Genetic variation in ERCC1 and XPF genes and breast cancer risk.

PubMed

Pei, X H; Yang, Z; Lv, X Q; Li, H X

2014-03-31

Breast cancer is one of the most frequently diagnosed cancer in women worldwide, and we conducted a case-control study by genotyping seven potentially functional SNPs, three in ERCC1 and four in XPF, in a Chinese population of 417 breast cancer cases and 417 cancer-free controls. Three SNPs in ERCC1 and four SNPs in XPF were genotyped by using the Taqman Universal PCR Master Mix in the GeneAmp(®) PCR System 9700 with Dual 384-Well Sample Block Module, and assays were performed on a 384-well plate on the Sequenom MassARRAY platform. We found that elevated breast cancer risk was associated with those who had a family history of breast cancer and history of breast disease, and those who were over 25 years old at first full-term pregnancy. We found that decreased risk of breast cancer was associated with those who had a history of full-term pregnancies. Compared with the ERCC1 rs11615 T/T genotype, a significantly higher risk of breast cancer was found in the C/C genotype in codominant and dominant models after adjusting for potential risk factors. Similarly, we found that ERCC1 rs3212986 C/C genotype was associated with an increased risk of breast cancer in codominant, dominant and recessive models. Our study indicated that the ERCC1 rs11615 and rs2298881 polymorphisms are associated with breast cancer in a Chinese population. Further studies with large sample size are greatly needed to elucidate the SNPs of ERCC1 and XPF genes in the development of breast cancer.

CYP gene family variants as potential protective factors in drug addiction in Han Chinese.

PubMed

Zhang, Hongxing; Yang, Qi; Zheng, Wenkai; Ouyang, Yongri; Yang, Min; Wang, Fengjiao; Jin, Tianbo; Zhang, Ji; Wang, Zhenyuan

2016-08-01

There is growing evidence that genetic factors also contribute to drug addiction. The human cytochrome P450 has shown special interest because of pharmacokinetic variation in different individuals and populations, which is largely determined by the relevant genes. The present study aimed to investigate the polymorphism of the CYP/addicts relationship. We genotyped 13 tag single-nucleotide polymorphisms (tSNPs) from three genes, including 692 cases and 700 controls. Sequenom MassARRAY RS1000 (Sequenom, Inc., San Diego, CA, USA) was used for SNP genotyping. Statistical analysis of the association between tSNPs and drug addiction was performed using the chi-squared test and SNP Stats software (http://bioinfo.iconcologia.net). The T/T genotype of rs2242480 in CYP3A4 was associated with decreased risk in the recessive model (p = 0.0002). Allele frequency at rs3743484 in CYP1A2 showed significant differences between addicts and controls (p = 0.046; odds ratio = 0.80; 95% confidence interval = 0.65-1.00). In genetic model analyses, the minor C allele of rs3743484 in CYP1A2 was associated with a reduced risk of drug addiction based on analysis using codominant and additive models (p = 0.027 dominant model; p =0.038 additive model). Our findings show that at allelic and genotypic level polymorphisms in CYP3A4 and CYP1A2 are significantly associated with a reduced risk of drug addiction in X'ian Han Chinese individuals. However, this result needs to be confirmed in additional studies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

GSTM1, GSTP1, and GSTT1 genetic variability in Turkish and worldwide populations.

PubMed

Karaca, Sefayet; Karaca, Mehmet; Cesuroglu, Tomris; Erge, Sema; Polimanti, Renato

2015-01-01

Glutathione S-transferase (GST) variants have been widely investigated to better understand their role in several pathologic conditions. To our knowledge, no data about these genetic polymorphisms within the Turkish population are currently available. The aim of this study was to analyze GSTM1 positive/null, GSTT1 positive/null, GSTP1*I105V (rs1695), and GSTP1*A114V (rs1138272) variants in the general Turkish population, to provide information about its genetic diversity, and predisposition to GST-related diseases. Genotyping was performed in 500 Turkish individuals using the Sequenom MassARRAY platform. A comparative analysis was executed using the data from the HapMap and Human Genome Diversity Projects (HGDP). Sequence variation was deeply explored using the Phase 1 data of the 1,000 Genomes Project. The variability of GSTM1, GSTT1, and GSTP1 polymorphisms in the Turkish population was similar to that observed in Central Asian, European, and Middle Eastern populations. The high linkage disequilibrium between GSTP1*I105V and GSTP1*A114V in these populations may have a confounding effect on GSTP1 genetic association studies. In analyzing GSTM1, GSTT1, and GSTP1 sequence variation, we observed other common functional variants that may be candidates for associated studies of diseases related to GST genes (e.g., cancer, cardiovascular disease, and allergy). This study provides novel data about GSTM1 positive/null, GSTT1 positive/null, GSTP1*I105V, and GSTP1*A114V variants in the Turkish population, and other functional variants that may affect GSTM1, GSTT1, and GSTP1 functions among worldwide populations. This information can assist in the design of future genetic association studies investigating oxidative stress-related diseases. © 2014 Wiley Periodicals, Inc.

Association of α-, β-, and γ-Synuclein With Diffuse Lewy Body Disease

PubMed Central

Nishioka, Kenya; Wider, Christian; Vilariño-Güell, Carles; Soto-Ortolaza, Alexandra I.; Lincoln, Sarah J.; Kachergus, Jennifer M.; Jasinska-Myga, Barbara; Ross, Owen A.; Rajput, Alex; Robinson, Christopher A.; Ferman, Tanis J.; Wszolek, Zbigniew K.; Dickson, Dennis W.; Farrer, Matthew J.

2016-01-01

Objective To determine the association of the genes that encode α-, β-, and γ-synuclein (SNCA, SNCB, and SNCG, respectively) with diffuse Lewy body disease (DLBD). Design Case-control study. Subjects A total of 172 patients with DLBD consistent with a clinical diagnosis of Parkinson disease dementia/dementia with Lewy bodies and 350 clinically and 97 pathologically normal controls. Interventions Sequencing of SNCA, SNCB, and SNCG and genotyping of single-nucleotide polymorphisms performed on an Applied Biosystems capillary sequencer and a Sequenom MassArray pLEX platform, respectively. Associations were determined using χ2 or Fisher exact tests. Results Initial sequencing studies of the coding regions of each gene in 89 patients with DLBD did not detect any pathogenic substitutions. Nevertheless, genotyping of known polymorphic variability in sequence-conserved regions detected several single-nucleotide polymorphisms in the SNCA and SNCG genes that were significantly associated with disease (P=.05 to <.001). Significant association was also observed for 3 single-nucleotide polymorphisms located in SNCB when comparing DLBD cases and pathologically confirmed normal controls (P=.03-.01); however, this association was not significant for the clinical controls alone or the combined clinical and pathological controls (P>.05). After correction for multiple testing, only 1 single-nucleotide polymorphism in SNCG (rs3750823) remained significant in all of the analyses (P=.05-.009). Conclusion These findings suggest that variants in all 3 members of the synuclein gene family, particularly SNCA and SNCG, affect the risk of developing DLBD and warrant further investigation in larger, pathologically defined data sets as well as clinically diagnosed Parkinson disease/dementia with Lewy bodies case-control series. PMID:20697047

MiR-608, pre-miR-124-1 and pre-miR26a-1 polymorphisms modify susceptibility and recurrence-free survival in surgically resected CRC individuals.

PubMed

Ying, Hou-Qun; Peng, Hong-Xin; He, Bang-Shun; Pan, Yu-Qin; Wang, Feng; Sun, Hui-Ling; Liu, Xian; Chen, Jie; Lin, Kang; Wang, Shu-Kui

2016-11-15

Genetic variation within microRNA (miRNA) may result in its abnormal folding or aberrant expression, contributing to colorectal turmorigenesis and metastasis. However, the association of six polymorphisms (miR-608 rs4919510, miR-499a rs3746444, miR-146a rs2910164, pre-miR-143 rs41291957, pre-miR-124-1 rs531564 and pre-miR-26a-1 rs7372209) with colorectal cancer (CRC) risk, therapeutic response and survival remains unclear. A retrospective study was carried out to investigate the association in 1358 0-III stage resected CRC patients and 1079 healthy controls using Sequenom's MassARRAY platform. The results showed that rs4919510 was significantly associated with a decreased susceptibility to CRC in co-dominant, allele and recessive genetic models, and the protective role of rs4919510 allele G and genotype GG was more pronounced among stage 0-II cases; significant association between rs531564 and poor RFS was observed in cases undergoing adjuvant chemo-radiotherapy in co-dominant, allele and dominant models; moreover, there was a positive association between rs7372209 and recurrence-free survival in stage II cases in co-dominant and over-dominant models; additionally, a cumulative effect of rs531564 and rs7372209 at-risk genotypes with hazard ratio at 1.30 and 1.95 for one and two at-risk genotypes was examined in stage II cases, respectively. Our findings indicated that rs4919510 allele G and genotype GG were protective factors for 0-II stage CRC, rs7372209 and rs531564 could decrease RFS in II stage individuals and resected CRC patients receiving adjuvant chemo-radiology.

Associations between INSR and MTOR polymorphisms in type 2 diabetes mellitus and diabetic nephropathy in a Northeast Chinese Han population.

PubMed

Zhu, A N; Yang, X X; Sun, M Y; Zhang, Z X; Li, M

2015-03-13

We explored the associations of INSR and mTOR, 2 key genes in the insulin signaling pathway, and the susceptibility to type 2 diabetes mellitus and diabetic nephropathy. Three single-nucleotide polymorphisms (SNPs) (rs1799817, rs1051690, and rs2059806) in INSR and 3 SNPs (rs7211818, rs7212142, and rs9674559) in mTOR were genotyped using the Sequenom MassARRAY iPLEX platform in 89 type 2 diabetes patients without diabetic nephropathy, 134 type 2 diabetes patients with diabetic nephropathy, and 120 healthy control subjects. Statistical analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95% confidence interval (95%CI) for each SNP. Combination analyses between rs2059806 and rs7212142 were also performed using the X(2) test and logistic regression. Among these 6 SNPs, 4 (rs1799817, rs1051690, rs7211818, and rs9674559) showed no association with type 2 diabetes mellitus or diabetic nephropathy. However, rs2059806 in INSR was associated with both type 2 diabetes mellitus (P = 0.033) and type 2 diabetic nephropathy (P = 0.018). The rs7212142 polymorphism in mTOR was associated with type 2 diabetic nephropathy (P = 0.010, OR = 0.501, 95%CI = 0.288- 0.871), but showed no relationship with type 2 diabetes mellitus. Combination analysis revealed that rs2059806 and rs7212142 had a combined effect on susceptibility to type 2 diabetes mellitus and diabetic nephropathy. Our results suggest that both INSR and mTOR play a role in the predisposition of the Han Chinese population to type 2 diabetic nephropathy, but the genetic predisposition may show some differences.

Impact of IL1B gene polymorphisms and interleukin 1B levels on susceptibility to spontaneous preterm birth.

PubMed

Langmia, Immaculate M; Apalasamy, Yamunah D; Omar, Siti Z; Mohamed, Zahurin

2016-11-01

Genetic factors influence susceptibility to preterm birth (PTB) and the immune pathway of PTB that involves the production of cytokines such as interleukins has been implicated in PTB disease. The aim of this study is to investigate the association of interleukin 1β (IL1B) gene polymorphisms and IL1B levels with spontaneous PTB. Peripheral maternal blood from 495 women was used for extraction of DNA and genotyping was carried out using the Sequenom MassARRAY platform. Maternal plasma was used to measure IL1B levels. There was no significant association between the allelic and genotype distribution of IL1B single nucleotide polymorphism (SNP) (rs1143634, rs1143627, rs16944) and the risk of PTB among Malaysian Malay women (rs1143634, P=0.722; rs1143627, P=0.543; rs16944, P=0.615). However, IL1B levels were significantly different between women who delivered preterm compared with those who delivered at term (P=0.030); high mean levels were observed among Malay women who delivered at preterm (mean=32.52) compared with term (mean=21.68). IL1B SNPs were not associated with IL1B plasma levels. This study indicates a significant association between IL1B levels and reduced risk of PTB among the Malaysian Malay women. This study shows the impact of IL1B levels on susceptibility to PTB disease; however, the high levels of IL1B observed among women in the preterm group are not associated with IL1B SNPs investigated in this study; IL1B high levels may be because of other factors not explored in this study and therefore warrant further investigation.

Association between the CpG island methylator phenotype and its prognostic significance in primary pulmonary adenocarcinoma.

PubMed

Koh, Young Wha; Chun, Sung-Min; Park, Young-Soo; Song, Joon Seon; Lee, Geon Kook; Khang, Shin Kwang; Jang, Se Jin

2016-08-01

Aberrant methylation of promoter CpG islands is one of the most important inactivation mechanisms for tumor suppressor and tumor-related genes. Previous studies using genome-wide DNA methylation microarray analysis have suggested the existence of a CpG island methylator phenotype (CIMP) in lung adenocarcinomas. Although the biological behavior of these tumors varies according to tumor stage, no large-scale study has examined the CIMP in lung adenocarcinoma patients according to tumor stage. Furthermore, there have been no reported results regarding the clinical significance of each of the six CIMP markers. To examine the CIMP in patients with pulmonary adenocarcinoma after a surgical resection, we performed methylation analysis of six genes (CCNA1, ACAN, GFRA1, EDARADD, MGC45800, and p16 (INK4A)) in 230 pulmonary adenocarcinoma cases using the SEQUENOM MassARRAY platform. Fifty-four patients (28 %, 54/191) were in the CIMP-high (CIMP-H) group associated with high nodal stage (P = 0.007), the presence of micropapillary or solid histology (P = 0.003), and the absence of an epidermal growth factor receptor (EGFR) mutation (P = 0.002). By multivariate analysis, CIMP was an independent prognostic marker for overall survival (OS) and disease-specific survival (P = 0.03 and P = 0.43, respectively). In the stage I subgroups alone, CIMP-H patients had lower OS rates than the CIMP-low (CIMP-L) group (P = 0.041). Of the six CIMP markers, ACAN alone was significantly associated with patient survival. CIMP predicted the risk of progression independently of clinicopathological variables and enables the stratification of pulmonary adenocarcinoma patients, particularly among stage I cases.

A functional haplotype of NFKB1 influence susceptibility to oral cancer: a population-based and in vitro study.

PubMed

Chen, Fa; Liu, Fengqiong; Yan, Lingjun; Lin, Lisong; Qiu, Yu; Wang, Jing; Wu, Junfeng; Bao, Xiaodan; Hu, Zhijian; Cai, Lin; He, Baochang

2018-05-01

Genetic variations of NF-κB and its inhibitor IκB genes and their biological mechanism in oral cancer were not well recognized. The purpose of this study was to evaluate the associations of polymorphisms in NFKB1 and NFKBIA with oral cancer susceptibility, and further explore their potential mechanism in vitro. First, the polymorphisms of NFKB1 and NFKBIA were genotyped through iPLEX Sequenom MassARRAY platform in a case-control study with 425 oral cancer patients and 485 healthy controls. Then, the function was explored by a luciferase reporter assay and an electrophoretic mobility shift assay (EMSA) in human tongue squamous cell carcinoma cell lines. The results indicated that NFKB1 rs28362491 Del/Del and rs72696119 G/G genotypes were associated with the risk of oral cancer, with a strong linkage disequilibrium (D' = 0.991, r 2  = 0.971). Moreover, DG haplotype of NFKB1 also showed a significant increased risk (OR = 1.25, 95% CI: 1.02-1.53, P = 0.030). Dual-luciferase reporter assays further revealed that the plasmids with DG or IG or DC haplotype transfected with Tca-8113 cells or CAL-27 cells had a lower luciferase expression than that with IC haplotype. EMSA demonstrated that 4-bp ATTG deletion in the promoter of NFKB1 abolished the binding site of transcription factor. Our preliminary findings suggest that the haplotype of rs28362491 and rs72696119 in NFKB1 could act as a novel genetic marker to predict oral cancer risk in the southeast of China, but much more extensive researches still need to be conducted. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

G6PD deficiency from lyonization after hematopoietic stem cell transplantation from female heterozygous donors.

PubMed

Au, W-Y; Pang, A; Lam, K K Y; Song, Y-Q; Lee, W-M; So, J C C; Kwong, Y-L

2007-10-01

To determine whether during hematopoietic stem cell transplantation (HSCT), X-chromosome inactivation (lyonization) of donor HSC might change after engraftment in recipients, the glucose-6-phosphate dehydrogenase (G6PD) gene of 180 female donors was genotyped by PCR/allele-specific primer extension, and MALDI-TOF mass spectrometry/Sequenom MassARRAY analysis. X-inactivation was determined by semiquantitative PCR for the HUMARA gene before/after HpaII digestion. X-inactivation was preserved in most cases post-HSCT, although altered skewing of lyonization might occur to either of the X-chromosomes. Among pre-HSCT clinicopathologic parameters analyzed, only recipient gender significantly affected skewing. Seven donors with normal G6PD biochemically but heterozygous for G6PD mutants were identified. Owing to lyonization changes, some donor-recipient pairs showed significantly different G6PD levels. In one donor-recipient pair, extreme lyonization affecting the wild-type G6PD allele occurred, causing biochemical G6PD deficiency in the recipient. In HSCT from asymptomatic female donors heterozygous for X-linked recessive disorders, altered lyonization might cause clinical diseases in the recipients.

Filaggrin gene polymorphism associated with Epstein-Barr virus-associated tumors in China.

PubMed

Yang, Yang; Liu, Wen; Zhao, Zhenzhen; Zhang, Yan; Xiao, Hua; Luo, Bing

2017-08-01

Mutations of filaggrin gene (FLG) have been identified as the cause of ichthyosis vulgaris, while recently FLG mutations were found to be associated with gastric cancer. This study aimed to investigate the association of filaggrin polymorphism with Epstein-Barr virus-associated tumors in China. A total of 200 patients with three types of tumors and 117 normal control samples were genotyped at three common FLG mutation loci (rs3126085, K4671X, R501X) by using Sequenom MassARRAY technique. The χ 2 test was used to evaluate the relationship between the mutation and the three kinds of tumors. A two-sided P value of <0.05 was considered statistically significant. The results showed that two single-nucleotide polymorphism (SNP) loci (rs3126085, K4671X) were significantly associated with nasopharyngeal carcinoma in genetic model. In addition, the two SNPs K4671X and rs3126085 were related to Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) and EBV-negative gastric carcinoma (EBVnGC), respectively. Furthermore, allele distributions in EBVaGC and EBVnGC were verified to be different in both SNP loci.

Outcomes of methotrexate therapy for psoriasis and relationship to genetic polymorphisms.

PubMed

Warren, R B; Smith, R L; Campalani, E; Eyre, S; Smith, C H; Barker, J N W N; Worthington, J; Griffiths, C E M

2009-02-01

The use of methotrexate is limited by interindividual variability in response. Previous studies in patients with either rheumatoid arthritis or psoriasis suggest that genetic variation across the methotrexate metabolic pathway might enable prediction of both efficacy and toxicity of the drug. To assess if single nucleotide polymorphisms (SNPs) across four genes that are relevant to methotrexate metabolism [folypolyglutamate synthase (FPGS), gamma-glutamyl hydrolase (GGH), methylenetetrahydrofolate reductase (MTHFR) and 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC)] are related to treatment outcomes in patients with psoriasis. DNA was collected from 374 patients with psoriasis who had been treated with methotrexate. Data were available on individual outcomes to therapy, namely efficacy and toxicity. Haplotype-tagging SNPs (r(2) > 0.8) for the four genes with a minor allele frequency of > 5% were selected from the HAPMAP phase II data. Genotyping was undertaken using the MassARRAY spectrometric method (Sequenom). There were no significant associations detected between clinical outcomes in patients with psoriasis treated with methotrexate and SNPs in the four genes investigated. Genetic variation in four key genes relevant to the intracellular metabolism of methotrexate does not appear to predict response to methotrexate therapy in patients with psoriasis.

SMAD7 loci contribute to risk of hepatocellular carcinoma and clinicopathologic development among Chinese Han population.

PubMed

Ji, Jiansong; Xu, Min; Zhao, Zhongwei; Tu, Jianfei; Gao, Jun; Lu, Chenying; Song, Jingjing; Chen, Weiqian; Chen, Minjiang; Fan, Xiaoxi; Cheng, Xingyao; Lan, Xilin; Li, Jie

2016-04-19

Genome-wide association studies (GWAS) have identified three loci at 18q21 (rs4939827, rs7240004, and rs7229639), which maps to SMAD7 loci, were associated with risk of diseases of the digestive system. However, their associations with hepatocellular carcinoma (HCC) risk remain unknown. A case-control study was conducted to assess genetic associations with HCC risk and clinicopathologic development among Chinese Han population. Three SNPs were genotyped among 1,000 HCC cases and 1,000 controls using Sequenom Mass-ARRAY technology. We observed statistically significant associations for the three SMAD7 loci and HCC risk. Each copy of minor allele was associated with a 1.24-1.36 fold increased risk of HCC. We also found that significant differences were observed between rs4939827 and clinical TNM stage and vascular invasion, as well as rs7240004 and vascular invasion. We also established a genetic risk score (GRS) by summing the risk alleles. The GRS was significantly associated with increased risk of HCC and vascular invasion. Our data revealed the SMAD7 loci is associated with HCC susceptibility and its clinicopathologic development.

Epistatic SNP interaction of ERCC6 with ERCC8 and their joint protein expression contribute to gastric cancer/atrophic gastritis risk.

