-12 with other dishes).
Prepare ahead by heating the oil in a pan, add the onion and fry for about 5 minutes until softened. Add the garlic, tomatoes, tomato purée, two types of paprika, chilli powder, sugar and salt and bring to the boil, stirring. Simmer for 10 minutes until pulpy. Set aside for up to 24 hours.
To serve, preheat the oven to 200C/gas 6/fan oven 180°C Cut the potatoes into small cubes and pat dry with kitchen paper.
Spread over a roasting tin and toss in the oil, then season. Roast for 40-50 minutes, until the potatoes are crisp and golden.
Tip the potatoes into dishes and spoon over the reheated sauce.
Sprinkle with the parsley. Serve with cocktail sticks.
Print Recipe (without
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Goettl is an air conditioning company. They are based in Arizona, but they now have locations that are in Southern California as well. They do what they can to help people battle the heat that can be relentless in both of these areas and they know what they are doing so that they can help all of their customers. This is something that has allowed them the chance to try different things and to do more than what other companies have available. They are committed to their clients and they remain positive for all of their clients so that they can help them with their air conditioning needs.
In the past, Goettl sometimes struggled with the things that they were doing. They did not always have as much success as what they currently have and that made things harder on them as a company. They tried their hardest to build themselves back up and they were able to be successful because of the opportunities that they had thanks to the clients that they knew a lot about. It was what gave them the chance to show others what they were able to do and the chance to experience more out of the situations that they were in. Visit Azcentral for more info.
As things got better for Goettl, they continued to expand. They wanted to be able to make more money and help more people. According to their site, they are always looking for different expansion opportunities. They want to be able to show their clients that they can expand to different areas and that they will be able to enjoy all of the expansion opportunities that they have. It is something that has allowed the company to grow and something that has made it easier for them to make the best choices possible when it comes to their business.
According to The Bro Talk, the newest company is going to be a positive addition to Goettl. They are going to be able to use this to reach more people in areas that they didn't have a chance to do different things with. It was a great way for the industry to change and it was something that most of the people were happy with because of the opportunities that they now had to use Goettl to get the air conditioning needs that they had in different situations that they were working on so that they could be successful with these things.
Read more: https://www.reviewbuzz.com/web-widget/GoettlsHighDesertMechanical


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The Pundamentalist
The Pundamentalist
Clare Pepper • Education Coordinator • Compost Education Centre
"Thank you for your beautiful work on our new logo... The staff all love it and we've received lots of compliments from customers and community partners as well."
Travis O'brian • Rector • Saint Barnabas Church
"Simeon does great work. He was very helpful in creating, and leading the development of, our visual identity from its application to business cards to signage and our new website. He is very personable and fun to work with as well; while he generated the visuals it really felt like a team project. We would certainly recommend Simeon to anyone seeking a graphic designer."
Fulya Ozkul • Communications Coordinator • Victoria Film Festival
"Simeon is a unique graphic designer as his approach to design and brand representation goes outside the box and allows him to approach jobs from a new perspective. With a focus on customer satisfaction and graphic design, including hand drawn illustration, his designs are always clean, polished and carefully attuned to the clients' needs. I would highly recommend him for any design work required."
Kim Perkins • Manager of Communications • Burnside Gorge Community Association
"Simeon provided professional and informative advice on our existing promotional materials and helped us improve the consistency of our organization's branding."
Stacey Curtis • Editor
"Working with Simeon Goa has been a treat in my editorial career. He not only meets deadlines in delivering illustrations and cover art, but often beats them. Simeon is an exceptional communicator and open to discussion; two qualities that are integral to any artistic or professional collaboration."
Kristofer Covlin • Musician • Ryot Project
"Simeon was great to work with. I needed an identity that solidified the experimental nature of our group and I had to have it within a very short timeline. He presented two ideas to [us] and the one he helped us choose satisfied how we wanted to look. I would certainly encourage anyone who needs a graphic designer to choose Simeon to work with."
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"Working with Simeon was a real pleasure. As a rookie business owner he put me at ease. He was clear in what the process was going to be, how it would unfold and approximately how long it would take. Simeon was extremely patient with all my questions, never once dismissing any! Simeon probed into my business, my clients as well as my own vision. Simeon listened to what I said I wanted and connected that with his creativity. He presented two incredibly original and appropriate logos for my business. Truthfully it was difficult to choose between the two! What a wonderful problem. Simeon's price was reasonable and certainly competitive. Should I ever need a graphic designer again Simeon is who I will hire! "
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"It's a pleasure to work with Simeon. He asks thoughtful questions, and listens well. He is easy to work with, as he is calm, polite and punctual. His professionalism is evident in the design side, as well as the business side, of the work. We were very pleased with the process of deciding on a design, as well as the final product. We will definitely contact Simeon for any further design work we have, and we highly recommend him to others."
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"Simeon is incredibly multi-talented. I really enjoy working with him, have used him multiple times and have recommended him more times than I can remember. He is dedicated to providing exactly what his client wants by doing all the necessary research and putting his best creative foot forward."


