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Complement C3 and C4 play key roles in the main physiological activities of complement system, and their deficiencies or over-expression are associated with many clinical infectious or immunity diseases. A two-stage genome-wide association study (GWAS) was performed for serum levels of C3 and C4. The first stage was conducted in 1,999 healthy Chinese men, and the second stage was performed in an additional 1,496 subjects. We identified two SNPs, rs3753394 in CFH gene and rs3745567 in C3 gene, that are significantly associated with serum C3 levels at a genome-wide significance level (P = 7.33×10−11 and P = 1.83×10−9, respectively). For C4, one large genomic region on chromosome 6p21.3 is significantly associated with serum C4 levels. Two SNPs (rs1052693 and rs11575839) were located in the MHC class I area that include HLA-A, HLA-C, and HLA-B genes. Two SNPs (rs2075799 and rs2857009) were located 5′ and 3′ of C4 gene. The other four SNPs, rs2071278, rs3763317, rs9276606, and rs241428, were located in the MHC class II region that includes HLA-DRA, HLA-DRB, and HLA-DQB genes. The combined P-values for those eight SNPs ranged from 3.19×10−22 to 5.62×10−97. HBsAg-positive subjects have significantly lower C3 and C4 protein concentrations compared with HBsAg-negative subjects (P<0.05). Our study is the first GWAS report which shows genetic components influence the levels of complement C3 and C4. Our significant findings provide novel insights of their related autoimmune, infectious diseases, and molecular mechanisms.
Author Summary
The complement system plays important roles in the innate and adaptive immune functions. C3 and C4 participate in almost all physiological activities and activated pathways as key complement members and host defense proteins. Identifying the genes that influence serum levels of C3 and C4 may help to elucidate the factors and mechanisms underlying the complement system. The genome-wide association studies (GWAS) have shown great success in revealing robust associations in both quantitative and qualitative traits. In this study, we performed a two-stage GWAS in a large cohort from the Chinese male population to examine the roles of common genetic variants on serum C3 and C4 levels. Our research identified genetic determinants associated with the quantitative levels of C3 and C4. Overall, our study highlights an intricate regulation of complement levels and potentially reveals novel mechanisms that may be followed up with additional functional studies.
Citation: Yang X, Sun J, Gao Y, Tan A, Zhang H, Hu Y, et al. (2012) Genome-Wide Association Study for Serum Complement C3 and C4 Levels in Healthy Chinese Subjects. PLoS Genet8(9): e1002916. https://doi.org/10.1371/journal.pgen.1002916
Editor: Takashi Gojobori, National Institute of Genetics, Japan
Received: February 16, 2012; Accepted: July 6, 2012; Published: September 13, 2012
Copyright: © Yang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was partially supported by grants from the National Natural Science Foundation of China (81060234, 30945204, 30360124, 30260110), Key Program and University Talents Highland Innovation Team of Guangxi (2012012D003, GJR201147-09), Chairman Science and Technology Fund and Tackle Program of Guangxi (1116-03, GKG1298003-07-01), Guangxi Science Fund for Distinguished Young Scholars (2012GXNSFFA060009), Guangxi Provincial Department of Finance and Education (2009GJCJ150), intramural funding from Fudan-VARI Center for Genetic Epidemiology, and intramural funding from Fudan University Institute of Urology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
The complement has been recognized as one pivotal part of innate and adaptive immune system, and it had three well-known physiologic activities, including host defense against infection, bridging interface between innate and adaptive immunity, and disposal of waste immune complexes or apoptotic cells [1], [2]. There are approximately 30 serum complement proteins, which can be activated by classical, alternative, and lectin pathways [3]. Among these complement members, C3 and C4 are almost involved in all physiological activities and activated pathways, and exert their powerful roles as host defense proteins [4]. Their abnormal expression, especially, complement deficiency and dysfunction, is associated with the pathogenesis of numerous inflammatory and autoimmune disorder diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis, asthma [1], [5]. C4 deficiency also has been reported to be associated with SLE, immune complex glomerulonephritis, virus infection, regardless of ethnicity background [6], [7], [8].
Both Serum C3 and C4 levels are heritable traits even in individuals without immune diseases such as SLE. Recent reports also showed that the heritability for serum C3 and C4 were 39.6% and 45.4%, respectively, based on Bayesian variance components model [9], [10]. Therefore, it is important to identify the genetic loci which influence the serum levels of C3 and C4. In this study, we carried out a two-stage Genome-Wide Association Study (GWAS) to identify novel loci that are associated with the serum levels of C3 and C4 in a healthy Chinese male population of 3,495 subjects.
Study samples
A total of 2,012 men from the Fangchenggang Area Male Health and Examination Survey (FAMHES) participated in the stage 1 of GWAS study as healthy volunteers. The FAMHES project was conducted in Fangchenggang city, Guangxi, southern China in 2009. A total of 4,303 Chinese men ranged from age 17 to 88 years-old were recruited [11]. The subjects used in our stage 1 were limited to age 20 to 69 years-old, and were all self-reported southern Chinese Han ethnicity. The replication subjects in the stage 2 included 1,496 men age 20 to 70 years-old, who were recruited in conjunction with health examinations that were performed at three collaborating hospitals in Guangxi, China.
Written informed consents to participate in the present study were obtained from all of the subjects. Standardized health questionnaires were then used through a face-to-face interview conducted by trained physicians. Collected data included demographic, lifestyle characteristics (smoking, alcohol consumption), health status, family history, and medical histories. The subjects who self-reported with diabetes mellitus, coronary heart disease, stroke, hyperthyroidism, rheumatoid arthritis, and tumors were excluded from the study population. The detected samples with abnormal liver function (ALT) were also excluded. The study was approved by the Ethics and Human Subject Committee of Guangxi Medical University.
Measurement of complement C3 and C4
Overnight fasting venous blood specimens were drawn between 7:00 and 10:00 am, and serum samples were extracted and stored at −80°C, until required for detection in the laboratory. Both serum C3 and C4 were measured with Immunoturbidimetric methods on the HITACHI 7600 biochemistry analyzer (Hitachi Corp, Tokyo, Japan), using complement C3 and C4 assay kits (Zhicheng Bio Company, Shanghai, China), and their inter-assay coefficients of variation were 2.1% and 2.5%, respectively.
SNP genotyping
Two different platforms were used for SNP genotyping. The Illumina Omini one platform was used for the genome-wide assay of samples in stage 1. For SNPs that were followed in the 2nd stage, the iPLEX of Sequenom platform was used for genotyping (Sequenom, Inc., San Diego, CA). Polymerase chain reaction (PCR) and extension primers were designed using MassARRAY Assay Design 3.1 software (Sequenom, Inc., San Diego, CA). Genotyping procedures were performed according to the manufacturer's iPLEX Application Guide (Sequenom Inc. SanDiego, CA). All genotyping reactions were performed in 384-well plates. Each plate included a duplicate for three or four subjects selected at random, as well as six to nine negative controls in which water was substituted for DNA. The average concordance rate was 99.8%.
CNV analysis for C4 gene
To evaluate the C4 copy number variations (CNV), quantitative PCR (qPCR) was performed using SYBR green chemistry on the 100 randomly selected subjects from Stage 1 population. Three pairs of specific primers were designed at the front, middle rear position of C4 gene. Two pairs of internal primers based on RPP14 and ALB genes were selected to normalize the nonspecific error. Relative gene dosage determination was carried out using an ABI 7900 Real time PCR System. Total 12 µl PCR reaction mixture contained 3 µl free water, 6 µl 2×SYBR (ABI, Part no. 4304886), 1.8 µl primers, and 1.2 µl genomic DNA template. The delta-delta Ct method was used to calculate the copy numbers of C4 gene. The average C4 copy number was set at 4 based on previous reports.
Statistical analysis
Quality Control (QC) procedures were first applied to 2,012 individuals that were genotyped using the Illumina Omni one platform. A total of 1,999 individuals passed the call rate of 95% and were used in the final statistical analysis. We then applied the following QC criteria to filter SNPs: P<0.001 for the Hardy-Weinberg Equilibrium (HWE) test, minor allele frequency (MAF) <0.01, and genotype call rate <95%. A total of 709,211 SNPs remained in the final analysis. The IMPUTE computer program was then used to infer the genotypes of SNPs (e.g. SNPs catalogued in Hapmap Phase II CHB population release #24) in the genome that were not directly genotyped [12]. A posterior probability of >0.90 was applied to call genotypes that were imputed from IMPUTE software. A total of 1,940,245 SNPs remained in our final analysis after applying the same QC criteria, as mentioned above.