PubMed

Jing, Jing-Jing; Lu, You-Zhu; Sun, Li-Ping; Liu, Jing-Wei; Gong, Yue-Hua; Xu, Qian; Dong, Nan-Nan; Yuan, Yuan

2017-06-27

Excision repair cross-complementing group 6 and 8 (ERCC6 and ERCC8) are two indispensable genes for the initiation of transcription-coupled nucleotide excision repair pathway. This study aimed to evaluate the interactions between single nucleotide polymorphisms of ERCC6 (rs1917799) and ERCC8 (rs158572 and rs158916) in gastric cancer and its precancerous diseases. Besides, protein level analysis were performed to compare ERCC6 and ERCC8 expression in different stages of gastric diseases, and to correlate SNPs jointly with gene expression. Sequenom MassARRAY platform method was used to detect polymorphisms of ERCC6 and ERCC8 in 1916 subjects. In situ ERCC6 and ERCC8 protein expression were detected by immunohistochemistry in 109 chronic superficial gastritis, 109 chronic atrophic gastritis and 109 gastric cancer cases. Our results demonstrated pairwise epistatic interactions between ERCC6 and ERCC8 SNPs that ERCC6 rs1917799-ERCC8 rs158572 combination was associated with decreased risk of chronic atrophic gastritis and increased risk of gastric cancer. ERCC6 rs1917799 also showed a significant interaction with ERCC8 rs158916 to reduce gastric cancer risk. The expressions of ERCC6, ERCC8 and ERCC6-ERCC8 combination have similarities that higher positivity was observed in chronic superficial gastritis compared with chronic atrophic gastritis and gastric cancer. As for the effects of ERCC6 and ERCC8 SNPs on the protein expression, single SNP had no correlation with corresponding gene expression, whereas the ERCC6 rs1917799-ERCC8 rs158572 pair had significant influence on ERCC6 and ERCC6-ERCC8 expression. In conclusion, ERCC6 rs1917799, ERCC8 rs158572 and rs158916 demonstrated pairwise epistatic interactions to associate with chronic atrophic gastritis and gastric cancer risk. The ERCC6 rs1917799-ERCC8 rs158572 pair significantly influence ERCC6 and ERCC6-ERCC8 expression.

Transforming Growth Factor β1 Induces the Expression of Collagen Type I by DNA Methylation in Cardiac Fibroblasts

PubMed Central

Pan, Xiaodong; Chen, Zhongpu; Huang, Rong; Yao, Yuyu; Ma, Genshan

2013-01-01

Transforming growth factor-beta (TGF-β), a key mediator of cardiac fibroblast activation, has a major influence on collagen type I production. However, the epigenetic mechanisms by which TGF-β induces collagen type I alpha 1 (COL1A1) expression are not fully understood. This study was designed to examine whether or not DNA methylation is involved in TGF-β-induced COL1A1 expression in cardiac fibroblasts. Cells isolated from neonatal Sprague-Dawley rats were cultured and stimulated with TGF-β1. The mRNA levels of COL1A1 and DNA methyltransferases (DNMTs) were determined via quantitative polymerase chain reaction and the protein levels of collagen type I were determined via Western blot as well as enzyme-linked immunosorbent assay. The quantitative methylation of the COL1A1 promoter region was analyzed using the MassARRAY platform of Sequenom. Results showed that TGF-β1 upregulated the mRNA expression of COL1A1 and induced the synthesis of cell-associated and secreted collagen type I in cardiac fibroblasts. DNMT1 and DNMT3a expressions were significantly downregulated and the global DNMT activity was inhibited when treated with 10 ng/mL of TGF-β1 for 48 h. TGF-β1 treatment resulted in a significant reduction of the DNA methylation percentage across multiple CpG sites in the rat COL1A1 promoter. Thus, TGF-β1 can induce collagen type I expression through the inhibition of DNMT1 and DNMT3a expressions as well as global DNMT activity, thereby resulting in DNA demethylation of the COL1A1 promoter. These findings suggested that the DNMT-mediated DNA methylation is an important mechanism in regulating the TGF-β1-induced COL1A1 gene expression. PMID:23560091

The effects of maternal anxiety during pregnancy on IGF2/H19 methylation in cord blood

PubMed Central

Mansell, T; Novakovic, B; Meyer, B; Rzehak, P; Vuillermin, P; Ponsonby, A-L; Collier, F; Burgner, D; Saffery, R; Ryan, J; Vuillermin, Peter; Ponsonby, Anne-Louise; Carlin, John B; Allen, Katie J; Tang, Mimi L; Saffery, Richard; Ranganathan, Sarath; Burgner, David; Dwyer, Terry; Jachno, Kim; Sly, Peter

2016-01-01

Compelling evidence suggests that maternal mental health in pregnancy can influence fetal development. The imprinted genes, insulin-like growth factor 2 (IGF2) and H19, are involved in fetal growth and each is regulated by DNA methylation. This study aimed to determine the association between maternal mental well-being during pregnancy and differentially methylated regions (DMRs) of IGF2 (DMR0) and the IGF2/H19 imprinting control region (ICR) in newborn offspring. Maternal depression, anxiety and perceived stress were assessed at 28 weeks of pregnancy in the Barwon Infant Study (n=576). DNA methylation was measured in purified cord blood mononuclear cells using the Sequenom MassArray Platform. Maternal anxiety was associated with a decrease in average ICR methylation (Δ=−2.23% 95% CI=−3.68 to −0.77%), and across all six of the individual CpG units in anxious compared with non-anxious groups. Birth weight and sex modified the association between prenatal anxiety and infant methylation. When stratified into lower (⩽3530 g) and higher (>3530 g) birth weight groups using the median birth weight, there was a stronger association between anxiety and ICR methylation in the lower birth weight group (Δ=−3.89% 95% CI=−6.06 to −1.72%), with no association in the higher birth weight group. When stratified by infant sex, there was a stronger association in female infants (Δ=−3.70% 95% CI=−5.90 to −1.51%) and no association in males. All the linear regression models were adjusted for maternal age, smoking and folate intake. These findings show that maternal anxiety in pregnancy is associated with decreased IGF2/H19 ICR DNA methylation in progeny at birth, particularly in female, low birth weight neonates. ICR methylation may help link poor maternal mental health and adverse birth outcomes, but further investigation is needed. PMID:27023171

Association of six CpG-SNPs in the inflammation-related genes with coronary heart disease.

PubMed

Chen, Xiaomin; Chen, Xiaoying; Xu, Yan; Yang, William; Wu, Nan; Ye, Huadan; Yang, Jack Y; Hong, Qingxiao; Xin, Yanfei; Yang, Mary Qu; Deng, Youping; Duan, Shiwei

2016-07-25

Chronic inflammation has been widely considered to be the major risk factor of coronary heart disease (CHD). The goal of our study was to explore the possible association with CHD for inflammation-related single nucleotide polymorphisms (SNPs) involved in cytosine-phosphate-guanine (CpG) dinucleotides. A total of 784 CHD patients and 739 non-CHD controls were recruited from Zhejiang Province, China. Using the Sequenom MassARRAY platform, we measured the genotypes of six inflammation-related CpG-SNPs, including IL1B rs16944, IL1R2 rs2071008, PLA2G7 rs9395208, FAM5C rs12732361, CD40 rs1800686, and CD36 rs2065666). Allele and genotype frequencies were compared between CHD and non-CHD individuals using the CLUMP22 software with 10,000 Monte Carlo simulations. Allelic tests showed that PLA2G7 rs9395208 and CD40 rs1800686 were significantly associated with CHD. Moreover, IL1B rs16944, PLA2G7 rs9395208, and CD40 rs1800686 were shown to be associated with CHD under the dominant model. Further gender-based subgroup tests showed that one SNP (CD40 rs1800686) and two SNPs (FAM5C rs12732361 and CD36 rs2065666) were associated with CHD in females and males, respectively. And the age-based subgroup tests indicated that PLA2G7 rs9395208, IL1B rs16944, and CD40 rs1800686 were associated with CHD among individuals younger than 55, younger than 65, and over 65, respectively. In conclusion, all the six inflammation-related CpG-SNPs (rs16944, rs2071008, rs12732361, rs2065666, rs9395208, and rs1800686) were associated with CHD in the combined or subgroup tests, suggesting an important role of inflammation in the risk of CHD.

The Impact of Polymorphic Variations in the 5p15, 6p12, 6p21 and 15q25 Loci on the Risk and Prognosis of Portuguese Patients with Non-Small Cell Lung Cancer

PubMed Central

de Mello, Ramon Andrade; Ferreira, Mónica; Soares-Pires, Filipa; Costa, Sandra; Cunha, João; Oliveira, Pedro; Hespanhol, Venceslau; Reis, Rui Manuel

2013-01-01

Introduction Polymorphic variants in the 5p15, 6p12, 6p21, and 15q25 loci were demonstrated to potentially contribute to lung cancer carcinogenesis. Therefore, this study was performed to assess the role of those variants in non-small cell lung cancer (NSCLC) risk and prognosis in a Portuguese population. Materials and Methods Blood from patients with NSCLC was prospectively collected. To perform an association study, DNA from these patients and healthy controls were genotyped for a panel of 19 SNPs using a Sequenom® MassARRAY platform. Kaplan-Meier curves were used to assess the overall survival (OS) and progression-free survival (PFS). Results One hundred and forty-four patients with NSCLC were successfully consecutively genotyped for the 19 SNPs. One SNP was associated with NSCLC risk: rs9295740 G/A. Two SNPs were associated with non-squamous histology: rs3024994 (VEGF intron 2) T/C and rs401681 C/T. Three SNPs were associated with response rate: rs3025035 (VEGF intron 7) C/T, rs833061 (VEGF –460) C/T and rs9295740 G/A. One SNP demonstrated an influence on PFS: rs401681 C/T at 5p15, p = 0.021. Four SNPs demonstrated an influence on OS: rs2010963 (VEGF +405 G/C), p = 0.042; rs3025010 (VEGF intron 5 C/T), p = 0.047; rs401681 C/T at 5p15, p = 0.046; and rs31489 C/A at 5p15, p = 0.029. Conclusions Our study suggests that SNPs in the 6p12, 6p21, and 5p15 loci may serve as risk, predictive and prognostic NSCLC biomarkers. In the future, SNPs identified in the genomes of patients may improve NSCLC screening strategies and therapeutic management as well. PMID:24039754

Relation of polymorphism of arsenic metabolism genes to arsenic methylation capacity and developmental delay in preschool children in Taiwan.

PubMed

Hsieh, Ru-Lan; Su, Chien-Tien; Shiue, Horng-Sheng; Chen, Wei-Jen; Huang, Shiau-Rung; Lin, Ying-Chin; Lin, Ming-I; Mu, Shu-Chi; Chen, Ray-Jade; Hsueh, Yu-Mei

2017-04-15

Inefficient arsenic methylation capacity has been associated with developmental delay in children. The present study was designed to explore whether polymorphisms and haplotypes of arsenic methyltransferase (AS3MT), glutathione-S-transferase omegas (GSTOs), and purine nucleoside phosphorylase (PNP) affect arsenic methylation capacity and developmental delay. A case-control study was conducted from August 2010 to March 2014. All participants were recruited from the Shin Kong Wu Ho-Su Memorial Teaching Hospital. In total, 179 children with developmental delay and 88 children without delay were recruited. Urinary arsenic species, including arsenite (As III ), arsenate (As V ), monomethylarsonic acid (MMA V ), and dimethylarsinic acid (DMA V ) were measured using a high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphisms of AS3MT, GSTO, and PNP were performed using the Sequenom MassARRAY platform with iPLEX Gold chemistry. Polymorphisms of AS3MT genes were found to affect susceptibility to developmental delay in children, but GSTO and PNP polymorphisms were not. Participants with AS3MT rs3740392 A/G+G/G genotype, compared with AS3MT rs3740392 A/A genotype, had a significantly lower secondary methylation index. This may result in an increased OR for developmental delay. Participants with the AS3MT high-risk haplotype had a significantly higher OR than those with AS3MT low-risk haplotypes [OR and 95% CI, 1.59 (1.08-2.34)]. This is the first study to show a joint dose-response effect of this AS3MT high-risk haplotype and inefficient arsenic methylation capacity on developmental delay. Our data provide evidence that AS3MT genes are related to developmental delay and may partially influence arsenic methylation capacity. Copyright © 2017 Elsevier Inc. All rights reserved.

Polymorphisms of the resistin gene and their association with obesity and resistin levels in Malaysian Malays.

PubMed

Apalasamy, Yamunah Devi; Rampal, Sanjay; Salim, Agus; Moy, Foong Ming; Su, Tin Tin; Majid, Hazreen Abdul; Bulgiba, Awang; Mohamed, Zahurin

2015-06-01

Single nucleotide polymorphisms (SNP) in the resistin gene (RETN) are linked to obesity and resistin levels in various populations. However, results have been inconsistent. This study aimed to investigate association between polymorphisms in the resistin gene with obesity in a homogenous Malaysian Malay population. This study is also aimed to determine association between resistin levels with certain SNPs and haplotypes of RETN. A total of 631 Malaysian Malay subjects were included in this study and genotyping was carried out using Sequenom MassARRAY. There was no significant difference found in both allelic and genotype frequencies of each of the RETN SNPs between the obese and non-obese groups after Bonferroni correction. RETN rs34861192 and rs3219175 SNPs were significantly associated with log-resistin levels. The GG genotype carriers are found to have higher levels of log-resistin compared to A allele carriers. The RETN haplotypes (CAG, CGA and GA) were significantly associated with resistin levels. However, the haplotypes of the RETN gene were not associated with obesity. Resistin levels were not correlated to metabolic parameters such as body weight, waist circumference, body mass index, and lipid parameters. RETN SNPs and haplotypes are of apparent functional importance in the regulation of resistin levels but are not correlated with obesity and related markers.

A novel strategy for forensic age prediction by DNA methylation and support vector regression model

PubMed Central

Xu, Cheng; Qu, Hongzhu; Wang, Guangyu; Xie, Bingbing; Shi, Yi; Yang, Yaran; Zhao, Zhao; Hu, Lan; Fang, Xiangdong; Yan, Jiangwei; Feng, Lei

2015-01-01

High deviations resulting from prediction model, gender and population difference have limited age estimation application of DNA methylation markers. Here we identified 2,957 novel age-associated DNA methylation sites (P < 0.01 and R2 > 0.5) in blood of eight pairs of Chinese Han female monozygotic twins. Among them, nine novel sites (false discovery rate < 0.01), along with three other reported sites, were further validated in 49 unrelated female volunteers with ages of 20–80 years by Sequenom Massarray. A total of 95 CpGs were covered in the PCR products and 11 of them were built the age prediction models. After comparing four different models including, multivariate linear regression, multivariate nonlinear regression, back propagation neural network and support vector regression, SVR was identified as the most robust model with the least mean absolute deviation from real chronological age (2.8 years) and an average accuracy of 4.7 years predicted by only six loci from the 11 loci, as well as an less cross-validated error compared with linear regression model. Our novel strategy provides an accurate measurement that is highly useful in estimating the individual age in forensic practice as well as in tracking the aging process in other related applications. PMID:26635134

Association between RTEL1, PHLDB1, and TREH Polymorphisms and Glioblastoma Risk: A Case-Control Study

PubMed Central

Yang, Bo; Heng, Liang; Du, Shuli; Yang, Hua; Jin, Tianbo; Lang, Hongjuan; Li, Shanqu

2015-01-01

Background Glioblastoma (GBM) is a highly invasive, aggressive, and incurable brain tumor. Genetic factors play important roles in GBM risk. The aim of this study was to elucidate the influence of gene polymorphism on GBM susceptibility. Material/Methods In this case-control study, we included 72 GBM patients and 320 healthy controls to analyze the association between 29 single-nucleotide polymorphisms and GBM cancer risk in the Chinese Han population. The single-nucleotide polymorphisms were determined by Sequenom MassARRAY RS1000 and statistical analysis was performed using SPSS software and SNPStats software. Results Using the χ2 test, we found that rs2297440 and rs6010620 in RTEL1 increased risk of GBM. In the recessive model, we also found that the genotypes “CC” of rs2297440 and “GG” of rs6010620 in RTEL1 significantly increased GBM risk. The variant TT genotype of TREH rs17748 and the variant TT genotype of PHLDB1 rs498872 decreased GBM risk in the recessive model. We also found that the TREH rs17748 variant C allele showed an increased risk in males in the dominant model. Conclusions Our results suggest a significant association between the RETL1, TREH, and PHLDB1 genes and GBM development in the Han Chinese population. PMID:26156397

Association between RTEL1, PHLDB1, and TREH Polymorphisms and Glioblastoma Risk: A Case-Control Study.

PubMed

Yang, Bo; Heng, Liang; Du, Shuli; Yang, Hua; Jin, Tianbo; Lang, Hongjun; Li, Shanqu

2015-07-09

Glioblastoma (GBM) is a highly invasive, aggressive, and incurable brain tumor. Genetic factors play important roles in GBM risk. The aim of this study was to elucidate the influence of gene polymorphism on GBM susceptibility. In this case-control study, we included 72 GBM patients and 320 healthy controls to analyze the association between 29 single-nucleotide polymorphisms and GBM cancer risk in the Chinese Han population. The single-nucleotide polymorphisms were determined by Sequenom MassARRAY RS1000 and statistical analysis was performed using SPSS software and SNPStats software. Using the χ(2) test, we found that rs2297440 and rs6010620 in RTEL1 increased risk of GBM. In the recessive model, we also found that the genotypes "CC" of rs2297440 and "GG" of rs6010620 in RTEL1 significantly increased GBM risk. The variant TT genotype of TREH rs17748 and the variant TT genotype of PHLDB1 rs498872 decreased GBM risk in the recessive model. We also found that the TREH rs17748 variant C allele showed an increased risk in males in the dominant model. Our results suggest a significant association between the RETL1, TREH, and PHLDB1 genes and GBM development in the Han Chinese population.

Association of ADIPOQ gene with obesity and adiponectin levels in Malaysian Malays.

PubMed

Apalasamy, Yamunah Devi; Rampal, Sanjay; Salim, Agus; Moy, Foong Ming; Bulgiba, Awang; Mohamed, Zahurin

2014-05-01

Studies have shown that single-nucleotide polymorphisms (SNPs) on the ADIPOQ gene have been linked with obesity and with adiponectin levels in various populations. Here, we aimed to investigate the association of ADIPOQ rs17366568 and rs3774261 SNPs with obesity and with adiponectin levels in Malaysian Malays. Obesity parameters and adiponectin levels were measured in 574 subjects. Genotyping was performed using real-time polymerase chain reaction and Sequenom MassARRAY. A significant genotypic association was observed between ADIPOQ rs17366568 and obesity. The frequencies of AG and AA genotypes were significantly higher in the obese group (11%) than in the non-obese group (5%) (P=0.024). The odds of A alleles occurring among the obese group were twice those among the non-obese group (odds ratio 2.15; 95% confidence interval 1.13-4.09). However, no significant association was found between allelic frequencies of ADIPOQ rs17366568 and obesity after Bonferroni correction (P>0.025) or between ADIPOQ rs3774261 and obesity both at allelic and genotypic levels. ADIPOQ SNPs were not significantly associated with log-adiponectin levels. GA, GG, and AG haplotypes of the ADIPOQ gene were not associated with obesity. We confirmed the previously reported association of ADIPOQ rs17366568 with the risk of obesity. ADIPOQ SNPs are not important modulators of adiponectin levels in this population.

Genetic Variants of TPCN2 Associated with Type 2 Diabetes Risk in the Chinese Population

PubMed Central

Zhang, Yu; Fan, Xiaofang; Zhang, Ning; Zheng, Hui; Song, Yuping; Shen, Chunfang; Shen, Jiayi; Ren, Fengdong; Yang, Jialin

2016-01-01

Objective The aim of this study was to determine whether TPCN2 genetic variants are associated with type 2 diabetes and to elucidate which variants in TPCN2 confer diabetes susceptibility in the Chinese population. Research Design and Methods The sample population included 384 patients with type 2 diabetes and 1468 controls. Anthropometric parameters, glycemic and lipid profiles and insulin resistance were measured. We selected 6 TPCN2 tag single nucleotide polymorphisms (rs35264875, rs267603153, rs267603154, rs3829241, rs1551305, and rs3750965). Genotypes were determined using a Sequenom MassARRAY SNP genotyping system. Results Ultimately, we genotyped 3 single nucleotide polymorphisms (rs3750965, rs3829241, and rs1551305) in all individuals. There was a 5.1% higher prevalence of the rs1551305 variant allele in type 2 diabetes individuals (A) compared with wild-type homozygous individuals (G). The AA genotype of rs1551305 was associated with a higher diabetes risk (p<0.05). The distributions of rs3829241 and rs3750965 polymorphisms were not significantly different between the two groups. HOMA-%B of subjects harboring the AA genotype of rs1551305 decreased by 14.87% relative to the GG genotype. Conclusions TPCN2 plays a role in metabolic regulation, and the rs1551305 single nucleotide polymorphism is associated with type 2 diabetes risk. Future work will begin to unravel the underlying mechanisms. PMID:26918892

NRAS and EPHB6 mutation rates differ in metastatic melanomas of patients in the North Island versus South Island of New Zealand

PubMed Central

Jones, Angela M.; Ferguson, Peter; Gardner, Jacqui; Rooker, Serena; Sutton, Tim; Ahn, Antonio; Chatterjee, Aniruddha; Bickley, Vivienne M.; Sarwar, Makhdoom; Emanuel, Patrick; Kenwright, Diane; Shepherd, Peter R.; Eccles, Michael R.

