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|By PR Newswire
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|January 10, 2014 09:00 AM EST
Additions expand firm's industrial and office presence in Charlotte
CHARLOTTE, NC, Jan. 10, 2014 /PRNewswire/ - John Linderman, Avison Young Principal and Managing Director of the company's North Carolina offices, announced today that commercial real estate veterans Ted Haley and A.J. Whitehead have joined the company in Charlotte.
Effective immediately, Haley joins Avison Young as a Principal, specializing in industrial brokerage. Whitehead will serve as a Vice-President in Charlotte and will spearhead office tenant-representation services. Haley and Whitehead have a combined 24 years of commercial real estate industry experience.
"We are extremely pleased to have Ted Haley and A.J. Whitehead join our growing operation in Charlotte," comments Linderman. "They are proven professionals in the Charlotte market, and their comprehensive commercial real estate experience and in-depth knowledge of the local market will enhance our ability to provide best-in-class service to our valued clients."
Haley and Whitehead will work as part of a team headed by Avison Young Principal Christopher Skibinski, who joined Avison Young in 2013 to help grow the Charlotte office as well as lead all industrial transactions in North Carolina.
"Chris has built an incredibly strong team in Charlotte in a short amount of time," adds Linderman. "We are excited about now being able to offer our clients a full scope of real estate service solutions across North Carolina."
Avison Young opened its first offices in North Carolina in October 2012 in Raleigh and Chapel Hill when the company acquired Raleigh-based Thomas Linderman Graham Inc. The acquisition added 60 employees to Avison Young's operations, with Linderman joining as a Principal and Managing Director of the Raleigh-Durham offices. The company opened the Charlotte office in May 2013 with Skibinski joining as a Principal.
"The additions of Ted and A.J. expand Avison Young's industrial and office presence in Charlotte. Their arrival demonstrates Avison Young's increasing commitment to the Charlotte market and serves as another important step in the execution of our company's aggressive growth plan," states Skibinski.
Haley brings 13 years of commercial real estate experience to Avison Young. He most recently served as a Vice-President for Lincoln Harris in Charlotte where he focused on representing owners and end users of office and industrial space. In his new role he will solely focus on all facets of the industrial sector.
Haley holds a Bachelor of Arts degree from the University of North Carolina at Chapel Hill. He is a licensed broker in both North Carolina and South Carolina and serves as a member of the Charlotte Region Commercial Board of Realtors.
"I am thrilled to join Avison Young as it continues its aggressive expansion across the U.S.," says Haley. "I am particularly excited for the opportunity to become part of the company's ownership group and to participate in its principal-led culture."
Whitehead joins Avison Young from Grubb Properties, where he was a senior commercial broker overseeing the sales, marketing and leasing of the company's 500,000-square-foot commercial portfolio in the Charlotte region. Prior to that, he served as a Vice-President for Jones Lang LaSalle. Whitehead has negotiated 1.2 million square feet of lease transactions valued in excess of $100 million in various parts of the country, including New York City, Chicago and Charlotte.
Whitehead is a graduate of Miami University in Oxford, OH, where he earned a Bachelor of Science degree in business administration with a concentration in marketing and management information systems. He is currently a member of the Charlotte Region Commercial Board of Realtors and is a licensed real estate professional in both North Carolina and South Carolina.
"The ongoing growth of Avison Young throughout North America has been exciting to witness, and I look forward to enhancing the company's expansion efforts in the Charlotte region," says Whitehead. "Avison Young's culture of collaboration across offices and service lines will be a tremendous asset in providing the highest caliber of service possible to clients."
Today's announcement comes on the heels of Avison Young acquiring Atlanta-based The Eidson Group yesterday.
Over the past five years, Avison Young has grown from 11 to 53 offices and from 300 to more than 1,500 real estate professionals across Canada and the U.S.
Avison Young is the world's fastest-growing commercial real estate services firm. Headquartered in Toronto, Canada, Avison Young is a collaborative, global firm owned and operated by its principals. Founded in 1978, the company comprises 1,500 real estate professionals in 53 offices, providing value-added, client-centric investment sales, leasing, advisory, management, financing and mortgage placement services to owners and occupiers of office, retail, industrial and multi-family properties.
Editors/Reporters: Please click on links to view and download photos of
Ted Haley and A.J. Whitehead
For further information/comment/photos:
•Sherry Quan, National Director of Communications & Media Relations, Avison Young:
604.647.5098; cell: 604.726.0959
• John Linderman, Principal and Managing Director, North Carolina, Avison Young:
• Christopher Skibinski, Principal, Avison Young: 704.226.5990
• Ted Haley, Principal, Avison Young: 704.651.8459
Avison Young was a winner of Canada's Best Managed Companies program in 2011 and requalified in 2012 to maintain its status as a Best Managed company.
Follow Avison Young on Twitter:
For industry news, press releases and market reports: www.twitter.com/avisonyoung
For Avison Young listings and deals: www.twitter.com/AYListingsDeals
Follow Avison Young Bloggers: http://blog.avisonyoung.com
Follow Avison Young on LinkedIn: http://www.linkedin.com/company/avison-young-commercial-real-estate
SOURCE Avison Young Commercial Real Estate (BC)
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Insulin clearance: confirmation as a highly heritable trait, and genome-wide linkage analysis
- First Online:
- Received:
- Accepted:
DOI: 10.1007/s00125-012-2577-2
- Cite this article as:
- Guo, X., Cui, J., Jones, M.R. et al. Diabetologia (2012) 55: 2183. doi:10.1007/s00125-012-2577-2
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We have previously documented a high heritability of insulin clearance in a Hispanic cohort. Here, our goal was to confirm the high heritability in a second cohort and search for genetic loci contributing to insulin clearance.
Hyperinsulinaemic–euglycaemic clamps were performed in 513 participants from 140 Hispanic families. Heritability was estimated for clamp-derived insulin clearance and a two-phase genome-wide linkage scan was conducted using a variance components approach. Linkage peaks were further investigated by candidate gene association analysis in two cohorts.
The covariate-adjusted heritability of insulin clearance was 73%, indicating that the majority of the phenotypic variance is due to genetic factors. In the Phase 1 linkage scan, no signals with a logarithm of odds (LOD) score >2 were detected. In the Phase 2 scan, two linkage peaks with an LOD >2 for insulin clearance were identified on chromosomes 15 (LOD 3.62) and 20 (LOD 2.43). These loci harbour several promising candidate genes for insulin clearance, with 12 single nucleotide polymorphisms (SNPs) on chromosome 15 and six SNPs on chromosome 20 being associated with insulin clearance in both Hispanic cohorts.
In a second Hispanic cohort, we confirmed that insulin clearance is a highly heritable trait and identified chromosomal loci that harbour genes regulating insulin clearance. The identification of such genes may improve our understanding of how the body clears insulin, thus leading to improved risk assessment, diagnosis, prevention and therapy of diabetes, as well as of other hyperinsulinaemic disorders, such as the metabolic syndrome and polycystic ovary syndrome.
KeywordsCandidate gene Heritability Insulin clearance Linkage Type 2 diabetes mellitus
Cytochrome P450, family 1, subfamily A, polypeptide 2
c-Src tyrosine kinase
Genome-wide association study
HOMA of beta cell function
HOMA of insulin resistance
Hypertension–Insulin Resistance cohort
Identity by descent
Logarithm of odds
- M value
Marker of insulin sensitivity
Mexican–American Coronary Artery Disease cohort
Phospholipase C, γ1
Single nucleotide polymorphism
Steady-state plasma insulin
Zinc fingers and homeoboxes 3
The incidence of type 2 diabetes mellitus has reached epidemic proportions and continues to grow; it has been estimated that one in three Americans (one in two in some minority groups) born in 2000 will develop diabetes in their lifetime [1]. The prevalence of diagnosed diabetes is twice as high in non-Hispanic blacks and Mexican–Americans compared with non-Hispanic whites [2, 3]. Therefore, an improved understanding of the pathophysiology of diabetes is imperative in minority populations.
The investigation of the pathophysiology of type 2 diabetes has focused on insulin resistance and defective insulin secretion, both of which must be present for type 2 diabetes to develop [4]. Intact insulin secretion maintains normoglycaemia in the presence of insulin resistance via compensatory hyperinsulinaemia. Consistent with this notion, most type 2 diabetes susceptibility genes appear to affect insulin secretion [5]. To avoid type 2 diabetes, insulin levels must increase to overcome tissue unresponsiveness. The resultant hyperinsulinaemia, while maintaining normal glucose levels, contributes to cardiometabolic risk [6].
A much overlooked factor in studies of the pathophysiology of diabetes is the role of insulin clearance, i.e. removal of insulin from the circulation. A few physiological studies have demonstrated that insulin resistance elicits a reduction in insulin clearance, suggesting that altering insulin clearance is an additional means of achieving compensatory hyperinsulinaemia [7, 8, 9, 10]. We were the first to report that whole-body insulin clearance, as measured by hyperinsulinaemic–euglycaemic clamps performed in Mexican–Americans, had a heritability (h2) of 0.58, which was greater than other insulin-related traits examined (fasting insulin h2 0.38, insulin resistance h2 0.44) [11]. The high heritability of insulin clearance raises the possibility that inherited variability in insulin clearance may affect an individual's risk of developing diabetes by influencing the ability to achieve compensatory hyperinsulinaemia in response to insulin resistance. Whether this is the case is at present unknown because insulin clearance has not been measured in any large candidate gene or genome-wide association studies (GWAS) probing type 2 diabetes susceptibility.
In the current study, our goal was to confirm the high heritability of insulin clearance in an independent cohort of Mexican–Americans and to conduct the first genome-wide linkage scan to search for regions possibly harbouring genes for insulin clearance. Linkage peaks were further investigated by association studies to search for loci involved in insulin clearance.
Participants and phenotyping
The participants in the heritability, linkage and association studies were drawn from the Hypertension–Insulin Resistance (HTN–IR) cohort, which consists of Los Angeles Hispanic–American families ascertained via a proband with essential hypertension. The recruitment and phenotyping of this cohort have been described previously [12]. The linkage study in that cohort used prior microsatellite genotyping conducted on 754 participants from 145 families. Subsequently, additional participants were recruited (bringing the total to 922 participants in 163 families), all of whom were genotyped in the present genetic association study. Approximately 75% of the HTN–IR participants had undergone the euglycaemic clamp with steady-state plasma insulin (SSPI) levels and were therefore ultimately analysed in this study. Flowcharts in electronic supplementary material [ESM] Fig. 1 provide details on the number of participants used in the current linkage and association studies.
Participants from the Mexican–American Coronary Artery Disease (MACAD) study [11] were used in the association analyses conducted in conjunction with the HTN–IR cohort. In the present report, after data cleaning as described below, 179 families were included, comprising 676 participants from the offspring generation (adult offspring of probands with coronary artery disease and the spouses of those offspring) who underwent phenotyping for insulin clearance.
By design, participants undergoing detailed phenotyping in both cohorts were free of known diabetes and clinically manifest cardiovascular disease, thus avoiding secondary changes in phenotype caused by overt disease. A small percentage of participants in both cohorts were newly diagnosed with diabetes as a result of their participation in the studies. These participants were not taking any glucose-lowering medications when they were phenotyped.
Participants in the HTN–IR and MACAD cohorts underwent the hyperinsulinaemic–euglycaemic clamp procedure, performed with the same techniques and assays (described in the ESM Methods). The metabolic clearance rate of insulin (ml m−2 min−1) is the insulin infusion rate divided by the final SSPI level (average of insulin levels at 100, 110 and 120 min) of the euglycaemic clamp. Because all of our participants received the same insulin infusion rate (60 mU m−2 min−1), the SSPI is a direct measure of insulin clearance at steady state and was the trait used in genetic analysis in this study. Insulin sensitivity was quantified using the marker of insulin sensitivity (M value) from the euglycaemic clamp, as previously described [11]. Insulin secretion was estimated using the HOMA of beta cell function (HOMA-%B) using fasting glucose and insulin levels; HOMA of insulin resistance (HOMA-IR) was also calculated [13].
All studies were approved by the Institutional Review Boards at the participating institutions. All participants gave informed consent before participation.
Microsatellite marker genotyping
A 10 cM genome scan using microsatellite markers was conducted on 754 participants (570 with SSPI data) from 145 families of the HTN–IR cohort in two separate batches. According to the original study design, a Phase 1 linkage scan was conducted, followed by recruitment of additional participants who comprised a Phase 2 linkage scan. Phase 1 consisted of 71 families with 354 individuals; Phase 2 comprised 74 families with 400 individuals (includes non-phenotyped parents and phenotyped offspring). For the Phase 1 sample, 378 fluorescently tagged microsatellite markers (Marshfield Version 9; http://research.marshfieldclinic.org/genetics) were successfully genotyped at the University of California at Los Angeles (UCLA); for the Phase 2 sample, 377 microsatellite markers (Screening Set 13, see http://research.marshfieldclinic.org/genetics and Ghebranious et al. [14]) were successfully genotyped at PreventionGenetics (Marshfield, WI, USA). The number of overlapping markers between Phase 1 and Phase 2 was 246; we therefore report the individual as well as the combined linkage analyses.
After data cleaning, described in detail in the ESM Methods, 513 individuals from 140 families (227 individuals from 67 families in Phase 1, 286 individuals from 73 families in Phase 2) had SSPI data and were used in the heritability and linkage analyses (ESM Fig. 1).
Linkage analysis
Linkage was tested by evaluating the null hypothesis that the additive genetic variance due to a quantitative trait locus (QTL) equals zero. The linkage analyses were adjusted for age, sex, BMI and diabetes status. To calculate empirical p values, we simulated a fully informative marker and applied gene dropping for offspring using the LODADJ option in SOLAR. The data were simulated 10,000 times and subsequent linkage analyses were performed to obtain the distribution of the test statistic under the null hypothesis of no linkage. The empirical p values were obtained as the proportion of the 10,000 replicates that had a logarithm of odds (LOD) score greater than or equal to the nominal LOD score observed for the original linked locus. p values were converted to LOD scores by: \( {\text{LOD}} = {\chi^2}/\left[ {2 * \ln \left( {10} \right)} \right] \).
Positional candidate single nucleotide polymorphisms
We sought candidate loci under the −1 LOD interval of any linkage peaks with an LOD score greater than 2. We took advantage of the fact that the HTN–IR and MACAD cohorts have recently been genotyped on the Cardio-Metabochip as part of a separate project (unpublished data, M.O. Goodarzi, J.I. Rotter). The Cardio-Metabochip was designed to provide high-throughput genotyping for replication and fine-mapping of GWAS results for cardiac (e.g. myocardial infarction, QT interval), metabolic (e.g. diabetes, fasting glucose, fasting insulin), anthropometric (e.g. BMI, WHR) and lipid traits (detailed description of Cardio-Metabochip design, see the ESM Methods). Besides providing a relatively dense set of markers under the −1 LOD intervals, this chip provides single nucleotide polymorphism (SNPs) of particular interest to the study of insulin clearance, given the close relationship between insulin levels and most of the traits represented on the chip. Only the SNPs under the −1 LOD intervals of the two linkage peaks with an LOD >2 were examined here. Details of Cardio-Metabochip genotyping, quality control and population stratification analysis in the HTN–IR and MACAD studies are given in the ESM Methods. After quality control (ESM Fig. 1), 638 HTN–IR and 676 MACAD genotyped participants with SSPI were available for association analysis (clinical characteristics, see ESM Table 1).
Association analysis
Association between individual candidate SNPs and insulin clearance measures was evaluated using the general estimating equations (GEE1) method implemented in the Genome-Wide Association Analyses with Family Data (GWAF) program [16]. GWAF uses functions in existing R packages to properly model the residual correlations within families in the test of genotype–phenotype association. The additive genetic model was used in both cohorts. Potential confounding factors, including age, sex, BMI and diabetes status were included as covariates in all analyses. We sought loci associated with SSPI in HTN–IR and MACAD. The power of this two-cohort study to detect association is displayed in ESM Table 2. With the two cohorts studied, we had 81% power to detect SNPs that explain 1.6% of SSPI variance. Even for a SNP that explains as little as 1.2% of variance, we had a power of 65% to detect association.
For those SNPs associated with SSPI in HTN–IR and MACAD, the proportion of variance explained by each associated SNP was estimated using variance components analysis methods. For these SNPs, we also combined the results of HTN–IR and MACAD using fixed-effects, inverse-variance weighting meta-analysis as implemented in METAL [17].
Characteristics of the participants in the heritability and linkage studies
Phase 1
Phase 2
p value
Families (n)
Participants (n)
Male sex (%)
Age (years)
32.7 ± 10.9
29.7 ± 8.7
35.1 ± 11.9
BMI (kg/m2)
28.5 ± 5.9
28.2 ± 5.9
28.8 ± 6.0
Diabetes (%)
Fasting insulin (pmol/l)
90.6 ± 59.4
94.8 ± 57.1
87.0 ± 61.2
Fasting glucose (mmol/l)
5.31 ± 0.46
5.33 ± 0.47
5.30 ± 0.44
3.9 ± 3.4
4.2 ± 3.6
3.6 ± 3.3
184.6 ± 134.2
212.1 ± 150.4
160.8 ± 113.4
M value (μmol m−2 min−1)
1,308.8 ± 575.0
1,306.6 ± 593.9
1,310.5 ± 561.2
SSPI (pmol/l)
832.2 ± 197.4
814.8 ± 201.6
830.2 ± 193.8
Loci with evidence of association with SSPI in two Hispanic cohorts
Gene locus
Base P
SNP in gene
Nearest gene(s)b
p value
p value
p value
9.13 × 10–3
1.10 × 10–2
2.90 × 10–4
CYP1A2 (4 kb), CSK (21.5 kb)
2.53 × 10–2
1.68 × 10–2
1.07 × 10–3
CYP1A2 (14.3 kb), CSK (11.2 kb)
5.98 × 10–3
3.41 × 10–3
6.04 × 10–5
2.88 × 10–2
3.92 × 10–2
2.82 × 10–3
3.15 × 10–2
3.92 × 10–2
3.04 × 10–3
4.74 × 10–2
4.97 × 10–2
5.45 × 10–3
CHRNB4 (45.7 kb), ADAMTS7 (53 kb)
3.17 × 10–2
2.47 × 10–3
2.17 × 10–4
CHRNB4 (45.9 kb), ADAMTS7 (52.8 kb)
3.17 × 10–2
1.92 × 10–3
1.73 × 10–4
CHRNB4 (54 kb), ADAMTS7 (44.7 kb)
2.59 × 10–2
3.71 × 10–3
2.58 × 10–4
CHRNB4 (55.1 kb), ADAMTS7 (43.6 kb)
5.98 × 10–3
4.80 × 10–2
1.02 × 10–3
CHRNB4 (66.7 kb), ADAMTS7 (31.9 kb)
9.68 × 10–3
3.48 × 10–2
1.03 × 10–3
CHRNB4 (67.3 kb), ADAMTS7 (31.4 kb)
5.98 × 10–3
3.48 × 10–2
7.06 × 10–4
3.77 × 10–2
4.92 × 10–2
4.46 × 10–3
3.89 × 10–2
1.55 × 10–2
1.47 × 10–3
3.77 × 10–2
3.24 × 10–2
2.93 × 10–3
3.77 × 10–2
3.69 × 10–2
3.33 × 10–3
3.83 × 10–2
3.69 × 10–2
3.38 × 10–3
3.77 × 10–2
3.69 × 10–2
3.33 × 10–3
For the 18 SNPs identified above (12 on chromosome 15, six on chromosome 20) and found to be associated with SSPI in the HTN–IR and MACAD cohorts, we conducted a meta-analysis, the results of which are given in Table 2. Meta-analysis p values ranged from 5 × 10−3 to 6 × 10−5. We also estimated the percentage of variance explained by the SNP(s). The 18 SNPs individually accounted for 0.32% to 2.0% of the variance in SSPI in the HTN–IR and for 0.33% to 1.5% in the MACAD cohorts. Considered jointly, the 18 SNPs accounted for 5.5% and 6.1% of the variance in SSPI in HTN–IR and MACAD, respectively.
This study confirmed the high heritability of insulin clearance in Mexican–Americans. We also identified, via linkage and association, regions of chromosomes 15 and 20 that may harbour quantitative trait loci that influence insulin clearance.
While many studies have implicated insulin resistance and defective insulin secretion in the pathophysiology of type 2 diabetes, a few studies suggest that reductions of insulin clearance may be an adaptive response to insulin resistance, aimed at maintaining normoglycaemia [7, 10]. Insulin resistance has been found to have an inverse correlation with insulin clearance [8, 9], while weight loss resulted in an increase in clearance [9]. Studies of rats [18] and dogs [19] with diet-induced obesity have also found that reduced insulin clearance accompanies insulin resistance. Treatment with the insulin-sensitising agent rosiglitazone resulted in reduced insulin secretion and increased clearance [20]. Thus, a reduction of insulin clearance accompanies increasing insulin secretion in response to insulin resistance. An improved understanding of this trait and its genetic determinants may therefore provide insight into why some insulin-resistant individuals develop diabetes.
In pursuit of this goal, we examined Mexican–Americans, an ethnic group with a high prevalence of the metabolic syndrome [21] and diabetes [2, 3]. Our logic was that study of a group with a high prevalence of abnormalities in the insulin system could increase the chances of discovering the responsible genetic variants. The high heritability of insulin clearance may be unique to Mexican–Americans and perhaps related to their high rates of diabetes. Studies in other ethnic groups will be needed to determine whether insulin clearance is similarly heritable in other populations.
We used SNPs from the Cardio-Metabochip in our association study of the −1 LOD intervals under the two linkage peaks. While not representing all SNPs contained in the intervals of interest, these SNPs are of particular relevance because they have been previously implicated in traits relevant to diabetes, obesity, coronary artery disease, dyslipidaemia and hypertension. Given that hyperinsulinaemia is a common feature of these conditions, Cardio-Metabochip SNPs are particularly pertinent to our study of insulin clearance, a major factor determining circulating insulin levels [22].
SNPs in or near the MEGF11, CYP1A2, CSK, LMAN1L, CHRNB4 and ADAMTSL7 genes located under the chromosome 15 linkage peak were associated with insulin clearance in two independent Hispanic cohorts. As commonly occurs in systematic association studies (e.g. GWAS), the identified genes do not have an immediately clear relevance to insulin clearance. These genes were localised to three regions (Fig. 2). The first region contains MEGF11, which has no known relationship to insulin but is expressed in the kidney [23], which clears insulin. The MEGF11 locus was not extensively covered on the Cardio-Metabochip; further genotyping will be necessary to elucidate its association with insulin clearance.
The second region, comprising CYP1A2, CSK and LMAN1L, was fine-mapped on the Cardio-Metabochip to investigate a strong GWAS signal for blood pressure (rs1378942) [24]. Insulin binding to its receptor triggers internalisation of the insulin–insulin receptor complex by endocytosis. Within the resulting endosome, insulin is cleaved by insulin-degrading enzyme, protein disulfide isomerase and other enzymes. c-Src tyrosine kinase (CSK) participates in actin cytoskeleton remodelling [25], which might affect insulin clearance via vesicular trafficking along the actin cytoskeleton. Insulin has been found to promote the association of CSK with phosphorylated caveolin-1, which is located at points of contact of the actin cytoskeleton with the plasma membrane [26]. Given that ligand-bound insulin receptors localise to caveolae [27], the interaction of CSK with caveolin might play a role in the internalisation of the insulin receptor–insulin complex. A GWAS meta-analysis associated a variant in CYP1A2 with caffeine consumption [28]. Cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2) metabolises xenobiotics such as caffeine; it is not known whether CYP1A2 participates in insulin metabolism. Thus, while further studies are needed, CSK appears the most likely of the three candidate genes mentioned above to be involved in insulin clearance.
The third region on chromosome 15, flanked by CHRNB4 and ADAMTS7, was fine-mapped on the Cardio-Metabochip in follow-up of a signal for coronary artery disease. A missense variant (rs3825807) in ADAMTS7 was associated with coronary artery disease [29], but none of the SNPs associated with SSPI was in linkage disequilibrium with this variant. ADAMTS7, which codes for a disintegrin/metalloproteinase, is expressed in tissues that clear insulin, including liver, kidney and skeletal muscle [30]; however, a role in insulin clearance has yet to be discovered. CHRNB4, which codes for a neuronal nicotinic receptor, has no known role in insulin metabolism, but appears to have a role in central regulation of food intake [31].
The −1 LOD interval of the chromosome 20 peak overlapped portions of the PLCG1 and ZHX3 genes. Interestingly, several previous studies have identified linkage with type 2 diabetes on chromosome 20q, with LOD scores >2 found at 30 to 70 cM [32], overlapping one of our insulin clearance linkage peaks. However, a subsequent meta-analysis of 23 type 2 diabetes linkage scans found evidence, at 62 cM, of linkage with diabetes in European whites, but not in Mexican–American samples [33]. A type 2 diabetes linkage study encompassing the entire long arm of chromosome 20 in Europeans identified not only the above linkage signal at ~55 cM, but also a second linkage peak at ~15 cM; this latter signal contains the PLCG1 gene [34]. Phospholipase C, γ1 (PLCG1) catalyses the conversion of phosphatidylinositol 4,5-bisphosphate to inositol 1,4,5-trisphosphate and diacylglycerol, playing a role in the signal transduction of receptor tyrosine kinases. Its relationship to insulin receptor function is unknown. PLCG1 also plays a role in membrane trafficking and endocytosis [35], and therefore might participate in insulin clearance. Zinc fingers and homeoboxes 3 (ZHX3), a ubiquitous transcriptional repressor [36], has no known relationship to insulin clearance.
One challenge in the future investigation of the genetics of insulin clearance is that it is not a trait routinely available in large epidemiological studies. Thus in the recent GWAS that have dramatically advanced our knowledge of type 2 diabetes genes, most novel genes discovered have been implicated as factors affecting insulin secretion, largely based on association with OGTT-derived measures of insulin secretion (e.g. insulinogenic index) [5]. The impact of insulin clearance on insulin levels during the OGTT is unclear; moreover, insulin clearance is not readily derived from standard OGTT data. As has been recognised for insulin resistance [37], the lack of an accurate measure of insulin clearance in diabetes cohorts will limit the ability to investigate whether insulin clearance is altered by any of the type 2 diabetes genes. Therefore focused studies specifically attempting to associate diabetes genes with insulin clearance will be needed. So far, variants in only two type 2 diabetes loci, HHEX/IDE and PPARG, have been associated with insulin clearance [38, 39]. HHEX/IDE encompasses insulin-degrading enzyme (IDE), the main enzyme responsible for insulin breakdown.
An understanding of the genetics of insulin clearance will be relevant not only to diabetes, but to a number of other common genetic conditions characterised by hyperinsulinaemia, such as obesity, the metabolic syndrome, polycystic ovary syndrome, non-alcoholic fatty liver disease, hypertension and coronary artery disease. These metabolic conditions are highly prevalent in our society and all appear to be, in part, genetically determined. Thus, inherited factors regulating insulin clearance may influence these conditions by modulating circulating insulin levels.
One limitation of our study is the accuracy of SSPI as a measurement of the metabolic clearance rate of insulin. Because we did not measure C-peptide levels during the euglycaemic clamps to document suppression of endogenous insulin secretion, our estimates of insulin clearance may underestimate the true values. However, because the proportion of SSPI represented by residual insulin secretion is expected to be small during hyperinsulinaemic infusion, we are confident that this had a minimal effect on our linkage and association results.
In our association study, we considered a value of p < 0.05 to be significant. In general, correction for multiple testing is critical in genetic association studies, particularly when a large number of SNPs is being tested. However, in this study, the 3,761 SNPs analysed in the association study were not randomly selected, but chosen on the basis of their location under two linkage peaks. In this case, while it is not certain how multiple testing should be accounted for, it is clear that a standard approach based on the number of independent SNPs would be overly conservative. We observed 18 SNPs associated with SSPI in two cohorts, a marked excess over the nine expected by chance (3,761 × 0.05 × 0.05). Association in two independent cohorts is one solution to the multiple testing issue; moreover, the observation that meta-analysis of the two studies resulted in greater statistical significance (Table 2) adds further credence to these associations. Our study benefited from being able to use two cohorts of the same ethnicity, originating from the same geographical region and with phenotyping performed using the same techniques. Nevertheless, additional independent confirmation will be needed to unequivocally establish these loci as factors influencing insulin clearance.
Future efforts will involve additional fine-mapping of the linkage signals for insulin clearance, as well as investigation of additional positional candidate genes under these peaks. Under the two linkage peaks we identified (chromosomes 15 and 20), 18 SNPs were associated with SSPI in two cohorts. These SNPs account for only small to moderate proportions of the total variance, indicating that other genetic variants may also contribute to variation in SSPI. Further large-scale studies are necessary to confirm these observations. This report represents an early step in the much-needed genetic characterisation of insulin clearance, a trait with relevance to type 2 diabetes and several other common metabolic disorders.
This study was supported by National Institutes of Health (NIH) grants R01-DK079888, R01-HL067974, P50-HL055005 and P30-DK063491, and by General Clinical Research Center grants M01-RR000425 and M01-RR000043. The study was also supported by the National Center for Research Resources, Grant UL1-RR033176, now at the National Center for Advancing Translational Sciences, Grant UL1-TR000124. Further support came from the Cedars-Sinai Winnick Clinical Scholars Award (to M.O. Goodarzi) and the Cedars-Sinai Board of Governors' Chair in Medical Genetics (to J.I. Rotter).
Duality of interest
The authors declare that there is no duality of interest associated with this manuscript.
Contribution statement
All authors made substantial contributions to conception and design, the acquisition of data or analysis and interpretation of data, as well as to the drafting of the article or its critical revision for important intellectual content. All authors gave final approval of the version to be published.