Serum C4 levels were logarithmic transformed to normalize the distribution. The associations of the SNPs with serum C3 and C4 levels were evaluated using a linear regression model assuming additive effects of the alleles (0, 1 and 2). In the regression models, the age, logBMI were adjusted as covariates for both C3 and C4, and smoking also adjusted for C3.The PLINK software package was used to perform this statistical analysis [13]. The EIGENSTRAT software was applied for the evaluation of population stratification by a principal component approach [14]. The top two eigenvectors were adjusted as covariates in the linear regression analysis. Quantile-Quantile plots were generated using R package. For regions with multiple SNPs that were significant at a genome-wide significant level of 5×10−8, a stepwise (forwards - backwards) regression modeling was performed to select the independent SNPs to be confirmed in the 2nd stage. Firstly, the most significant SNP within each of the associated region with C3 (1q21.3 and 19p13) and C4 (MHC region in 6p21.3) was entered into the linear regression model. Secondly, the step-wise procedure iteratively added SNPs (forwards) that reach genome-wide significant level in the single SNP analysis (with adjustment of covariates). A SNP remains in the model if goodness-of-fit (the Arkaike Information Criterion (AIC) metric) improves. A SNP that is already in the model can also be removed if the AIC improves by doing so. The stepwise procedure was performed by SAS 9.2 (Cary, NC). The combined analysis of two-stage data was performed using a linear regression, adjusting for the covariates and stage information. ANOVA analysis was used to evaluate the difference of serum C4 levels among the varied C4 gene dose groups.
General subjects characters
The first stage was composed of 1999 healthy Chinese men, and the second stage with 1496 male subjects. No significant difference was found between samples of the first and the second stage (Table 1) regarding to the mean age, smoking distribution and mean body mass index, P>0.05, respectively. The frequency distribution of C3 and C4 levels among the stage 1 healthy population were shown in the Figure S1. An analysis of the correlation between serum levels of C3 and C4 revealed a significantly positive relationship (r = 0.521, P<0.01).
In stage 1, limited population stratification was observed (Figure S2). In addition, we did not observe any evidence for the systematic bias of the association for either C3 or C4 phenotype, as indicated by the Quantile-Quantile (Q-Q) plots (Figure S3). The inflation factor was estimated to be 1.046 and 1.054 for C3 and C4, respectively.
GWAS for serum C3 levels
For C3 level, there are two genomic loci that were significant at a P-value cutoff of 5×10−8, including one loci on 1q31.3 and one loci on chromosome 19p13.3, respectively (Figure 1 and Figure S4). For the region on 1q31.3, a total of four SNPs reached a P-value cutoff of 10−8. Rs3753394 was the only SNP that remained in the stepwise model selection procedure. Therefore, only rs3753394 was selected to be followed up in stage 2. For the region on chr19p13.3, the only SNP (rs3745567) that reached a P-value of 5×10−8 was followed in stage 2. In stage 2, both rs3753394 and rs3745567 were confirmed to be significantly associated with C3 levels at a P cut-off of 0.025 (Bonferroni correction of 2 tests) (P = 1.08×10−3 and P = 3.58×10−4, respectively). The combined analysis of stage 1 and stage 2 data revealed highly significant association with C3 level for rs3753394 and rs374567 (P = 7.33×10−11 and P = 1.83×10−9, respectively) (Table 2). The estimated decrease for C3 level for rs3753394 was 0.05 g/l for each additional T allele (SE = 0.01). For rs3745567, the estimated increase for C3 level was 0.08 g/l for each additional T allele (SE = 0.02). In addition, the proportion of variability in the C3 level explained by the two SNPs was 59.0% (R2 = 0.59) in our multivariate linear regression model.
X-axis shows chromosomal positions. Y-axis shows –log10 P-values from linear regression adjusted for age, smoking, and logBMI. The horizontal solid line indicates the preset threshold of P = 5×10−8.
GWAS for serum C4 levels
In the first stage, only one genomic locus was significantly associated with serum level of C4 at a genome-wide significant level (Figure 2). All those SNPs that reached a P-value cutoff of 5×10−8 are located on the 6p21.3 region. A total of eight independent SNPs were selected based on the stepwise procedure, and were followed in the second stage (Figure S5). These significant SNPs reside in a 2-Mb MHC region on chromosome 6p21.3 (Figure 3). Two SNPs (rs1052693 with a P-value of 3.26×10−10, and rs11575839 with a P-value of 9.70×10−35) were located in the MHC class I area that include HLA-A, HLA-C, and HLA-B genes. Two SNPs (rs2075799 with a P-value of 1.08×10−49, and rs2857009 with a P-value of 3.46×10−24) were located 5′ and 3′ of C4 gene. The other four SNPs, rs2071278, rs3763317, rs9276606, and rs241428 were located in the MHC class II region that includes HLA-DRA, HLA-DRB, and HLA-DQB genes. In stage 2, all eight SNPS were confirmed to be associated with C4 level at a P-value cutoff of 0.006 (Bonferroni correction of eight tests) (P value between 3.04×10−10 and 2.53×10−48). The combined analysis also showed that these SNPs were highly significant associated with C4 levels and reached a genome-wide significant level (P value between 3.19×10−22 and 5.62×10−97) (Table 2). In addition, among the eight SNPs we identified, the range of the increase for C4 level per allele was from 0.08 g/l for rs2857009 (SE = 0.01, P = 1.43×10−22), and 0.23 g/l for rs1157839 (SE = 0.01, P = 1.22×10−54). Finally, the proportion of variability in the C4 level explained by the eight SNPs reached 80.5% (R2 = 0.805) in our multi-linear regression model.
X-axis shows chromosomal positions. Y-axis shows −log10 Pvalues from linear regression adjusted for age and logBMI. C4 level are log-transformed and fit for a normal distribution. The horizontal solid line indicates the preset threshold of P=5×10−8.
X-axis shows base positions from 30,900 Kb to 32,950 Kb. Y-axis shows –log10 P-values from linear regression adjusted for age and logBMI. C4 level are log-transformed and fit for a normal distribution. The horizontal solid line indicates the preset threshold of P = 5×10−8. The bottom panels describe all genes in the region.
Correlation of C4 gene CNV and serum C4 levels
As shown in Table 3, significant difference of serum C4 level among the varied C4 gene dose groups were observed, with a P value = 3.94×10−12. The serum C4 level was significantly higher with each more copy of C4 gene, with a Ptrend = 5.18×10−18. The lowest C4 gene dose group (N = 3, CNV = 2) only has a mean levels of 0.16±0.03 g/L of C4, which is significantly lower than the group with average number of C4 gene dose (N = 56, CNV = 4; mean value: 0.33±0.01 g/L, P = 5.06×10−6). The highest C4 gene dose group (N = 3, CNV = 7 or 8) had the mean levels of 0.48±0.04 g/L of C4, which is significantly higher than the general dose group, with a P-value of 8.24×10−5.
To our knowledge, our study represents one of the first efforts to identify genetic loci that determine the serum levels of C3 and C4 using a two-stage GWAS approach. We identified three independent genetic loci that were significant at a genome-wide significant level (P value<1×10−8) in a Chinese population of 3,495 healthy men, with a P-value range from 1.83×10−9 to 5.62×10−99. Those include SNPs rs3745567 (C3 gene) and rs3753394 (CFH-CFHR1 gene cluster) and eight independent SNPs in the ∼2 Mb MHC region on chr6 that were significantly associated with serum level of C3 and C4, respectively.
The first confirmed SNP was rs3753394, which is located within the complement factor H (CFH) and CFH-related gene (CFHR1-5) cluster on 1q31.3. CFH encodes the complement factor H that regulates complement activation on self cells by possessing both cofactor activity for the factor I mediated C3b cleavage, and decay accelerating activity against the alternative pathway C3 convertase [15], [16]. CFHRs contain similar surface recognition region of CFH and there has been evidence that they may play a role in C3b inactivation by binding with C3b [17]. rs3753394 was located in a ∼200 kb LD block region that CFH, CFHR1 and CFHR3 genes. Thus one possibility is that the genetic variants of rs3753394, may affect the expression or function of one of these three genes, which in turn may cause different modulatory activities towards complement C3 and lead to different levels of C3 proteins. We further used the Genevar (GENE Expression VARiation) database to examine whether rs3753394 is associated with gene expression of CFH and CFH-related genes. rs3753394 was found to be significantly associated with the gene expression level of CFHR1 (P = 0.0187) in 156 lymphoblastoid cell line derived from a subset of healthy female twins of the MuTHER resource [18]. No association between rs3753394 and CFH or other CFH family members was found (P>0.05). Thus one plausible hypothesis is that the observed rs3753394-C3 association may be causally related with CFHR1 expression.
The second associated SNP with serum level of C3, rs3745567, is located in the intron region of C3. Two previous candidate gene studies from Japan and UK SLE families, also showed that genetic variants located in C3 gene region significantly influence serum C3 levels in SLE patients. The reported SNPs were rs344555 in the 3′ (P = 0.007) and rs7951 in the exon 35 (P = 0.0024) of C3 [10], [19]. However, neither rs7951 nor rs344555 was significantly associated with C3 level in our healthy study subjects (P = 0.51 and P = 0.16, respectively). We then carefully examined the LD structure for CEU, CHB and JPT based on the HapMap Phase II data. The LD structure greatly differed among those three populations in C3 region (data not shown). Therefore, we may speculate that the previously reported SNP, and the SNP we identified may represent different tagging SNPs for the functional causal SNP in C3 region. The functional variants that reside in C3 gene region need to be further identified.