2016-01-01

Melanoma, the most aggressive skin cancer type, is responsible for 75% of skin cancer related deaths worldwide. Given that New Zealand (NZ) has the world's highest melanoma incidence, we sought to determine the frequency of mutations in NZ melanomas in recurrently mutated genes. NZ melanomas were from localities distributed between North (35°S-42°S) and South Islands (41°S-47°S). A total of 529 melanomas were analyzed for BRAF exon 15 mutations by Sanger sequencing, and also by Sequenom MelaCarta MassARRAY. While, a relatively low incidence of BRAFV600E mutations (23.4%) was observed overall in NZ melanomas, the incidence of NRAS mutations in South Island melanomas was high compared to North Island melanomas (38.3% vs. 21.9%, P=0.0005), and to The Cancer Genome Atlas database (TCGA) (38.3% vs. 22%, P=0.0004). In contrast, the incidence of EPHB6G404S mutations was 0% in South Island melanomas, and was 7.8% in North Island (P=0.0002). Overall, these data suggest that melanomas from geographically different regions in NZ have markedly different mutation frequencies, in particular in the NRAS and EPHB6 genes, when compared to TCGA or other populations. These data have implications for the causation and treatment of malignant melanoma in NZ. PMID:27191502

Association between PPAP2B gene polymorphisms and coronary heart disease susceptibility in Chinese Han males and females.

PubMed

Sun, Yu-Xiao; Gao, Chuan-Yu; Lu, Yang; Fu, Xin; Jia, Jun-Ge; Zhao, Yu-Jie; Li, Lian-Dong; Dui, Hong-Zhi; Zhang, Xing-Yu; Li, Zhi-Ying; Lei, Lei; Zhang, Wei-Feng; Yuan, Yi-Qiang

2017-02-21

Little is known about gender-related differences in the association between PPAP2B single nucleotide polymorphisms (SNPs) and coronary heart disease (CHD) in Chinese Han males and females. We therefore conducted a case-control study with 456 cases and 685 healthy controls divided into male and female subgroups. Five PPAP2B polymorphisms (SNPs) were selected and genotyped using Sequenom Mass-ARRAY technology. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression adjusting for age and gender. Allelic model analysis revealed that for PPAP2B rs1759752, allele frequency distributions differed between cases and controls in the male subgroup (p = 0.015, OR: 1.401, 95%CI: 1.066-1.481). Genetic model analysis revealed that in the male subgroup, rs1759752 was associated with increased CHD risk in the dominant model (p = 0.035) and overdominant model (p = 0.045). In the female subgroup, rs12566304 was associated with a decreased CHD risk in the codominant model (p = 0.038) and overdominant model (p = 0.031). Additionally, the "GC" haplotypes of rs1759752 and rs1930760 were protective against CHD in males. These observations shed new light on gender-related differences in the association between PPAP2B gene polymorphisms and CHD susceptibility in the Chinese Han population.

Leptin gene promoter DNA methylation in WNIN obese mutant rats

PubMed Central

2014-01-01

Background Obesity has become an epidemic in worldwide population. Leptin gene defect could be one of the causes for obesity. Two mutant obese rats WNIN/Ob and WNIN/GROb, isolated at National Centre for Laboratory Animal Sciences (NCLAS), Hyderabad, India, were found to be leptin resistant. The present study aims to understand the regulatory mechanisms underlying the resistance by promoter DNA methylation of leptin gene in these mutant obese rats. Methods Male obese mutant homozygous, carrier and heterozygous rats of WNIN/Ob and WNIN/GROb strain of 6 months old were studied to check the leptin gene expression (RT-PCR) and promoter DNA methylation (MassARRAY Compact system, SEQUENOM) of leptin gene by invivo and insilico approach. Results Homozygous WNIN/Ob and WNIN/GROb showed significantly higher leptin gene expression compared to carrier and lean counterparts. Leptin gene promoter DNA sequence region was analyzed ranging from transcription start site (TSS) to-550 bp length and found four CpGs in this sequence among them only three CpG loci (-309, -481, -502) were methylated in these WNIN mutant rat phenotypes. Conclusion The increased percentage of methylation in WNIN mutant lean and carrier phenotypes is positively correlated with transcription levels. Thus genetic variation may have effect on methylation percentages and subsequently on the regulation of leptin gene expression which may lead to obesity in these obese mutant rat strains. PMID:24495350

Association of BDNF Polymorphisms with the Risk of Epilepsy: a Multicenter Study.

PubMed

Sha'ari, Hidayati Mohd; Haerian, Batoul Sadat; Baum, Larry; Tan, Hui Jan; Rafia, Mohd Hanip; Kwan, Patrick; Cherny, Stacey S; Sham, Pak Chung; Gui, Hongsheng; Raymond, Azman Ali; Lim, Kheng Seang; Mohamed, Zahurin

2016-07-01

Epilepsy is a common neurological disease characterized by recurrent unprovoked seizures. Evidence suggested that abnormal activity of brain-derived neurotrophic factor (BDNF) contributes to the pathogenesis of epilepsy. Some previous studies identified association between genetic variants of BDNF and risk of epilepsy. In this study, this association has been examined in the Hong Kong and Malaysian epilepsy cohorts. Genomic DNA of 6047 subjects (1640 patients with epilepsy and 4407 healthy individuals) was genotyped for rs6265, rs11030104, rs7103411, and rs7127507 polymorphisms by using Sequenom MassArray and Illumina HumanHap 610-Quad or 550-Duo BeadChip arrays techniques. Results showed significant association between rs6265 T, rs7103411 C, and rs7127507 T and cryptgenic epilepsy risk (p = 0.00003, p = 0.0002, and p = 0.002, respectively) or between rs6265 and rs7103411 and symptomatic epilepsy risk in Malaysian Indians (TT vs. CC, p = 0.004 and T vs. C, p = 0.0002, respectively) as well as between rs6265 T and risk of cryptogenic epilepsy in Malaysian Chinese (p = 0.005). The Trs6265-Crs7103411-Trs7127507 was significantly associated with cryptogenic epilepsy in Malaysian Indians (p = 0.00005). In conclusion, our results suggest that BDNF polymorphisms might contribute to the risk of epilepsy in Malaysian Indians and Chinese.

Analysis of Major Genome Loci Underlying Artemisinin Resistance and pfmdr1 Copy Number in pre- and post-ACTs in Western Kenya

PubMed Central

Ngalah, Bidii S.; Ingasia, Luiser A.; Cheruiyot, Agnes C.; Chebon, Lorna J.; Juma, Dennis W.; Muiruri, Peninah; Onyango, Irene; Ogony, Jack; Yeda, Redemptah A.; Cheruiyot, Jelagat; Mbuba, Emmanuel; Mwangoka, Grace; Achieng, Angela O.; Ng'ang'a, Zipporah; Andagalu, Ben; Akala, Hoseah M.; Kamau, Edwin

2015-01-01

Genetic analysis of molecular markers is critical in tracking the emergence and/or spread of artemisinin resistant parasites. Clinical isolates collected in western Kenya pre- and post- introduction of artemisinin combination therapies (ACTs) were genotyped at SNP positions in regions of strong selection signatures on chromosome 13 and 14, as described in Southeast Asia (SEA). Twenty five SNPs were genotyped using Sequenom MassArray and pfmdr1 gene copy number by real-time PCR. Parasite clearance half-life and in vitro drug sensitivity testing were performed using standard methods. One hundred twenty nine isolates were successfully analyzed. Fifteen SNPs were present in pre-ACTs isolates and six in post-ACTs. None of the SNPs showed association with parasite clearance half-life. Post-ACTs parasites had significantly higher pfmdr1 copy number compared to pre-ACTs. Seven of eight parasites with multiple pfmdr1 were post-ACTs. When in vitro IC50s were compared for parasites with single vs. multiple gene copies, only amodiaquine and piperaquine reached statistical significance. Data showed SNPs on chromosome 13 and 14 had different frequency and trend in western Kenya parasites compared SEA. Increase in pfmdr1 gene copy is consistent with recent studies in African parasites. Data suggests genetic signature of artemisinin resistance in Africa might be different from SEA. PMID:25655315

NRAS and EPHB6 mutation rates differ in metastatic melanomas of patients in the North Island versus South Island of New Zealand.

PubMed

Jones, Angela M; Ferguson, Peter; Gardner, Jacqui; Rooker, Serena; Sutton, Tim; Ahn, Antonio; Chatterjee, Aniruddha; Bickley, Vivienne M; Sarwar, Makhdoom; Emanuel, Patrick; Kenwright, Diane; Shepherd, Peter R; Eccles, Michael R

2016-07-05

Melanoma, the most aggressive skin cancer type, is responsible for 75% of skin cancer related deaths worldwide. Given that New Zealand (NZ) has the world's highest melanoma incidence, we sought to determine the frequency of mutations in NZ melanomas in recurrently mutated genes. NZ melanomas were from localities distributed between North (35°S-42°S) and South Islands (41°S-47°S). A total of 529 melanomas were analyzed for BRAF exon 15 mutations by Sanger sequencing, and also by Sequenom MelaCarta MassARRAY. While, a relatively low incidence of BRAFV600E mutations (23.4%) was observed overall in NZ melanomas, the incidence of NRAS mutations in South Island melanomas was high compared to North Island melanomas (38.3% vs. 21.9%, P=0.0005), and to The Cancer Genome Atlas database (TCGA) (38.3% vs. 22%, P=0.0004). In contrast, the incidence of EPHB6G404S mutations was 0% in South Island melanomas, and was 7.8% in North Island (P=0.0002). Overall, these data suggest that melanomas from geographically different regions in NZ have markedly different mutation frequencies, in particular in the NRAS and EPHB6 genes, when compared to TCGA or other populations. These data have implications for the causation and treatment of malignant melanoma in NZ.

MALDI-TOF mass spectrometry for quantitative gene expression analysis of acid responses in Staphylococcus aureus.

PubMed

Rode, Tone Mari; Berget, Ingunn; Langsrud, Solveig; Møretrø, Trond; Holck, Askild

2009-07-01

Microorganisms are constantly exposed to new and altered growth conditions, and respond by changing gene expression patterns. Several methods for studying gene expression exist. During the last decade, the analysis of microarrays has been one of the most common approaches applied for large scale gene expression studies. A relatively new method for gene expression analysis is MassARRAY, which combines real competitive-PCR and MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry. In contrast to microarray methods, MassARRAY technology is suitable for analysing a larger number of samples, though for a smaller set of genes. In this study we compare the results from MassARRAY with microarrays on gene expression responses of Staphylococcus aureus exposed to acid stress at pH 4.5. RNA isolated from the same stress experiments was analysed using both the MassARRAY and the microarray methods. The MassARRAY and microarray methods showed good correlation. Both MassARRAY and microarray estimated somewhat lower fold changes compared with quantitative real-time PCR (qRT-PCR). The results confirmed the up-regulation of the urease genes in acidic environments, and also indicated the importance of metal ion regulation. This study shows that the MassARRAY technology is suitable for gene expression analysis in prokaryotes, and has advantages when a set of genes is being analysed for an organism exposed to many different environmental conditions.

The associations between VDR BsmI polymorphisms and risk of vitamin D deficiency, obesity and insulin resistance in adolescents residing in a tropical country.

PubMed

Rahmadhani, Rayinda; Zaharan, Nur Lisa; Mohamed, Zahurin; Moy, Foong Ming; Jalaludin, Muhammad Yazid

2017-01-01

The vitamin D receptor (VDR) gene is expressed abundantly in different tissues; including adipocytes and pancreatic beta cells. The rs1544410 or BsmI single nucleotide polymorphism (SNP) in the intronic region of the VDR gene has been previously associated with vitamin D levels, obesity and insulin resistance. This study was aimed to examine the association between BsmI polymorphism and risk of vitamin D deficiency, obesity and insulin resistance in adolescents living in a tropical country. Thirteen-year-old adolescents were recruited via multistage sampling from twenty-three randomly selected schools across the city of Kuala Lumpur, Malaysia (n = 941). Anthropometric measurements were obtained. Obesity was defined as body mass index higher than the 95th percentile of the WHO chart. Levels of fasting serum vitamin D (25-hydroxyvitamin D (25(OH)D)), glucose and insulin were measured. HOMA-IR was calculated as an indicator for insulin resistance. Genotyping was performed using the Sequenom MassARRAY platform (n = 807). The associations between BsmI and vitamin D, anthropometric parameters and HOMA-IR were examined using analysis of covariance and logistic regression. Those with AA genotype of BsmI had significantly lower levels of 25(OH)D (p = 0.001) compared to other genotypes. No significant differences was found across genotypes for obesity parameters. The AA genotype was associated with higher risk of vitamin D deficiency (p = 0.03) and insulin resistance (p = 0.03) compared to GG. The A allele was significantly associated with increased risk of vitamin D deficiency compared to G allele (adjusted odds ratio (OR) = 1.63 (95% Confidence Interval (CI) 1.03-2.59, p = 0.04). In those with concurrent vitamin D deficiency, having an A allele significantly increased their risk of having insulin resistance compared to G allele (adjusted OR = 2.66 (95% CI 1.36-5.19, p = 0.004). VDR BsmI polymorphism was significantly associated with vitamin D deficiency and insulin resistance, but not with obesity in this population.

The associations between VDR BsmI polymorphisms and risk of vitamin D deficiency, obesity and insulin resistance in adolescents residing in a tropical country

PubMed Central

Mohamed, Zahurin; Moy, Foong Ming; Jalaludin, Muhammad Yazid

2017-01-01

Background The vitamin D receptor (VDR) gene is expressed abundantly in different tissues; including adipocytes and pancreatic beta cells. The rs1544410 or BsmI single nucleotide polymorphism (SNP) in the intronic region of the VDR gene has been previously associated with vitamin D levels, obesity and insulin resistance. Aims This study was aimed to examine the association between BsmI polymorphism and risk of vitamin D deficiency, obesity and insulin resistance in adolescents living in a tropical country. Methods Thirteen-year-old adolescents were recruited via multistage sampling from twenty-three randomly selected schools across the city of Kuala Lumpur, Malaysia (n = 941). Anthropometric measurements were obtained. Obesity was defined as body mass index higher than the 95th percentile of the WHO chart. Levels of fasting serum vitamin D (25-hydroxyvitamin D (25(OH)D)), glucose and insulin were measured. HOMA-IR was calculated as an indicator for insulin resistance. Genotyping was performed using the Sequenom MassARRAY platform (n = 807). The associations between BsmI and vitamin D, anthropometric parameters and HOMA-IR were examined using analysis of covariance and logistic regression. Result Those with AA genotype of BsmI had significantly lower levels of 25(OH)D (p = 0.001) compared to other genotypes. No significant differences was found across genotypes for obesity parameters. The AA genotype was associated with higher risk of vitamin D deficiency (p = 0.03) and insulin resistance (p = 0.03) compared to GG. The A allele was significantly associated with increased risk of vitamin D deficiency compared to G allele (adjusted odds ratio (OR) = 1.63 (95% Confidence Interval (CI) 1.03–2.59, p = 0.04). In those with concurrent vitamin D deficiency, having an A allele significantly increased their risk of having insulin resistance compared to G allele (adjusted OR = 2.66 (95% CI 1.36–5.19, p = 0.004). Conclusion VDR BsmI polymorphism was significantly associated with vitamin D deficiency and insulin resistance, but not with obesity in this population. PMID:28617856

IL-1B rs16944 polymorphism is related to septic shock and death.

PubMed

Jiménez-Sousa, María Ángeles; Medrano, Luz M; Liu, Pilar; Almansa, Raquel; Fernández-Rodríguez, Amanda; Gómez-Sánchez, Esther; Rico, Lucía; Heredia-Rodríguez, María; Gómez-Pesquera, Estefanía; Tamayo, Eduardo; Resino, Salvador

2017-01-01

IL-1β is a primary mediator of systemic inflammatory response syndrome (SIRS) and it may lead to shock septic. Our aim was to analyse whether IL-1B rs16944 polymorphism is associated with the onset of septic shock and death after major surgery. We performed a case-control study on 467 patients who underwent major cardiac or abdominal surgery. Of them, 205 patients developed septic shock (cases, SS group) and 262 patients developed SIRS (controls, SIRS group). The primary outcome variables were the development of septic shock and death within 90 days after diagnosis of septic shock. The IL-1B rs16944 polymorphism was genotyped by Sequenom's MassARRAY platform. The association analysis was performed under a recessive genetic model (AA vs. GG/GC). The frequency of septic shock was higher in patients with IL-1B rs16944 AA genotype than in patients with IL-1B rs16944 GG/AG genotype when all patients were taken into account (63·6% vs. 41·8%; P = 0·006), cardiac surgery (52·2% vs. 33·3%; P = 0·072) and abdominal surgery (76·2% vs. 50·2%; P = 0·023). However, the IL-1B rs16944 AA genotype was only associated with higher likelihood of septic shock in the analysis of all population [adjusted odds ratio (aOR) = 2·26 (95%CI = 1·03; 4·97; P = 0·042], but not when it was stratified by cardiac surgery (P = 0·175) or abdominal surgery (P = 0·467). Similarly, IL-1B rs16944 AA genotype was also associated with higher likelihood of septic shock-related death in all population [aOR = 2·67 (95%CI = 1·07; 4·97); P = 0·035]. IL-1B rs16944 AA genotype seems to be related to the onset of septic shock and death in patients who underwent major surgery. © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

Association of genetic polymorphisms of interleukins with gastric cancer and precancerous gastric lesions in a high-risk Chinese population.

PubMed

Wang, Yu-Mei; Li, Zhe-Xuan; Tang, Fu-Bing; Zhang, Yang; Zhou, Tong; Zhang, Lian; Ma, Jun-Ling; You, Wei-Cheng; Pan, Kai-Feng

2016-02-01

Helicobacter pylori (H. pylori) infection and cytokine-mediated inflammatory responses play important roles in gastric cancer (GC) pathogenesis. To investigate an association between genetic polymorphisms in interleukin (IL)-1β, IL-4R, IL-8, IL-10, IL-16, IL-18RAP, IL-22, and IL-32 and risks of GC and its precursors, a population-based study was conducted in Linqu County. Genotypes were determined by Sequenom MassARRAY platform in 132 GC cases and 1198 subjects with gastric lesions. The H. pylori status was determined by (13)C-urea breath test ((13)C-UBT) or enzyme-linked immunosorbent assay (ELISA). Among 11 candidate single nucleotide polymorphisms (SNPs), subjects carrying IL-18RAP rs917997 AA genotype were associated with risk of GC [adjusted odds ratio (OR) = 1.83, 95 % confidence interval (CI) 1.14-2.92] or chronic atrophic gastritis (CAG; OR = 1.55, 95 % CI 1.07-2.24). The risk of GC was also increased in subjects carrying IL-32 rs2015620 A allele (AA + AT; OR = 1.92, 95 % CI 1.09-3.39). Moreover, elevated risks of CAG (OR = 2.64, 95 % CI 1.89-3.69), intestinal metaplasia (IM; OR = 5.58, 95 % CI 3.86-8.05), and dysplasia (DYS; OR = 1.64, 95 % CI 1.18-2.26) were observed in subjects with IL-22 rs1179251 CC genotype. Stratified analysis indicated that risks of GC and its precursors were elevated in subjects with IL-32 rs2015620 A allele (AA + AT) or IL-22 rs1179251 CC genotype and H. pylori infection, and significant interactions between these two SNPs and H. pylori infection were found. These findings suggested that IL-18RAP rs917997, IL-32 rs2015620, IL-22 rs1179251, and interactions between these polymorphisms and H. pylori infection were associated with risks of gastric lesions. Genetic polymorphisms of interleukins may play crucial roles in H. pylori-induced gastric carcinogenesis.

LncRNA ANRIL Expression and ANRIL Gene Polymorphisms Contribute to the Risk of Ischemic Stroke in the Chinese Han Population.

PubMed

Yang, Jialei; Gu, Lian; Guo, Xiaojing; Huang, Jiao; Chen, Zhaoxia; Huang, Guifeng; Kang, Yiwen; Zhang, Xiaoting; Long, Jianxiong; Su, Li

2018-06-07

The aim of the present study was to explore the role of lncRNA ANRIL in the pathogenesis of ischemic stroke (IS) and coronary artery disease (CAD) and to determine the association between ANRIL variants and the genetic susceptibility of IS and CAD in the Chinese Han population. A genetic association study including 550 IS patients, 550 CAD patients, and 550 healthy controls was conducted. The expression levels of lncRNA ANRIL, CDKN2A, and CDKN2B were detected using qRT-PCR. Genotyping was performed by Sequenom MassARRAY on an Agena platform. Our study showed that IS patients had an increased lncRNA ANRIL expression (P = 0.002) and a decreased CDKN2A expression (P < 0.001) compared with normal controls. A significant difference with regard to the genotype distribution of rs2383207 was found between male IS patients and controls (P = 0.011). The minor allele of rs2383207 significantly increased the IS risk under a recessive model (OR = 1.52, 95% CI = 1.05-2.21, P = 0.027). The minor allele of rs1333049 was significantly associated with the risk of IS among the male patients under a recessive model (OR = 1.56, 95% CI = 1.04-2.35, P = 0.031). However, no significant association was found between the ANRIL variants and the risk of CAD (all P > 0.050). In addition, we found a decreased lncRNA ANRIL expression in IS patients who carried the GG genotype of rs1333049 compared with IS patients who carried the CC or CG genotype (P = 0.041). In summary, we found that IS patients had an increased lncRNA ANRIL expression and a decreased CDKN2A expression compared with the controls, which might play an impellent role in pathological processes of IS. The ANRIL variants rs2383207 and rs1333049 were significantly associated with the risk of IS among males but not females in the Chinese Han population.