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As a child, I used to get pretty excited in April, about the impending holidays. Around this time of the year, you could still find the red and orange Palash flowers on the hilly trails of Jharkhand. The Lantana bushes would be overgrown and messy, and one would have to wade through them to stay on the beaten track. Then, the summer would quickly arrive. The bushes would become dry and shriveled, and the afternoon sun would be too bright to make a trip outside the house possible. Around an hour after lunch, when everyone would have fallen asleep, a black crow, which used to live in the tree behind the house, would start cawing incessantly. For some reason, it always reminded me of my English teacher.
Right before the school closed for vacation, our English teacher would remind us that at our age, he knew every single word in the English dictionary. And so, inevitably, on most afternoons, after the crow stopped cawing, I would take out my well-worn edition of "The Oxford's English Dictionary", and turn to page one, with the resolve that I too would become the dictionary one day. But it was always the first word, that stopped me dead in my tracks. How in the world, would a snouty ant eater, make it to the most coveted spot in the English dictionary. The Aardvark, I always thought, must have friends in really high places.
Since the two As put the Aardvark in quite an enviable spot in the English dictionary, I always wondered if India's newest political party with national ambitions, had similar objectives, when they chose their name. The Aam Aadmi Party (common man's party), would easily appear at the top of any alphabetical list of political parties in India. Were you to abbreviate it to AAP instead, you still wouldn't be able to dislodge it from the top. In fact, I have had a gnawing suspicion for quite some time, that someone in the AAP, in his or her childhood, had come to envy the Aardvark -- just like me.
Since we are talking politics, and since the largest democracy in the known universe is going through its largest transfer of responsibility and blame, from the huddled masses to a few chosen ones, I thought that I too, should express my opinion by cawing a bit. And trust me, I would not have. In fact, I was planning to quietly march up to the nearest polling booth on election day, and vote. Simply. And then, came the postman.
The Economist, our favorite family magazine, has decided to usher in the daybreak this week, by playing the Lark. I don't like to beat about the bush, and so, I will just say it -- this week's edition disappointed me.
On the cover, they have put a photograph of a stern looking Mr. Narendra Modi, who has also thrown in a frown -- for good measure. In its editorial, the "newspaper" has expressed its inability to "back" Mr. Modi for India's highest office. First, it acknowledges the fact that Mr. Modi is perhaps better qualified than anyone else, to lead India to better times and deliver the fruits of economic development to the aspirational youth of today. Next, it reaffirms that in spite of the good things that Mr. Modi might have done, he has not yet apologized for the riots of 2002, from which, the judicial system may have exonerated him. And then, it chides Mr. Modi, for not wearing a skullcap in atonement.
While Mr. Modi may have been condemned for being biased, the esteemed "newspaper" cannot claim to be completely free of the same hazardous human infliction. What if I called The Economist a magazine, generally written for, and read by the rich white anglo-saxon man? What if I said that expressing public distrust in the judicial system of an "inferior brown-black" country, shows bias of the kind that cannot be washed down with the choicest of single malts, that the Scottish bureau might dispatch respectfully to the editor, from time to time? And what if, the fact that the editorial staff does not show up for work in turbans, can be construed as utter disrespect for the Sikh community in Britain?
Nonsense, they would say. And so do I.


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Camera Switching
Called cameras for Disney, the HealthSouth "Go For It!" Roadshow, and a variety of corporate and entertainment events. Familiar with Panasonic, For-A and Ross Carbonite switchers.
Creative Writing
BA in Communication, Editor of University of Tampa newspaper, two novels on Amazon.com and written several screenplays and short film scripts.
Video Engineering
Completed rigs for the Jimmy Buffett "Carnival" tour and a variety of corporate events.
Directing/ Producing
Directed/ produced short films and proficient in the Gorilla Scheduling and Budgeting software.
Large Display Switching
Proficient in the Analog Way LiveCore. Evolve Academy-certified Barco Event Series Operator.
Generally a Funny Guy
...at least that's what people tell me.