For C4, all the eight significant SNPs reside in a 2-Mb MHC region on chromosome 6p21. Interestingly, both the complement C4A and C4B genes whose gene products contribute to serum C4 located in the class III region of MHC on 6p21.3 [8], so the C4 locus is the most likely candidate with the MHC. Within the MHC region, the C4 locus (C4A and C4B paralogues) is the most likely candidate gene that is responsible for serum level of C4. Copy number variations of C4 gene, as well as gene size polymorphisms of C4 (short or long form) copy number, are known to determine the serum level of C4 [20], [21]. Based on our CNV analysis from the 100 subjects of the stage 1 population, we showed that the total C4 gene dosages were positively correlated with serum levels of C4. Therefore, we can't exclude the possibilities that the SNPs identified in MHC region may be in LDs with C4 gene copy number or gene size variations. To answer the above question, we evaluated the correlation between C4 gene copy number and the eight SNPs identified. The Pearson correlation coefficients between the eight SNPs and C4 copy number are moderate, with a range of 0.21 to 0.36 (Table S2). However, seven out of eight SNPs were no longer significant after adjustment for C4 copy number variation (Table S2). One SNP (rs2857009) still remained significant after adjustment for copy number variation. This suggested that although the majority of SNPs identified may be correlated with copy numbers of C4, one SNP (rs2857009) may confer independent effect on affecting the concentration of C4. The combination of C4 gene CNV and the SNP information can better explain the genetic components which influence the complement C4 variation. However, we would also like to point out that the above results are based on a relatively small sample size, future studies with a larger sample size is needed to confirm our finding.
Since the identified C4-associated SNPs were located in the MHC region, it will be interesting to know the relationship between those SNPs and known Human Leukocyte Antigens (HLA) alleles. We evaluated whether those eight SNPs and their perfect proxies (r2 = 1 based on HapMap 3 plus 1,000 genome project) tag the known HLA alleles, based on the HLA and SNP haplotype map developed by de Bakker et al [22]. However, none of the eight SNPs or their perfect proxies was found to tag the known HLA alleles in CHB population. Two reasons may potentially explain it. First, the number of individuals that were used to construct such map was small (N = 45). Therefore, haplotypes with relatively low frequencies were not detected. In a recent study, a new HLA and SNP haplotype map was available based on a relatively larger population (N = 3,000), which represented an improved haplotype map with much higher resolution [23]. However, this map was currently available for Caucasians only. Second, our study population represents a southern Chinese population. The LD structure of our population may differ from CHB population, which represents a northern Chinese population. The LD structure may even differ significantly in the highly polymorphic MHC region between CHB and our study population. Therefore, a HLA and SNP haplotype map that is specific to this study population may be more informative to infer the LD between the identified C4 associated SNPs and known HLA alleles.
Some confounding factors, such as age, smoking, BMI, and hsCRP, are predictive of the C3 or C4 levels, however, the most significant covariate for C3 is the BMI (P = 2.88×10−7) , and age for C4 (P = 5.56×10−11) in our multivariate linear model which also included novel SNPs identified in this study. Together, those variables could explain more than 90% of variance of C4 level (R2>0.90). Serum level of high-sensitivity Chronic Reactive Protein (hsCRP) levels, which is a potential confounder for the acute phase reactants C3 and C4 protein, was also available in our dataset. Further adjustment of hsCRP revealed similar results (Table S1). Considering the high infection rate of hepatitis B virus in the general Chinese population and its potential influence for complement, we furthermore carried out interaction analysis of infection-by-genotype. Although both the C3 and C4 levels in the HBsAg positive group were significantly lower than the negative group in the combined 3495 subjects (1.09±0.21 vs1.18±0.34 for C3 and 0.32±0.09 vs 0.34±0.10 for C4, P<0.05, respectively), however, no significant interaction was observed between HBsAg infection and previous identified SNPs in our multivariate linear regression model, P>0.05, respectively. The potential cause could be that the synthesis ability of complements was still normal in the liver organ.
In summary, through a two-stage GWAS of 3,495 healthy Chinese male subjects, we identified CFH and C3 loci were significantly associated with serum level of C3, and a ∼2 Mb loci on 6p21.3 region was significantly associated with serum level of C4. The selection of healthy subjects from one centralized resource and the stringent inclusion and exclusion criteria were considered as two of the advantages of our study design. Our study would contribute to the understanding of genetic components that affect individual level of complement variation. It may also shed light on the etiology and molecular mechanisms for C3 and C4 related diseases.
Supporting Information
Figure S1.
Distribution of C3 and C4 levels among the Stage 1 population. The histogram figure showing the frequency of C3 and C4 levels, respectively, and the C4 are logarithmic transformed to normalize the distribution.
Figure S2.
Principal component analysis of GWAS sample. HapMap individuals (CHB+JPT, CEU and YRI) for the first two dimensions. The plot presents the top two eigen vectors identified by principal component analysis using Eigenstrat software.
Figure S3.
Quantile–quantile plots. Quantile–quantile plot showing the distribution of expected compared to observed –log10 P for the association test results before (red circles) and after genomic control adjustment (blue circles).
Figure S4.
Association of serum C3 levels with SNPs at 1q32 and 19p13.3. The top panel presents association results in the first stage of GWAS, the middle panel describes genes in the region based on the UCSC database, and the bottom panel describes LD of SNPs in the region based on the HapMap CHB population (release 24).
Figure S5.
Association of serum C3 levels with SNPs at 6p21.3. The top panel presents association results in the first stage of GWAS, the middle panel describes genes in the region based on the UCSC database, and the bottom panel describes LD of SNPs in the region based on the HapMap CHB population (release 24).
Table S1.
SNPs associated with C3 and C4 levels from two-stage GWAS study in Chinese population, adjusting for chronic reactive protein (CRP).
Table S2.
Correlation estimates between the significant SNPs with C4 copy number variation.
We thank the local research teams from Fangchenggang First People's Hospital, Guigang People's Hospital, and Yulin First People's Hospital for their contribution to the recruitment of study subjects. We thank X.-W. Zou, H.-C. Zheng, and O. Li at the Genergy Biotechnology (Shanghai) Co., Ltd., for their assistance in the genotyping. Finally, we thank all study subjects for participating in this study.
Author Contributions
Conceived and designed the experiments: Zengnan Mo, Jianfeng Xu. Performed the experiments: Yanling Hu, Yong Gao, Aihua Tan, Linjian Mo, Xiaoling Lin, S. Lilly Zheng. Analyzed the data: Jielin Sun, Junjie Feng, Sha Tao, Seong-Tae Kim, Zhuo Chen, Ming Liao, Minzhong Tang. Contributed reagents/materials/analysis tools: Xue Qin, Tao Peng, Li Li, S. Lilly Zheng, Zengnan Mo. Wrote the paper: Xiaobo Yang, Jielin Sun. Sample collection and preparation: Xiaobo Yang, Yong Gao, Aihua Tan, Haiying Zhang, Zhengjia Liang, Deyi Shi, Zhang Huang, Xianghua Huang, Ming Liu, Qian Liu, Shijun Zhang. Review and revision of the manuscript: Xiaobo Yang, Jielin Sun, Junjie Feng, Jianfeng Xu, Zengnan Mo. Intellectual input: Zengfeng Zhang, Jeffrey M Trent.
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- 14. Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, et al. (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38: 904–909.
- 15. Pangburn MK (2000) Host recognition and target differentiation by factor H, a regulator of the alternative pathway of complement. Immunopharmacology 49: 149–157.
- 16. Rodriguez de Cordoba S, Esparza-Gordillo J, Goicoechea de Jorge E, Lopez-Trascasa M, Sanchez-Corral P (2004) The human complement factor H: functional roles, genetic variations and disease associations. Molecular immunology 41: 355–367.
- 17. Jozsi M, Zipfel PF (2008) Factor H family proteins and human diseases. Trends Immunol 29: 380–387.
- 18. Nica AC, Parts L, Glass D, Nisbet J, Barrett A, et al. The architecture of gene regulatory variation across multiple human tissues: the MuTHER study. PLoS Genet 7: e1002003 doi:10.1371/journal.pgen.1002003.
- 19. Miyagawa H, Yamai M, Sakaguchi D, Kiyohara C, Tsukamoto H, et al. (2008) Association of polymorphisms in complement component C3 gene with susceptibility to systemic lupus erythematosus. Rheumatology 47: 158–164.
- 20. Yang Y, Chung EK, Zhou B, Blanchong CA, Yu CY, et al. (2003) Diversity in intrinsic strengths of the human complement system: serum C4 protein concentrations correlate with C4 gene size and polygenic variations, hemolytic activities, and body mass index. J Immunol 171: 2734–2745.
- 21. Saxena K, Kitzmiller KJ, Wu YL, Zhou B, Esack N, et al. (2009) Great genotypic and phenotypic diversities associated with copy-number variations of complement C4 and RP-C4-CYP21-TNX (RCCX) modules: a comparison of Asian-Indian and European American populations. Mol Immunol 46: 1289–1303.
- 22. de Bakker PI, McVean G, Sabeti PC, Miretti MM, Green T, et al. (2006) A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC. Nat Genet 38: 1166–1172.
- 23. Raychaudhuri S, Sandor C, Stahl EA, Freudenberg J, Lee HS, et al. Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nat Genet 44: 291–296.