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Some footage from our first ever Gone Chocco where we demonstrated how easy it is to make a chocolate basket to use for a dessert. ... features many more chocolate recipes and instructional videos to help you make amazing meals at home.
by My Art
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Ahhh Life.
Sometimes we think we're hearing God speak, but we're not sure. How can we tell the difference between our thoughts and God's thoughts? Double click on the image to read the 5-minute devotion, Hungry for God: "How to Know It's God Speaking to You."
We all have bad thoughts sometimes. They can even be horrible or overwhelming. The best defense is God's Word and seeking his presence in prayer. If you trust in the truth of Christ's resurrection, he is certain to free you. Let his Spirit make you strong to resist the lies and attacks of the enemy. Christ's victory is absolute and eternal.
Finding Financial Peace: How I plan on saving an extra $1000 in 2015
A prayer for when you feel 'not' good enough...
How to pray fot your husband. Or future husband in my case.
.Wow... these are so wonderfully thought provoking, and without doing them, the six things mean almost nothing. I am going to do this, if I can remember.
Praying for husbands bookmark ~ can be downloaded and printed. I use this, love it. husband..future husband..guy friends.. It's so perfect!
Ways to pray over your children every day
Ever feel like you're drowning in your emotions? Learn to balance them with BetterHelp - an online counseling service. Fill out a short questionnaire and you will be personally matched to a licensed counselor. Get the support and guidance needed to start making a change. BetterHelp offers a free week-long trial and affordable pricing so financial obstacles don't stand in the way of a better life. Reach out and get help today.