Gene-Based Single Nucleotide Polymorphism Markers for Genetic and Association Mapping in Common Bean

PubMed Central

2012-01-01

Background In common bean, expressed sequence tags (ESTs) are an underestimated source of gene-based markers such as insertion-deletions (Indels) or single-nucleotide polymorphisms (SNPs). However, due to the nature of these conserved sequences, detection of markers is difficult and portrays low levels of polymorphism. Therefore, development of intron-spanning EST-SNP markers can be a valuable resource for genetic experiments such as genetic mapping and association studies. Results In this study, a total of 313 new gene-based markers were developed at target genes. Intronic variation was deeply explored in order to capture more polymorphism. Introns were putatively identified after comparing the common bean ESTs with the soybean genome, and the primers were designed over intron-flanking regions. The intronic regions were evaluated for parental polymorphisms using the single strand conformational polymorphism (SSCP) technique and Sequenom MassARRAY system. A total of 53 new marker loci were placed on an integrated molecular map in the DOR364 × G19833 recombinant inbred line (RIL) population. The new linkage map was used to build a consensus map, merging the linkage maps of the BAT93 × JALO EEP558 and DOR364 × BAT477 populations. A total of 1,060 markers were mapped, with a total map length of 2,041 cM across 11 linkage groups. As a second application of the generated resource, a diversity panel with 93 genotypes was evaluated with 173 SNP markers using the MassARRAY-platform and KASPar technology. These results were coupled with previous SSR evaluations and drought tolerance assays carried out on the same individuals. This agglomerative dataset was examined, in order to discover marker-trait associations, using general linear model (GLM) and mixed linear model (MLM). Some significant associations with yield components were identified, and were consistent with previous findings. Conclusions In short, this study illustrates the power of intron-based markers for linkage and association mapping in common bean. The utility of these markers is discussed in relation with the usefulness of microsatellites, the molecular markers by excellence in this crop. PMID:22734675

Relation of polymorphism of arsenic metabolism genes to arsenic methylation capacity and developmental delay in preschool children in Taiwan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsieh, Ru-Lan

Inefficient arsenic methylation capacity has been associated with developmental delay in children. The present study was designed to explore whether polymorphisms and haplotypes of arsenic methyltransferase (AS3MT), glutathione-S-transferase omegas (GSTOs), and purine nucleoside phosphorylase (PNP) affect arsenic methylation capacity and developmental delay. A case-control study was conducted from August 2010 to March 2014. All participants were recruited from the Shin Kong Wu Ho-Su Memorial Teaching Hospital. In total, 179 children with developmental delay and 88 children without delay were recruited. Urinary arsenic species, including arsenite (As{sup III}), arsenate (As{sup V}), monomethylarsonic acid (MMA{sup V}), and dimethylarsinic acid (DMA{sup V}) weremore » measured using a high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphisms of AS3MT, GSTO, and PNP were performed using the Sequenom MassARRAY platform with iPLEX Gold chemistry. Polymorphisms of AS3MT genes were found to affect susceptibility to developmental delay in children, but GSTO and PNP polymorphisms were not. Participants with AS3MT rs3740392 A/G + G/G genotype, compared with AS3MT rs3740392 A/A genotype, had a significantly lower secondary methylation index. This may result in an increased OR for developmental delay. Participants with the AS3MT high-risk haplotype had a significantly higher OR than those with AS3MT low-risk haplotypes [OR and 95% CI, 1.59 (1.08–2.34)]. This is the first study to show a joint dose-response effect of this AS3MT high-risk haplotype and inefficient arsenic methylation capacity on developmental delay. Our data provide evidence that AS3MT genes are related to developmental delay and may partially influence arsenic methylation capacity. - Highlights: • AS3MT genotypes were found to affect susceptibility to developmental delay. • AS3MT rs3740392 A/G and G/G genotype had a significantly low SMI (DMA/MMA) index. • AS3MT high-risk haplotype was significantly associated with developmental delay.« less

Breast cancer association studies in a Han Chinese population using 10 European-ancestry-associated breast cancer susceptibility SNPs.

PubMed

Guan, Yan-Ping; Yang, Xue-Xi; Yao, Guang-Yu; Qiu, Fei; Chen, Jun; Chen, Lu-Jia; Ye, Chang-Sheng; Li, Ming

2014-01-01

Genome-wide association studies (GWAS) have identified various genetic susceptibility loci for breast cancer based mainly on European-ancestry populations. Differing linkage disequilibrium patterns exist between European and Asian populations. Ten SNPs (rs2075555 in COL1A1, rs12652447 in FBXL17, rs10941679 in 5p12/MRPS30, rs11878583 in ZNF577, rs7166081 in SMAD3, rs16917302 in ZNF365, rs311499 in 20q13.3, rs1045485 in CASP8, rs12964873 in CDH1 and rs8170 in 19p13.1) were here genotyped in 1009 Chinese females (487 patients with breast cancer and 522 control subjects) using the Sequenom MassARRAY iPLEX platform. Association analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95% confidence interval (95% CI) for each SNP. Stratification analyses were carried out based on the estrogen receptor (ER) and progesterone receptor (PR) status. Among the 10 SNPs, rs10941679 showed significant association with breast cancer when differences between the case and control groups in this Han Chinese population were compared (30.09% GG, 45.4% GA and 23.7% AA; P = 0.012). Four SNPs (rs311499, rs1045485, rs12964873 and rs8170) showed no polymorphisms in our study. The remaining five SNPs showed no association with breast cancer in the present population. Immunohistochemical tests showed that rs2075555 was associated with ER status; the AA genotype showed greater association with ER negative than ER positive (OR = 0.54, 95% CI, 0.29-0.99; P = 0.046). AA of rs7166081 was also associated with ER status, but showed a greater association with ER positive than negative (OR = 1.59, 95% CI = 1.04-2.44; P = 0.031). However, no significant associations were found among the SNPs and PR status. In this study using a Han Chinese population, rs10941679 was the only SNP associated with breast cancer risk, indicating a difference between European and Chinese populations in susceptibility loci. Therefore, confirmation studies are necessary before utilization of these loci in Chinese.

The relationship of 19 functional polymorphisms in iodothyronine deiodinase and psychological well-being in hypothyroid patients.

PubMed

Young Cho, Yoon; Jeong Kim, Hye; Won Jang, Hye; Hyuk Kim, Tae; Ki, Chang-Seok; Wook Kim, Sun; Hoon Chung, Jae

2017-07-01

Levothyroxine supplementation is insufficient for the management of one tenth of patients with hypothyroidism. Iodothyronine deiodinases have been suggested to play a role in residual hypothyroid symptoms of these patients by controlling local thyroid hormone homeostasis. Previous research has suggested a relationship between commonly inherited variations in type 2 iodothyronine deiodinase and impaired well-being. We evaluated the prevalence of iodothyronine deiodinase genotypes and their association with psychological well-being in the Korean hypothyroid population. A prospective observational study. We enrolled 196 hypothyroid subjects (136 chronic autoimmune thyroiditis and 60 thyroid cancer) and assessed baseline well-being using six validated questionnaires. Genotyping was conducted for 19 single nucleotide polymorphisms in type 1, 2, and 3 iodothyronine deiodinase using Sequenom MassARRAY matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in all patients. Frequencies of iodothyronine deiodinase genotypes and well-being scores were not different in hypothyroid subjects according to their disease types. Minor genotypes of a few iodothyronine deiodinase 1 variants (rs11206244, rs2294512, and rs4926616) were associated with reduced psychological well-being. However, iodothyronine deiodinase 2 and 3 variants had no effect on baseline well-being. Minor variations in iodothyronine deiodinase 1 were associated with decreased well-being in the Korean hypothyroid population, whereas iodothyronine deiodinase 2 and 3 were not. Due to controversial results among different ethnicities, further studies to clarify the effects of iodothyronine deiodinase polymorphisms on psychological well-being are warranted in hypothyroid individuals.

HDL-cholesterol concentration in pregnant Chinese Han women of late second trimester associated with genetic variants in CETP, ABCA1, APOC3, and GALNT2.

PubMed

Cui, Mingxuan; Li, Wei; Ma, Liangkun; Ping, Fan; Liu, Juntao; Wu, Xueyan; Mao, Jiangfeng; Wang, Xi; Nie, Min

2017-08-22

To investigate whether HDL-C level in pregnant Chinese Han women of late second trimester correlated with loci in high-density lipoprotein-cholesterol (HDL-C)-related genes found in genome-wide association studies (GWAS). Seven single-nucleotide polymorphisms (rs3764261 in CETP , rs1532085 in LIPC , rs7241918 in LIPG , rs1883025 in ABCA1 , rs4225 in APOC3 , rs1059611 in LPL , and rs16851339 in GALNT2 ) were genotyped using the Sequenom MassArray system for 1,884 pregnant women. The following polymorphisms were statistically associated with HDL-C level after adjusting for age, gestational week, pre-pregnancy BMI and state of GDM or HOMAIR: (i) rs3764261 (b = -0.055 mmol/L, 95% CI -0.101 to -0.008, p = 0.021), (ii) rs1883025 (b = -0.054 mmol/L, 95% CI -0.097 to -0.012, p = 0.013), (iii) rs4225 (b = -0.071 mmol/L, 95% CI -0.116 to -0.027, p = 1.79E-3) and (iv) rs16851339 (b = -0.064 mmol/L, 95% CI -0.120 to -0.008, p = 0.025). The more risk alleles the pregnant women have, the lower the plasma HDL-C levels of the subjects are. Several risk alleles found to be related to HDL-C in GWAS are also associated with HDL-C levels in pregnant Chinese Han women and these risk loci contribute additively to low HDL-C levels.

SLC6A1 gene involvement in susceptibility to attention-deficit/hyperactivity disorder: A case-control study and gene-environment interaction.

PubMed

Yuan, Fang-Fen; Gu, Xue; Huang, Xin; Zhong, Yan; Wu, Jing

2017-07-03

Attention-deficit/hyperactivity disorder (ADHD) is an early onset childhood neurodevelopmental disorder with an estimated heritability of approximately 76%. We conducted a case-control study to explore the role of the SLC6A1 gene in ADHD. The genotypes of eight variants were determined using Sequenom MassARRAY technology. The participants in the study were 302 children with ADHD and 411 controls. ADHD symptoms were assessed using the Conners Parent Symptom Questionnaire. In our study, rs2944366 was consistently shown to be associated with the ADHD risk in the dominant model (odds ratio [OR]=0.554, 95% confidence interval [CI]=0.404-0.760), and nominally associated with Hyperactive index score (P=0.027). In addition, rs1170695 has been found to be associated with the ADHD risk in the addictive model (OR=1.457, 95%CI=1.173-1.809), while rs9990174 was associated with the Hyperactive index score (P=0.010). Intriguingly, gene-environmental interactions analysis consistently revealed the potential interactions of rs1170695 with blood lead (P mul =0.044) to modify the ADHD risk. Expression quantitative trait loci analysis suggested that these positive single nucleotide polymorphisms (SNPs) may mediate SLC6A1 gene expression. Therefore, our results suggest that selected SLC6A1 gene variants may have a significant effect on the ADHD risk. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic variation in WDR1 is associated with gout risk and gout-related metabolic indices in the Han Chinese population.

PubMed

Liu, L J; Zhang, X Y; He, N; Liu, K; Shi, X G; Feng, T; Geng, T T; Yuan, D Y; Kang, L L; Jin, T B

2016-04-28

Gout is the most common form of inflammatory arthritis affecting men, and current evidence suggests that genetic factors contribute to its progression. As a previous study identified that WD40 repeat protein 1 (WDR1) is associated with gout in populations of European descent, we sought to investigate its relationship with this disease in the Han Chinese population. We genotyped six WDR1 single nucleotide polymorphisms in 143 gout cases and 310 controls using Sequenom MassARRAY technology. The SPSS 16.0 software was used to perform statistical analyses. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression, with adjustments for age and gender. In an analysis using an allelic model, we identified that the minor alleles of rs3756230 (OR = 0.64, 95%CI = 0.450-0.911, P = 0.013) and rs12498927 (OR = 1.377, 95%CI = 1.037-1.831, P = 0.027) were associated with gout risk. In addition, we found that the "A/A" genotype of rs12498927 was associated with increased risk of gout under codominant (OR = 2.22, 95%CI = 1.12- 4.40, P = 0.042) and recessive models (OR = 2.24, 95%CI = 1.20-4.17, P = 0.012). We also determined the "A/G" genotype of rs12498927 to be significantly associated with higher urea levels in gout patients (P = 0.017). Our data shed new light on the association between genetic variations in the WDR1 gene and gout susceptibility in the Han Chinese population.

Perinatal maternal alcohol consumption and methylation of the dopamine receptor DRD4 in the offspring: the Triple B study

PubMed Central

Fransquet, Peter D.; Hutchinson, Delyse; Olsson, Craig A.; Wilson, Judy; Allsop, Steve; Najman, Jake; Elliott, Elizabeth; Mattick, Richard P.; Saffery, Richard; Ryan, Joanne

2016-01-01

Maternal alcohol use during the perinatal period is a major public health issue, the higher ends of which are associated with foetal alcohol spectrum disorder and a range of adverse health outcomes in the progeny. The underlying molecular mechanisms remain largely unknown but may include the epigenetic disruption of gene activity during development. Alcohol directly activates the neurotransmitter dopamine, which plays an essential role in neurodevelopment. To investigate whether antenatal and early postnatal alcohol consumption were associated with differential dopamine receptor DRD4 promoter methylation in infants (n = 844). Data were drawn from the large population based Triple B pregnancy cohort study, with detailed information on maternal alcohol consumption in each trimester of pregnancy and early postpartum. DNA was extracted from infant buccal swabs collected at 8-weeks. DRD4 promoter DNA methylation was analysed by Sequenom MassARRAY. No strong evidence was found for an association between alcohol consumption during pregnancy and infant DRD4 methylation at 8-weeks postpartum. However, maternal alcohol consumption assessed contemporaneously at 8-weeks postpartum was associated with increased methylation at 13 of 19 CpG units examined (largest Δ + 3.20%, 95%Confidence Interval:1.66,4.75%, P = 0.0001 at CpG.6). This association was strongest in women who breastfeed, suggesting the possibility of a direct effect of alcohol exposure via breast milk. The findings of this study could influence public health guidelines around alcohol consumption for breastfeeding mothers; however, further research is required to confirm these novel findings. PMID:29492300

HDL-cholesterol concentration in pregnant Chinese Han women of late second trimester associated with genetic variants in CETP, ABCA1, APOC3, and GALNT2

PubMed Central

Cui, Mingxuan; Li, Wei; Ma, Liangkun; Ping, Fan; Liu, Juntao; Wu, Xueyan; Mao, Jiangfeng; Wang, Xi; Nie, Min

2017-01-01

Objective To investigate whether HDL-C level in pregnant Chinese Han women of late second trimester correlated with loci in high-density lipoprotein-cholesterol (HDL-C)-related genes found in genome-wide association studies (GWAS). Methods Seven single-nucleotide polymorphisms (rs3764261 in CETP, rs1532085 in LIPC, rs7241918 in LIPG, rs1883025 in ABCA1, rs4225 in APOC3, rs1059611 in LPL, and rs16851339 in GALNT2) were genotyped using the Sequenom MassArray system for 1,884 pregnant women. Results The following polymorphisms were statistically associated with HDL-C level after adjusting for age, gestational week, pre-pregnancy BMI and state of GDM or HOMAIR: (i) rs3764261 (b = -0.055 mmol/L, 95% CI -0.101 to -0.008, p = 0.021), (ii) rs1883025 (b = -0.054 mmol/L, 95% CI -0.097 to -0.012, p = 0.013), (iii) rs4225 (b = -0.071 mmol/L, 95% CI -0.116 to -0.027, p = 1.79E-3) and (iv) rs16851339 (b = -0.064 mmol/L, 95% CI -0.120 to -0.008, p = 0.025). The more risk alleles the pregnant women have, the lower the plasma HDL-C levels of the subjects are. Conclusions Several risk alleles found to be related to HDL-C in GWAS are also associated with HDL-C levels in pregnant Chinese Han women and these risk loci contribute additively to low HDL-C levels. PMID:28915626

Association between TPMT*3C and decreased thiopurine S-methyltransferase activity in patients with neuromyelitis optica spectrum disorders in China.

PubMed

Gong, Xiaoqing; Mei, Shenghui; Li, Xindi; Li, Xingang; Zhou, Heng; Liu, Yonghong; Zhou, Anna; Yang, Li; Zhao, Zhigang; Zhang, Xinghu

2018-06-01

Thiopurines are effective drugs in treating neuromyelitis optica spectrum disorders and other diseases. Thiopurines' toxicity is mainly imputed to thiopurine S-methyltransferase activity. In Chinese population, the most common and important variation of thiopurine S-methyltransferase is TPMT*3C (rs1142345). This study aims to reveal the association between thiopurine S-methyltransferase activity and genetic polymorphisms of thiopurine S-methyltransferase in patients with neuromyelitis optica spectrum disorders in China. A liquid chromatography tandem mass/mass method was used to evaluate the thiopurine S-methyltransferase activity by using 6-mercapthioprine as the substrate in human erythrocyte haemolysate via 1 h incubation at 37 °C to form its methylated product 6-methylmercaptopurine. The amount of 6-methylmercaptopurine was adjusted by haematocrit and normalized to 8 × 10 8 erythrocytes. The selected polymorphisms of thiopurine S-methyltransferase were identified using MassARRAY system (Sequenom) and multiple SNaPshot technique. In 69 patients with neuromyelitis optica spectrum disorders, thiopurine S-methyltransferase activity was 80.29-154.53 (127.51 ± 16.83) pmol/h/8 × 10 8 erythrocytes. TPMT*3C (rs1142345) was associated with lower thiopurine S-methyltransferase activity (BETA = -25.37, P = 0.011). Other selected variants were not associated with thiopurine S-methyltransferase activity. TPMT*3C affects TPMT activity in Chinese patients with neuromyelitis optica spectrum disorders. Further studies are warranted to confirm the results. TPRs = thiopurines; NMOSD = neuromyelitis optica spectrum disorders; TPMT = thiopurine S-methyltransferase; LC-MS/MS = liquid chromatography tandem mass/mass; 6-MMP = 6-methylmercaptopurine; IS = internal standard; SNP = single nucleotide polymorphism; MAF = minor allele frequency; HWE = Hardy-Weinberg equilibrium; BETA = regression coefficients; UTR-3 = untranslated region 3.

A non-synonymous SNP in the NOS2 associated with septic shock in patients with sepsis in Chinese populations.

PubMed

Wang, Zhifu; Feng, Kai; Yue, Maoxing; Lu, Xiaoguang; Zheng, Qihan; Zhang, Hongxing; Zhai, Yun; Li, Peiyao; Yu, Lixia; Cai, Mi; Zhang, Xiumei; Kang, Xin; Shi, Weihai; Xia, Xia; Chen, Xi; Cao, Pengbo; Li, Yuanfeng; Chen, Huipeng; Ling, Yan; Li, Yuxia; He, Fuchu; Zhou, Gangqiao

2013-03-01

Sepsis represents a systemic inflammatory response to infection and its sequelae include severe sepsis, septic shock, multiple organ dysfunction syndrome (MODS) and death. Studies in mice and humans indicate that the inducible nitric oxide synthase (iNOS, NOS2) plays an important role in the development of sepsis and its sequelae. It was reported that several single nucleotide polymorphisms (SNPs) within NOS2 could influence the production or activity of NOS2. In this study, we assessed whether SNPs within NOS2 gene were associated with severity of sepsis in Chinese populations. A case-control study was conducted, which included 299 and 280 unrelated patients with sepsis recruited from Liaoning and Jiangsu provinces in China, respectively. Six SNPs within NOS2 were genotyped using Sequenom MassARRAY system. The associations between the SNPs and risk of sepsis complications were estimated by a binary logistic regression model adjusted for confounding factors. Functional assay was performed to assess the biological significance. The GA + AA genotype of a non-synonymous SNP in the exon 16 of NOS2 (rs2297518: G>A) was significantly associated with increased susceptibility to septic shock compared with GG genotype in Liaoning population (OR = 3.29, 95% CI = 1.40-7.72, P = 0.0047). This association was confirmed in the Jiangsu population (OR = 3.49, 95% CI = 1.57-7.79, P = 0.0019). Furthermore, the functional assay performed in the immortalized lymphocyte cell lines indicated that the at-risk GA genotype had a tendency of higher NOS2 activity than the GG genotype (P = 0.32). Our findings suggest that the NOS2 rs2297518 may play a role in mediating the susceptibility to septic shock in patients with sepsis in Chinese populations.

Whole-genome single-nucleotide polymorphism (SNP) marker discovery and association analysis with the eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content in Larimichthys crocea

PubMed Central

Xiao, Shijun; Wang, Panpan; Dong, Linsong; Zhang, Yaguang; Han, Zhaofang; Wang, Qiurong

2016-01-01

Whole-genome single-nucleotide polymorphism (SNP) markers are valuable genetic resources for the association and conservation studies. Genome-wide SNP development in many teleost species are still challenging because of the genome complexity and the cost of re-sequencing. Genotyping-By-Sequencing (GBS) provided an efficient reduced representative method to squeeze cost for SNP detection; however, most of recent GBS applications were reported on plant organisms. In this work, we used an EcoRI-NlaIII based GBS protocol to teleost large yellow croaker, an important commercial fish in China and East-Asia, and reported the first whole-genome SNP development for the species. 69,845 high quality SNP markers that evenly distributed along genome were detected in at least 80% of 500 individuals. Nearly 95% randomly selected genotypes were successfully validated by Sequenom MassARRAY assay. The association studies with the muscle eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content discovered 39 significant SNP markers, contributing as high up to ∼63% genetic variance that explained by all markers. Functional genes that involved in fat digestion and absorption pathway were identified, such as APOB, CRAT and OSBPL10. Notably, PPT2 Gene, previously identified in the association study of the plasma n-3 and n-6 polyunsaturated fatty acid level in human, was re-discovered in large yellow croaker. Our study verified that EcoRI-NlaIII based GBS could produce quality SNP markers in a cost-efficient manner in teleost genome. The developed SNP markers and the EPA and DHA associated SNP loci provided invaluable resources for the population structure, conservation genetics and genomic selection of large yellow croaker and other fish organisms. PMID:28028455

ALK rearrangement in a large series of consecutive non-small cell lung cancers: comparison between a new immunohistochemical approach and fluorescence in situ hybridization for the screening of patients eligible for crizotinib treatment.