subset: commoncrawl


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Korean War Collection
This Collection includes a narrative of the Marines in Korea, and a finding aid that describes the various items available (official and unofficial records, correspondence, commendations, miscellaneous documents, photos and artifacts, and more) and their location within the Collection.
Contact the Archives if you have questions about any of the items in this collection, including how to request copies of items or view them in person.
The following narrative is taken from A Brief History of the United States Marine Corps, Marine Corps Historical Reference Series, reprinted 1964.
On 25 June 1950, the Russian-trained North Korean People's Army [NKPA] attacked the Republic of Korea [ROK]. The United Nations immediately branded the North Koreans as aggressors, and requested the United States to dispatch military assistance to the South Korean Republic. Within a month, ROK and UN troops were holding on a small beachhead [about 90 by 60 miles] around the southeastern seaport of Pusan.
On 2 July 1950, Marine Commandant General Clifton B. Cates had cabled the Far East Commander, General Douglas MacArthur, volunteering Marines for combat duty. MacArthur enthusiastically accepted this offer and persuaded the joint Chiefs of Staff to concur. The 5th Marines and MAG-33 received the assignment, and on 7 July, they became the major elements of the 1st Provisional Marine Brigade. One week later, the brigade sailed for Korea.
On 2 August, the Marines arrived in Pusan. The brigade commander, Brigadier General Edward A. Craig, had been given the temporary assignment of "plugging holes in the dike," reinforcing the defensive lines as weak spots opened up. While the ground troops were accomplishing this mission, MAG-33 had arrived in Japan, and by 3 August, two fighter-bomber squadrons were flying close air support missions from the decks of carriers. A night fighter squadron [VMF (N) -513] flew missions from Japan, and an observation squadron [VMO-6], with its helicopters and light planes, joined ground elements in Korea to provide direct support.
Within the Pusan perimeter, the Marines became "trouble shooters" for hard-pressed Army troops. On three separate occasions, the brigade counterattacked the enemy, stopped his attack, and eliminated the penetration. Several NKPA divisions were decimated. On 5 September, the brigade moved to Pusan in preparation for joining the 1st Marine Division which had recently arrived in Japan.
In one month, the brigade had killed and wounded an estimated 10,000 communists while executing three arduous counterattacks and traveling some 300 miles in the process. The enemy had been thrown back some 8,000 to 10,000 yards. Now plans for a major amphibious assault on communist-held territory were formulated.
As late as 20 July, the Joint Chiefs of Staff had informed General MacArthur that a Marine division could not be sent before November or December, but incredibly swift action within the Marine Corps exceeded that expectation. A war-strength 1st Marine Division [which absorbed the brigade], commanded by Major General Oliver P. Smith, arrived off the coast of Korea by 14 September. The 1st Marine Aircraft Wing was on hand to provide air support. Thousands of reserves had been mobilized, and Marines from posts and stations all over the world had poured into these units.
Five days of continual pounding by air and naval gunfire preceded the arrival of the assault troops at Inchon, on the South Korean west coast, the morning of 15 September. By the afternoon of D plus 1, almost exactly 24 hours after beginning the assault, the force beachhead line had been secured, and the amphibious assault phase of the landing, launched under extremely unfavorable hydrographic conditions, completed.
By the afternoon of the 27th, Korean and United States flags had been raised in Seoul, the capital city. The battle for its possession was over.
The Marine infantry troops established blocking positions around the city. On the morning of the 29th, General MacArthur and American and Korean dignitaries gathered for a ceremony in a bombed building, and the Korean capital was returned to the control of civil government.
From 5-7 October, Marines of the 1st Division reembarked and prepared to move to the east coast. As they did, they could look back with pride. In accounting for some 14,000 North Korean casualties and 6,500 POWS, while paying a price of 400 killed and 2,000 wounded, Marines had accomplished the important morale uplift of liberating Seoul.
Along the east coast, meanwhile, the ROK and Allied troops of the Eighth United States Army [EUSAK] had advanced rapidly northward after the Inchon landing and crossed the 38th parallel on 1 October. The drive to the north continued. On 25 October, the Marines on board ship reached Wonsan harbor. This campaign was to be one of the most demanding in the entire history of the Corps.
The United Nations Forces, of which the 1st Marine Division was a part, had spread all over North Korea. With the North Koreans seemingly beaten, the Chinese Communist Forces [CCF] entered the war.
In early November, after four days of fierce fighting, the 7th Marines became the first United States unit to defeat the Chinese Communists in battle. By 27 November, other Allied units had received the full force of a CCF counterattack and retreated rapidly south of the 38th parallel. The 1st Marine Division was still attacking. That night, assault battalions of the CCF Ninth Army Group, a ten-division force sent to Korea specifically to annihilate the 1st Marine Division, began to attack. Enemy units struck all around Marine positions from Yudam-ni to Hagaru, the Marine base camp 14 miles to the south. On 29 November, the U.S. X Army Corps issued to the Marine division an oral warning order for redeployment of Marine units in the Yudam-ni area to Hagaru. General Smith ordered his assault regiments to fight their way back to Hagaru. On the afternoon of 4 December, 79 hours and 14 miles after the division commenced its attack, the last elements of the 5th and 7th Marines reached the base camp.
While the two regiments plus supporting troops were fighting their way down to Hagaru, the 1st Marines and attacked elements repulsed the continued assaults of CCF divisions coming up from the south to cut off Marine logistical support. Once the division was inside the Hagaru perimeter, General Smith ordered the division to strike out for the Hamhung area, 56 miles away to the southeast. Since the Marines were completely surrounded by communists armies, press correspondents asked the commanding general if he intended to retreat. They quoted him as giving an immediate reply: "Retreat hell! We're just attacking in another direction."
Within two days, the men at Hagaru had moved south to Koto-ri, arriving on the afternoon of the 7th. As usual, the invaluable close air support of Marine pilots continued to provide that overhead protection so necessary to defeat the numerically superior enemy. Continuing the attack to the south, the Marines moved on towards the harbor at Hungnam, where shipping awaited. There they boarded ships and moved into South Korea.
During the two and a half years that followed the Chosin Reservoir fighting, the 1st Marine Division and the 1st Marine Aircraft Wing fought as a part of EUSAK, not as an amphibious force, but as part of a land army. The Marines were assigned missions similar to Army divisions, and aviation elements were placed under overall control of the Air Force. Although the Marines were not employed in their amphibious assault role, there certainly was a need for their proven combat ability and courage.
The division's operations, as part of EUSAK, continued. After a brief rest from the strenuous Reservoir campaign, the Marines spent some time hunting down vanishing guerrillas around Pohang, some 65 miles north of Pusan.
In February 1951, the order came to attack to the north. By the 4th of April, the Marines were among the first United Nations troops to recross the 38th parallel in central Korea. The advance continued. Two weeks later, the CCF started a gigantic counteroffensive. After heavy fighting and many casualties on both sides, the enemy was stopped. Once again the Marines attacked north.
The fighting continued, and counterattack followed attack. In June, the lines were again north of the 38th parallel. The following month, July 1951, an armistice appeared on the horizon. Communist and UN negotiators met to discuss armistice meetings. The truce talks continued periodically, while the fighting intermittently grew cold and flared hot.
During this time, both sides engaged in limited offensives across the entire front, mainly for the purpose of securing more territory, either for bargaining purposes or for better defensive positions. Extensive trench systems were dug, and log and earthen bunkers were built. The war at times became static while both sides awaited the results of the drawn-out truce negotiations. At other times the fighting reached ferocious intensity.
In March of 1952, the Marines moved from the eastern front to the western front in order to ensure the security of the section of the Allied line near Panmunjom, the site of truce talks. The 1st Marine Aircraft Wing, rendered outstanding service flying close support missions for the Marine Division as well as for other ground troops. Marine air support was constantly in demand by all frontline units.
Finally, after two years of frustrating and often fruitless meetings with the obdurate communist negotiators, an armistice was signed and the fighting ended on 27 June 1953. Notwithstanding that the end was in sight, and a truce was imminent, the opposing armies did not slack off. Some of the most fierce fighting in the war occurred during that month--the struggle for Outpost Berlin.
After the signing of an armistice, the Marines were relieved of any further combat responsibility, but the division remained in Korea until 1955, when it returned to Camp Pendleton, California. The 1st Marine Aircraft Wing remained in the Far East, and a few Marines continued on duty in Korea as military advisors to various ROK units, but combat in Korea was finished.
Online Resources
View more Korean War images on our Flickr site.


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Hello everyone,
I was wondering what is the best way to approach a function calling program.
Suppose someone has written a function that I need to use in my program. Basically the program is suppose to output a greeting message, then the user enters a guess (its a guessing game), and the computer outputs whether the guess is correct based on the conditions of the function that was written....
I am completely new to this and I am probably over-complicating things, but what would be the best way to approach such a problem?
thank you,
Matt H.


text:
Copyright © University of Cambridge. All rights reserved.
'Searching for Mean(ing)' printed from http://nrich.maths.org/
Show menu
Imagine you have a large supply of 3kg and 8kg weights.
Two 3kg weights and three 8kg weights have a mean weight of 6kg.
Can you find other combinations of 3kg and 8kg weights whose mean weight is a whole number of kg?
What's the smallest?
What's the largest?
Can you make all the whole numbers in between?
What if you have a different pair of weights (for example 2kg and 7kg)?
Which whole numbers is it possible to have as the mean weight now?
Try other different pairs of weights.
What do you notice about your results?
Can you use what you notice to find the combination of 17kg and 57kg weights that have a mean weight of 44kg......of 52kg.......of 21kg.....?
Explain an efficient way of doing this.
Can you explain why your method works?
Click here for a poster of this problem


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WW2 German Air Force RLM / Pioneer Noncomissioned Officers Collar tabs / kragenspiegel. Three Zinc "Gulls" on a black wool felt tab. No reaction to UV. Pair. VG+.
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text: > This is all worked, but it won?t work. Exactly because what you said, I > need to generate the superblock and directory structure, but this have to be > based on what I have been recorded on the DVD. Those are the parts I need > help. Does anyone can tell me how to generate directory structure on DVD > based on what have been recorded? You have to take some words more literally. In particular "you have to ... generate superblock and directory structure" rather means "*you* have to write a program, which would generate superblock and directory structure for you," than "you can do it with program X." The question might have been what does it take to write such a program. Well, it takes knowledge of UDF, programming skills and an effort. A.