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Fall prevention program to expand
The Community Health Foundation of Western and Central New York will expand its falls prevention initiative both inside and outside of the Western New York region with $300,000 in new grant funding.
The foundation will invest the funds in support of its Fall Prevention Collaborative, helping to expand new community coalitions and initiatives throughout Western and Central New York.
The foundation cites data from the State Department of Health showing that falls are not accidents or random, uncontrollable acts of fate. Instead, falls occur in predictable patterns, with recognizable risk factors and among identifiable populations -- making them a predictable and preventable event.
The new funding includes grants of $25,000 to the following Erie County organizations to expand work already in progress: Learning Partners; Catholic Health Partners in Rehab; Brothers of Mercy; UB Foundation Services Inc.; Independent Health; and the Geriatric Center of Western New York.
Additionally, lead agencies outside of Erie County will receive grants of $10,000 to begin developing a multi-dimensional falls prevention plan to address the specific needs of their regions working with community-based organizations. Upon successful completion of a plan for each community, each coalition will then be eligible to share an additional $100,000 in grants to support implementation of their respective plans.
These lead agencies (along with their counties) are: Allegany/Western Steuben Rural Health Network Inc., Allegany; Health Community Alliance Inc., Cattaraugus; Chautauqua County Office for Aging, Chautauqua; Genesee County Office of the Aging, Genesee; Kaleida Health, Niagara; Onondaga County Department of Aging and Youth, Onondaga; and Tompkins County Human Services Coalition, Tompkins.
Additional data comes from Univera Healthcare: Each year, 15,000 older adults in Upstate New York are hospitalized as a result of injuries due to falls, according to a new Univera report, which also found that more than 50 percent of fall-related hospitalizations among older adults in New York are from falls that occurred in the home.
First established by Community Health Foundation of Western and Central New York in 2007 as the Western New York Falls Prevention Plan, the initiative includes a focus on prevention and maintaining independence in the community through behavior change and support for professional and caregiver practice change. The foundation has invested more than $600,000 in grants and related projects to reduce or eliminate the risks associated with falls.
More information is available online at www.chfwcny.org.