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Clearing Trail
Am I addicted?
A PA colleague of mine who has dabbled in dog mushing says that it is a totally addictive behavior and there should be a twelve-step program for it. It is certainly true that once you get bitten with "dog fever" it is very hard to quit. If I am a blogaholic, am I also a mushaholic? Just maybe.
Southwest Alaska has been whipped with wind the last two days, and it is coming from the north. That means cold. It was ten below zero this morning under a clear blue sky, with wind steady at 25 MPH and gusting higher. That gave us a wind chill of about minus forty. Serious frostbite weather.
Henry has been running dogs every day for the past week, and had no plan for today to be an exception.
"You're not wimping out on me, are you?" he said on the phone this morning. Who, me? Nah!
We were dressed in maximum gear, with eight dogs on the gangline when we left the yard at 2 pm. The few inches of snow we've had in the last few days has helped the trail a little, but it is still mostly hard-packed snow and ice. Teeth-rattling bumpiness at times and loud plastic runner noise on the trail. We couldn't even hear the dogs' panting as they ran, though white puffs of breath were sometimes visible before the wind snatched them away. As usual with a hard trail, it was also a fast one, gliding quickly around corners and sliding easily across ponds. There were moments that had the exhilarating feel of a rocket blast as we careened down sections of half-pipe shaped trail that frequently had the sled teetering on one runner.
We got to Hangar Lake in jiffy, and without rolling the sled, and stopped to look at the near ground-blizzard of wind and snow blowing across its nearly mile-wide surface. Glare ice alternated with good-sized drifts, and to follow our blown-out trail we had to cut directly across the wind. This is a very difficult skill for a sled dog team to acquire, and out here is an essential skill for a good lead dog. The leader must follow voice command alone to head the team to a point in the distance that looks no different from any other point on the far side of the lake. The dogs' natural instinct is to follow the shoreline, staying close to the trees and as protected from the wind as possible. A well-trained leader will go against instinct and follow the musher's command. In a race situation, it can mean the difference between winning and losing.
With a full-on side wind hitting the team, both dogs and sled are blown off course, and frequent corrections are required. If the ground blizzard becomes a white-out, it is very easy to lose any sense of direction. Though it is only two miles from town, it is quite possible to be lost on Hangar Lake, and have to hunker down and wait out the blow.
It was bitter cold in that wind as we crossed the lake, and the leaders, Pistol and Speedo, did well following commands. Once on the other side, the willows and cottonwoods protected us from the worst of the torrent.
The trail we were following winds through several small sloughs and stands of willow before coming to the edge of Steamboat Slough, which connects to the Kuskokwim River. The Slough is a winter parking place for huge barges which are tied up there at the end of summer and allowed to freeze in. It is kind of eerie to walk right up to them, with their huge mooring lines connecting them to the shore like umbilical cords.
We parked the dog team at the edge of the willows and unpacked the sled. Henry had brought his small chainsaw so that we could work on clearing the "pingos" from the new cut-off trail we put in last year. The snow had been a foot higher then, and now the new trail was a nail bed of short stobby willow stumps.
With an hour's diligent labor we managed to clear about half of the trail. There was little wind among the trees, and though it was ten below, we were both overly warm when we decided to quit. Still glad to have a thermos of coffee, however, and a quiet spot out of the wind to drink it and work on our tans.
The trip home was smooth, as homeward legs usually are. All the dogs were pulling hard, focused on their work, eager for the warm meat soup they knew awaited them back in the dog yard. It was about a three hour trip altogether, and I was only cold during the Hangar Lake crossings. Wind is the killer when it comes to cold.
Three hours outdoors on a windy day at minus ten degrees, just for fun. And it was a blast! Yeah, I'm hooked. Dog mushing is just the most incredible sport.
Photos by The Tundra PA. Henry straightens a harness problem at the edge of Hangar Lake. Huge barges are silent inhabitants of Steamboat Slough in the winter. Henry attacks the pingos.
Labels: Dog Mushing