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PITTSBURGH, Dec. 2 (UPI) -- PNC Wealth Management of Pittsburgh said its annual analysis using "The Twelve Days of Christmas" found the holiday's price went up 7.7 percent.
The company said its 30th annual PNC Christmas Price Index, which calculates the price of Christmas using the gifts outlined in the classic holiday song, found the price of Christmas rose $1,192 since last year to a total $27,393.17.
PNC said the price jump was the largest since 2010, which saw a 9.2 percent boost in the price of Christmas.
Jim Dunigan, managing executive for investments with PNC Wealth Management, said the tongue-in-cheek tradition may be a somewhat accurate economic indicator.
"While there are exceptions in given years, what's most interesting about the index's history is that since the beginning, year-over-year increases have averaged 2.9 percent, which is exactly the same number as the U.S. inflation index," he said.
The prices calculated by PNC for "The Twelve Days of Christmas" were:
One Partridge in a Pear Tree: $199.99
Two Turtle Doves: $125
Three French Hens: $165
Four Calling Birds: $599.96
Five Gold Rings: $750
Six Geese-a-Laying: $210
Seven Swans-a-Swimming: $7,000
Eight Maids-a-Milking: $58
Ten Lords-a-Leaping: $5,243.37
Eleven Pipers Piping: $2,635.20
Twelve Drummers Drumming: $2,854.80


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When we talk of exercise, staying fit, the image of a slime person immediately comes to mind. We all view staying fit as staying thin, but this is not necessarily true.
Many young woman and now, with the advent of the Modern Age, even men are obsessed with staying thin, good looking as they term it. A person can be fit even though he or she may seem obese to the rest of the world. Exercise is the key to keeping oneself fit. Exercise is not necessarily standing in one place and moving your arms and legs as one used to do in school. One can incorporate exercise into or along with any activity one enjoy. Dancing is an exercise, provided that the pace is fast, Climbing upstairs is can cause your knees to pain, as I found out the hard way last year . One can do power walks as well as an exercise in order to stay fit.
But then, enough advise for those who are further away from the fitness regime. Exercise must be combined with a proper diet. Regular exercise is not a license to unhealthy eating habits. At time one does indulge in a binge but it should be once in a while only. One's diet should be well packaged with proteins, carbohydrate as well as minerals. Yoga has becomes a fad stay fit these days. It has a rich and famous clientele outside of India, and now, thanks to various TV channels ( cable TV is really a boon) , it is becoming quite popular in the country of its origin , Better late than never. The Pranayam is quite popular in my neighborhood with the ladies swearing by its benefits. Many other wake up early each morning and go for walks to a school nearby where they walk bare feet on the grass, still wet withdrew from the previous night. However, this stop during winter's and children examination season. Most men, I can't fail to notice, display a prominent pot bell by middle age, a sign of prosperity, they call it. Lack of exercise is what it really should be attributed to. The ladies should really convince them to come along for morning walks. Of course, having hot-hot jalebis or chat pakodas while returning from morning walks is no permitted. Exercise is for fitness, it is in an order to create an appetite.
We eat in order that we live, we do not live to eat. Fast food is the single biggest cause for making people unhealthy or unfit. The whole problem is that fast food seems tastier than the normal, proper healthy food. Promises, resolutions are hard to keep when temptation is at hand and saliva is literally dripping in your mouth. The battle however continues. I have a very simple policy of keeping fit. Enjoy your favourite dishes, but within limits, if however you do overindulge, as we or rather I usually do, control your diet immediately. For small errands such as provisions for the house, a visit to the market etc., try to walk out as far as possible. It is always good (a boon in one way) if a few things on the provision's list are out of stock for the moment, so that another trip becomes necessary.
Keeping fit and healthy , is all in the mind , if you believe that keeping fit is necessary for better living only then can you succeed in the battle of good health verses the various types to a healthy living that are laid down in any walk of life . Those obsessed with healthy skin, keeping fit keeps your skin smooth, firm and also clear and glowing. Our skin has its own way of showing off when it is in good, health condition and its benefits are for the whole words to see. To frighten other into staying fit I must add that heart problem, blood pressure, breathlessness, fatigue can be caused by having an unhealthy body. I do sincerely hope that by now all who read this are convinced or coerced into exercising in order to stay fit, to live a healthier and a longer life. Don't overdo it. Make an exercise programme which you are able to maintain over a long period of time.


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TAMPA — A new wine and food concept, Cooper's Hawk Winery and Restaurant, is moving into the already cramped local wine bar market with a Napa-style tasting room, full-service restaurant, retail store and wine club.
Opening March 11 across from International Plaza, the restaurant will be the 12th for the Illinois-based chain and first outside the Midwest. Two others are planned for Orlando.
Cooper's Hawk sells only its name brand wine made from grapes grown at vineyards in California, Washington, Oregon and Michigan. The grapes are trucked to its production plant outside Chicago where the fruit is turned into wine, bottled and shipped to restaurants in Illinois, Indiana, Missouri, Ohio and Wisconsin.
"We source from all over so we can blend California and Washington grapes and produce unique and complex wines that are different than what you'd find elsewhere," said winemaker Rob Warren.
Cooper's Hawk enters an increasingly competitive field of wine bars. Sharon Stewart, who opened the Wine Studio on Henderson Boulevard in Tampa six months ago, said that while she's curious about Cooper's Hawk, she isn't worried about it cannibalizing the market.
"I think there's plenty of room for all of us because wine is becoming so popular,'' she said. "Everyone has their own niche. We're known for being a more top-shelf wine bar. Some competitors are more boutique-y.''
Stewart hasn't tried Cooper's Hawk but expects the concept will do well, provided the wine is good.
Cooper's Hawk has received more than 200 wine awards, mostly regional and state competitions such as the Florida State Fair, but hasn't received much press from Wine Enthusiast or other respected wine publications. Warren said they don't solicit reviews because the wine isn't available at grocery stores or other retail outlets.
"We can put our $20 bottle against any other $20 bottle and feel confident we would come out on top,'' he said. "We have some entry-level wines for people getting into the wine world and we've got wines for people who are very knowledgeable in wines.''
The winery serves 40 different wines, each paired with menu items ranging from pistachio crusted grouper to red wine and mustard short ribs. In a departure from typical restaurant pricing strategy, buying wine at the 350-seat restaurant costs the same as buying it in the store, $12 to $40 a bottle. Restaurant wine drinkers pay a corkage fee, and tastings of eight wines start at $7.
Jennifer Bingham, a certified sommelier who owns Cru Cellars on MacDill Avenue in Tampa, visited a Cooper's Hawk near Chicago several years ago and rated the wine "decent but not amazing.'' More impressive, she said, was the business model.
"Their profit margins have got to be really high because they are bypassing all the distributors,'' she said. "It's pretty brilliant. It's a business, though. There's no romance of a winery.''
Cooper's Hawk was founded in 2005 by Tim McEnery, who started in the hospitality business as a dishwasher at age 11. He saw an opportunity to build off the popular brew pub trend with an unusual dining experience centered around wine.
The company chose Tampa because of the high number of wine club members from the area and large population of Midwest transplants. It also liked the location in the MetWest complex at 4110 W Boy Scout Blvd. near the mall and specifically the Cheesecake Factory, which targets a similar, upscale clientele.
Cooper's Hawk has 60,000 wine club members who pay $18.99 a month for a bottle of red or white wine made exclusively for members. The wine must be picked up at the restaurant. To ship it costs more.
The company was forecast to reach $75 million in revenue in 2012.
Susan Thurston can be reached at [email protected] or (813) 225-3110.


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Beginning next January, Delta Air Lines will change its SkyMiles frequent-flier program from a mileage-based system to one based on dollars spent.
In other words, the more you pay for your ticket, the more points you'll earn.
The winners: people who buy more-expensive tickets, like business travelers and first-class customers.
The losers: people who buy the cheapest ticket available, like most vacationers.
"The updated mileage-earning plan, for travel beginning Jan. 1, 2015, will better recognize frequent business travelers and those less frequent leisure customers who purchase premium fares," Delta said in its announcement Wednesday.
"The move is consistent with a trend in the travel industry of rewarding customer behavior based on price."
The question now is whether Delta's two biggest U.S.-based rivals, American Airlines and United Airlines, will imitate the Atlanta-based carrier or stick to their current systems, which are based on miles flown.
The change at Delta will come as American prepares to merge its AAdvantage program with the Dividend Miles program of US Airways.
And that presents an interesting decision for American, frequent-flier guru Randy Petersen said Wednesday.
On one hand, American officials may decide to focus on putting the two frequent-flier programs together now, Petersen said. Two or three years later, it can review its progress and the success of Delta's program and decide if it needs to change, he said.
Or they could decide "if you're going to do it, you might as well do it all at once. Get it done with," said Petersen, president of Frequent Flyer Services of Colorado Springs, Colo.
He said he understands that US Airways and its then-chief executive, Doug Parker, were studying the idea of a revenue-based frequent-flier system before it began the chase of American Airlines that concluded with the two carriers' merger last year. Parker is now CEO of American Airlines Group Inc.
"Does this not look like something Doug Parker would do? I think it's got Doug Parker's DNA all over it," Petersen said. "That's the way he would have done things."
American wouldn't say Wednesday whether any changes are in the works as the result of Delta's revamp. It said in a Jan. 10 filing with the National Mediation Board that it expects to combine the AAdvantage and Dividend Miles programs by the end of the first quarter of 2015.
"We are constantly watching the competitive landscape in a variety of areas — from flights to services and loyalty programs," spokesman Casey Norton said. "AAdvantage was the industry's first frequent flier program, and as we build the world's greatest global airline, we will offer a loyalty program that supports and reflects that position."
Petersen said that both United and American could benefit if Delta's changes aren't a hit with consumers.
While most carriers still use a mileage-based system, with bonus miles for buying expensive tickets, Dallas-based Southwest Airlines changed its Rapid Rewards frequent-flier system on March 1, 2011, to go to a dollars-spent system.
Previously, Southwest awarded a point for each trip taken, whether the trip was a 250-mile flight bought for $69 or a 1,000-mile trip bought for $300. Sixteen trips got you a free round trip.
Now, customers get points based on dollars spent. The price of awards is also based on dollars spent, with advance-purchase tickets requiring the fewest points and full-fare tickets requiring the most.
In the United States, Virgin America and JetBlue Airways also have frequent-flier programs that are based on dollars spent, not miles flown. Delta is just the latest — and biggest — to adopt the method.
"It's not revolutionary," Petersen said. "It's evolutionary. At last count, there's about 11 airlines in the world who have some sort of revenue component in their program. Delta just seems to be joining those."
The Delta system will award miles based on what the customer paid and his or her level in the SkyMiles program. A SkyMiles member with no special status gets five miles for every dollar spent. A "Diamond" tier member, a very high-mileage flier, would get 11 miles per $1 spent.
As it works out, all members, both regular and high-status, would probably be worse off with a cheap ticket on many routes. But high-dollar tickets, like business-class fares, would bring a bonanza of extra miles for all tiers of the SkyMiles membership.
Follow Terry Maxon on Twitter at @tmaxon.