text:
No products
Prices include VAT
80mm chuck with backplate to fit the...
£70.00 Inc. VAT
80mm chuck with backplate to fit the HV4 & HV6 Rotary Tables. All new design, massive improvement throughout.
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Ideal addition to the HV4.
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Includes everything needed to fit. Zero machining required - just fit straight on.
Note this is designed to fit 4 slot rotary tables (HV4/HV6), not compatible with 3 slot rotary tables.
Top quality chuck, supplied complete and ready to attach to a rotary table.
Price includes VAT & UK mainland delivery.


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Question about Car Audio & Video
Security code please four digits
Posted by carmen7777 on
have a 10 year old philips car radio/cassette....battery flat, radio dead, now need to recode...lose code, dc155/97 please
SOURCE: I have freestanding Series 8 dishwasher. Lately during the filling cycle water hammer is occurring. How can this be resolved
a 6ya expert can help you resolve that issue over the phone in a minute or two.
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click here to download the app (for users in the US for now) and get all the help you need.
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text: Slávek Slávek is 28 years old male from Kourim, Czech Republic. He is interested in meet new people. 28, male, Hradec Králové Likes: 394x Facebook profile Who s/he liked? Send message Favorite May she/he ask you for a date? Never Maybe Sure Relationship: ShowSexuality: ShowHeight: ShowWeight: ShowBody type: ShowEye color: ShowHair color: ShowLiving: ShowKids: ShowSmoking: ShowDrinking: Show Report photo Sign up to see all photos Facebook Twitter Google+ Pinterest Similar users Jose 24, New York online 13 James 28, Hampton online 24 Art Cory 25, Sharon 93 Deco 26, San Mateo 49 LaVon 27, Los Angeles 120 Jason 27, Moline 107 Matthew 28, Quincy 138 Edgars 28, Newark 34 Clayton 26, Mobile 75


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Welcome to John Whitgift Academy. We hope you like our website. Watch our promotional video here: https://www.youtube.com/watch?v=urO-F75FDaA» Read More
JWA Journal
Click here to read the latest copy of the JWA Journal http://edition.pagesuite-professional.co.uk/Launch.aspx?EID=90fe0b8d-260c-4ed7-90fe-68f8697c35ec» Read More
Welcome to John Whitgift Academy
John Whitgift Academy is a fully inclusive, caring academy which promotes community and social cohesion based on the simple principles of courtesy, co-operation, tolerance and mutual respect.
We demand personal excellence from students of all ages and abilities, providing them with the necessary support to become responsible citizens.
John Whitgift Academy is committed to providing an innovative, enterprising and energising curriculum with a variety of enrichment opportunities for all.
We offer each student a personalised and dynamic learning pathway with opportunities for early entry and national accreditation.
Mr R. Spendlow
Watch our Academy results video here:https://youtu.be/TaIxjLZoATo
Latest News» View All
Ski Trip 201711th May 2017
On the first Saturday of the Easter Holidays a groups of 39 students and 6 staff (including Mrs Macdonald, Mrs Smith, Mr Tufnell, Miss Rowe and Mr Burkill) boar... » Read More
Train to Teach Event Sheffield8th May 2017
Train to Teach Event at Sheffield Hallam University, Charles Street on 24th May 2017 from 4.30pm Interested in teaching? Come and meet us and find out more.Disc... » Read More
Maths BBQ5th May 2017
On Thursday 4th May 2017 our year 11 students got together for the first Maths twilight revision session taking place after school. We had 51 students attend th... » Read More
Train to Teach with Delta TSA12th April 2017
School Direct is a national teacher training initiative, which offers an exciting opportunity to train alongside outstanding practitioners, gaining valuable kn... » Read More
Student excels at Pi Day celebrations15th March 2017
Pi Day is celebrated on March 14th around the world. Pi (Greek letter "π") is the symbol used in mathematics to represent a constant — the ratio of the circumf... » Read More
Year 6 maths challenge13th March 2017
On 10th March JWA hosted the Y6 maths challenge. Led by Miss Rowe, local Primaries were invited to participate in this annual challenge, working in teams to com... » Read More


text:
Deputy Education Minister Ahmed Al Geyoushi said Wednesday that the second stage of the development of technical and vocational schools in Egypt would cover sixty schools nationwide, including five facilities in Aswan.
According to the deputy minister, this phase is part of a seven-year-program that is funded by the European Union. The second phase would cost about 117 million euros.
The development plan reflects a successful partnership between Egypt and the EU with the aim of increasing competitiveness of Egyptian industrial products, the deputy minister said.
The second step of the program covers governance and promoting vocational education in the community to meet the needs of Egypt's employment market, he added
Source : MENA
GMT 14:02 2017 Thursday ,11 MayIndian School Salalah students excel in Green Olympiad
GMT 03:09 2017 Thursday ,11 MayFirst study on Down Syndrome in Oman
GMT 03:06 2017 Thursday ,11 MayOman Education Council seminar discusses future trends
GMT 02:34 2017 Thursday ,11 MayIndian School Muscat will close early during Ramadan
GMT 17:28 2017 Saturday ,06 MayFuel tanker gas leak in Indian capital puts 30 school pupils in hospital
GMT 04:55 2017 Monday ,01 MayAl Injaz Private School exhibition showcases works of students
GMT 04:41 2017 Monday ,01 MayPakistani student in Oman tops CA exam
GMT 03:15 2017 Monday ,01 May'Oman needs to improve the quality of education'