PubMed

Alì, Greta; Proietti, Agnese; Pelliccioni, Serena; Niccoli, Cristina; Lupi, Cristiana; Sensi, Elisa; Giannini, Riccardo; Borrelli, Nicla; Menghi, Maura; Chella, Antonio; Ribechini, Alessandro; Cappuzzo, Federico; Melfi, Franca; Lucchi, Marco; Mussi, Alfredo; Fontanini, Gabriella

2014-11-01

Echinoderm microtubule associated proteinlike 4-anaplastic lymphoma receptor tyrosine kinase (EML4-ALK) translocation has been described in a subset of patients with non-small cell lung cancer (NSCLC) and has been shown to have oncogenic activity. Fluorescence in situ hybridization (FISH) is used to detect ALK-positive NSCLC, but it is expensive, time-consuming, and difficult for routine application. To evaluate the potential role of immunohistochemistry (IHC) as a screening tool to identify candidate cases for FISH analysis and for ALK inhibitor therapy in NSCLC. We performed FISH and IHC for ALK and mutational analysis for epidermal growth factor receptor (EGFR) and KRAS in 523 NSCLC specimens. We conducted IHC analysis with the monoclonal antibody D5F3 (Ventana Medical Systems, Tucson, Arizona) and a highly sensitive detection system. We also performed a MassARRAY-based analysis (Sequenom, San Diego, California) in a small subset of 11 samples to detect EML4-ALK rearrangement. Of the 523 NSCLC specimens, 20 (3.8%) were positive for ALK rearrangement by FISH analysis. EGFR and KRAS mutations were identified in 70 (13.4%) and 124 (23.7%) of the 523 tumor samples, respectively. ALK rearrangement and EGFR and KRAS mutations were mutually exclusive. Of 523 tumor samples analyzed, 18 (3.4%) were ALK(+) by IHC, 18 samples (3.4%) had concordant IHC and FISH results, and 2 ALK(+) cases (0.3%) by FISH failed to show ALK protein expression. In the 2 discrepant cases, we did not detect any mass peaks for the EML4-ALK variants by MassARRAY. Our results show that IHC may be a useful technique for selecting NSCLC cases to undergo ALK FISH analysis.

Variants in the CXCL12 gene was associated with coronary artery disease susceptibility in Chinese Han population

PubMed Central

Gao, Jie; Kong, Shu; You, Jiangtao; Sheng, Ying

2017-01-01

Background Coronary artery disease (CAD) is one of the most serious diseases all around the world. Previous studies have shown the function of CXCL12 in the process of atherosclerosis. The aim of this research is to examine whether variants of CXCL12 contribute to CAD. Materials and Methods To examine whether variants of CXCL12 contribute to CAD, we selected 6 single nucleotide polymorphisms (SNPs) of CXCL12, and genotyped by Sequenom MassARRAY technology in 597 CAD patients and 685 healthy control. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusted for age and gender. We also analysis the differences in continuous variables among the subjects with three genotypes of related genes were assessed using the ANOVA. Results We found significant differences in apoB concentrations with rs1065297 and rs10793538 different genotype. In the allele model, rs1065297, rs266089 and rs10793538 in CXCL12 gene associated with the risk of CAD. Stratified according to gender, rs266089 and rs2839693 in CXCL12 gene were associated with the risk of CAD in men, while rs1065297 and rs10793538 in CXCL12 gene were associated with the risk of CAD in women. Stratified according to age, rs197452 decreased the risk of CAD in less than 50 years old group. While in more than 50 years old group, not find significant results. Haplotype analysis shown that haplotype “TGCC” in the block increased CAD risk (OR=1.26, 95%CI: 1.00-1.58, p=0.046). Conclusion This study provides an evidence for polymorphism of CXCL12 gene associated with CAD development in Chinese Han population. PMID:28903360

Evaluation of methylation status of the eNOS promoter at birth in relation to childhood bone mineral content

PubMed Central

Harvey, Nicholas C.; Lillycrop, Karen A.; Garratt, Emma; Sheppard, Allan; McLean, Cameron; Burdge, Graham; Slater-Jefferies, Jo; Rodford, Joanne; Crozier, Sarah; Inskip, Hazel; Emerald, Bright Starling; Gale, Catharine R; Hanson, Mark; Gluckman, Peter; Godfrey, Keith; Cooper, Cyrus

2013-01-01

Aim Our previous work has shown associations between childhood adiposity and perinatal methylation status of several genes in umbilical cord tissue, including endothelial nitric oxide synthase (eNOS). There is increasing evidence that eNOS is important in bone metabolism; we therefore related the methylation status of the eNOS gene promoter in stored umbilical cord to childhood bone size and density in a group of 9-year old children. Methods We used Sequenom MassARRAY to assess the methylation status of 2 CpGs in the eNOS promoter, identified from our previous study, in stored umbilical cords of 66 children who formed part of a Southampton birth cohort and who had measurements of bone size and density at age 9 years (Lunar DPXL DXA instrument). Results Percentage methylation varied greatly between subjects. For one of the two CpGs, eNOS chr7:150315553+, after taking account of age and sex there was a strong positive association between methylation status and the child’s whole body bone area (r=0.28,p=0.02), bone mineral content (r=0.34,p=0.005) and areal bone mineral density (r=0.34,p=0.005) at age 9 years. These associations were independent of previously documented maternal determinants of offspring bone mass. Conclusions Our findings suggest an association between methylation status at birth of a specific CpG within the eNOS promoter and bone mineral content in childhood. This supports a role for eNOS in bone growth and metabolism and implies that its contribution may at least in part occur during early skeletal development. PMID:22159788

Follow-up study identifies two novel susceptibility loci PRKCB and 8p11.21 for systemic lupus erythematosus.

PubMed

Sheng, Yu-Jun; Gao, Jin-Ping; Li, Jian; Han, Jian-Wen; Xu, Qiang; Hu, Wen-Long; Pan, Ting-Meng; Cheng, Yi-Lin; Yu, Ze-Ying; Ni, Cheng; Yao, Sha; He, Cai-Feng; Liu, Yang-Sheng; Li, Yun; Ge, Hong-Mei; Xiao, Feng-Li; Sun, Liang-Dan; Yang, Sen; Zhang, Xue-Jun

2011-04-01

We have performed a large-scale replication study based on our previous genome-wide association study (GWAS) of SLE in the Chinese Han population to further explore additional genetic variants affecting susceptibility to SLE. Thirty-eight single nucleotide polymorphisms from our GWAS were genotyped in two additional Chinese Han cohorts (total 3152 cases and 7050 controls) using the Sequenom Massarray system. Association analyses were performed using logistic regression with gender or sample cohorts as a covariate. Association evidence for rs16972959 (PRKCB at 16p11.2) and rs12676482 (8p11.21) with SLE was replicated independently in both replication cohorts (P < 0.05), showing high significance for SLE in combined all 4199 cases and 8255 controls of Chinese Han [rs16972959: odds ratio (OR) = 0.81; 95% CI 0.76, 0.87; P(combined) = 1.35 × 10(-9); rs12676482: OR = 1.26; 95% CI 1.15, 1.38; P(combined) = 6.68 × 10(-7)). PRKCB is related to the established SLE immune-related pathway (NF-κB) and 8p11.21 contains important candidate genes such as IKBKB and DKK4. IKBKB is a critical component of NF-κB and DKK4 is an inhibitor of canonical Wnt signalling pathway. Interestingly, PRKCB is required for recruiting IKBKB into lipid rafts, up-regulating NF-κB-dependent survival signal. Our findings provided novel insights into the genetic architecture of SLE and emphasized the contribution of multiple variants of modest effect. Further study focused on PRKCB, 8p11.21, should advance our understanding on the pathogenesis of SLE.

Cannabis use by women during pregnancy does not influence infant DNA methylation of the dopamine receptor DRD4.

PubMed

Fransquet, Peter D; Hutchinson, Delyse; Olsson, Craig A; Allsop, Steve; Elliott, Elizabeth J; Burns, Lucinda; Mattick, Richard; Saffery, Richard; Ryan, Joanne

2017-11-01

Maternal cannabis use in pregnancy is linked with long-term adverse behavioral outcomes in offspring. Epigenetic processes established in utero that affect dopaminergic (reward) signaling may mediate risks. Associations between cannabis use and offspring DNA methylation have not been investigated; however, maternal tobacco smoking in pregnancy is associated with distinct patterns of DNA methylation at birth and beyond. To determine whether maternal cannabis use is associated with methylation of the dopamine receptor gene DRD4 promoter in infants. Mothers in the Triple B study provided detailed information on drug use in each trimester of pregnancy. Buccal swabs were collected from neonates at 8 weeks (n = 804, 51.7% male, and 48.3% female). DRD4 promoter DNA methylation was measured using SEQUENOM MassARRAY. Fifty-seven of the women in the study reported drug use during pregnancy, of whom 44 used cannabis. Of 19 cytosine-phosphate-guanine dinucleotides (CpG) units tested in DRD4, gestational cannabis use was associated with offspring methylation at 1 CpG unit in multivariate models (β + 1.48, CI: 0.02 to 2.93, and p = 0.047). At another site there was weak evidence that both cannabis and other drug use were independently associated with increased methylation, while the association with tobacco was in the reverse direction (cannabis use β + 0.67, CI: -0.12 to 1.46, and p = 0.09; other drug use β + 1.11, CI: 0.17 to 2.05, and p = 0.02; tobacco use β -0.41, CI: -0.85 to 0.03, and p = 0.07). None of the associations would remain significant after correction for multiple testing. There is no strong evidence that maternal cannabis use in pregnancy is associated with offspring DRD4 methylation.

Strong effect of SNP rs4988300 of the LRP5 gene on bone phenotype of Caucasian postmenopausal women.

PubMed

Horváth, Péter; Balla, Bernadett; Kósa, János P; Tóbiás, Bálint; Szili, Balázs; Kirschner, Gyöngyi; Győri, Gabriella; Kató, Karina; Lakatos, Péter; Takács, István

2016-01-01

The purpose of this study was to identify relationships between single nucleotide polymorphisms (SNPs) in the genes of the Wnt pathway and bone mineral density (BMD) of postmenopausal women. We chose this pathway due to its importance in bone metabolism that was underlined in several studies. DNA samples of 932 Hungarian postmenopausal women were studied. First, their BMD values at different sites (spine, total hip) were measured, using a Lunar Prodigy DXA scanner. Thereafter, T-score values and the patients' body mass indices (BMIs) were calculated, while information about the fracture history of the sample population was also collected. We genotyped nine SNPs of the following three genes: LRP5, GPR177, and SP7, using a Sequenom MassARRAY Analyzer 4 instrument. The genomic DNA samples used for genotyping were extracted from the buccal mucosa of the subjects. Statistical analyses were carried out using the SPSS 21 and R package. The results of this analysis showed a significant association between SNP rs4988300 of the LRP5 gene and total hip BMD values. We could not reveal any associations between the markers of GPR177, SP7, and bone phenotypes. We found no effect of these genotypes on fracture risk. We could demonstrate a significant gene-gene interaction between two SNPs of LRP5 (rs4988300 and rs634008, p = 0.009) which was lost after Bonferroni correction. We could firmly demonstrate a significant association between rs4988300 of the LRP5 gene and bone density of the hip on the largest homogeneous postmenopausal study group analyzed to date. Our finding corroborates the relationship between LRP5 genotype and bone phenotype in postmenopausal women, however, the complete mechanism of this relationship requires further investigations.

Genome-Wide Association Study among Four Horse Breeds Identifies a Common Haplotype Associated with In Vitro CD3+ T Cell Susceptibility/Resistance to Equine Arteritis Virus Infection ▿

PubMed Central

Go, Yun Young; Bailey, Ernest; Cook, Deborah G.; Coleman, Stephen J.; MacLeod, James N.; Chen, Kuey-Chu; Timoney, Peter J.; Balasuriya, Udeni B. R.

2011-01-01

Previously, we have shown that horses could be divided into susceptible and resistant groups based on an in vitro assay using dual-color flow cytometric analysis of CD3+ T cells infected with equine arteritis virus (EAV). Here, we demonstrate that the differences in in vitro susceptibility of equine CD3+ T lymphocytes to EAV infection have a genetic basis. To investigate the possible hereditary basis for this trait, we conducted a genome-wide association study (GWAS) to compare susceptible and resistant phenotypes. Testing of 267 DNA samples from four horse breeds that had a susceptible or a resistant CD3+ T lymphocyte phenotype using both Illumina Equine SNP50 BeadChip and Sequenom's MassARRAY system identified a common, genetically dominant haplotype associated with the susceptible phenotype in a region of equine chromosome 11 (ECA11), positions 49572804 to 49643932. The presence of a common haplotype indicates that the trait occurred in a common ancestor of all four breeds, suggesting that it may be segregated among other modern horse breeds. Biological pathway analysis revealed several cellular genes within this region of ECA11 encoding proteins associated with virus attachment and entry, cytoskeletal organization, and NF-κB pathways that may be associated with the trait responsible for the in vitro susceptibility/resistance of CD3+ T lymphocytes to EAV infection. The data presented in this study demonstrated a strong association of genetic markers with the trait, representing de facto proof that the trait is under genetic control. To our knowledge, this is the first GWAS of an equine infectious disease and the first GWAS of equine viral arteritis. PMID:21994447

Contribution of TIMP4 rs3755724 polymorphism to susceptibility to focal epilepsy in Malaysian Chinese.

PubMed

Haerian, Batoul Sadat; Sha'ari, Hidayati Mohd; Fong, Choong Yi; Tan, Hui Jan; Wong, Sau Wei; Ong, Lai Choo; Raymond, Azman Ali; Tan, Chong Tin; Mohamed, Zahurin

2015-01-15

Neuroinflammation can damage the brain and plays a critical role in the pathophysiology of epilepsy. Tissue inhibitor of metalloproteinase 4 (TIMP4) is an inflammation-induced apoptosis and matrix turnover factor involved in several neuronal disorders and inflammatory diseases. Evidence has shown linkage disequilibrium between rs3755724 (-55C/T) of this gene with synapsin 2 (SYN2) rs3773364 and peroxisome proliferator-activated G receptor (PPARG) rs2920502 loci, which contribute to epilepsy in Caucasians. The aim of this study was to examine the association of these loci alone or their haplotypes with the risk of epilepsy in the Malaysian population. Genomic DNA of 1241 Malaysian Chinese, Indian, and Malay subjects (670 patients with epilepsy and 571 healthy individuals) was genotyped for the candidate loci by using the Sequenom MassArray method. Allele and genotype association of rs3755724 with susceptibility to epilepsy was significant in the Malaysian Chinese with focal epilepsy under codominant and dominant models (C vs. T: 1.5 (1.1-2.0), p=0.02; CT vs. TT: 1.8 (1.2-2.8), p=0.007 and 1.8 (1.2-2.7), p=0.006, respectively). The T allele and the TT genotype were more common in patients than in controls. No significant association was found between rs2920502 and rs3773364-rs3755724-rs2920502 haplotypes for susceptibility to epilepsy in each ethnicity. This study provides evidence that the promoter TIMP4 rs3755724 is a new focal epilepsy susceptibility variant that is plausibly involved in inflammation-induced seizures in Malaysian Chinese. Copyright © 2014 Elsevier B.V. All rights reserved.

TESTIN Induces Rapid Death and Suppresses Proliferation in Childhood B Acute Lymphoblastic Leukaemia Cells

PubMed Central

Weeks, Robert J.; Ludgate, Jackie L.; LeMée, Gwenn; Morison, Ian M.

2016-01-01

Background Childhood acute lymphoblastic leukaemia (ALL) is the most common malignancy in children. Despite high cure rates, side effects and late consequences of the intensive treatments are common. Unquestionably, the identification of new therapeutic targets will lead to safer, more effective treatments. We identified TES promoter methylation and transcriptional silencing as a very common molecular abnormality in childhood ALL, irrespective of molecular subtype. The aims of the present study were to demonstrate that TES promoter methylation is aberrant, to determine the effects of TES re-expression in ALL, and to determine if those effects are mediated via TP53 activity. Methods Normal fetal and adult tissue DNA was isolated and TES promoter methylation determined by Sequenom MassARRAY. Quantitative RT-PCR and immunoblot were used to confirm re-expression of TES in ALL cell lines after 5’-aza-2’-deoxycytidine (decitabine) exposure or transfection with TES expression plasmids. The effects of TES re-expression on ALL cells were investigated using standard cell proliferation, cell death and cell cycle assays. Results In this study, we confirm that the TES promoter is unmethylated in normal adult and fetal tissues. We report that decitabine treatment of ALL cell lines results in demethylation of the TES promoter and attendant expression of TES mRNA. Re-expression of TESTIN protein in ALL cells using expression plasmid transfection results in rapid cell death or cell cycle arrest independent of TP53 activity. Conclusions These results suggest that TES is aberrantly methylated in ALL and that re-expression of TESTIN has anti-leukaemia effects which point to novel therapeutic opportunities for childhood ALL. PMID:26985820

Genetic Testing as a New Standard for Clinical Diagnosis of Color Vision Deficiencies.

PubMed

Davidoff, Candice; Neitz, Maureen; Neitz, Jay

2016-09-01

The genetics underlying inherited color vision deficiencies is well understood: causative mutations change the copy number or sequence of the long (L), middle (M), or short (S) wavelength sensitive cone opsin genes. This study evaluated the potential of opsin gene analyses for use in clinical diagnosis of color vision defects. We tested 1872 human subjects using direct sequencing of opsin genes and a novel genetic assay that characterizes single nucleotide polymorphisms (SNPs) using the MassArray system. Of the subjects, 1074 also were given standard psychophysical color vision tests for a direct comparison with current clinical methods. Protan and deutan deficiencies were classified correctly in all subjects identified by MassArray as having red-green defects. Estimates of defect severity based on SNPs that control photopigment spectral tuning correlated with estimates derived from Nagel anomaloscopy. The MassArray assay provides genetic information that can be useful in the diagnosis of inherited color vision deficiency including presence versus absence, type, and severity, and it provides information to patients about the underlying pathobiology of their disease. The MassArray assay provides a method that directly analyzes the molecular substrates of color vision that could be used in combination with, or as an alternative to current clinical diagnosis of color defects.

Genetic Testing as a New Standard for Clinical Diagnosis of Color Vision Deficiencies

PubMed Central

Davidoff, Candice; Neitz, Maureen; Neitz, Jay

2016-01-01

Purpose The genetics underlying inherited color vision deficiencies is well understood: causative mutations change the copy number or sequence of the long (L), middle (M), or short (S) wavelength sensitive cone opsin genes. This study evaluated the potential of opsin gene analyses for use in clinical diagnosis of color vision defects. Methods We tested 1872 human subjects using direct sequencing of opsin genes and a novel genetic assay that characterizes single nucleotide polymorphisms (SNPs) using the MassArray system. Of the subjects, 1074 also were given standard psychophysical color vision tests for a direct comparison with current clinical methods. Results Protan and deutan deficiencies were classified correctly in all subjects identified by MassArray as having red–green defects. Estimates of defect severity based on SNPs that control photopigment spectral tuning correlated with estimates derived from Nagel anomaloscopy. Conclusions The MassArray assay provides genetic information that can be useful in the diagnosis of inherited color vision deficiency including presence versus absence, type, and severity, and it provides information to patients about the underlying pathobiology of their disease. Translational Relevance The MassArray assay provides a method that directly analyzes the molecular substrates of color vision that could be used in combination with, or as an alternative to current clinical diagnosis of color defects. PMID:27622081

Identification of susceptibility genes and genetic modifiers of human diseases

NASA Astrophysics Data System (ADS)

Abel, Kenneth; Kammerer, Stefan; Hoyal, Carolyn; Reneland, Rikard; Marnellos, George; Nelson, Matthew R.; Braun, Andreas

2005-03-01

The completion of the human genome sequence enables the discovery of genes involved in common human disorders. The successful identification of these genes is dependent on the availability of informative sample sets, validated marker panels, a high-throughput scoring technology, and a strategy for combining these resources. We have developed a universal platform technology based on mass spectrometry (MassARRAY) for analyzing nucleic acids with high precision and accuracy. To fuel this technology, we generated more than 100,000 validated assays for single nucleotide polymorphisms (SNPs) covering virtually all known and predicted human genes. We also established a large DNA sample bank comprised of more than 50,000 consented healthy and diseased individuals. This combination of reagents and technology allows the execution of large-scale genome-wide association studies. Taking advantage of MassARRAY"s capability for quantitative analysis of nucleic acids, allele frequencies are estimated in sample pools containing large numbers of individual DNAs. To compare pools as a first-pass "filtering" step is a tremendous advantage in throughput and cost over individual genotyping. We employed this approach in numerous genome-wide, hypothesis-free searches to identify genes associated with common complex diseases, such as breast cancer, osteoporosis, and osteoarthritis, and genes involved in quantitative traits like high density lipoproteins cholesterol (HDL-c) levels and central fat. Access to additional well-characterized patient samples through collaborations allows us to conduct replication studies that validate true disease genes. These discoveries will expand our understanding of genetic disease predisposition, and our ability for early diagnosis and determination of specific disease subtype or progression stage.

Prolactin rs1341239 T allele may have protective role against the brick tea type skeletal fluorosis.