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Gretchen Holt Witt
Cookies for Kids' Cancer
Califon, New Jersey
Gretchen Holt Witt is one smart cookie. In February of 2007, when her 2-year-old son, Liam Witt, was diagnosed with neuroblastoma, an aggressive form of cancer, Gretchen was outraged to learn how little money is spent on research for pediatric cancer. She wanted a cure for Liam and others like him, and she wanted it fast. "The topic of children's cancer is such a monster in the closet that nobody wants to talk about it. I had to come up with something nobody could resist. And who can resist a cookie?" asks Gretchen, who loves to bake. "It's so innocent and pure."
So in 2008, as she juggled her job in public relations with rounds of chemo, surgery, and tests for valiant "Prince Liam"--while trying to keep life normal for him and his little sister, Ella--she masterminded a plan to bake 96,000 cookies over the holidays. She rented a commercial kitchen in New York City, sent out calls for volunteers, and watched in amazement as they trooped in, including an entire shift of firefighters from a nearby station. Cookies for Kids' Cancer has raised $2 million from what has become a 365-day online national project, with bake sales also held all over the country. Start-to-finish steps for hosting a local bake sale--from planning and staffing to downloadable signs, brochures, and press releases--are available on the Web site of the organization.
As for 6-year-old Liam, he loves his namesake "Liam's Lemon Sugar Cookies" and doesn't know he has cancer--just ouchies. "It's our job to worry," Gretchen says of herself and husband Larry. "It's Liam's job to be a little boy."
Gretchen Holt Witt


text:
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Werder Bremen clinched one of the three remaining places in the last 16 by crushing Panathinaikos 5-1 at the Weser Stadion. The Greek club's coach Alberto Malesani had opted for a defensive line-up because his side would qualify for the Uefa Cup with a draw, but his plans were thrown into disarray after two minutes when Werder's Miroslav Klose was brought down in the area.
The French playmaker Johan Micoud converted the spot kick and Nelson Valdez scored a further two goals before half-time to settle the contest. Strikes from Klose and Torsten Frings inflicted more misery on the visitors - but the Germans still needed an understrength Barcelona to win at the Fruili against Udinese to go through.
The Catalans were without the rested Ronaldinho, the injured Samuel Eto'o and Xavi Hernández and started with Lionel Messi on the bench. Udinese defended galliantly throughout the game but the goals finally arrived, Santiago Ezquerro scoring in the 86th minute and the substitute Andres Iniesta making it 2-0 in the last minute.
In Manchester United's group Villarreal won 1-0 at home to Lille with the substitute Antonio Guayre scoring midway through the second half. It was only the Spaniards' third goal in six games - as many as United mustered and two more than their opponents on the night.
Lille poured forward towards the end and Villarreal were grateful for a magnificent save by Sebastián Viera late on as he thwarted the young Lille substitute Kevin Mirallas's volley. Stéphane Dumont hit the post but the hosts held on and Lille will be rewarded for their rate of one goal in six games with a place in the Uefa Cup.
Juventus sealed top spot in Group A with a commanding 3-1 away to Rapid Vienna. The Italian champions had already qualified for the knockout phase but Fabio Capello fielded a strong team. Alessandro Del Piero scored twice with a Zlatan Ibrahimovic strike in between in 10 frantic first-half minutes.
Bayern Munich rested some key players and duly drew 1-1 with Club Bruges. The Germans finish second behind Juve and could face Arsenal or Liverpool in the last 16. Claudio Pizarro gave Bayern an early lead but Javier Portillo equalised after 32 minutes. Bayern hit the bar and had a goal disallowed in the second half but could not find a winner. In Group B Thun eked out a 0-0 draw away to Sparta Prague to clinch a place in the Uefa Cup.


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Sat 18th Jun 2011 12:00pmRapturecamps's Balangan Surf Report
Today the swell had decent size with offshore winds and clean glassy sets at Balangan. Rain didn't hang around for the whole day with a bright sunny afternoon for all to enjoy. Our first session had beginners a little hesitant but all it takes is that first mad wipe out then your set to tackle anything. We all had a great time though with little crowds and good vibes in the water all day.
View the Balangan Surf Report and Forecast. Rapturecamps's Reports have received a total of 158355 views.
This report has received 311 views since 18/6/11.


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Simeon has been used to train the younger horses out on the trail, ponying them until they are ready to ride. He gets along well with other horses, crosses water, swims with rider in streams, used to hills.
We breed and sell quality Tennessee Walkers, Spotted Saddle and Racking Horses. We have several fine Tennessee Walking Horse stallions standing at stud and For Sale. We have a Gypsy Vanner Stallion - A King's Ransom (grandson of The Lion King) standing, as well as 2 of his colts for sale.
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By Trade Guide Bollywood Hungama News Network
Some stories seem very interesting on paper, but lose their sheen on celluloid. That's the problem with DEKH RE DEKH. The idea could've translated into an engrossing fare, but the story development as also its execution leaves a lot to be desired. Even its short running time doesn't salvage the situation.
Babli's marriage in a rich family has already turned into a nightmare and she is back home after getting divorced. But a robbery involves her childhood friend Shyam into her plan; Shyam also is in need of money to bribe the minister for a government job. At this juncture, one more character joins them, Yadav, a struggling politician in need of money for his party fund to get ticket for election. Since they have no experience of robbery, they plan to involve a professional thief in the mission: Charan.
DEKH RE DEKH establishes the characters well, but the screenplay unravels in such a casual manner that it becomes the biggest drawback as it moves further. One can never tell when the film rolls into flashback mode and back. It's only later that you realize that there actually were flashbacks and by that time, you've already lost track of where the story is headed.
The film's tagline states 'laughter behind darkness' but neither does the film make you laugh, nor is it a dark subject from any angle. The comedy just doesn't evoke mirth. Music is irksome.
Vijay Raaz is the best of the lot. He's excellent. Gracy Singh is plain average. Siddhartha Koirala is just about okay. Raghubir Yadav does a fine job.
On the whole, DEKH RE DEKH is not the type that would catch the viewer's eye.
Bollywood.com Rating: 1


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Detail Information
- Neural circuits as computational dynamical systemsDavid Sussillo
Department of Electrical Engineering and Neurosciences Program, Stanford University, Stanford, CA 94305, United States Electronic address
Curr Opin Neurobiol 25:156-63. 2014..I summarize recent theoretical and technological advances and highlight an example of how RNNs helped to explain perplexing high-dimensional neurophysiological data in the prefrontal cortex...
- Opening the black box: low-dimensional dynamics in high-dimensional recurrent neural networksDavid Sussillo
Department of Electrical Engineering, Neurosciences Program, Stanford University, Stanford, CA 94305 9505, USA
Neural Comput 25:626-49. 2013..In all cases, the mechanisms of trained networks could be inferred from the sets of fixed and slow points and the linearized dynamics around them...
- A recurrent neural network for closed-loop intracortical brain-machine interface decodersDavid Sussillo
Department of Electrical Engineering, Stanford University, Stanford, CA 94305 9505, USA
J Neural Eng 9:026027. 2012..Taken together, these results suggest that RNNs in general, and the FORCE decoder in particular, are powerful tools for BMI decoder applications...
- Transferring learning from external to internal weights in echo-state networks with sparse connectivityDavid Sussillo
Department of Electrical Engineering, Stanford University, Stanford, California, United States of America
PLoS ONE 7:e37372. 2012..Through an analysis of the conditions required to make transfer of learning work, we define the concept of a "self-sensing" network state, and we compare and contrast this with compressed sensing...


text: On Wed, Jun 29, 2011 at 4:56 PM, Clemens <clemens.zeidler@xxxxxxxxxxxxxx>wrote: > On Thu, 30 Jun 2011 04:28:38 +1200, Travis D. Reed <tdreed@xxxxxxxxx> > wrote: > > Thanks! True maximaization = zooming without entering full screen. If >> someone wants to use fullscreen, they can just press F11. >> > > yes, thats the original function of the zoom button, I don' know why to > change the semantics for web+? f11 is the shortcut I know. > > I would more like a zoom to an optimal size, e.g. using full height but > just a reasonable width, on wide screens there would still be space beside > the browser. Maximized windows often look odd on wide screens. Tracker does > this optimal resize and the old BeIDE did it too which was pretty handy to > place two editors beside each other. Miss this behaviour in Pe. By the way, > this was one of the wow things when I first used BeOS, that was so much > better than just dump maximize the window! > > If having more space was the reason for the fullscreen mode I would reduce > the UI a bit, e.g. chrome and opera are very space efficient in this > regards... > I assume that this discussion of zoom to "optimal" size vs 100% of screen is coming from my recent post commenting on stippi's Deskbar Rewrite blog post. In my post I advocated allowing developers to reuse the Zoom button to go to 100% of the screen ala F11 in some popular browsers. I like the idea, but, it is a Post-R1 feature at the very earliest. Zoom will, I suspect, remain the way it is now for the foreseeable future. And that is a good thing. Allowing Zoom to make the window take 100% of the screen is helpful for small screen devices like netbooks. Using a standard key such as F11 instead of the Zoom button might make things more consistent. My real, and perhaps hidden point, was that Deskbar should not be modified to support Zooming at this point and that a better solution should be thought out later. John Scipione