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If only the NHL would take into consideration the fans they are going to loose.
So who blinks first if there's an NHL lockout in less than 30 days? The billionaires or the millionaires? The NHL owners or the hired hands?
If we don't have hockey in October or November or into December, we all know the owners win because they're not forking over any salaries. But we also know when the NHL home office will get very, very nervous — Jan. 1, 2013.
"I don't think it's going past the outdoor game," said agent Igor Larionov, the Hall of Famer who now represents Nail Yakupov and was in Edmonton the last few days.
With NBC giving the NHL $200 million in that long-term arrangement, the Winter Classic is the league's great advertising baby to showcase their product to U.S. folks who wouldn't know Evgeni Malkin was if he was in their soup.
This year, the event is at the University of Michigan's football stadium…
View original post 860 more words


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Komfie Manalo, Opalesque Asia:
The Brazilian local bond market offers more profits than offshore bond markets, said George Wachsmann, a partner with GPS Investments, the largest independent wealth manager in Latin America, at the recent Opalesque Brazil Roundtable.
"Rates are very compressed in Brazil, but last week we bought 10-year paper for our clients at inflation plus 7.5%," Wachsmann said and added, "The month before we bought inflation plus 6.5% with a tax exemption. That investment gives you almost twice the return you will get with the CDI (the Brazilian benchmark interest rate), so it's a huge opportunity."
He added that his firm continues to have confidence in the local hedge funds space because they can tactically hedge in challenging times for the Brazilian economy. In addition a number of local fund managers invest offshore and hedge against currency fluctuations.
Nathan Sor, one of the founders of Galloway Capital, a global emerging market fixed income asset management house, pointed out why the local bond markets are better because Brazilian large local issuers pay lower yields than their issues offshore primarily because big local pension funds, foundations and other institutional investors do not invest abroad yet.
"Local demands will accept to buy bonds that just pay over local CDI, equivalent to L......................
To view our full article Click here
In the week ending 19 May, 2017, Seema Hingorani, a former chief investment officer of New York City's five pension plans, is said to be raising $500m to help five to seven new women-
Komfie Manalo, Opalesque Asia: J.P. Morgan Asset Management, the $1.5tln investment management arm of JPMorgan Chase&Co., has launched the JPMorgan Ultra-Short Income ETF (JPST), an actively managed ETF that seeks to provide current incom
Komfie Manalo, Opalesque Asia: Investors who bought Catalyst Hedged Futures Strategy Fund's Class A, C and I shares have until June 27, 2017 to file lead plaintiff applications in a securities class action lawsuit against the hedge fund, said Charles C. Foti, Jr., a partner at law firm
Matthias Knab, Opalesque: Franklin Templeton Investments writes on Harvest Exchange:
Truth be told, 2016 was not a stellar year for hedge funds, as unceremoniously summed in this head
Opalesque Industry Update - Wilshire Consulting, the institutional investment advisory and outsourced-CIO (OCIO) business unit of Wilshire Associates, announced today that Daniel Ingram has been hired to serve as Vice President of Responsible Investment Research&Consulting. In this role, Ingram wi
Opalesque Industry Update - Advent Capital Management, an investment management firm with approximately $9 billion in assets under management and founded in 1995, announced today that Scott Reid has joined the firm in the newly created position of Chief of Staff and Strategy.
Based in New York,
Opalesque Industry Update - Craig Goos has joined GPB Capital as Managing Partner and Chief Operating Officer. Mr. Goos, who has more than 20 years of experience in wealth management and financial services, will work closely with the GPB executive team to develop and implement plans for enhancing op
Meta Alpha, LLC - Submitted to Opalesque as Guest Article - Confidential and Proprietary 1. Is it really machine learning, i.e. does it really learn? Many systems depend on traditional statistical techniques such as GARCH and other techniques but are not really machine learning. In othe
Bailey McCann, Opalesque New York: Famed short seller Jim Chanos of Kynikos Associates used his presentation at the SkyBridge Alternative Conference (SALT) along with a separate media Q&A to take the US healthcare system to task and more specifically, announce shorts on Mallinckrodt Pharmaceutica
Bailey McCann, Opalesque New York: When hedge fund impresario Anthony Scaramucci abruptly sold his firm SkyBridge Capital to HNA Group, a large Chinese conglomerate, in January in order to pursue a position in the Trump White House, the deal made news. The transaction is expected to close in June
Bailey McCann, Opalesque New York: While hedge fund managers used the first day of the SkyBridge Alternatives Conference (SALT) to spotlight investments abroad, the second day offered a few ideas for the US.
The Carlyle Group's David Rubenstein opened the day by voicing what many investor
Komfie Manalo, Opalesque Asia: The rise of high-frequency trading in Europe, dominating over 80% of the market, has become a challenge for traditional asset managers especially when it comes to risk management, said Philippe Malaise, chairman of advisory firm
Bailey McCann, Opalesque New York: One of the biggest themes emerging at SALT is investing with a global mindset. Panelists throughout the afternoon encouraged investors to consider Europe as well as emerging markets as sources of yield.
At a lunch presentation that replicated much of his pre
Bailey McCann, Opalesque New York: London-based BlockEx, a provider of blockchain based technologies has partnered with Winston & Strawn, an international law firm on a blockchain backed smart contracts project. BlockEx is working with the law firm to create legal documentation templates which wi
Bailey McCann, Opalesque New York: The annual gathering of hedge funds and the investors that love to hate them - the SkyBridge Alternatives Conference or SALT, is currently underway in Las Vegas. As usual, the schedule is dominated by celebrities and investment managers, but this year attendees
Benedicte Gravrand, Opalesque Geneva for New Managers: The London-based manager of the RoboCap UCITS Fund talks to Opalesque about the robotics revolution
Komfie Manalo, Opalesque Asia: The U.S. and Europe offer contrasting performance and outlook for merger arbitrage funds in 2016 and this year, said participants of the Opalesque 2017 France Roundtable.
While 2016
Benedicte Gravrand, Opalesque Geneva for New Managers: The London-based, Swiss-born manager of the RoboCap UCITS Fund, talks to Opalesque about investing
Komfie Manalo, Opalesque Asia: Activist hedge fund firm Elliott Management Corporation has claimed the support of every large shareholder in the proxy fight against Arconic Inc., and said that these major stakeholders have taken a public posit
Benedicte Gravrand, Opalesque Geneva for New Managers: David Verlander has been an investor for more than 20 years with a long history of analysing financial services companies. He saw a unique opportunity set in th
In the week ending 13 May, 2017, Opalesque reported how Professor Desmond Lun is using cell biology to understand the financial markets. Much like the genes and
Bailey McCann, Opalesque New York for New Managers: In Computational Biology, researchers will sometimes look at gene networks to determine how they cross with each other and what the outcomes are. A lot of that wor
Executive Summary
Where clients are looking to benchmark hedge fund investments against a relevant market, or peer
average, we recommend that clients use HFRI Fund Weighted Indices as opposed to indices from other
providers or the newer Asset Weighted indices from HFRI.
In some situatio
A growing stream of thinking in microeconomics is the concept of "winner-take-all" dynamics. The idea seems simple. A combination of networking economics and classic economies of scale creates situations where there are just a few dominant firms or economic agents who are able to capture significant
By: Richard H. Baker
Even in times of pressure, research shows that investors particularly institutional investors such as pensions, foundations and endowments continue to use hedge funds as tools to help meet their unique financial and risk management needs.
This is especially true in the
From Christen Thomson, Citigate Dewe Rogerson: Reading some of the mainstream financial press, you would be forgiven for thinking that the hedge fund business model is dead. One august news organisation headlined one particularly gloomy story, "The Golden Era of Hedge Funds Draws to a Close With
By Alex Gavrish, Etalon Investment Research .
Alex Gavrish explains why best investments are just like good stories or movies: with three-part structure, important turning points, intrigue, drama, and surprises.
Over past few year
John Huber from Saber Capital Management writes on Harvest Exchange:
Buffett talks a lot about the concept he calls the "institutional imperative". In his 1
By: Thomas Walek
President-elect Donald Trump's precedent-shattering approach to press relations has set a new tone in the media.
Executives and business leaders from all industry sectors who sit for interviews should know that they will now face a more aggressive "and defensive&quo
Ryan Morris, President at Meson Capital Partners, writes on Harvest Exchange:
The term activist investor is by no means a uniform character, there are as many
Benedicte Gravrand, Opalesque Geneva for New Managers: The London-based, Swiss-born manager of the RoboCap UCITS Fund, talks to Opalesque about investing
Hedge funds have been selling big winners this year
From CNBC.com: Hedge fund managers' most popular stock to start the year has been a familiar name that is falling short in terms of performance, while the least popular companies all have been crushing the market.
Procter & Gamble
Third Point's Loeb surfs on as hedge fund washout continues
From Reuters/Nasdaq.com: Billionaire investor Daniel Loeb said on Thursday that he is still making money even as the hedge fund industry struggles.
Loeb, who oversees the $16 billion hedge fund firm Third Point LLC, sa
Tudor Jones backs AI hedge funds
From FT.com: Hedge fund magnate Paul Tudor Jones has invested in a brace of artificial-intelligence powered "quantitative" hedge funds, underscoring the increasing acceptance that the industry will need to turn more to technology and away from traditional
Komfie Manalo, Opalesque Asia: The rise of high-frequency trading in Europe, dominating over 80% of the market, has become a challenge for traditional asset managers especially when it comes to risk management, said Philippe Malaise, chairman of advisory firm
Featuring : BBL Commodities: 2017 Opportunities in Crude Oil, Refined Products and Natural Gas.Jonathan Goldberg is the Founder and Chief Investment Officer of BBL Commodities LP, an investment manager which employs a fundamental, discretionary relative value strategy focused on the petroleum complex and natural gas. Jon ha...» Watch the video
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Near Term Trend: PositiveFriday's Close: 44.73 (+ 0.79%)UPDATE: The iShares Europe ETF (IEV) appears to be in the latter stages of wave "iii" higher of a five wave sequence. Targets for this wave are just above at 44.87 and higher at 46.23. I would expect a pullback off of one of those levels to either 42.97 or 41.79 based on Fibonacci analysis.Take profits on longs at 44.87, short at 46.23 with stops on closes above 46.50 and use 42.97 as a downside target to cover shorts and go long.
Near Term Trend: Positive
Friday's Close: 44.73 (+ 0.79%)
UPDATE: The iShares Europe ETF (IEV) appears to be in the latter stages of wave "iii" higher of a five wave sequence. Targets for this wave are just above at 44.87 and higher at 46.23. I would expect a pullback off of one of those levels to either 42.97 or 41.79 based on Fibonacci analysis.
Take profits on longs at 44.87, short at 46.23 with stops on closes above 46.50 and use 42.97 as a downside target to cover shorts and go long.