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At Forrester, Hope tells Brooke that Liam got home very late and she hasn't talked to him yet. She still thinks it's best that she moves out, and wishes she knew what happened in Aspen after she left. Hope worries that she's starting to form a pattern of breaking promises to people. She thinks she should move out, but worries about leaving the way clear for Steffy. Brooke advises against it. Hope declares she is moving out and won't go back until the wedding. Brooke says they'd better get planning. Brooke thinks they should have it far from Los Angeles. She suggests the south of Italy. Hope gushes. Brooke says the day Liam's divorce is final, they'll make it official.
He'll Never Stop Loving Me.
Steffy talks to Stephanie, Brooke wants to start wedding planning, and Liam talks to Bill about Aspen.
At home, Liam thinks about kissing Steffy in Aspen and smiles. Bill arrives and starts asking questions - he knows Liam flew home with Steffy. Liam tells him Hope wiped out Steffy on the mountain. He admits that Hope took a 'feel good' pill because of the press before the incident with Steffy. They discuss Hope leaving Aspen. Liam admits he was with Steffy when he went back to the house. Liam tells Bill that Steffy gave him the signed annulment papers. Bill sighs. Liam blurts that he tore them up - he doesn't want to pretend the marriage never happened. Bill says maybe Steffy got tired of waiting. Liam says he kissed her. Bill muses that he's the smartest guy he knows, but he can't keep up. Liam sighs. Bill says Steffy is the woman for him and it looks like he's finally realizing it. Hope appears. Bill exits. Hope tells Liam she needs to apologize to Steffy, and promises she's done with the pills. Hope says she didn't stay true to herself throughout this, and needs to fix it by moving out. She tells Liam not to let Bill and Steffy get to him - she's not crazy, and they will be married. She asks if he still wants to marry her.
Steffy and Stephanie talk at Forrester. Steffy tells her grandmother what happened on the mountain with Hope, and that it was Liam who found her. She goes on to say that she had an epiphany in Aspen and signed the annulment papers. Stephanie is taken aback. Steffy talks about how Liam stayed by her side and cared for her - she realized she didn't need to worry about the annulment because he'll never stop loving her. Stephanie is still upset that she signed the papers. Steffy tells Stephanie that when she gave Liam the papers he ripped them up and they kissed. She muses that he's still with Hope though. Stephanie says she needs a drink - when will Liam make up his mind?
Spoilers for Tomorrow on The Bold and the Beautiful:
Caroline observes Rick's softer side.
Steffy gives her family some news.
Please abide by the Guidelines when posting and Contact a moderator if one is required to handle bad posts. Feel free to check out The Bold and the Beautiful News Room, Comings and Goings, and Spoilers! Screen shots may not be used without express permission from Soaps.com.
We invite you to join us on Twitter @soapoperafan, and Facebook. Come tweet and Facebook with us about "Bold and the Beautiful" all the other soap operas, "Dallas," "Glee," "Grey's Anatomy," "Scruples," "Vampire Diaries," and "Venice The Series."
- Candace Young


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Highland Tower
The water tower is a Highland neighborhood landmark located at the intersection of Snelling Avenue and Ford Parkway.
The tower, which was designed by Clarence Wigington, was completed in 1928. Wigington, a city of Saint Paul architect from 1915 to 1949, also designed many other important structures in the area, including the the Saint Paul Public Safety Building (1929–30) and Como Park Pavilion (1934).
The construction of the Highland water tower includes facings of Kasota and Bedford stone and a riveted steel-plate tank with a capacity of 200,000 gallons.
The 127-foot tower is no longer in service.
The tower is open to the public twice a year:
- The weekend of Highland Fest, July 20 - 21, 2019.
- The second weekend in October, for the viewing of the fall colors. Oct. 12 -13, 2019.
- The tower is open from 9 a.m. to 5 p.m. both Saturday and Sunday.
Did you miss the open house this year?
Get a virtual tour of some of the sights!
For more information, please contact Saint Paul Regional Water Services at 651-266-6350.


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Community Performance Series Welcomes Brian Blade & The Fellowship Band on April 14
Grammy-winning Jazz Drummer Brian Blade along with The Fellowship Band to Perform CPS Season Finale on April 14 at SUNY Potsdam
POTSDAM, NY (04/06/2018) (readMedia)-- Community Performance Series (CPS) will present jazz veterans Brain Blade & The Fellowship Band on Saturday, April 14 at 7:30 p.m. in Helen M. Hosmer Concert Hall at SUNY Potsdam's Crane School of Music.
The group will perform songs from their latest release "Body & Shadow (2017)," along with tunes spanning their illustrious career. Brian Blade & The Fellowship Band marked its 20th anniversary in 2017 with the release of their fifth album, "Body and Shadow," a nine-track meditation on lightness/darkness that arrives like a balm for the soul, ebbing and flowing with grace, subtlety and no shortness of beauty.
Formed in 1997, the band released their Blue Note debut in 1998, but the bond among the musicians goes back even further. Brian Blade, the band's namesake and drummer, first met pianist Jon Cowherd in 1988 while attending Loyola University in New Orleans, and they met bassist Chris Thomas in the Crescent City a year later. With Myron Walden (alto saxophone and bass clarinet) and Melvin Butler (tenor saxophone), the Fellowship Band's sturdy unified bond has evolved with every album, and this latest release is an extension of that evolution.
"We humbly welcome this accomplished group to Potsdam. Throughout his career, Brian has worked with some of this generations greatest musicians, inside and out of the jazz scene," said CPS Executive Director Jason L. Dominie.
Tickets can be purchased prior the performance by visiting the CPS Box Office, located in the lobby of SUNY Potsdam's Performing Arts Center, by calling (315) 267-2277 or by visiting www.cpspotsdam.org. Tickets can also be purchased in-person at Brick & Mortar Music in downtown Potsdam. The event night box office will open one-hour prior to the performance in the lobby of Helen M. Hosmer Concert Hall.
Regular ticket prices differ depending on seat location. Student tickets are currently free, and adult tickets range from $20 to $30. Discounts are also available for senior citizens and SUNY Potsdam faculty/staff.
For more information, visit www.cpspotsdam.org, or check out the CPS Facebook page, at www.facebook.com/cpspotsdam.
CPS is a college-community partnership presenting distinctive and renowned performing artists and arts education opportunities in Northern New York. This rich mixture of programming links communities, classrooms and audiences of all ages and preserves access to the performing arts for future generations. For more information, visit www.cpspotsdam.org.
Founded in 1816, The State University of New York at Potsdam is one of only three arts campuses in the entire SUNY system. SUNY Potsdam's arts curriculum offers the full palette: music, theatre, dance, fine arts and creative writing. No matter the discipline, people from all backgrounds can find their creative compass at Potsdam, with myriad arts immersion experiences available for both campus and community.