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text:
Youth is serving the Padres very well of late. Even the offense is helping out.
A night after Odrisamer Despaigne's dazzling debut, Jesse Hahn outdueled veteran Tim Hudson on Tuesday night, striking out a career-high eight batters after taking a no-hitter into the fifth inning in a 7-2 win over the Giants at AT&T Park.
His ailing back much improved, Chase Headley reached base twice in his return to the lineup, Alexi Amarista drove in three runs on three hits and the Padres mounted their best offensive showing in a month three days after baseball's worst offense played a pivotal role in General Manager Josh Byrnes' firing.
Yet, here the Padres are, looking for a sweep of the NL West-leading Giants. They have also moved back to 10 games under .500 after scoring 13 runs in the first two games of the series, their most since scoring 13 against the Cubs on May 23-24, 11 of them coming in one game.
"It had to come at some point; we can't play bad the whole year," catcher Yasmani Grandal said. "I've been saying it since Day 1. It's going to happen. I really believed it would happen. … Hopefully we keep on doing the same thing."
That hope extends to a pair of rookie pitchers breathing fresh life into the rotation.
On Tuesday, Hahn (3-1) added yet another quality start to his run since the Padres recalled him a second time from Double-A San Antonio, scattering two runs on four hits and a walk over six strong innings, four of them perfect right off the bat.
"I felt really relaxed out there; it just feels like an ordinary game now," said Hahn, who has fashioned a 0.95 ERA over his last three starts. "The first couple starts I still had some nerves and jitters in there. I've learned to calm that down a little bit. Now I'm just focused on winning for the team."
Indeed he is.
In fact, including the seven shutout innings that Despaigne threw at the Giants on Monday, Padres rookie pitchers were working on 24 straight innings without yielding an earned run – 17 from Hahn – when San Francisco scratched something together in the fifth.
To that point, Hahn had retired the first 12 batters he faced, six by strikeout.
"I had good tempo," Hahn said. "I was getting right back on the rubber and making the next pitch, and I think that helped."
Then Pablo Sandoval ended any budding no-hitter hopes, as premature as they were, with an infield single that ricocheted off Hahn. The Giant's hefty third baseman moved to third on Michael Morse's ensuing single and scored on Tyler Colvin's groundout.
After a strikeout and a two-out walk, Hahn retired Hudson on groundout to second to escape the fifth with the Padres still leading 3-1.
The Giants adding one more run in the sixth on Buster Posey's one-out double did little to disrupt Hahn's night, with the Padres rookie retiring Sandoval and Morse in order to get out of the inning.
Of course, it helped having the Padres score three more runs in the top half of the sixth off Hudson (7-4), two of them scoring on Amarista's single. In all, the Giants starter allowed six runs – four earned – on nine hits and two walks in 5 2/3 innings.
Meanwhile, three Padres relievers combined for three scoreless innings, Tommy Medica added his first career pinch-hit homer in the eighth and Will Venable even drove in two runs with a pair of productive outs, the sort that eluded the Padres all season as baseball's worst offense cast a harsh limelight on Byrnes' job security.
For now, four starts into his big league career, count Hahn among Byrnes' victories.
Acquired along with the left-handed Torres in the deal that sent Logan Forsythe and four minor leaguers to Tampa Bay, Hahn is taking a giant leap forward as he progresses further and further away from his 2010 Tommy John surgery.
The comeback trail under the Padres began in Double-A San Antonio. With each passing start, it's becoming clearer and clearer that Hahn will throw the bulk of his approximate 110-inning cap in the majors.
Tuesday's effort included quite a few more developing change-ups mixed among his career-high 95 pitches, 68 for strikes, as Hahn pushed his punchout total to 27 through four games, the second most to start a career in franchise history behind Bob Shirley's 28 in 1977.
"I thought tonight the fastball came into play a little bit more," Padres manager Bud Black said. "I thought good movement to the fastball. Located the fastball in to the righties. Made some good pitches down and away. He had some riding action to cutting action at times.
"I think the fastball resulted in some outs, and again, I think the curve was just like it's been his previous two. It's a good pitch. It's an old-school curveball. It's a 12-6, top-to-bottom curveball that you don't see a lot of major league pitchers throw."


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SUNRISE, Fla. -- The original Floridian Superman was none other than Gary Roberts.
Clueless to the fact he was streaking around the rink with a cape flapping behind him, the former Calgary Flames star proved to be an inspiration of sorts.
Florida Panthers defenceman Steve Montador has run with his original practical joke on Roberts and taken a page from his own Calgary days to create an unsung hero award in Sunrise this season -- a red and blue cape with a yellow crest and large white 'H' adorning it.
The cape goes to the most deserving teammate after every win, just as the old hard hat did in the Flames room for a couple of years courtesy of an idea implemented by Craig Conroy.
"The first cape we actually ever had was last year. I went home for a game in Toronto. My mom, I asked her if I had one. She said I used to wear a little black cape that had an 'S' on it -- which was either for Superman or for Steve, I don't know," said Montador, who wanted to start a similar tradition in Southern Florida but didn't want to copy the since-retired hard hat idea.
"I brought it back here and put some double-sided tape on it. I put it on Gary Roberts without him knowing before practice.
"He's been around since the stone age, and he's skating around the ice and this thing's flapping, and he doesn't know what's going on. He's a very respectable guy, commands respect, a serious guy.
"There's a bunch of young guys, and everyone's staring at this guy wearing a cape he doesn't even know he has."
Now, the cape is a symbol of pride. Unless you count the times the inventor has put in on to prance through the dressing room.
"I've put it on when I've been naked before and walked through the dressing room. What of it?" joked Montador when told his teammates claim he likes to have the most fun with the prop.
The cape, ordered online at superherocapes.com, didn't come with any special powers.
"I wouldn't say that I could go end-to-end on the ice," said Montador. "But certainly, looking really cool is my main objective."
While the Flames have abandoned their unsung hero award -- which spawned the All-Business Tie a year ago after a year with a gold hard hat that followed the original green one that came to the forefront during the run to the Stanley Cup finals -- Montador says the cape is an important part of the Panthers' moral.
"I think it's really important. This is one element of a greater thing -- and that's building team bonding, team unity," said Montador.
"You want to have as many uplifting, light things as you can, and I think that's part of it."


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BALTIMORE (WJZ)—President Barack Obama orders immigration officials to stop deporting illegal immigrants in Baltimore.
Political reporter Pat Warren explains Baltimore is a test city for a new policy.
Baltimore and Denver are the two cities the administration is using to test a policy that restricts who can be deported to people with criminal records.
This action by the president is more far-reaching for the Baltimore immigrant community than the dream of in-state tuition for students here illegally.
Obama is testing a policy that freezes deportation of those with no criminal records. That puts about 85 percent of cases on hold.
Crowds of people in the United States illegally have staged demonstrations, such as one in California over the years protesting U.S. immigration laws.
This new policy has immigration lawyers here rejoicing.
"Of course from a Maryland perspective it's great because now you have law enforcement, our financial resources, everything being focused where it needs to be focused most, which is to try and deal with convicted criminals," said Sheila Murthy, immigration lawyer.
State Delegate Pat McDonough tells WJZ that Baltimore was picked because it is considered a sanctuary city for illegal immigrants.
"The federal people felt that Baltimore City was not complying with the law, that Baltimore City already had a policy of not arresting this 85-90 percent and as a result they felt that Baltimore City, which is a sanctuary city, was violating federal law. Now Obama is saying it's OK to do that, the federal government agrees with you, and the Congress believes he's violating the law," McDonough said.
While Congress hashes out its own issues, the test policy starts here Dec. 4. The test program runs six weeks, but could be expanded in January.
Fewer than 20 percent of the immigration cases in courts around the country involve people with criminal records.


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Artist description:
A portrait of my sister - you'll have to take my word for it!
Flash Draw Created Nov 11, 2012 460 x 640px Unless noted Copyright 2012 nealart.
We encourage you to submit a comment and let the artist know what you think of this drawing. Please log in or join to post a comment.
Post a comment
beautiful to see her coming alive..pretty face!! 5/5..
nice portrait..she is pretty...5h
Thanks - I knocked a couple years off of her!


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High End Power Supply Roundup - Summer 2006
Posted by Philipp Esselbach on: 09/11/2006 12:06 PM [ Print | 0 comment(s) ]
Madshrimps posted a High End Power Supply Roundup
Today's computers desire more and more power, and that power has to be clean and stable. For those that want to push their computers a little above their specifications, these devices have become a deciding factor for reaching maximum performance. We have models from Silverstone, OCZ and Sharkoon on our testbed.
High End Power Supply Roundup - Summer 2006
Related Threads
07/18/2001 09:35 PM: 3Com Home Connect (High End Model) and XP Rc1 (0) by GPRaider