text:
Juventus director of sport Fabio Paratici watched Brazil-Scotland on Sunday in London to keep tabs on Santos striker Neymar.
The 19-year-old put on a virtuoso display scoring both goals in a handsome 2-0 victory for Mano Menezes' young side.
Juventus already had their scouts track Neymar's progress at the Sub 20 tournament in Peru earlier this year.
Il Corriere dello Sport understands representatives from Barcelona, Chelsea and both Manchester clubs were also in attendance.
Neymar is expected to cost as much as €30m and very nearly joined Chelsea in the January transfer window.
Tickets for the Champions League final between Juventus and Real Madrid are still on sale with reseller Viagogo - Click to find out more


text:
NYC Subway Performer Will Blow Your Mind
Added on February 15 2017
This video of New York-based singer Mike Yung has been around for just a few months, but when it went to the top of Reddit.com subsection /r/videos, it really started getting traction! Mr. Yung even noticed the post and shared his side of the story for all to appreciate how difficult a career he has had, and why, with such amazing talent, he is still busking in the New York City subway with his small band.
After reading THAT, you really don't want to miss out on his amazing performance of Sam Cooke's "A Change Is Gonna Come":
If you can't get enough of Mike Yung, another Reddit user has shared a unch more videos to look at:
Such talent, in such an unexpected place!
- All videos
- Interviews
- Events
- Shows
- Holidays
Added on May 23 2017
Lana Del Ray Releases new 'Lust For Life' Video ft. The Weeknd
The retro-looking video sees the two dancing atop the "Hollywood" sign.
Added on May 19 2017
She Conquered her Stage Fright in a BIG way
Britain's Got Talent can be a very intimidating stage to perform on.
Added on May 19 2017
Harry Styles Carpool Karaoke!
Harry Styles really nailed it, this is sure to become a CLASSIC James Corden Carpool Karaoke episode.
Added on May 18 2017
Watch Harry Styles Perform 'Carolina' on the Late Late Show
His self-titled debut album was released last week to popular acclaim.
Added on May 16 2017
New Video: 'Malibu' by Miley Cyrus
Miley dancing on the beach will give you a bad case of wanderlust!
Added on April 27 2017
Amazing: Ricky Martin dances 'Footloose' in Lip Sync Battle!
Kate Upton has got nothing on RICKY!!
Added on April 19 2017
TB1's Playoff Crash Course
Everyone likes to feel involved in the Habs playoff fever! TB1's got you covered with a crash course.
Added on February 13 2017
Katy Perry - 'Chained To The Rhythm' Lyric Video
Her new video is the cutest! You need to watch it.
Added on February 07 2017
Emma Stone: 'I'm not a highly choreographed person.'
The 'La La Land' star revisited her awkward Golden Globes moment with Jimmy Kimmel.
Text to 92925
To get the 24 hour forecast
For the last 5 songs played


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tag:blogger.com,1999:blog-3304214645369805060.comments2017-05-23T14:19:24.142-05:00Saint Louis Catholicthetimmanhttp://firstname.lastname@example.com:blogger.com,1999:blog-3304214645369805060.post-80249692261840395352017-05-23T13:24:13.125-05:002017-05-23T13:24:13.125-05:00Most apropos.Most apropos.M. Prodigalhttp://email@example.com:blogger.com,1999:blog-3304214645369805060.post-48540603543511005022017-05-23T09:57:29.228-05:002017-05-23T09:57:29.228-05:00I do buy the free exercise argument, but first the...I do buy the free exercise argument, but first the freedom of speech and assembly. thetimmanhttp://firstname.lastname@example.com:blogger.com,1999:blog-3304214645369805060.post-48553626990926903792017-05-23T07:56:20.127-05:002017-05-23T07:56:20.127-05:00"In a country governed by the U.S. Constituti..."In a country governed by the U.S. Constitution, this ordinance would be struck down on quickly, beginning with a TRO."

So, in your mind, what part of the Constitution is triggered by this ordinance? It doesn't sound like you buy the free exercise argument, but it sounds like that is the main point of contention for the Archdiocese (i.e., the ordinance prohibits an employer from firing or refusing to hire someone based on their decision to have an abortion, and the Church must be free to fire/refuse to hire those who choose not to live in accordance with its mission.) But I don't see how the 5th or 14th Amendments are triggered here, since the ordinance does not actually say anything with respect to abortion regulations.

I've always understood the term "religious liberty" to refer to one's freedom to true worship of God, so I do not understand the issue with this language. What else should it be called? Even if the result is that opinions differ regarding what is true worship, I am not sure that the government is authorized to go any further (and I am pretty sure most of us do not want it to go any further).
yoobeehttp://firstname.lastname@example.com:blogger.com,1999:blog-3304214645369805060.post-89587417978311323172017-05-19T16:48:34.571-05:002017-05-19T16:48:34.571-05:00Thanks for pointing out the criticism of St. Franc...Thanks for pointing out the criticism of St. Francisco's account of our Lady's mercy. I suppose that, if one wanted to give Pope Francis the benefit of the doubt, we could blame the author of the homily. Assuming, with fair reason, that he doesn't write all of his homilies. But still, the buck falls on him and, I assume with fair reason, that he is not much interested in corrections to what he's said. Fr. Andrewhttp://email@example.com:blogger.com,1999:blog-3304214645369805060.post-9071406429122962462017-05-19T10:22:40.909-05:002017-05-19T10:22:40.909-05:firstname.lastname@example.com:blogger.com,1999:blog-3304214645369805060.post-54384198177956925302017-05-17T19:06:04.356-05:002017-05-17T19:06:04.356-05:00Thanks for the feedback, Timmman. I suspected tha...Thanks for the feedback, Timmman.

I suspected that might be the case.Athelstanehttp://firstname.lastname@example.com:blogger.com,1999:blog-3304214645369805060.post-68209701987359465232017-05-17T17:51:34.984-05:002017-05-17T17:51:34.984-05:00Athelstane, The person you are referring to is a ...Athelstane,

The person you are referring to is a loon and I will not give him any attention by linking. Story false and based upon the delusions of his mind. I can't get more specific without committing detraction, though if the word is out enough I could say plenty to defend the good name of those whom he slanders.

Pax.thetimmanhttp://email@example.com:blogger.com,1999:blog-3304214645369805060.post-62224786136279683152017-05-17T15:41:34.354-05:002017-05-17T15:41:34.354-05:00I read that article as well. Spot on! I am, howe...I read that article as well. Spot on!

I am, however, very dejected, disconcerted, dismayed, etc, at the state of our Church and our nation. Francis' destruction of our Faith; the massive war on Trump, duly elected by the People. It's becoming too much. (At least, somehow, MM got his marching orders and is putting a better product on the field. That's something in all this mess, eh?)