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Why See Walk the Moon?
Let's Dance!
Expect an evening of infectious indie anthems set to bubbly synth with big oh-oh-oh choruses. One of 2015's biggest breakouts, Walk the Moon, are the glittery feel-good rockers behind 2010's song of the summer 'Anna Sun' and the energetic foot-stomper 'Shut up & Dance'. Walk the Moon bring a charmingly joyous celebration to the stage that dares you not to get up and dance along!
Now they're back on tour once again, still supporting their 2017 hit record 'What If Nothing'. Favorites at festivals around the word, this is your chance to see them in a much more personal concert-setting for once! Though that doesn't mean you can't bring the glitter and face-paint with...
Additional Information
Performance date: 1 February 2019
And before you stop reading
Image attribution: Neon Tommy Used under Creative Commons License
Image attribution: Neon Tommy Used under Creative Commons License
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Please note: The term Lupos Heart Break Hotel and/or Walk the Moon as well as all associated graphics, logos, and/or other trademarks, tradenames or copyrights are the property of the Lupos Heart Break Hotel and/or Walk the Moon and are used herein for factual descriptive purposes only. We are in no way associated with or authorized by the Lupos Heart Break Hotel and/or Walk the Moon and neither that entity nor any of its affiliates have licensed or endorsed us to sell tickets, goods and or services in conjunction with their events.


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"Hello Developer,
We've reviewed your application Pull My Finger. We have determined that this application is of limited utility to the broad iPhone and iPod touch user community, and will not be published to the App Store.
It may be very appropriate to share with friends and family, and we recommend you review the Ad Hoc method on the Distribution tab of the iPhone Developer Portal for details on distributing this application among a small group of people of your choosing.
Victor Wang
Worldwide Developer Relations
Apple, Inc."
Here's a developer video of Pull My Finger being demonstrated:


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mclcreate up for 'Best Event Provider' at M&IT awards
Friday, 11 September 2015
The contest is organised by M&IT magazine, and seeks to reward excellent services, products and companies in the events industry.
Over 1,150 event industry professionals attended the ceremony in 2015, where winners included British Airways, Visit Scotland and Hotel Arts Barcelona.
A key aspect of the awards is that prizes are awarded based on votes cast by people within the events industry, meaning that mclcreate would like your votes to help us reach our goal.
We set out to become a one-stop-shop for events, and we now successfully offer a joined-up service – from technology provision right through to delegate and event management.
The company has worked with many UK and international clients from Mamas & Papas and JTI to The AA and Royal Mail Group, and our focus on client satisfaction and delegate experience has seen many of our clients come back to us repeatedly.
We operate across the UK, from Edinburgh to London, meaning we are able to help event organisers wherever they are.
We also have experience in the international arena. Recent months have seen our account managers and crew delivering events for clients in Abu Dhabi, Mallorca and Milan.
Some of our most exciting projects this year have included Election Night projection mapping on the National Monument in Edinburgh, to assembling a giant 36 metre screen at Minecon at ExCeL which was streamed online to over 3 million viewers worldwide via YouTube, Xbox Live and Twitch,
Our greatest asset is our brilliant team of account managers, technicians, business teams and project managers who work hard all year round to deliver memorable events. A few of them even found time to win a football tournament!
Voting is now closed. Thank you to everyone who voted mclcreate for the category of 'Best Event Provider'.
The awards announcement is Friday, 26th February.


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BEST SUPREME Speed Wax is fast and easy one-step gloss wax that cleans, polishes and protects in one operation. Gently removes fine scratches, buffer marks and light oxidation. Natural oils restore gloss and enhance depth. Imported waxes and co-polymers offer long term, high gloss protection. Safe for all paint finishes with a pleasant banana scent.
Direction on how to use:
Professional use only. Never wax directly under sunlight. Shake product well. Apply by hand with an applicator. Allow to haze and dry. Wipe with soft and clean cloth or buff to shine with equipment.
For best result use Best Supreme Finishing Pad
Shake well. Apply in shade on a cool dry surface. When using a polisher or a high speed buffer, apply enough material to the paint surface to work a two foot by two foot area. For best results using a dual action polisher work at a speed of 2 to 4 and apply ample pressure. For best results using a high speed rotary, buffer speed should be set between 800 and 1200 RPM. To achieve maximum gloss, ease up on buffer pressure and burnish to a high gloss.