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Garrett Gottlieb | CEO & Founder
Since the ninth grade, Garrett has been experimenting with powerful technologies (some less legal than others). During one of his co-op work terms at the University of Waterloo, he developed a workout-generating algorithm to spice up his routine. Fast forward a couple of years, and PumpUp was born. Garrett leads the vision, design, and development of PumpUp. When he's not dreaming up the next big PumpUp update, you can catch him working out, drinking kale shakes, and playing smash bros.
Phil Jacobson | President & Co-Founder
Phil loves building companies that improve the lives of people across the globe. He leads the business at PumpUp (operations, finance, marketing, external relations, biz dev). Phil holds a BBA degree from Wilfrid Laurier University and held brand management positions at Unilever and PepsiCo. While in school, he was the President of his Fraternity, Alpha Epsilon Pi. In his spare time, Phil enjoys intellectual debates, extreme hiking adventures, music festivals, and keeping on top of the latest in tech.
Amsul Naeem | Lead Front-End Developer
A self-taught developer from the age of 12, Amsul is a front-end savant, obsessed with designing the next generation of digital experiences. Although his mother-tongue is JavaScript, it is rumoured he occasionally speaks English and Urdu. Amsul loves the open web and dabbles in some open source projects. While not glued to his machines, he enjoys chilling with his cat (Hercules) or jamming on his guitars.
Erin Morris | Lead Product Designer
Erin is a well-rounded designer who always has user experience in mind. Erin earned a degree from the University of Toronto, majoring in Art History, but has always had a focus on design. Erin loves exploring Toronto and catching shows at the Mirvish Theatre. When Erin isn't using her creative talents for PumpUp, she is volunteering with Girls Learning Code, teaching the next generation of techies.
David Yu | Head of Growth
Part ninja, part nerd, and complete go-getter, David is the guy you want and we have. He is in charge of growing our community well into the millions, all while maintaining the positivity that everyone loves. In addition to his surprisingly endless supply of soy sauce, David is great at ripping his jeans when attempting to play hackey sack. When he's not eating sushi, you can find him listening to epic soundtracks and watching anime and manga.
Ian Benedict | Back-End Developer
A brilliant back-end developer, Ian has a magical touch that keeps PumpUp running smoothly and efficiently. He hails from the University of Toronto with a degree in Computer Science and his knack for programming led to roles at other awesome start-ups, like Tab Payments. During his spare time, you can find Ian practicing his supersonic tennis serve, cruising on his motorcycle, and jamming on his guitar.
Addison Gill | Marketing Manager
A self-starter from a very young age, Addison has always been meticulously organized and ready for anything you throw at her. Addison has travelled the globe, walked the runways at numerous fashion shows and has appeared on the pages of some of your favourite magazines. Addison attended the University of Toronto, where she became an expert in business and social media. When you can get Addison to unplug, you can find her working on her memoir or going for a walk on Toronto's waterfront paths.
Roman Pavlovskyi | Back-end Developer
When Roman isn't trail blazing across the globe, you can find him in PumpUp HQ writing stellar code and improving the PumpUp community! Roman studied at the University of Waterloo, earning a degree in Computer Science. Roman is an adrenaline junkie who loves skydiving, bungee jumping and biking. Roman is an avid adventurer who is alway up for a new challenge and we're excited to have him here at PumpUp!


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Hearing service providers
Hearing service providers can provide hearing aids (and rehabilitation) to workers with hearing loss as a result of noise in the workplace.
Providing hearing aids
The hearing aid fees order contains information on providing hearing aids. The order includes information on:
- medical support for the provision of hearing aids
- selection of hearing aid
- insurer approval
- fitting and supply of hearing aid
- review of hearing aid
- additional batteries and minor maintenance.
Replacing hearing aids
Hearing aids can be replaced when the hearing aid:
- has been lost or damaged and is not covered by warranty or other insurance, or
- the worker can no longer communicate effectively using the current hearing aid.
You need to complete a declaration form when requesting a replacement.
SIRA approved hearing service providers are entitled to charge a fee in accordance with the current hearing aid Fees Order.
See invoicing for additional information.
Approval of hearing service providers
Any contracted hearing service provider with the Office of Hearing Services is eligible to apply for SIRA approval as a hearing service provider.
To apply, fill out the hearing service provider application form and submit to email@example.com.
You can email email@example.com or call 13 10 50 for more information.


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Learn to Lead: Trad Course is Full
Our Learn to Lead: Trad course is now full. Be the first one on the wait list!
Let the mountains be your playground
To progress is a human trait that we all strive to achieve. Let this spill over into your climbing career with progressing into traditional climbing. We all love playing with climbing gear, let's admit it, but now it's time to walk the walk!
The Canadian Rockies are a world class destination that host thousands of climbers from around the world to test themselves on our rock. To have the access that we have as Canadians is easily taken for granted. As climbers, this isn't an option for each time we drive a road, each time we round a corner, our heads swivel looking out and up, imagining what we can do, could do, what we will do.
Next Level Climbing
Our Learn to Lead: Trad Edition camp is designed to take you to the next level in climbing. Starting indoors, then top roping outside, to clipping bolts on lead and now placing your own gear, the world starts to look a lot different when the mountains you have stared at open up in front of you. Now you can look at any mountain and with the skills learned form this course, you can stick your nose in and explore a lot more terrain.
Led and taught by experienced ACMG guides, we will take you through the skills and decision you need to be confident when trad climbing. From gear, to placements, to anchors, communication and all that lies between, you will come out of this course empowered to expand your horizons. Climbing isn't hard, but your mind certainly plays enough tricks on you to make you think it. With the knowledge and confidence you will gain from the ACC's Learn to Lead course, take yourself up a notch and give yourself the credit you deserve as you finish the last pitch of the day.
Top slider: all images by Kris Irwin
Planned Itinerary
- Saturday
- Meet at Rocky Mountain Bagel Co. at 8:00 am
- Car pool to climbing area and hike in
- Review safety and basic climbing skills
- Lear and practice gear placements
- Rappelling and cleaning
- Progress from top rope, to mock lead to leading
- Sunday
- Meet at Rocky Mountain Bagel Co at 8:00 am
- Car pool to climbing area and hike in
- Review lessons from previous day
- Practice gear placements
- Continue progression from mock lead to lead
Gear, Food, Lodging
- Instruction throughout the camp by ACMG guides
- Ropes and group gear
Participants must provide:
- Accommodation
- Transportation to/from Canmore and climbing areas (participants are expected to car pool)
- All your meals
- Personal gear (see equipment list in Info Pack)
- National Park passes (if required)
Level of Difficulty
For those that already lead climb sport and with rope-handling and belay skills, this is the course for you. Difficulty of grade is not important for this course as hard skills will focus on lead trad climbing development. This is not a learn to climb course. This course is designed for those that already sport climb and want to develop their trad skills.


text: The Comfort Hotel is located in Chambray Les Tours at the south of Tours,in the heart of a green park. Tours is only 10mins. away. The property is near the main road & highways. Ideal stopover to discover the Loire Valley prestigious castles,Chambord,Chenonceau & Villandry. Perfect location for leisure or business. You will enjoy the amenities of our rooms(Free WIFI & flat screens). Specific rates on Half Board & renewed rooms at 55EUR on weekend & at 60EUR on weekly nights. Restaurant open during the week for dinner buffet.Breakfast buffet at 8EUR,subject to change. Free car park. Pet fee:5EUR per night/pet. Restaurant open for dinner & closed for lunch. Restaurant closed Fri evening & Sat to Sun. Reception open Mon-Fri 6:30am - 10pm,Sat 8am - 10pm & Sun 8am - 12pm;in case of arrival outside these hours,please call hotel.


text: Suited for Chanel\nA Bold Redesign Invigorates the Flagship Boutique in Manhattan\nThe entrance to Manhattan's Chanel boutique on 57th Street, designed by architect Peter Marino, echoes the modern lines of the No. 5 perfume box.\nAccessories are displayed in a first-floor sitting area. Black carbon-fiber cloth covers the walls.\nA freestanding light wall intersects the second-floor gallery.\n"The library in Chanel's apartment in Paris was the inspiration for this design," says Marino.\nSteel-framed niches showcase ready-to-wear fashions, including Chanel's signature tweed suits.\nFloor-to-ceiling sheers descend from an illuminated ceiling in the VIP salon on the top floor. "You reach the space, and there's a shaft of light coming down," says Marino.


text:
DOVER — Residents Steven and Cheryll Smith will appear in court March 28 to be arraigned on charges alleging abuse toward a 2-year-old girl in November.
Indicted on charges of simple assault and second-degree assault, Steven Smith, 25, of 149 Portland Ave., is accused of striking the child in the face and causing a red mark on her skin and also of striking the girl behind her legs causing bruising.
Cheryll Smith, 23, also of 149 Portland Ave., and who, at the time of her arrest was known as Cheryll Morgan, was indicted on one charge alleging simple assault for recklessly causing bodily injury to the 2-year-old in November by striking her in the face.
According to an earlier report by Foster's Daily Democrat, officers from the Dover Police Department had begun investigating the alleged child abuse when responding to the couple's Royal Oaks apartment for reports of a domestic disturbance on Nov. 26.
An officer noticed injuries on the girl and told Smith to take her daughter to Wentworth-Douglass Hospital. The state's Division of Children, Youth and Families was notified of the girl's condition and she was subsequently placed in foster care.
The two reportedly turned themselves in after warrants were issued for their arrests. Bail conditions from their arraignments in district court included that they have no contact with each other or the child and prohibited each of them from using drugs or alcohol and from owning any firearms.
Both will appear in Strafford County Court following these recent indictments and could face jail time for the alleged charges.


text:
Hey folks,
It occurred to me that the readers of this forum may not know about Intel Press, which writes some pretty amazing books. They just released a new VTune book which looks pretty impressive in its scope and I am NOT saying that just cuz I have a spiffy signed copy of it right here at my desk.
Check it out:
"VTune Performance Analyzer Essentials -- Measurement and Tuning Techniques for Software Developers" by James Reinders.
James is a VTune geek from way back, and I have to tell you: this is one good book. Whether you're a novice or an experienced app profiler, you'll find a lot of neat tips and guidelines on everything from hotspot hunting to multithreaded program analysis.
Another book that has been out a while, and is certainly worth taking a look at is "The Software Optimization Cookbook - High-performance Recipes for the Intel Architecture," by Rich Gerber.
You can learn more about these books and how to get a hold of them directly at Intel Press:
Message Edited by jdgallag on 06-09-2005 11:47 AM
Message Edited by jdgallag on 06-09-2005 11:48 AM
Message Edited by jdgallag on 06-09-2005 11:48 AM