PubMed

Li, Bing-Yun; Yang, Yan-Mei; Liu, Yang; Sun, Jing; Ye, Yan; Liu, Xiao-Na; Liu, Hong-Xu; Sun, Zhen-Qi; Li, Mang; Cui, Jing; Sun, Dian-Jun; Gao, Yan-Hui

2017-01-01

Prolactin (PRL) has been reported to be associated with increased bone turnover, and increased bone turnover is also a feature of skeletal fluorosis (SF). Autocrine/paracrine production of PRL is regulated by the extrapituitary promoter and a polymorphism in the extrapituitary PRL promoter at -1149 (rs1341239) is associated with disturbances of bone metabolism in other diseases. Here, we have investigated the possibility that the rs1341239 polymorphism is associated with SF, which results from the consumption of brick tea. We conducted a cross-sectional study in Sinkiang, Qinghai, Inner Mongolia in China. Demography survey questionnaires were completed and physical examination and X-ray diagnoses were used to diagnose SF. Brick tea water fluoride intake (IF) and urinary fluoride (UF) were tested by an F-ion selective electrode method. A Sequenom MassARRAY system was used to determine PRL gene polymorphisms. Subjects who were younger than 45 years of age and carried the T allele had a significantly decreased risk of SF [OR = 0.279 (95%CI, 0.094-0.824)] compared to those carrying the homozygous G allele. This phenomenon was only observed in Kazakh subjects [OR = 0.127 (95%CI, 0.025-0.646)]. Kazakh females who carried T alleles has a decreased risk of SF [OR = 0.410 (95%CI, 0.199-0.847)]. For Kazakh subjects which IF is less than 3.5 mg/d, a decreased risk of SF was observed among the participants who carried T alleles [OR = 0.118 (95%CI, 0.029-0.472)]. Overall, subjects with 1.6-3.2 mg/L UF and carried T alleles had a significantly decreased risk of SF [OR = 0.476 (95%CI, 0.237-0.955)] compared to homozygous G allele carriers. This phenomenon was only observed in Kazakh subjects [OR = 0.324 (95%CI, 0.114-0.923)]. Our results suggested that the PRL rs1341239 T allele decreases the risk of brick tea SF.

Polymorphisms in ERAP1 and ERAP2 are shared by Caninae and segregate within and between random- and pure-breeds of dogs.

PubMed

Pedersen, N C; Dhanota, J K; Liu, H

2016-10-15

Specific polymorphisms in the endoplasmic reticulum amino peptidase genes ERAP1 and ERAP2, when present with certain MHC class receptor types, have been associated with increased risk for specific cancers, infectious diseases and autoimmune disorders in humans. This increased risk has been linked to distinct polymorphisms in both ERAPs and MHC class I receptors that affect the way cell-generated peptides are screened for antigenicity. The incidence of cancer, infectious disease and autoimmune disorders differ greatly among pure breeds of dogs as it does in humans and it is possible that this heightened susceptibility is also due to specific polymorphisms in ERAP1 and ERAP2. In order to determine if such polymorphisms exist, the ERAP1 and ERAP2 genes of 10 dogs of nine diverse breeds were sequenced and SNPs causing synonymous or non-synonymous amino acid changes, deletions or insertions were identified. Eight ERAP1 and 10 ERAP2 SNPs were used to create a Sequenom MassARRAY iPLEX based test panel which defined 24 ERAP1, 36 ERAP2 and 128 ERAP1/2 haplotypes. The prevalence of these haplotypes was then measured among dog, wolf, coyote, jackal and red fox populations. Some haplotypes were species specific, while others were shared across species, especially between dog, wolf, coyote and jackal. The prevalence of these haplotypes was then compared among various canid populations, and in particular between various populations of random- and pure-bred dogs. Human-directed positive selection has led to loss of ERAP diversity and segregation of certain haplotypes among various dog breeds. A phylogenetic tree generated from 45 of the most common ERAP1/2 haplotypes demonstrated three distinct clades, all of which were rooted with haplotypes either shared among species or specific to contemporary dogs, coyote and wolf. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

The association of AGTR2 polymorphisms with preeclampsia and uterine artery bilateral notching is modulated by maternal BMI.

PubMed

Zhou, A; Dekker, G A; Lumbers, E R; Lee, S Y; Thompson, S D; McCowan, L M E; Roberts, C T

2013-01-01

This study aimed to determine the association of AGTR1 and AGTR2 polymorphisms with preeclampsia and whether these are affected by environmental factors and fetal sex. Overall 3234 healthy nulliparous women, their partners and babies were recruited prospectively to the SCOPE study in Adelaide and Auckland. Data analyses were confined to 2121 Caucasian parent-infant trios, among whom 123 had preeclamptic pregnancies. 1185 uncomplicated pregnancies served as controls. DNA was extracted from buffy coats and genotyped by utilizing the Sequenom MassARRAY system. Doppler sonography on the uterine arteries was performed at 20 weeks' gestation. Four polymorphisms in AGTR1 and AGTR2 genes, including AGTR1 A1166C, AGTR2 C4599A, AGTR2 A1675G and AGTR2 T1134C, were selected and significant associations were predominately observed for AGTR2 C4599A. When the cohort was stratified by maternal BMI, in women with BMI ≥ 25 kg/m(2), the AGTR2 C4599A AA genotype in mothers and neonates was associated with an increased risk for preeclampsia compared with the CC genotype [adjusted OR 2.1 (95% CI 1.0-4.2) and adjusted OR 3.0 (95% CI 1.4-6.4), respectively]. In the same subset of women, paternal AGTR2 C4599A A allele was associated with an increased risk for preeclampsia and uterine artery bilateral notching at 20 weeks' gestation compared with the C allele [adjusted OR 1.9 (95% CI 1.1-3.3) and adjusted OR 2.1 (95% CI 1.3-3.4), respectively]. AGTR2 C4599A in mothers, fathers and babies was associated with preeclampsia and this association was only apparent in pregnancies in which the women had a BMI ≥ 25 kg/m(2), suggesting a gene-environment interaction. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cannabis use by women during pregnancy does not influence infant DNA methylation of the dopamine receptor DRD4

PubMed Central

Fransquet, Peter D.; Hutchinson, Delyse; Olsson, Craig A.; Allsop, Steve; Elliott, Elizabeth J.; Burns, Lucinda; Mattick, Richard; Saffery, Richard; Ryan, Joanne

2017-01-01

ABSTRACT Background: Maternal cannabis use in pregnancy is linked with long-term adverse behavioral outcomes in offspring. Epigenetic processes established in utero that affect dopaminergic (reward) signaling may mediate risks. Associations between cannabis use and offspring DNA methylation have not been investigated; however, maternal tobacco smoking in pregnancy is associated with distinct patterns of DNA methylation at birth and beyond. Objectives: To determine whether maternal cannabis use is associated with methylation of the dopamine receptor gene DRD4 promoter in infants. Methods: Mothers in the Triple B study provided detailed information on drug use in each trimester of pregnancy. Buccal swabs were collected from neonates at 8 weeks (n = 804, 51.7% male, and 48.3% female). DRD4 promoter DNA methylation was measured using SEQUENOM MassARRAY. Results: Fifty-seven of the women in the study reported drug use during pregnancy, of whom 44 used cannabis. Of 19 cytosine-phosphate-guanine dinucleotides (CpG) units tested in DRD4, gestational cannabis use was associated with offspring methylation at 1 CpG unit in multivariate models (β + 1.48, CI: 0.02 to 2.93, and p = 0.047). At another site there was weak evidence that both cannabis and other drug use were independently associated with increased methylation, while the association with tobacco was in the reverse direction (cannabis use β + 0.67, CI: −0.12 to 1.46, and p = 0.09; other drug use β + 1.11, CI: 0.17 to 2.05, and p = 0.02; tobacco use β −0.41, CI: −0.85 to 0.03, and p = 0.07). None of the associations would remain significant after correction for multiple testing. Conclusion: There is no strong evidence that maternal cannabis use in pregnancy is associated with offspring DRD4 methylation. PMID:28448718

Polymorphisms in heterocyclic aromatic amines metabolism-related genes are associated with colorectal adenoma risk

PubMed Central

Eichholzer, Monika; Rohrmann, Sabine; Barbir, Aline; Hermann, Silke; Teucher, Birgit; Kaaks, Rudolf; Linseisen, Jakob

2012-01-01

Colorectal adenoma (CRA) and colorectal cancer (CRC) risks have been linked to the intake of red and processed meat. Heterocyclic aromatic amines (HCA) formed herein during high temperature cooking, are metabolized by a variety of enzymes, and allelic variation in the coding genes could influence individual CRA risk. Associations of polymorphisms in NAT1, NAT2, GSTA1, SULT1A1, CYP1A2, UGT1A7, UGT1A9, GSTP1 genes with colorectal adenoma risk were investigated in a nested case-control study of the EPIC-Heidelberg cohort including 428 cases matched by age, sex and year of recruitment with one or two controls (n=828) with negative colonoscopy per case. Genoyping was preformed with the Sequenom MassArray system and the LightCycler 480. Conditional logistic regression was used to compute odds ratios (OR) and corresponding 95% confidence intervals (CI). For rs15561 (NAT1) and rs1057126 (NAT1), the rarer allel was significantly inversely associated with adenoma risk OR=0.80 (95% CI 0.65-0.97) and (OR=0.81 (95% CI 0.65-0.99) and, respectively). For the combined NAT2 alleles encoding for enzymes with medium (versus slow) activity we also observed a significantly inverse association with adenoma risk (OR=0.75; 95% CI 0.85-0.97). In addition, homozygous carriers of the A allele of rs3957357 (GSTA1), i.e., those with a decreased enzyme activity, had a decreased risk of colorectal adenoma with an OR of 0.68 (95% CI 0.50-0.92; AA versus GG/GA). Polymorphisms in the other tested genes did not modify the risk of colorectal adenomas. In conclusion, polymorphisms in NAT1, NAT2, and GSTA1 are related to colorectal adenoma risk in this German cohort. PMID:22724046

Polymorphisms in heterocyclic aromatic amines metabolism-related genes are associated with colorectal adenoma risk.

PubMed

Eichholzer, Monika; Rohrmann, Sabine; Barbir, Aline; Hermann, Silke; Teucher, Birgit; Kaaks, Rudolf; Linseisen, Jakob

2012-01-01

Colorectal adenoma (CRA) and colorectal cancer (CRC) risks have been linked to the intake of red and processed meat. Heterocyclic aromatic amines (HCA) formed herein during high temperature cooking, are metabolized by a variety of enzymes, and allelic variation in the coding genes could influence individual CRA risk. Associations of polymorphisms in NAT1, NAT2, GSTA1, SULT1A1, CYP1A2, UGT1A7, UGT1A9, GSTP1 genes with colorectal adenoma risk were investigated in a nested case-control study of the EPIC-Heidelberg cohort including 428 cases matched by age, sex and year of recruitment with one or two controls (n=828) with negative colonoscopy per case. Genoyping was preformed with the Sequenom MassArray system and the LightCycler 480. Conditional logistic regression was used to compute odds ratios (OR) and corresponding 95% confidence intervals (CI). For rs15561 (NAT1) and rs1057126 (NAT1), the rarer allel was significantly inversely associated with adenoma risk OR=0.80 (95% CI 0.65-0.97) and (OR=0.81 (95% CI 0.65-0.99) and, respectively). For the combined NAT2 alleles encoding for enzymes with medium (versus slow) activity we also observed a significantly inverse association with adenoma risk (OR=0.75; 95% CI 0.85-0.97). In addition, homozygous carriers of the A allele of rs3957357 (GSTA1), i.e., those with a decreased enzyme activity, had a decreased risk of colorectal adenoma with an OR of 0.68 (95% CI 0.50-0.92; AA versus GG/GA). Polymorphisms in the other tested genes did not modify the risk of colorectal adenomas. In conclusion, polymorphisms in NAT1, NAT2, and GSTA1 are related to colorectal adenoma risk in this German cohort.

Contributions of Caucasian-associated bone mass loci to the variation in bone mineral density in Vietnamese population.

PubMed

Ho-Pham, Lan T; Nguyen, Sing C; Tran, Bich; Nguyen, Tuan V

2015-07-01

Bone mineral density (BMD) is under strong genetic regulation, but it is not clear which genes are involved in the regulation, particularly in Asian populations. This study sought to determine the association between 29 genes discovered by Caucasian-based genome-wide association studies and BMD in a Vietnamese population. The study involved 564 Vietnamese men and women aged 18 years and over (average age: 47 years) who were randomly sampled from the Ho Chi Minh City. BMD at the femoral neck, lumbar spine, total hip and whole body was measured by DXA (Hologic QDR4500, Bedford, MA, USA). Thirty-two single nucleotide polymorphisms (SNPs) in 29 genes were genotyped using Sequenom MassARRAY technology. The magnitude of association between SNPs and BMD was analyzed by the linear regression model. The Bayesian model average method was used to identify SNPs that are independently associated with BMD. The distribution of genotypes of all, but two, SNPs was consistent with the Hardy-Weinberg equilibrium law. After adjusting for age, gender and weight, 3 SNPs were associated with BMD: rs2016266 (SP7 gene), rs7543680 (ZBTB40 gene), and rs1373004 (MBL2/DKK1 gene). Among the three genetic variants, the SNP rs2016266 had the strongest association, with each minor allele being associated with ~0.02 g/cm(2) increase in BMD at the femoral neck and whole body. Each of these genetic variant explained about 0.2 to 1.1% variance of BMD. All other SNPs were not significantly associated with BMD. These results suggest that genetic variants in the SP7, ZBTB40 and MBL2/DKK1 genes are associated with BMD in the Vietnamese population, and that the effect of these genes on BMD is likely to be modest. Copyright © 2015 Elsevier Inc. All rights reserved.

Determination of IL-1B (rs16944) and IL-6 (rs1800796) genetic polymorphisms in IgA nephropathy in a northwest Chinese Han population.

PubMed

Zhang, Daofa; Xie, Maowei; Yang, Xiaohong; Zhang, Yin; Su, Yan; Wang, Yanni; Huang, Haiyang; Han, Hui; Li, Wenning; Fu, Keying; Su, Huiluan; Xu, Wentan; Han, Yeguang; Wang, Ru; Zhang, Pei; Wu, Wei; Huang, Yun; Chen, Daojun; Jin, Tianbo; Wei, Jiali

2017-09-22

IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide, but etiology and pathogenesis continue to be poorly understood. Polymorphisms in the cytokine genes may play a role in the etiology and pathogenesis of IgAN. The incidence of different between diverse ethnic groups suggested important genetic influences on its pathogenesis. We genotype 10 single nucleotide polymorphisms (SNPs) in IL-1B and IL-6 gene using Sequenom Mass-ARRAY technology from 417 IgAN patients and 463 healthy controls of the Chinese Han population. We evaluated these SNPs associated with IgAN utilising the chi-square tests and genetic model analysis. We identified that the minor alleles of rs16944 ("A"), rs1800796 ("G") in IL-1B, IL-6 were involved in an increasingly risk of IgAN in allelic model analysis, respectively. The rs16944 in IL-1B and rs1800796 in IL-6 were associated with 1.23-fold (95% CI, 1.02-1.48, P = 0.031) and 1.33-fold (95% CI, 1.11-1.66, P = 0.003) increases in the risk of developing IgAN, respectively. There was only rs1800796 still correlated with IgAN in the allelic model after adjustment by age and gender and the Bonferroni correction. In addition, Haplotype G rs1800796 A rs2069837 G rs2069840 ( P = 0.037) and G rs1800796 A rs2069837 C rs2069840 ( P = 0.042) in IL-6 were considered to be associated with increased IgAN risk. This study verified the IL-6, IL-1B genetic variants polymorphisms contributed to IgAN susceptibility in a Chinese Han population. Although we identified SNPs susceptibility, however, replication studies and functional research are required to confirm the genetic contribution in IgAN.

Determination of IL-1B (rs16944) and IL-6 (rs1800796) genetic polymorphisms in IgA nephropathy in a northwest Chinese Han population

PubMed Central

Zhang, Yin; Su, Yan; Wang, Yanni; Huang, Haiyang; Han, Hui; Li, Wenning; Fu, Keying; Su, Huiluan; Xu, Wentan; Han, Yeguang; Wang, Ru; Zhang, Pei; Wu, Wei; Huang, Yun; Chen, Daojun; Jin, Tianbo; Wei, Jiali

2017-01-01

IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide, but etiology and pathogenesis continue to be poorly understood. Polymorphisms in the cytokine genes may play a role in the etiology and pathogenesis of IgAN. The incidence of different between diverse ethnic groups suggested important genetic influences on its pathogenesis. We genotype 10 single nucleotide polymorphisms (SNPs) in IL-1B and IL-6 gene using Sequenom Mass-ARRAY technology from 417 IgAN patients and 463 healthy controls of the Chinese Han population. We evaluated these SNPs associated with IgAN utilising the chi-square tests and genetic model analysis. We identified that the minor alleles of rs16944 (“A”), rs1800796 (“G”) in IL-1B, IL-6 were involved in an increasingly risk of IgAN in allelic model analysis, respectively. The rs16944 in IL-1B and rs1800796 in IL-6 were associated with 1.23-fold (95% CI, 1.02-1.48, P = 0.031) and 1.33-fold (95% CI, 1.11-1.66, P = 0.003) increases in the risk of developing IgAN, respectively. There was only rs1800796 still correlated with IgAN in the allelic model after adjustment by age and gender and the Bonferroni correction. In addition, Haplotype Grs1800796A rs2069837G rs2069840 (P = 0.037) and G rs1800796A rs2069837C rs2069840 (P = 0.042) in IL-6were considered to be associated with increased IgAN risk. This study verified the IL-6, IL-1B genetic variants polymorphisms contributed to IgAN susceptibility in a Chinese Han population. Although we identified SNPs susceptibility, however, replication studies and functional research are required to confirm the genetic contribution in IgAN. PMID:29069743

Muscle strength is associated with vitamin D receptor gene variants.

PubMed

Bozsodi, Arpad; Boja, Sara; Szilagyi, Agnes; Somhegyi, Annamaria; Varga, Peter Pal; Lazary, Aron

2016-11-01

Vitamin D receptor (VDR) is an important candidate gene in muscle function. Scientific reports on the effect of its genetic variants on muscle strength are contradictory likely due to the inconsistent study designs. Hand grip strength (HGS) is a highly heritable phenotype of muscle strength but only limited studies are available on its genetic background. Association between VDR polymorphisms and HGS has been poorly investigated and previous reports are conflicting. We studied the effect of VDR gene variants on HGS in a sample of 706 schoolchildren. Genomic DNA was extracted from saliva samples and six candidate single nucleotide polymorphisms (SNPs) across the VDR gene were genotyped with Sequenom MassARRAY technique. HGS was measured with a digital dynamometer in both hands. Single marker and haplotype associations were adjusted for demographic parameters. Three SNPs, rs4516035 (A1012G; p = 0.009), rs1544410 (BsmI; p = 0.010), and rs731236 (TaqI; p = 0.038) and a 3' UTR haploblock constructed by three SNPs (Bsml-Taq1-rs10783215; p < 0.005) showed significantly associations with HGS of the dominant hand. In the non-dominant hand, the effects of the A1012G (p = 0.034) and the 3' UTR haploblock (p < 0.01) on HGS were also significant. Since the promoter SNP (A10112G) and the 3' UTR haplotype were proved to be associated with the expression and the stability of the VDR mRNA in earlier studies, VDR variants can be supposed to have a direct effect on muscle strength. The individual genetic patterns can also explain the inconsistency of the previously published clinical results on the association between vitamin D and muscle function. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2031-2037, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

DNA methylation and genetic variation of the angiotensin converting enzyme (ACE) in depression.

PubMed

Lam, Dilys; Ancelin, Marie-Laure; Ritchie, Karen; Saffery, Richard; Ryan, Joanne

2018-02-01

Depression is one of the most prevalent psychiatric disorders, and in older persons is associated with high levels of comorbidity and under-treatment. Dysfunction of the hypothalamic-pituitary-adrenal (HPA) stress axis is consistently observed in the older population as well as depressed patients, with the angiotensin converting enzyme (ACE) a key regulator of the stress response. Epigenetic regulation of ACE may play an important role in HPA axis (dys)regulation. To investigate ACE promoter methylation as a biomarker of late-life depression, and its association with genetic variation and cortisol secretion. The longitudinal general population ESPRIT study is aimed at investigating psychiatric disorders in older persons (n=1863, average age=73). Depression was assessed using the Mini International Neuropsychiatric Interview according to DSM-IV criteria and the Centre for Epidemiologic Studies Depression Scale (CES-D). Genotype information for seven polymorphisms across the ACE gene was also available. Blood and saliva samples collected at baseline and used to extract DNA and measure cortisol, respectively. Sequenom MassARRAY was used to measure promoter DNA methylation of the ACE gene (n=552). There was no evidence of an association between ACE promoter methylation and depression. However, there was evidence that ACE genetic variants influenced methylation, and modified the association between depression and methylation (Δ at various sites; -2.05% to 1.74%; p=0.019 to 0.039). Multivariate analyses were adjusted for participants' lifestyle, health and medical history. Independent of depression status, ACE methylation was inversely correlated with cortisol levels (r=-0.336, p=0.042). This study provides evidence that associations between ACE methylation and depression are genotype-dependent, suggesting that the development of reliable depression biomarkers may need to consider methylation levels in combination with underlying genetic variation. ACE methylation may also be a suitable biomarker of cortisol and/or HPA axis activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

FRZB1 rs2242070 polymorphisms is associated with brick tea type skeletal fluorosis in Kazakhs, but not in Tibetans, China.