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The use of magnetic resonance imaging (MRI) prior to breast-conserving surgery does not improve loco-regional staging compared with conventional staging methods among women with early breast cancer. These results were presented at the 2008 San Antonio Breast Cancer Symposium.
Staging for early breast cancer prior to surgery typically involves mammogram, ultrasound, and biopsy. Retrospective data has indicated that MRI used in this staging process may provide more accurate staging information, which may reduce unnecessary mastectomy or re-operation. However, no prospective randomized trials evaluating this issue have been performed until the COMICE trial.
The COMICE trial is the first prospective randomized trial evaluating MRI as a loco-regional staging method for women with breast cancer prior to surgery. The trial included 1,623 women who underwent triple staging assessment including mammogram, ultrasound, and biopsy prior to scheduled wide-excision. Half the women underwent MRI in addition to the other staging assessments, and half did not.
The researchers concluded that the of addition of MRI to other loco-regional staging procedures prior to breast-conserving surgery does not appear to warrant the extra cost as no significant differences in re-operation rates or disease-free survival were achieved compared with standard staging methods.
Reference: Drew PJ, et al. The UK NIHR multicentre randomised COMICE trial of MRI planning for breast conserving treatment for breast cancer. Proceedings from the 2008 San Antonio Breast Cancer Symposium. Abstract 51.
Copyright Breast Cancer Information Center on CancerConsultants.com
Copyright © 2010 CancerConsultants. All Rights Reserved.
Tags: Uncategorized, UNM CC Features


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- Technology
- Humor
- Programming
- Web Dev
- Design
C++ Qt GUI
Qt GUI Toolkit
Installing Qt 4.4.3 On Windows (Various Methods)
Qt GUI Toolkit is an opensource toolkit using C++ and other languages to code, it is the best GUI library there is. Qt allows you to make Windows, Linux, or Mac programs that work great. We'll explain how to install it on windows (it's much easier in linux).
QThread QMutex QSemaphore and Multi Threaded Applications
Ever wondered what a Thread Mutex is? How about a Semaphore? You know they deal with threads but you probably never understood how they work. This article will examine QThread, QMutex, QSemaphore in a multi-threaded application and explain it using Qt (though you don't need to know Qt to learn this important programming concept), it's actually easier than learning it using Win32 Programming.
Qt Splash Screen
Having a beautiful splash screen can give your program some class. Impress some of your clients as well if you use Qt to program. I'll show you how to edit the Splash Screen message, program the Splash screen, and play with the images.


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The latest research on human immunodeficiency virus (HIV) takes us a step closer to finding a permanent cure for the condition. Not only for HIV, but this cure is also said to help deal with other viral infections such as glandular fever virus that is usually associated with lymphoma, according to a capillary doctor.
Dr. Axel Kallies (Walter and Eliza Hall Institute) and Dr. Di Yu (Monash Biomedicine Discovery Institute) have discovered the importance of killer T Cells, which is considered a specific type of white blood cell, to find these infected cells and destroy them. This discovery is said to provide new insights into finding a permanent cure for HIV and other dreaded viral infections. These T cells are naturally found in the patient's body while he/she is infected with the virus. But the research team is finding a way to boost their numbers so that they can easily destroy the virus in the body. The research revealed that specialized T cells named follicular cytotoxic are able to enter the spots inside the lymphoid tissue where the virus could be hiding during treatments. In fact, the hidden spots are known as B cell follicles. The study revealed that although the HIV virus can hide within the B cell follicles, killer T cells are specialized enough to find these hidden spots and eradicate the virus.
This new discovery will help design effective treatment methods for numerous viral infections affecting humans. This will help develop new medications to treat viral infections, including HIV. The research is going on in this area and further breakthroughs are awaited.
Human immunodeficiency virus, or HIV, is the beginning stage of acquired immunodeficiency syndrome, or AIDS. HIV is a virus that cannot be fully eradicated from the body, currently, which means that once contracted, a person will have AIDS or HIV for the remainder of their life. Over time, we have gained a better understanding of the virus and are working to find a cure and prevention techniques.
The earliest known case of HIV in a human was diagnosed outside of the US in 1959. In 1981, the US began to see HIV cases beginning with males. Typically, homosexual men were going to the doctor because of symptoms similar to an infection caused by pneumonia. In 1982, the AIDS term was used by the CDC when they were describing the virus that was spreading across the nation. This is also the year that San Francisco opened a clinic specifically for the AIDS disease.
In 1984 it was discovered that AIDS was a complete syndrome while HIV was the virus that would cause the full blown disease. In 1985, The FDA gave the approval for a blood test that would be made available for people in the medical field to test a patient's blood to determine if they had the disease. After being identified, an epidemic occurred which resulted in AIDS being the main cause of death in 1994 in Americans between the age of 25 and 44.
By 1997, a treatment is known as HAART or highly active antiretroviral therapy. This therapy leads the field in the treatment of the disease. While the numbers of deaths did decrease, people were worried that this type of treatment may create resistant strains of the disease, or be too aggressive. In 2002, the first home test for HIV was approved by the FDA. In more recent times, it is believed that the spread of the HIV may be stopped by a daily intake of a medicine.
Although not as popular currently as it used to be, HIV and AIDS still plays a major part in many people's lives. The disease is not one that should be taken lightly as it still cannot be cured. Prevention may be our first step toward curing or vaccinations.
AZT Break. The worlds first drug against HIV/AIDS is what started it all. Learn more about this miracle drug.