I continue to pray for and actively seek employment for myself, in addition to all that.

God bless and keep you and all the firstname.lastname@example.com:blogger.com,1999:blog-3304214645369805060.post-30852347368478619492017-05-16T14:13:15.162-05:002017-05-16T14:13:15.162-05:00A wonderful article!!A wonderful firstname.lastname@example.com:blogger.com,1999:blog-3304214645369805060.post-28711089670125019692017-05-07T07:08:26.084-05:002017-05-07T07:08:26.084-05:00for a better perspective: http://www.italian-renai...for a better perspective:
http://email@example.com:blogger.com,1999:blog-3304214645369805060.post-85300377132532069712017-05-05T16:27:49.565-05:002017-05-05T16:27:49.565-05:00Is that a very bad reproduction of the Last Judgem...Is that a very bad reproduction of the Last Judgement? Or is there some reason there is purple that vaguely suggests a human face that is superimposed? What is going on there? Anyone?christinehttp://firstname.lastname@example.com:blogger.com,1999:blog-3304214645369805060.post-37731375700186769102017-05-03T14:42:16.827-05:002017-05-03T14:42:16.827-05:00We will pray for you over in St. Joseph. It is sa...We will pray for you over in St. Joseph. It is sad when the general population of a city named after a saint does not realize the glory of that saint. Didn't Belloc say something like, "Thank God we live in a world so easy to depart ourselves from."
Alison
firstname.lastname@example.com:blogger.com,1999:blog-3304214645369805060.post-69603060332036323452017-04-29T13:27:51.648-05:002017-04-29T13:27:51.648-05:00Wow ...how beautiful this is to read. The Institut...Wow ...how beautiful this is to read.
The Institute ...and their consecration to Mary Immaculate daily..I forgot about this myself until your post.
I must start again today to pray this daily prayer.
Thank you and God Bless !
Jeanne Hollerhttp://email@example.com:blogger.com,1999:blog-3304214645369805060.post-39561190044004997712017-04-29T08:03:41.118-05:002017-04-29T08:03:41.118-05:00"We also consecrate to thee the value of our ..."We also consecrate to thee the value of our good actions, past, present, and future, leaving to thee the entire and full right of disposing of us and all that belongs to us. "

Those were some of my first thoughts during the Shrine fire...PMKDhttp://firstname.lastname@example.com:blogger.com,1999:blog-3304214645369805060.post-80743756987863969332017-04-26T10:00:22.664-05:002017-04-26T10:00:22.664-05:00Thanks!Thanks!thetimmanhttp://email@example.com:blogger.com,1999:blog-3304214645369805060.post-67430565100043251422017-04-26T07:48:58.993-05:002017-04-26T07:48:58.993-05:00" It's a wonder, yet so typical, that it ..." It's a wonder, yet so typical, that it took me this long....It's as though Our dear Mother is rounding up a straggler, the rather dim-but-lost-without-her child, hurrying him into the storm cellar before the mother of all tornados hits the house."

You utterly nailed it....I felt the exact same stirring(?)/urgency(?) late last year...my husband (10 year convert :) and I made out consecration this past Feast of the Immaculate Conception. It has made a TREMENDOUS difference....just be aware; you summon the full attention of the enemy when you do this.

also, if you have not done this yet, DO BY ALL AND ANY MEANS read "True Devotion to Mary" by St. Louie de Montfort as part of your preparation....I found it absolutely necessary in adequately understanding her, and the gravity of what I (we) were about to do.

God bless you....you have my email@example.com:blogger.com,1999:blog-3304214645369805060.post-25914742174758285222017-04-19T08:15:16.947-05:002017-04-19T08:15:16.947-05:00They really should give lawyers an automatic disqu...They really should give lawyers an automatic disqualification. No trial lawyer who isn't insane would allow us to be impaneled firstname.lastname@example.com:blogger.com,1999:blog-3304214645369805060.post-26092971525916959832017-04-19T08:04:26.422-05:002017-04-19T08:04:26.422-05:00God bless you in your consecration to Our Mother. ...God bless you in your consecration to Our Mother. Frankhttp://email@example.com:blogger.com,1999:blog-3304214645369805060.post-70416604916257834342017-04-19T01:06:10.371-05:002017-04-19T01:06:10.371-05:00Timman, what a great t hing to do. I will definite...Timman, what a great t hing to do. I will definitely pray for you. Please pray for me that Our Lady will give me the courage and grace to do the same.
Noel Brownhttp://firstname.lastname@example.com:blogger.com,1999:blog-3304214645369805060.post-52458843928052787312017-04-18T15:07:02.582-05:002017-04-18T15:07:02.582-05:00I promise to pray for you in your preparation in t...I promise to pray for you in your preparation in thanksgiving
for those who prayed for me when I made mine.
What a glorious day to make the total consecration
 to Our Blessed Mother!A Seminarian's firstname.lastname@example.com:blogger.com,1999:blog-3304214645369805060.post-52823719411966565192017-04-16T01:28:50.950-05:002017-04-16T01:28:50.950-05:00Well, thank you Tim, but one of the Canons at SVDP...Well, thank you Tim, but one of the Canons at SVDP did that earlier before the Easter Vigil. Christ forgave Peter for denying Him, Not for being an atonal, raspy-voiced goofball. Aren't those all mortal sins? Have a Blessed and joyful Easter Timman, and never stop your blog. Noel email@example.com:blogger.com,1999:blog-3304214645369805060.post-33516477575651964702017-04-15T09:23:40.887-05:002017-04-15T09:23:40.887-05:00Oh, Nöel, Christ forgave Peter after he denied Him...Oh, Nöel, Christ forgave Peter after he denied Him. And I forgive you. 😀

Happy Easter!thetimmanhttp://firstname.lastname@example.com:blogger.com,1999:blog-3304214645369805060.post-47290405255402840082017-04-15T01:14:41.525-05:002017-04-15T01:14:41.525-05:00When they heard him try to sing did they know...th...When they heard him try to sing did they know...that he couldn't sing?. Have a joyful Easter Tim. Noel email@example.com:blogger.com,1999:blog-3304214645369805060.post-67589561567823287212017-04-14T20:53:29.740-05:002017-04-14T20:53:29.740-05:00If the Christ was crucified for speaking the truth...If the Christ was crucified for speaking the truth, then what makes you think that you will not be crucified? JBQhttp://email@example.com:blogger.com,1999:blog-3304214645369805060.post-53078072281902559792017-04-14T10:14:32.049-05:002017-04-14T10:14:32.049-05:00Please inform the St. Louis review about this. Mor...Please inform the St. Louis review about this. More Catholics may want to attend who haven't read the magazine. Thank you Jesus for giving us this opportunity to attend a Latin email@example.com


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Kids wanted to hit Subway to get a normal taste of home food for a change instead of what we found in Town elsewhere. Just as expected and friendly bilingual staff. No other customers when we went for dinner. As expected good food.
地址: 32 Principale Rue N, Sutton, Quebec J0E 2K0, Canada
地点: 加拿大 > 魁北克 > Sutton
电话号码: +1 450-538-4445