PubMed

Yang, Yanmei; Zhao, Qiaoshi; Liu, Yang; Liu, Xiaona; Chu, Yanru; Yan, Huazhu; Fan, Yumei; Huo, Simeng; Wang, Limei; Lou, Qun; Guo, Ning; Sun, Dianjun; Gao, Yanhui

2018-05-21

Skeletal fluorosis is a metabolic bone and joint disease caused by excessive accumulation of fluoride in the bones. Compared with Kazakhs, Tibetans are more likely to develop moderate and severe brick tea type skeletal fluorosis, although they have similar fluoride exposure. Single nucleotide polymorphisms (SNPs) in frizzled-related protein (FRZB) have been associated with osteoarthritis, but their association with the risk of skeletal fluorosis has not been reported. In this paper, we investigated the association of three SNPs (rs7775, rs2242070 and rs9288087) in FRZB1with brick tea type skeletal fluorosis risk in a cross-sectional case-control study conducted in Sinkiang and Qinghai, China. A total of 598 individuals, including 308 Tibetans and 290 Kazakhs, were enrolled in this study, in which cases and controls were 221 and 377, respectively. The skeletal fluorosis was diagnosed according to the Chinese diagnostic criteria of endemic skeletal fluorosis (WS192-2008). The fluoride content in tea water or urine was detected using the fluoride ion electrode. SNPs were assessed using the Sequenom MassARRAY system. Binary logistic regressions found evidence of association with rs2242070 AA genotype in only Kazakh participants [odds ratio (OR) 0.417, 95% CI 0.216-0.807, p = 0.009], but not in Tibetans. When stratified by age, this protective effect of AA genotype in rs2242070 was pronounced in Kazakh participants aged 46-65 (OR 0.321, 95% CI 0.135-0.764, p = 0.010). This protective association with AA genotype in rs2242070 in Kazakhs also appeared to be stronger with tea fluoride intake > 3.5 mg/day (OR 0.396, 95% CI 0.182-0.864, p = 0.020). Our data suggest there might be differential genetic influence on skeletal fluorosis risk in Kazakh and Tibetan participants and that this difference might be modified by tea fluoride intake.

EGFR T790M mutation testing within the osimertinib AURA Phase I study.

PubMed

Dearden, Simon; Brown, Helen; Jenkins, Suzanne; Thress, Kenneth S; Cantarini, Mireille; Cole, Rebecca; Ranson, Malcolm; Jänne, Pasi A

2017-07-01

Reliable epidermal growth factor receptor (EGFR) mutation testing techniques are required to identify eligible patients with EGFR mutation/T790M positive advanced non-small cell lung cancer (NSCLC), for treatment with osimertinib (AZD9291), an oral, potent, irreversible EGFR tyrosine kinase inhibitor (TKI) selective for EGFR-TKI-sensitizing and T790M resistance mutations over wild-type EGFR. There is no current consensus regarding the best method to detect EGFR T790M mutations. The aim of this study was to describe the concordance between local testing, which used a variety of methods, and central testing, using the cobas ® EGFR Mutation Test, for EGFR-sensitizing mutations and the T790M resistance mutation. Tumor samples were obtained from all patients screened for inclusion onto the osimertinib Phase I expansion component of the AURA Phase I/II study (NCT01802632). Samples underwent central laboratory testing for EGFR-sensitizing mutations and T790M resistance mutation using the cobas ® EGFR Mutation Test. Results were compared with local laboratory test results, based on other testing methodologies including Sanger sequencing, therascreen ® , PNAClamp™, and Sequenom MassARRAY ® . Central laboratory testing was successful in 99% of samples passing histopathology review and testing success rates were comparable across the three central laboratories. Concordance between central and local testing for common sensitizing mutations was high (>98%) and concordance for the T790M mutation was also high (>90%). Tumor heterogeneity, along with other technical factors may have influenced this result. Within the osimertinib AURA Phase I study, EGFR mutation testing across three centralized laboratories using the cobas ® EGFR Mutation Test was feasible and successful, with strong concordance between local and central laboratory results, including for T790M. The cobas ® EGFR Mutation Test has subsequently been approved as the companion diagnostic test for osimertinib in the USA and Japan. Copyright © 2017 Elsevier B.V. All rights reserved.

A multianalytical approach to evaluate the association of 55 SNPs in 28 genes with obesity risk in North Indian adults.

PubMed

Srivastava, Apurva; Mittal, Balraj; Prakash, Jai; Srivastava, Pranjal; Srivastava, Nimisha; Srivastava, Neena

2017-03-01

The aim of the study was to investigate the association of 55 SNPs in 28 genes with obesity risk in a North Indian population using a multianalytical approach. Overall, 480 subjects from the North Indian population were studied using strict inclusion/exclusion criteria. SNP Genotyping was carried out by Sequenom Mass ARRAY platform (Sequenom, San Diego, CA) and validated Taqman ® allelic discrimination (Applied Biosystems ® ). Statistical analyses were performed using SPSS software version 19.0, SNPStats, GMDR software (version 6) and GENEMANIA. Logistic regression analysis of 55 SNPs revealed significant associations (P < .05) of 49 SNPs with BMI linked obesity risk whereas the remaining 6 SNPs revealed no association (P > .05). The pathway-wise G-score revealed the significant role (P = .0001) of food intake-energy expenditure pathway genes. In CART analysis, the combined genotypes of FTO rs9939609 and TCF7L2 rs7903146 revealed the highest risk for BMI linked obesity. The analysis of the FTO-IRX3 locus revealed high LD and high order gene-gene interactions for BMI linked obesity. The interaction network of all of the associated genes in the present study generated by GENEMANIA revealed direct and indirect connections. In addition, the analysis with centralized obesity revealed that none of the SNPs except for FTO rs17818902 were significantly associated (P < .05). In this multi-analytical approach, FTO rs9939609 and IRX3 rs3751723, along with TCF7L2 rs7903146 and TMEM18 rs6548238, emerged as the major SNPs contributing to BMI linked obesity risk in the North Indian population. © 2016 Wiley Periodicals, Inc.

Prolactin rs1341239 T allele may have protective role against the brick tea type skeletal fluorosis

PubMed Central

Li, Bing-Yun; Yang, Yan-Mei; Liu, Yang; Sun, Jing; Ye, Yan; Liu, Xiao-Na; Liu, Hong-Xu; Sun, Zhen-Qi; Li, Mang; Cui, Jing; Sun, Dian-Jun; Gao, Yan-Hui

2017-01-01

Objective Prolactin (PRL) has been reported to be associated with increased bone turnover, and increased bone turnover is also a feature of skeletal fluorosis (SF). Autocrine/paracrine production of PRL is regulated by the extrapituitary promoter and a polymorphism in the extrapituitary PRL promoter at -1149 (rs1341239) is associated with disturbances of bone metabolism in other diseases. Here, we have investigated the possibility that the rs1341239 polymorphism is associated with SF, which results from the consumption of brick tea. Design We conducted a cross-sectional study in Sinkiang, Qinghai, Inner Mongolia in China. Demography survey questionnaires were completed and physical examination and X-ray diagnoses were used to diagnose SF. Brick tea water fluoride intake (IF) and urinary fluoride (UF) were tested by an F-ion selective electrode method. A Sequenom MassARRAY system was used to determine PRL gene polymorphisms. Results Subjects who were younger than 45 years of age and carried the T allele had a significantly decreased risk of SF [OR = 0.279 (95%CI, 0.094–0.824)] compared to those carrying the homozygous G allele. This phenomenon was only observed in Kazakh subjects [OR = 0.127 (95%CI, 0.025–0.646)]. Kazakh females who carried T alleles has a decreased risk of SF [OR = 0.410 (95%CI, 0.199–0.847)]. For Kazakh subjects which IF is less than 3.5 mg/d, a decreased risk of SF was observed among the participants who carried T alleles [OR = 0.118 (95%CI, 0.029–0.472)]. Overall, subjects with 1.6–3.2 mg/L UF and carried T alleles had a significantly decreased risk of SF [OR = 0.476 (95%CI, 0.237–0.955)] compared to homozygous G allele carriers. This phenomenon was only observed in Kazakh subjects [OR = 0.324 (95%CI, 0.114–0.923)]. Conclusions Our results suggested that the PRL rs1341239 T allele decreases the risk of brick tea SF. PMID:28152004

Replication of Associations of Genetic Loci Outside the HLA Region With Susceptibility to Anti–Cyclic Citrullinated Peptide–Negative Rheumatoid Arthritis

PubMed Central

Viatte, Sebastien; Massey, Jonathan; Bowes, John; Duffus, Kate; Eyre, Stephen; Barton, Anne; Loughlin, John; Arden, Nigel; Birrell, Fraser; Carr, Andrew; Deloukas, Panos; Doherty, Michael; McCaskie, Andrew W.; Ollier, William E. R.; Rai, Ashok; Ralston, Stuart H.; Spector, Tim D.; Valdes, Ana M.; Wallis, Gillian A.; Wilkinson, J. Mark; Zeggini, Eleftheria

2016-01-01

Objective Genetic polymorphisms within the HLA region explain only a modest proportion of anti–cyclic citrullinated peptide (anti‐CCP)–negative rheumatoid arthritis (RA) heritability. However, few non‐HLA markers have been identified so far. This study was undertaken to replicate the associations of anti‐CCP–negative RA with non‐HLA genetic polymorphisms demonstrated in a previous study. Methods The Rheumatoid Arthritis Consortium International densely genotyped 186 autoimmune‐related regions in 3,339 anti‐CCP–negative RA patients and 15,870 controls across 6 different populations using the Illumina ImmunoChip array. We performed a case–control replication study of the anti‐CCP–negative markers with the strongest associations in that discovery study, in an independent cohort of anti‐CCP–negative UK RA patients. Individuals from the arcOGEN Consortium and Wellcome Trust Case Control Consortium were used as controls. Genotyping in cases was performed using Sequenom MassArray technology. Genome‐wide data from controls were imputed using the 1000 Genomes Phase I integrated variant call set release version 3 as a reference panel. Results After genotyping and imputation quality control procedures, data were available for 15 non‐HLA single‐nucleotide polymorphisms in 1,024 cases and 6,348 controls. We confirmed the known markers ANKRD55 (meta‐analysis odds ratio [OR] 0.80; P = 2.8 × 10−13) and BLK (OR 1.13; P = 7.0 × 10−6) and identified new and specific markers of anti‐CCP–negative RA (prolactin [PRL] [OR 1.13; P = 2.1 × 10−6] and NFIA [OR 0.85; P = 2.5 × 10−6]). Neither of these loci is associated with other common, complex autoimmune diseases. Conclusion Anti‐CCP–negative RA and anti‐CCP–positive RA are genetically different disease subsets that only partially share susceptibility factors. Genetic polymorphisms located near the PRL and NFIA genes represent examples of genetic susceptibility factors specific for anti‐CCP–negative RA. PMID:26895230

HPV genotypes and associated cervical cytological abnormalities in women from the Pearl River Delta region of Guangdong province, China: a cross-sectional study

PubMed Central

2014-01-01

Background It is important to understand the specific HPV genotype distribution in screen-detected lesions. HPV Genotype is helpful for separating HPV-positive women at greater risk of cancer from those who can regress spontaneously and for preventing cervical cancer at early stage. The aim of this study was to investigate the high-risk HPV genotype distribution among cervical cytology abnormality in Pearl River Delta Region, Southern China Methods 5585 HPV-infected women were screened from 77069 women in Pearl River Delta Region. Information was obtained from 3226 screened subjects through questionnaires and personal interviews. Exfoliated cervical cells were collected by doctors for HPV test with MassARRAY (Sequenom, Sandiego, CA) technique based on the matrix-assisted laser desorption/ionization time-of flight (MALDI-TOF) mass spectrometry (MS). The ThinPrep cytology test was performed to screen for cervical cancer. Unconditional logistic was used to determine the most common HPV carcinogenic types. Results Of the 3226 HPV-positive samples tested, 1744 (54.1%) with normal cervical cytology, 1482 (45.9%) with abnormal cytology. The five most common HPV types in this study were HPV16 (20.2%), HPV52 (17.1%), HPV58 (13.2%), HPV18 (9.5%), HPV6 (7.6%). Overall, HPV16 (OR = 10.5, 95% CI: 3.7 ~ 29.6), HPV33 (OR = 9.1, 95% CI: 2.8 ~ 29.2), HPV58 (OR = 6.3, 95% CI: 2.1 ~ 18.6), HPV31 (OR = 4.5, 95% CI: 1.3 ~ 15.5), multiple genotype infection (OR = 3.0, 95% CI: 1.7 ~ 14.7), especially HPV16 and HPV33, increased the risk of cytology abnormalities. Conclusions HPV16, HPV31, HPV33, HPV58, and multiple HPV genotype infection increased the risk of cytology abnormalities in Pearl River Delta Region and might be useful for the screening, preventing, treating, and monitoring of pre-cancer lesions in southern China. PMID:25016305

Epigenetic Gene Promoter Methylation at Birth Is Associated With Child’s Later Adiposity

PubMed Central

Godfrey, Keith M.; Sheppard, Allan; Gluckman, Peter D.; Lillycrop, Karen A.; Burdge, Graham C.; McLean, Cameron; Rodford, Joanne; Slater-Jefferies, Joanne L.; Garratt, Emma; Crozier, Sarah R.; Emerald, B. Starling; Gale, Catharine R.; Inskip, Hazel M.; Cooper, Cyrus; Hanson, Mark A.

2011-01-01

OBJECTIVE Fixed genomic variation explains only a small proportion of the risk of adiposity. In animal models, maternal diet alters offspring body composition, accompanied by epigenetic changes in metabolic control genes. Little is known about whether such processes operate in humans. RESEARCH DESIGN AND METHODS Using Sequenom MassARRAY we measured the methylation status of 68 CpGs 5′ from five candidate genes in umbilical cord tissue DNA from healthy neonates. Methylation varied greatly at particular CpGs: for 31 CpGs with median methylation ≥5% and a 5–95% range ≥10%, we related methylation status to maternal pregnancy diet and to child’s adiposity at age 9 years. Replication was sought in a second independent cohort. RESULTS In cohort 1, retinoid X receptor-α (RXRA) chr9:136355885+ and endothelial nitric oxide synthase (eNOS) chr7:150315553+ methylation had independent associations with sex-adjusted childhood fat mass (exponentiated regression coefficient [β] 17% per SD change in methylation [95% CI 4–31], P = 0.009, n = 64, and β = 20% [9–32], P < 0.001, n = 66, respectively) and %fat mass (β = 10% [1–19], P = 0.023, n = 64 and β =12% [4–20], P = 0.002, n = 66, respectively). Regression analyses including sex and neonatal epigenetic marks explained >25% of the variance in childhood adiposity. Higher methylation of RXRA chr9:136355885+, but not of eNOS chr7:150315553+, was associated with lower maternal carbohydrate intake in early pregnancy, previously linked with higher neonatal adiposity in this population. In cohort 2, cord eNOS chr7:150315553+ methylation showed no association with adiposity, but RXRA chr9:136355885+ methylation showed similar associations with fat mass and %fat mass (β = 6% [2–10] and β = 4% [1–7], respectively, both P = 0.002, n = 239). CONCLUSIONS Our findings suggest a substantial component of metabolic disease risk has a prenatal developmental basis. Perinatal epigenetic analysis may have utility in identifying individual vulnerability to later obesity and metabolic disease. PMID:21471513

Association of colorectal cancer susceptibility variants with esophageal cancer in a Chinese population.

PubMed

Geng, Ting-Ting; Xun, Xiao-Jie; Li, Sen; Feng, Tian; Wang, Li-Ping; Jin, Tian-Bo; Hou, Peng

2015-06-14

To investigate the association between colorectal cancer (CRC) genetic susceptibility variants and esophageal cancer in a Chinese Han population. A case-control study was conducted including 360 esophageal cancer patients and 310 healthy controls. Thirty-one single-nucleotide polymorphisms (SNPs) associated with CRC risk from previous genome-wide association studies were analyzed. SNPs were genotyped using Sequenom Mass-ARRAY technology, and genotypic frequencies in controls were tested for departure from Hardy-Weinberg equilibrium using a Fisher's exact test. The allelic frequencies were compared between cases and controls using a χ(2) test. Associations between the SNPs and the risk of esophageal cancer were tested using various genetic models (codominant, dominant, recessive, overdominant, and additive). ORs and 95%CIs were calculated by unconditional logistic regression with adjustments for age and sex. The minor alleles of rs1321311 and rs4444235 were associated with a 1.53-fold (95%CI: 1.15-2.06; P = 0.004) and 1.28-fold (95%CI: 1.03-1.60; P = 0.028) increased risk of esophageal cancer in the allelic model analysis, respectively. In the genetic model analysis, the C/C genotype of rs3802842 was associated with a reduced risk of esophageal cancer in the codominant model (OR = 0.52, 95%CI: 0.31-0.88; P = 0.033) and recessive model (OR = 0.55, 95%CI: 0.34-0.87; P = 0.010). The rs4939827 C/T-T/T genotype was associated with a 0.67-fold (95%CI: 0.46-0.98; P = 0.038) decreased esophageal cancer risk under the dominant model. In addition, rs6687758, rs1321311, and rs4444235 were associated with an increased risk. In particular, the T/T genotype of rs1321311 was associated with an 8.06-fold (95%CI: 1.96-33.07; P = 0.004) increased risk in the codominant model. These results provide evidence that known genetic variants associated with CRC risk confer risk for esophageal cancer, and may bring risk for other digestive system tumors.

Environmental and genetic determinants of vitamin D insufficiency in 12-month-old infants.

PubMed

Suaini, Noor H A; Koplin, Jennifer J; Ellis, Justine A; Peters, Rachel L; Ponsonby, Anne-Louise; Dharmage, Shyamali C; Matheson, Melanie C; Wake, Melissa; Panjari, Mary; Tan, Hern-Tze Tina; Martin, Pamela E; Pezic, Angela; Lowe, Adrian J; Martino, David; Gurrin, Lyle C; Vuillermin, Peter J; Tang, Mimi L K; Allen, Katrina J

2014-10-01

We aimed to investigate the relationship between genetic and environmental exposure and vitamin D status at age one, stratified by ethnicity. This study included 563 12-month-old infants in the HealthNuts population-based study. DNA from participants' blood samples was genotyped using Sequenom MassARRAY MALDI-TOF system on 28 single nucleotide polymorphisms (SNPs) in six genes. Using logistic regression, we examined associations between environmental exposure and SNPs in vitamin D pathway and filaggrin genes and vitamin D insufficiency (VDI). VDI, defined as serum 25-hydroxyvitamin D3(25(OH)D3) level ≤50nmol/L, was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Infants were stratified by ethnicity determined by parent's country of birth. Infants formula fed at 12 months were associated with reduced odds of VDI compared to infants with no current formula use at 12 months. This association differed by ethnicity (Pinteraction=0.01). The odds ratio (OR) of VDI was 0.29 for Caucasian infants (95% CI, 0.18-0.47) and 0.04 for Asian infants (95% CI, 0.006-0.23). Maternal vitamin D supplementation during pregnancy and/or breastfeeding were associated with increased odds of infants being VDI (OR, 2.39; 95% CI, 1.11-5.18 and OR, 2.5; 95% CI, 1.20-5.24 respectively). Presence of a minor allele for any GC SNP (rs17467825, rs1155563, rs2282679, rs3755967, rs4588, rs7041) was associated with increased odds of VDI. Caucasian infants homozygous (AA) for rs4588 had an OR of 2.49 of being associated with VDI (95% CI, 1.19-5.18). In a country without routine infant vitamin D supplementation or food chain fortification, formula use is strongly associated with a reduced risk of VDI regardless of ethnicity. There was borderline significance for an association between filaggrin mutations and VDI. However, polymorphisms in vitamin D pathway related genes were associated with increased likelihood of being VDI in infancy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Analysis of epigenetic changes in survivors of preterm birth reveals the effect of gestational age and evidence for a long term legacy

PubMed Central

2013-01-01

Background Preterm birth confers a high risk of adverse long term health outcomes for survivors, yet the underlying molecular mechanisms are unclear. We hypothesized that effects of preterm birth can be mediated through measurable epigenomic changes throughout development. We therefore used a longitudinal birth cohort to measure the epigenetic mark of DNA methylation at birth and 18 years comparing survivors of extremely preterm birth with infants born at term. Methods Using 12 extreme preterm birth cases and 12 matched, term controls, we extracted DNA from archived neonatal blood spots and blood collected in a similar way at 18 years of age. DNA methylation was measured at 347,789 autosomal locations throughout the genome using Infinium HM450 arrays. Representative methylation differences were confirmed by Sequenom MassArray EpiTYPER. Results At birth we found 1,555 sites with significant differences in methylation between term and preterm babies. At 18 years of age, these differences had largely resolved, suggesting that DNA methylation differences at birth are mainly driven by factors relating to gestational age, such as cell composition and/or maturity. Using matched longitudinal samples, we found evidence for an epigenetic legacy associated with preterm birth, identifying persistent methylation differences at ten genomic loci. Longitudinal comparisons of DNA methylation at birth and 18 years uncovered a significant overlap between sites that were differentially-methylated at birth and those that changed with age. However, we note that overlapping sites may either differ in the same (300/1,555) or opposite (431/1,555) direction during gestation and aging respectively. Conclusions We present evidence for widespread methylation differences between extreme preterm and term infants at birth that are largely resolved by 18 years of age. These results are consistent with methylation changes associated with blood cell development, cellular composition, immune induction and age at these time points. Finally, we identified ten probes significantly associated with preterm individuals and with greater than 5% methylation discordance at birth and 18 years that may reflect a long term epigenetic legacy of preterm birth. PMID:24134860

An in-depth analysis identifies two new independent signals in 11q23.3 associated with vitiligo in the Chinese Han population.