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There is an important place for YOUNG ADULTS at Little Flower. How wonderful it is to witness the continuing growth in this area of parish membership!
We strive to nourish and support the spiritual growth and personal balance of young adults and young couples by creating comfortable settings for deepening friendships and forming new ones. There are a wide variety of service and volunteer opportunities available designed for serving God and helping others. Additionally, regular offerings are made available to learn more about the great adventure that the Catholic Faith truly is, along with discussing and discovering practical ways for our faith to impact the secular settings and duties that mark our daily living.
Regular opportunities will be posted here for your involvement.
Little Flower Parish Offerings for Young Adults:
Monday evenings, 6:30 pm, Parish House Living Room


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|Pagina PrincipalaRack Rail SQ HolePenn Elcom 28U Full Hole RacK Strip with Squre Holes 2mm/0.08" R0863/2MM-28
Penn Elcom 28U Full Hole RacK Strip with Squre Holes 2mm/0.08" R0863/2MM-28 £7.75
Full Hole Rack Strip with Square Holes.
Black Powder Coated.
Available Cut From 1 Space to 45 Spaces.
Please Specify length (Number of Spaces) when Ordering.
Mounting equipment on Rails:
-For an easy and economic solution, use our new innovative clip nuts for rack rails.
-Also compatible with S1170/ S1172 Captive Nuts, S1045 M6 Screws and S1940 - S1941 Cup Washers.
For Universal Rack Cage Nut Tool see part SX1100
Material: 2.00mm / 14 gauge Steel
Finished In Black
Jennifer de la United States Cere
Could you tell me if you have a 3D model available for this part so I can place it into my next higher assembly?
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( 0100 )
|Fleet Air Detachment,
U.S. Naval Air Station,
Kaneohe Bay, T.H.,
December 14, 1941.
|The Commander Patrol Squadron TWELVE.
|The Commander-in-Chief, Pacific Fleet.
|Report of Raid of December 7, 1941.
|CinCPac Des. 102102 of December, 1941.
Offensive measures taken:
Two duty sections were present in the hangar at the beginning of the attack. Two planes were moored in Kaneohe Bay, two were in the hangar and the remaining eight were parked on the parking apron.
Upon being attacked the two duty sections, augmented immediately by all other squadron personnel present on the station, manned machine guns in the planes, mounted machine guns in pits, and used rifles to fire against the enemy.
Damage to the enemy: (Combined effort of all squadrons and the Naval Air Station).
Two enemy planes were seen shot down.
A number of enemy planes were seen to have fuel tanks punctured so that loss of fuel probably prevented their return to their carrier.
The second wave of horizontal bombers did not release bombs, probably because the control bomber was incapacitated by bullets seen entering the leading plane.
Own losses and damage:
List of personnel casualties is submitted herewith as enclosure (A).
Distinguished conduct of personnel.
This commander being present during the attack personally witnessed the courageous conduct of all the officers and men of Patrol Squadron TWELVE in action against the enemy. No officer or man seemed concerned with his own personal safety but instead time and again exposed themselves to enemy machine gun fire while trying to conserve squadron material, caring for the wounded, and harassing the enemy. Some manned guns others supplied ammunition, all in the face of severe strafing attacks and bombing. The following personnel lost their lives or were maimed in courageous action against the enemy:
Ensign Lee FOX, Jr., A-V(N), U.S.N.R., (Deceased).
Ensign Robert W. UHLMANN, D-V(G), U.S.N.R. (Deceased)
INGRAM, George Washington, 272 58 92, Sea2c., USN (Deceased).
LAWRENCE, Charles (n), 393 33 98, AMM2c., USN (Deceased).
OTTERSTETTER, Carl William, 376 11 77, Sea2c., USN (Deceased).
PORTERFIELD, Robert Kirk, 250 49 63, AMM3c., USN (Deceased).
WATSON, Raphael August, 274 14 40, AMM1c., USN (Deceased).
BROWN, Walter Scott, 342 17 79, AMM2c, USN (Deceased).
GRIFFIN, Daniel Thornburg, 371 79 13, AMM1c.(NAP), USN (Deceased).
HELM, Thomas William, III, 265 94 49, RM1c, USN - Lost 4th and 4th fingers, left hand.
LLEWELLYN, Fred Morgan, 381 30 45, RM2c., USN - Lost left eye, penis and both testicles.
GRISHAM, Lester Alvin, 371 45 84, ACOM(PA), USN - Lost left leg.
LYONS, Dale Shipe, 258 01 48, AMM1c(NAP), USN - Lost left foot.
Other items of interest:
It is believed by this command that the enemy concentrates his operational center and communications in his hangar. The reason for this is that the enemy made his first objective the grounded aircraft and second the hangars. he apparently made no effort to destroy the operations building or radio center. he probably figured that they were kept in the hangar spaces.
Copy to:


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As the face of the Student Volunteer Army in the wake of the Christchurch earthquakes, Sam Johnson was an obvious candidate for the title of Young New Zealander of the Year. And now he can add Communicator of the Year to that, with PRINZ honouring him at an event for senior PR pros last week.
"Sam is passionate about what he does and galvanised an army of volunteers during the aftermath of the Christchurch earthquake through his ability to communicate and link with people," says Jane Dodd, president of PRINZ.
"His ongoing commitment, and even his latest 'The Concert' and the Ministry of Awesome, demonstrates his exceptional contribution to raising awareness of the plight experienced by Christchurch residents."
Johnson says the response of students and the community to the ongoing events in Christchurch has been remarkable.
"We have seen people young and old bind together to create a stronger fabric in communities," he says.
It's the second year running that a Christchurch leader has been given the award.
Bob Parker was named Communicator of the Year in 2011 and previous recipients include Judge Andrew Becroft, Hon Pita Sharples, Alan Duff, Dame Cath Tizard, Bruce Slane and Sir Peter Blake.
The work done for the Student Volunteer Army by PRINZ members Louis Brown of Social Innovation and Daniel O'Regan of Convergence Christchurch was also awarded joint Supreme Award winner at this year's annual PRINZ awards in May.


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Since I have gotten on the internet I have read a lot about this. The consensus is basically never blow your harp too loud. I am going to offer an different approach with the theory being based on my learning (in isolation from other harp players), blowing "too hard" with the greats, and some questions I would like to raise on the greats begining days of harp blowing. I will try to keep this real simple.
I began blowing the harp like a madman. I was way too hard. I was needing to do this because of all the stuff inside me found a way out. I was young, full of testostone, and troubled. To try and control it was not even in the thoughts. It felt good, so I did it.
Then I got to be around sonny terry. He made some huge sounds at low volumes. I was so confused by this. I would sit next to him while he played and physically felt this (no pa, amplification). When I would ask how to get there, he took my arm and said keep doing what I do and I will be there in about 35 years. I was blowing real hard trying to get the greats sounds. He never critized that. In fact one night, while my eyes were closed, he danced next to me while I wailed it to death (a friend told me he what he was doing). Well now I am getting to the point he told me about so it is time to share it.
As the years went on I began amplifying via amps and PA systems. I was still needing to blow hard to feel good and again, blowing soft never entered my mind. It came at times naturally and I loved it as much as blowing hard. Soon I was involved with the NYC and then the SF Bay area blues scenes. The harp players were almost always amped and played so controlled I was again confused. I would get up there and knock them out with sheer energy. Several asked me how I got certain sounds. I tried to explain them, but I never heard them play them back the same because they were so controlled. When I played with guys like Champion Jack Dupree, Louisiana Red, Lightning Hopkins, none said play easier.
Now I blow softly, in a different way, but will never put a limit on what I do to a harp. That kills the art of it. My harps last over a year and I play at least 30 hours a week and mainly in the key of A. People often comment that I really hit the reeds hard. I do, but have learned via not even knowing I was learning it, from blowing hard on the harp. It is about having a ton of air in the tank and funneling it out through the lips/shape of the mouth. Junior Wells did this wonderfully.
Todays beginning players in large are so controlled that I find no umph in most of their sounds. They are missing that because they never have messed with just letting the untamed youthful juice come out. I can hear this in their playing quite clearly. They tend to be paint by the numbers players.
Now, to the greats. We all have only listened to them in their zenith. They weren't recorded when they were kids starting out. Did they blow real hard to get this sonny terry thing I am referring to? We will never know because they are dead. So my theory is contradicting everyone elses. It is based on starting out as being a child, not a full grown adult. Play without fear. Jump high, fall, and scream. Laugh and cry. Forgive, forget, trust, try new things, have hope. It is all part of growing up and if we are living right, will stay with us through life. I see the learning of music and art the same way.