text:
JVC KD-G153EY Owner's Manual
Product Reviews
There are currently no product reviews.
Reviews of our other manuals
Haakon MacCallum - 2010-02-25
This is the only place I found this manual. Manual is complete and well worth the price. Thanks.
Karl Schmitz - 2011-02-18
I own two of these models. Wonderful to be able to get the operating manual for this radio. Thanx!
Fred Hofman - 2011-07-04
Good ligible copy. I do not use this player any more and I am giving it away to people in Senegal, so I needed a manual including the FR-version. (I only had NL and EN). This will help them much, against modest cost and effort. Thanks.
Customers who bought this product also purchased...
Text excerpt from page 11 (click to view)
What you can do with RDS
RDS (Radio Data System) allows FM stations to send an additional signal along with their regular programme signals. By receiving the RDS data, this receiver can do the following: � Programme Type (PTY) Search (see page 10) � Standby Reception of Traffic Announcement �TA (see the following) or your favorite programme (PTY) (see pages 12 and 18) � Tracing the same programme automatically �Network-Tracking Reception (see page 12) � Programme Search (see page 18)
3 Repeat steps 1 and 2 to store
other PTY codes into other preset numbers.
4 Finish the procedure.
Using the standby receptions
TA Standby Reception
TA Standby Reception allows the receiver to switch temporarily to Traffic Announcement (TA) from any source other than AM. The volume changes to the preset TA volume level (see page 18).
Storing your favorite programmes
You can store six favorite programme types. Preset programme types in the number buttons (1 � 6):
To activate TA Standby Reception
The TP indicator either lights up or flashes.
1 Perform steps ~ and Ÿ on page 10 to
select a PTY code.
2 Select the preset number (1 � 6) you
want to store into.
� If the TP indicator lights up, TA Standby Reception is activated. � If the TP indicator flashes, TA Standby Reception is not yet activated. (This occurs when you are listening to an FM station without the RDS signals required for TA Standby Reception.) To activate TA Standby Reception, tune in to another station providing these signals. The TP indicator will stop flashing and remain lit.
To deactivate the TA Standby Reception
The TP indicator goes off.
Ex.: When �ROCK M� is selected
We provide manuals to wide range of devices, including:
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text:
Design & UX
ArticleBy Jennifer Farley
Create A Better, More Realistic Drop Shadow In PhotoshopBy Jennifer Farley
You can add a simple drop shadow to any object on its own layer in Photoshop by clicking on the "Add a layer style" button at the bottom of the palette and choose Drop Shadow from the drop down menu. This opens up the Layer Style dialog box and you can choose your drop shadow settings from there. Simple. The drop shadow adds a little extra dimension to objects but it doesn't always look particularly realistic. Most objects such as paper or photographs do not always lie completely flat so let's take a look at how you can create a more realistic drop shadow with of a hint of a curl.
- Open up a photograph that you want to apply the effect to.
- Create a new document which is larger in width and height than your photograph.
- Now draw a shape like the one below which will eventually become the shadow under the photograph. You get the best results using the Pen Tool here, but you can also make the shape using a Brush if you don't feel happy using the Pen. The shape should be slightly bigger than your photograph.
- Blur the edge of the shape by using Filter > Blur >Gaussian Blur. I used a radius setting of 4 so that you get something that looks like this.
- Drag your photograph over the curl drop shadow. They should be on separate layers, with the photograph on the layer above the drop shadow.
- Once the photograph is placed over the drop shadow, select the drop shadow layer and Press Ctrl + T (windows) or Cmd + T (Mac) to Free Transform. You may need to scale the curl drop shadow up or down or even skew it, depending on the effect you want to achieve. Hit Enter/Return to commit the transformation.
- At this stage the shadow is too dark. Make sure the Shadow layer is selected and the reduce the opacity to about 40% to make it less obtrusive. If the shadow looks too big, or the picture looks like it is floating too far above the shadow, just drag the shadow so it is sitting mostly hidden under the photograph.
- Once you've made your drop shadow you can create different effects by transforming it. For example you can give the impression of lifting up three corners of the photo by offsetting the drop shadow horizontally and enlarging it vertically.
- You can also give the impression of lifting the photo higher off the "page" or surface by showing a larger but softer shadow. Or you can make it look like the top of the photo is lifting by shortening the shadow vertically.
- Finally, tilt the photograph and shadow together for a more natural look. Select both layers in the layers palette, then press Ctrl + T or Cmd + T to free transform. Then bring your mouse close to one of the corner so that it turns into a double curved arrow and drag around one corner. Press Return/Enter to commit the transformation.
Ta da! So it does involve a little more work than a simple layer style but you can certainly achieve some nice effects by playing around with it.
Inspirational UI Design Ideas for Your Next Website Project
Simon Codrington illustrates some stunning UI design ideas using CSS animation and gradients to inspire your creativity for your next...
Design & UX
New Podcast: #Ep1 - Designing for Scale: Inside Atlassian's Design Teams
True North Design Podcast: Ben Newton talks to the Atlassian Design Team about how design – and the teams behind it – can successfully...
Inspirational UI Design Ideas for Your Next Website Project
Simon Codrington illustrates some stunning UI design ideas using CSS animation and gradients to inspire your creativity for your next website project.
1h 19m
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Kray Mitchell, May 19


text:
12085, NY Rent to Own Homes
|157 Listings Found
-250-2261/917-548-3518 for showing, seller financing information & any questions. Jean Singleton has this 6 bedrooms / 3 bathroom
129 Western Ave, Altamont, NY, 12009Details »
$995 / two bedrooms - 925 feet - 2 BEDROOMs - Nice, State of the art in quiet wooded apartment building. Property Address. 3158 Carman...
3158 Carman Road, Schenectady, NY, 12303Details »
the park the lease has 977yrs left, with $1a year.
Schenectady, NY, 12303Details »
are not open to lease to own offers.) www.albanypinebush.infoShowings by appointment only. Adress: 13 Pines
13 Pines CT Albany, Albany, NY, 12203Details »
Shane Mahar reveal call info 2757 Broadway, Rotterdam, NY 12306 MULTIPLE LISTING SERVICE No: 201406359 Multi Family members...
Schenectady, NY, 12306Details »
Can Be Rented for $1,850/mo.
1 Laurel Lane 1700 Square, Schenectady, NY, 12304Details »
bedroom on attic that the second unit use so rent can be a bit higher. MUST SELL BRING AN OFFER...IS SOLD
606 Lansing St, Schenectady, NY, 12303Details »
basic star and are based on a $77,200 assessment, which can be challenged in may - you can own
42 Roland Place, Schenectady, NY, 12304Details »
and are based on a $77,200 assessment, which can be challenged in may - you can own this house & live here
42 Roland Place, Schenectady, NY, 12304Details »
I am looking for a room to rent. My name is Michelle and i am years old. I am taking classes
Schenectady, NYDetails »
selling home goods outdoor goods toys school supplies . Business for sale property for lease . any
Schenectady, NYDetails »
Kings Road Industrial Park phase power New overhead and entry doors Soaring ceilings Open (no beams in center) Loading Docks Available...
Schenectady, NYDetails »
to lease by sale. Rents are under market worth. 22 % cap fee at present rental charges. Car parking in rear
Schenectady, NY, 12307Details »
; 7 houses and one store/mini-market. Shop has 15yrs left on lease. All systems are occupied except 1
518-281-5336 862-864 Albany St, Schenectady, NY, 12307Details »
return.Basement is also rented @ $550.00, great for 2nd income opportunity. SELLER IS MOTIVATED BRING
217 Victory Avenue, Schenectady, NY, 12307Details »
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text:
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??Fear of a lack of regulation isn't a reason to agitate to ban it altogether, it's a reason to agitate for regulation. Attempt to engage in keeping on your own in the conflict while continuing to engage the other celebration with concerns that can help to settle the problem. Sirmione was became a Spa Town when in August 1889, a diver came from Venice to lay pipes on Lake Garda's clayish seabed.
And now let's take a closer look at the most important tips you'll need to follow so that you can enjoy your trip to Scotland as much as possible. Previous advert Next advert Save Remove Edit Print Email Report Ref #: AD 00A AIO Views: 0 Tweet Chestnut gelding 143' event prospect Call 07816349712 Email advertiser Could you recognise a bogus advert. You are responsible for returning the items in a re saleable condition at your own cost unless the goods are fault or mis described.


text: Petr Petr is 22 years old male from Slavkov U Brna, Czech Republic. He is interested in meet new people. 22, male, Slavkov u brna Likes: 133x Facebook profile Who s/he liked? Send message Favorite May she/he ask you for a date? Never Maybe Sure Relationship: ShowSexuality: ShowHeight: ShowWeight: ShowBody type: ShowEye color: ShowHair color: ShowLiving: ShowKids: ShowSmoking: ShowDrinking: Show Report photo Sign up to see all photos Facebook Twitter Google+ Pinterest Similar users Dijon 22, Springfield Gardens 168 Jonny 20, Missoula 195 Michael 21, Pinellas Park 63 Kylar 20, Champaign 121 Pablo 23, Smyrna 271 Kurt 25, Skowhegan 50 Brady 23, Pisgah 56 Andie 25, San Antonio 33 Simon 19, Lake Havasu City 176


text:
|Card draw simulator
Odds: 0% – 0% more
|Derived from
|None. Self-made deck here.
|Inspiration for
|None yet.
the BEAST 25
The main objective of this deck is to use your guardian ability and your removals to force your opponent to split damage. Try to deal as much damage as possible every turn. Always keep a resource or two for your removal and equip some upgrades on every character.
Tactical Mastery + We Have Them Now - with this combo, if you control the battlefield and have enough resources, you can do more than 8 damage and your opponent won't be able to block it.
Mos Eisley Spaceport - Tatooine + Hunker Down - with this combo, when one of your characters is maxed on shields, you can use the battlefield to reequip Hunker Down on another character and gain a resource.
Commanding Presence's combined with is a really powerfull way to prevent your oponnent from rerolling or removing your Most oponnent will be surprised since they're probably thinking you'll combine it with or
How to use some cards:
Squad Tactics - if your opponent has two / dice you want to remove, you can activate both of your guardian characters at once.
The Best Defense... - don't be scared to split some damage on Captain Phasma - Elite Trooper to keep your guardian characters alive longer
Disarm - I usually use Disarm to remove cards such as Sith Holocron especially if I have a useless + left
Aftermath - drop this support early in the game when your opponent doesn't have any you want to remove
Tactical Mastery - if you have , you can turn your to / and resolve them immediately.
By the way, don't forget Guavian Enforcer's and Imperial Discipline's ability
Use the redeploy weapons to your advantage and enjoy ;) - Please leave feedback in the comments if you enjoyed or you would replace anything!
|5 comments
Imperial discipline can't be played on guavian enforcer its red character only. Also bait a switch makes guavian have 5 damage sides and also works on trooper and phasma. I'm not keen on the 1 copy of aftermath its a big ask to draw it early and will only net you 2 resources.


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Question about Computers & Internet
Posted by minoukeb on
Well as i know its either the hard driver is dead
or the windows is corrupted.
so in case one you will need to replace the hard drive.
but in case two you will need to reinstall windows
so lets do the reinstallation first and see if that is gonna work
you know first you will need to go to the boot menu and make the CD drive the first boot device and insert your windows CD and then start the installation process.
by the way if u dont want to remove everything from your computer (due to installing windows) then when u have the installation options (enter, R -key or F3- key) select enter.
in the next list of options (select the repair option now).
that should fix your issue without removing your data
i hope that will help
Posted on Sep 03, 2008
Try pressing F8 while it's booting up, then choose last known good configuration and press enter,and then when the system will load or if not do same again but this time press safe mode and then when the minimum of drivers load click on your account and try system restore to a previos date.
Posted on Sep 03, 2008
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Posted on Jan 02, 2017
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