PubMed

Zhao, Suli; Fang, Fang; Tang, Xianfa; Dou, Jinfa; Wang, Wenjun; Zheng, Xiaodong; Sun, Liangdan; Zhang, Anping

2017-10-01

Vitiligo is an autoimmune disease, characterized by progressive loss of skin pigmentation, which is caused by the interactions of multiple factors, such as heredity, immunity and environment. Recently, a single nucleotide polymorphism (SNP) rs638893 at 11q23.3 region was identified as a risk factor for vitiligo in genome-wide association studies and multiple SNPs in this region have been associated with other autoimmune diseases. This study aims to identify additional susceptibility variants associated with vitiligo at 11q23.3 in the Chinese Han population. We selected and genotyped 26 SNPs at 11q23.3 in an independent cohort including 2924 cases and 4048 controls using the Sequenom MassArray iPLEX ® system. Bonferroni adjustment was used for multiple comparisons and P value <1.92×10 -3 (0.05/26) was considered statistically significant. The A allele of rs613791 and G allele of rs523604 located in CXCR5 were observed to be significantly associated with vitiligo (OR=1.21, 95% CI: 1.11-1.31, P=1.20×10 -5 ; OR=1.14, 95% CI: 1.07-1.23, P=1.90×10 -4 , respectively). The C allele of rs638893 (a previously reported one) located upstream of DDX6 was also significantly associated with vitiligo (OR=1.25, 95% CI: 1.12-1.38, P=3.04×10 -5 ). The genotypes distribution of 3 SNPs also showed significant differences between case and control (rs613791: P=7.00×10 -6 , rs523604: P=4.00×10 -3 , rs638893: P=1.20×10 -5 , respectively). The two newly identified SNPs (rs613791 and rs523604) showed independent associations with vitiligo by linkage disequilibrium analysis and conditional logistic regression. The study identified two new independent signals in the associated locus 11q23.3 for vitiligo. The presence of multiple independent variants emphasizes an important role of this region in disease susceptibility. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Association of HLA-B27 and ERAP1 with ankylosing spondylitis susceptibility in Beijing Han Chinese.

PubMed

Zhang, Z; Dai, D; Yu, K; Yuan, F; Jin, J; Ding, L; Hao, Y; Liang, F; Liu, N; Zhao, X; Long, J; Xi, Y; Sun, Y-Y

2014-05-01

This study investigated the genetic polymorphisms of HLA-B27, together with polymorphisms on endoplasmic reticulum aminopeptidase 1 (ERAP1), and susceptibility for ankylosing spondylitis (AS) in the Beijing Han population. A case-control study was carried out for 602 AS patient samples and 619 matched controls of Han Chinese. HLA-B27 genotyping was performed by polymerase chain reaction-sequence specific primers (PCR-SSP), and four ERAP1 SNPs (rs27037, rs27980, rs27582, and rs27434) were selected and genotyped on the Sequenom iPlex platform (Sequenom, San Diego, CA). Association analysis was performed using the likelihood ratio χ(2) test. This study identified four HLA-B27 alleles in Beijing Han AS patients, B*27:02, B*27:04, B*27:05, and B*27:07, of which B*27:05 was the most significant geographical different subtype among AS patients in Chinese. Our results confirmed that HLA-B27 was strongly associated with AS (P=1.9 × 10(-150) ), and the most strongly associated alleles were B*27:04, B*27:05, and B*27:02. Our study also confirmed a weak association between ERAP1 (rs27434) and AS. We also observed that for HLA-B*27:02 and HLA-B*27:04 positive AS patients, rs27434 and rs27582 were associated with AS. In contrast, for HLA-B27-negative and HLA-B*27:05-positive AS patients, this association was not observed. This is the first study to show that both B27 and ERAP1 are AS genetic susceptibility genes in Beijing Han. Interactions between ERAP1 and HLA-B*27:02 and B*27:04 may play an important role in the AS pathogenesis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Association between single-nucleotide polymorphisms in the IRAK-4 gene and allergic rhinitis].

PubMed

Zhang, Yuan; Xi, Lin; Zhao, Yan-ming; Zhao, Li-ping; Zhang, Luo

2012-06-01

To investigate the genetic association pattern between single-nucleotide polymorphisms (SNP) in the interleukin-1 receptor-associated kinase 4 (IRAK-4) gene and allergic rhinitis (AR). A population of 379 patients with the diagnosis of AR and 333 healthy controls who lived in Beijing region was recruited. A total of 8 reprehensive marker SNP which were in IRAK-4 gene region were selected according to the Beijing people database from Hapmap website. The individual genotyping was performed by MassARRAY platform. SPSS 13.0 software was used for statistic analysis. Subgroup analysis for the presence of different allergen sensitivities displayed associations only in the house dust mite-allergic cohorts (rs3794262: P = 0.0034, OR = 1.7388; rs4251481: P = 0.0023, OR = 2.6593), but not in subjects who were allergic to pollens as well as mix allergens. The potential genetic contribution of the IRAK-4 gene to AR demonstrated an allergen-dependant association pattern in Chinese population.

ZNF208 polymorphisms associated with ischemic stroke in a southern Chinese Han population.

PubMed

Yu, Jianzhong; Zhou, Feng; Luo, Dong; Wang, Nianzhen; Zhang, Chong; Jin, Tianbo; Liang, Xiongfei; Yu, Dan

2017-01-01

Ischemic stroke is one of the most common diseases with a high burden of neurological deficits, disability and death. Zinc finger protein 208 (ZNF208) was found to be involved in coronary heart disease, although little information is available about its association with ischemic stroke. We performed the present case-control study to clarify the association between single-nucleotide polymorphisms (SNPs) within ZNF208 and the risk of ischemic stroke in a southern Chinese Han population. A total of 799 subjects (400 cases and 399 healthy controls) were enrolled in the present study. Five SNPs within ZNF208 gene were selected and genotyped using Sequenom MassARRY technology (Sequenom, Inc., San Diego, CA, USA). Data management and statistical analyses were conducted using Sequenom Typer, version 4.0, and a chi-squared test, as well as unconditional logistic regression. Statistical results showed that three variants were associated with the risk of ischemic stroke under allele models (rs2188971, rs2188972, rs8103163 and rs7248488). The variant rs2188972 was also associated with the risk of ischemic stroke in a recessive model after adjustment for age and sex. Haplotype analysis suggested that a significant difference existed between the A rs2188972 T rs2188971 A rs8103163 A rs7248488 haplotype and the risk of ischemic stroke, although this disappeared after adjustment for sex and age. The results obtained in the present study indicate a potential association between ZNF208 variants and the risk of ischemic risk in a southern Chinese Han population. Copyright © 2016 John Wiley & Sons, Ltd.

Association of melanocortin-4 receptor gene polymorphisms with obesity-related parameters in Malaysian Malays.

PubMed

Apalasamy, Yamunah Devi; Ming, Moy Foong; Rampal, Sanjay; Bulgiba, Awang; Mohamed, Zahurin

2013-01-01

Melanocortin-4 receptor (MC4R) is an important regulator of body weight and energy intake. Genetic polymorphisms of the MC4R gene have been found to be linked to obesity in many recent studies across the globe. This study aimed to examine the effects of MC4R polymorphisms on obesity parameters, Linkage disequilibrium (LD) pattern and haplotypes in Malaysian Malays. The study subjects were 652 Malaysian Malays. Genomic DNA was extracted from buccal swabs. Genotyping was performed using Sequenom MassARRAY® iPLEX platform. Anthropometric and blood lipid profiles were measured. MC4R rs571312 SNP was associated with logBMI (p = 0.008) and systolic blood pressure (p = 0.005), while MC4R rs2229616 SNP was associated with total cholesterol (TC) levels (p = 0.016). The MC4R rs7227255 SNP did not show any association with obesity parameters. The strength of LD of the MC4R gene region is low and the haplotypes were not associated with obesity in Malaysian Malays.

Behavioural genetic differences between Chinese and European pigs.

PubMed

Chu, Qingpo; Liang, Tingting; Fu, Lingling; Li, Huizhi; Zhou, Bo

2017-09-01

Aggression is a heritable trait and genetically related to neurotransmitter-related genes. Behavioural characteristics of some pig breeds are different. To compare the genetic differences between breeds, backtest and aggressive behaviour assessments, and genotyped using Sequenom iPLEX platform were performed in 50 Chinese indigenous Mi pigs and 100 landrace-large white (LLW) cross pigs with 32 SNPs localized in 11 neurotransmitter-related genes. The genetic polymorphisms of 26 SNPs had notable differences (P < 0.05) between Mi and LLW. The most frequent haplotypes were different in DBH, HTR2A, GAD1, HTR2B,MAOA and MAOB genes between Mi and LLW. The mean of backtest scores was significantly lower (P < 0.001) for Mi than LLW pigs. Skin lesion scores were greater (P < 0.01) in LLW pigs than Mi pigs. In this study, we have confirmed that Chinese Mi pigs are less active and less aggressive than European LLW pigs, and the genetic polymorphisms of neurotransmitter-related genes, which have been proved previously associated with aggressive behaviour, have considerable differences between Mi and LLW pigs.

Polymorphism discovery and allele frequency estimation using high-throughput DNA sequencing of target-enriched pooled DNA samples

PubMed Central

2012-01-01

Background The central role of the somatotrophic axis in animal post-natal growth, development and fertility is well established. Therefore, the identification of genetic variants affecting quantitative traits within this axis is an attractive goal. However, large sample numbers are a pre-requisite for the identification of genetic variants underlying complex traits and although technologies are improving rapidly, high-throughput sequencing of large numbers of complete individual genomes remains prohibitively expensive. Therefore using a pooled DNA approach coupled with target enrichment and high-throughput sequencing, the aim of this study was to identify polymorphisms and estimate allele frequency differences across 83 candidate genes of the somatotrophic axis, in 150 Holstein-Friesian dairy bulls divided into two groups divergent for genetic merit for fertility. Results In total, 4,135 SNPs and 893 indels were identified during the resequencing of the 83 candidate genes. Nineteen percent (n = 952) of variants were located within 5' and 3' UTRs. Seventy-two percent (n = 3,612) were intronic and 9% (n = 464) were exonic, including 65 indels and 236 SNPs resulting in non-synonymous substitutions (NSS). Significant (P < 0.01) mean allele frequency differentials between the low and high fertility groups were observed for 720 SNPs (58 NSS). Allele frequencies for 43 of the SNPs were also determined by genotyping the 150 individual animals (Sequenom® MassARRAY). No significant differences (P > 0.1) were observed between the two methods for any of the 43 SNPs across both pools (i.e., 86 tests in total). Conclusions The results of the current study support previous findings of the use of DNA sample pooling and high-throughput sequencing as a viable strategy for polymorphism discovery and allele frequency estimation. Using this approach we have characterised the genetic variation within genes of the somatotrophic axis and related pathways, central to mammalian post-natal growth and development and subsequent lactogenesis and fertility. We have identified a large number of variants segregating at significantly different frequencies between cattle groups divergent for calving interval plausibly harbouring causative variants contributing to heritable variation. To our knowledge, this is the first report describing sequencing of targeted genomic regions in any livestock species using groups with divergent phenotypes for an economically important trait. PMID:22235840

Investigation of Caucasian rheumatoid arthritis susceptibility loci in African patients with the same disease

PubMed Central

2012-01-01

Introduction The largest genetic risk to develop rheumatoid arthritis (RA) arises from a group of alleles of the HLA DRB1 locus ('shared epitope', SE). Over 30 non-HLA single nucleotide polymorphisms (SNPs) predisposing to disease have been identified in Caucasians, but they have never been investigated in West/Central Africa. We previously reported a lower prevalence of the SE in RA patients in Cameroon compared to European patients and aimed in the present study to investigate the contribution of Caucasian non-HLA RA SNPs to disease susceptibility in Black Africans. Methods RA cases and controls from Cameroon were genotyped for Caucasian RA susceptibility SNPs using Sequenom MassArray technology. Genotype data were also available for 5024 UK cases and 4281 UK controls and for 119 Yoruba individuals in Ibadan, Nigeria (YRI, HapMap). A Caucasian aggregate genetic-risk score (GRS) was calculated as the sum of the weighted risk-allele counts. Results After genotyping quality control procedures were performed, data on 28 Caucasian non-HLA susceptibility SNPs were available in 43 Cameroonian RA cases and 44 controls. The minor allele frequencies (MAF) were tightly correlated between Cameroonian controls and YRI individuals (correlation coefficient 93.8%, p = 1.7E-13), and they were pooled together. There was no correlation between MAF of UK and African controls; 13 markers differed by more than 20%. The MAF for markers at PTPN22, IL2RA, FCGR2A and IL2/IL21 was below 2% in Africans. The GRS showed a strong association with RA in the UK. However, the GRS did not predict RA in Africans (OR = 0.71, 95% CI 0.29 - 1.74, p = 0.456). Random sampling from the UK cohort showed that this difference in association is unlikely to be explained by small sample size or chance, but is statistically significant with p<0.001. Conclusions The MAFs of non-HLA Caucasian RA susceptibility SNPs are different between Caucasians and Africans, and several polymorphisms are barely detectable in West/Central Africa. The genetic risk of developing RA conferred by a set of 28 Caucasian susceptibility SNPs is significantly different between the UK and Africa with p<0.001. Taken together, these observations strengthen the hypothesis that the genetic architecture of RA susceptibility is different in different ethnic backgrounds. PMID:23121884

Investigation of Caucasian rheumatoid arthritis susceptibility loci in African patients with the same disease.

PubMed

Viatte, Sebastien; Flynn, Edward; Lunt, Mark; Barnes, Joanne; Singwe-Ngandeu, Madeleine; Bas, Sylvette; Barton, Anne; Gabay, Cem

2012-11-03

The largest genetic risk to develop rheumatoid arthritis (RA) arises from a group of alleles of the HLA DRB1 locus ('shared epitope', SE). Over 30 non-HLA single nucleotide polymorphisms (SNPs) predisposing to disease have been identified in Caucasians, but they have never been investigated in West/Central Africa. We previously reported a lower prevalence of the SE in RA patients in Cameroon compared to European patients and aimed in the present study to investigate the contribution of Caucasian non-HLA RA SNPs to disease susceptibility in Black Africans. RA cases and controls from Cameroon were genotyped for Caucasian RA susceptibility SNPs using Sequenom MassArray technology. Genotype data were also available for 5024 UK cases and 4281 UK controls and for 119 Yoruba individuals in Ibadan, Nigeria (YRI, HapMap). A Caucasian aggregate genetic-risk score (GRS) was calculated as the sum of the weighted risk-allele counts. After genotyping quality control procedures were performed, data on 28 Caucasian non-HLA susceptibility SNPs were available in 43 Cameroonian RA cases and 44 controls. The minor allele frequencies (MAF) were tightly correlated between Cameroonian controls and YRI individuals (correlation coefficient 93.8%, p = 1.7E-13), and they were pooled together. There was no correlation between MAF of UK and African controls; 13 markers differed by more than 20%. The MAF for markers at PTPN22, IL2RA, FCGR2A and IL2/IL21 was below 2% in Africans. The GRS showed a strong association with RA in the UK. However, the GRS did not predict RA in Africans (OR = 0.71, 95% CI 0.29 - 1.74, p = 0.456). Random sampling from the UK cohort showed that this difference in association is unlikely to be explained by small sample size or chance, but is statistically significant with p<0.001. The MAFs of non-HLA Caucasian RA susceptibility SNPs are different between Caucasians and Africans, and several polymorphisms are barely detectable in West/Central Africa. The genetic risk of developing RA conferred by a set of 28 Caucasian susceptibility SNPs is significantly different between the UK and Africa with p<0.001. Taken together, these observations strengthen the hypothesis that the genetic architecture of RA susceptibility is different in different ethnic backgrounds.

DNA methylation of the IGF2/H19 imprinting control region and adiposity distribution in young adults

PubMed Central

2012-01-01

Background The insulin-like growth factor 2 (IGF2) and H19 imprinted genes control growth and body composition. Adverse in-utero environments have been associated with obesity-related diseases and linked with altered DNA methylation at the IGF2/H19 locus. Postnatally, methylation at the IGF2/H19 imprinting control region (ICR) has been linked with cerebellum weight. We aimed to investigate whether decreased IGF2/H19 ICR methylation is associated with decreased birth and childhood anthropometry and increased contemporaneous adiposity. DNA methylation in peripheral blood (n = 315) at 17 years old was measured at 12 cytosine-phosphate-guanine sites (CpGs), analysed as Sequenom MassARRAY EpiTYPER units within the IGF2/H19 ICR. Birth size, childhood head circumference (HC) at six time-points and anthropometry at age 17 years were measured. DNA methylation was investigated for its association with anthropometry using linear regression. Results The principal component of IGF2/H19 ICR DNA methylation (representing mean methylation across all CpG units) positively correlated with skin fold thickness (at four CpG units) (P-values between 0.04 to 0.001) and subcutaneous adiposity (P = 0.023) at age 17, but not with weight, height, BMI, waist circumference or visceral adiposity. IGF2/H19 methylation did not associate with birth weight, length or HC, but CpG unit 13 to 14 methylation was negatively associated with HC between 1 and 10 years. β-coefficients of four out of five remaining CpG units also estimated lower methylation with increasing childhood HC. Conclusions As greater IGF2/H19 methylation was associated with greater subcutaneous fat measures, but not overall, visceral or central adiposity, we hypothesize that obesogenic pressures in youth result in excess fat being preferentially stored in peripheral fat depots via the IGF2/H19 domain. Secondly, as IGF2/H19 methylation was not associated with birth size but negatively with early childhood HC, we hypothesize that the HC may be a more sensitive marker of early life programming of the IGF axis and of fetal physiology than birth size. To verify this, investigations of the dynamics of IGF2/H19 methylation and expression from birth to adolescence are required. PMID:23148549

Association between regulator of telomere elongation helicase1 (RTEL1) gene and HAPE risk: A case-control study.

PubMed

Rong, Hao; He, Xue; Zhu, Linhao; Zhu, Xikai; Kang, Longli; Wang, Li; He, Yongjun; Yuan, Dongya; Jin, Tianbo

2017-09-01

High altitude pulmonary edema (HAPE) is a paradigm of pulmonary edema. Mutations in regulator of telomere elongation helicase1 (RTEL1) represent an important contributor to risk for pulmonary fibrosis. However, little information is found about the association between RTEL1 and HAPE risk. The present study was undertaken to tentatively explore the potential relation between single-nucleotide polymorphisms (SNPs) in RTEL1 and HAPE risk in Chinese Han population. A total of 265 HAPE patients and 303 healthy controls were included in our case-control study. Four SNPs in RTEL1 were selected and genotyped using the Sequenom MassARRAY method. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by unconditional logistic regression with adjustment for gender and age. All P values were Bonferroni corrected, and statistical significance was set at P < .0025 (.05/20). In allelic model analysis, we found that the allele "G" of rs6089953 and rs6010621 and the allele "A" of rs2297441 were associated with decreased risk of HAPE. In the genetic model analysis, we found that rs6010621, rs6089953, and rs2297441 were relevant to decreased HAPE risk under dominant model (rs6010621: OR = 0.55; 95% CI = 0.39-0.78; P = .001; rs6089953: OR = 0.68; 95% CI = 0.48-0.96; P = .027; rs2297441: OR = 0.63; 95% CI = 0.45-0.89; P = .008, respectively) and additive model (rs6010621: OR = 0.51; 95% CI = 0.46-0.81; P < .001; rs6089953: OR = 0.72; 95% CI = 0.55-0.95; P = .022; rs2297441: OR = 0.73; 95% CI = 0.57-0.95; P = .019, respectively). SNPs rs6010621 remained significant after Bonferroni correction (P < .0025). In addition, haplotype "GG, GT, AT" of rs6089953-rs6010621 were detected significantly associated with HAPE risk (P < .05), haplotype "GG" remained significant after Bonferroni correction (P < .0025). Our findings provide new evidence for the association between SNPs in RTEL1 and a decreased risk HAPE in the Chinese population. The results need further confirmation.

Association between regulator of telomere elongation helicase1 (RTEL1) gene and HAPE risk

PubMed Central

Rong, Hao; He, Xue; Zhu, Linhao; Zhu, Xikai; Kang, Longli; Wang, Li; He, Yongjun; Yuan, Dongya; Jin, Tianbo

2017-01-01

Abstract High altitude pulmonary edema (HAPE) is a paradigm of pulmonary edema. Mutations in regulator of telomere elongation helicase1 (RTEL1) represent an important contributor to risk for pulmonary fibrosis. However, little information is found about the association between RTEL1 and HAPE risk. The present study was undertaken to tentatively explore the potential relation between single-nucleotide polymorphisms (SNPs) in RTEL1 and HAPE risk in Chinese Han population. A total of 265 HAPE patients and 303 healthy controls were included in our case-control study. Four SNPs in RTEL1 were selected and genotyped using the Sequenom MassARRAY method. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by unconditional logistic regression with adjustment for gender and age. All P values were Bonferroni corrected, and statistical significance was set at P < .0025 (.05/20). In allelic model analysis, we found that the allele “G” of rs6089953 and rs6010621 and the allele “A” of rs2297441 were associated with decreased risk of HAPE. In the genetic model analysis, we found that rs6010621, rs6089953, and rs2297441 were relevant to decreased HAPE risk under dominant model (rs6010621: OR = 0.55; 95% CI = 0.39–0.78; P = .001; rs6089953: OR = 0.68; 95% CI = 0.48–0.96; P = .027; rs2297441: OR = 0.63; 95% CI = 0.45–0.89; P = .008, respectively) and additive model (rs6010621: OR = 0.51; 95% CI = 0.46–0.81; P < .001; rs6089953: OR = 0.72; 95% CI = 0.55–0.95; P = .022; rs2297441: OR = 0.73; 95% CI = 0.57–0.95; P = .019, respectively). SNPs rs6010621 remained significant after Bonferroni correction (P < .0025). In addition, haplotype “GG, GT, AT” of rs6089953-rs6010621 were detected significantly associated with HAPE risk (P < .05), haplotype “GG” remained significant after Bonferroni correction (P < .0025). Our findings provide new evidence for the association between SNPs in RTEL1 and a decreased risk HAPE in the Chinese population. The results need further confirmation. PMID:28953687

Methylation on the Circadian Gene BMAL1 Is Associated with the Effects of a Weight Loss Intervention on Serum Lipid Levels.

PubMed

Samblas, Mirian; Milagro, Fermin I; Gómez-Abellán, Purificación; Martínez, J Alfredo; Garaulet, Marta

2016-06-01

The circadian clock system has been linked to the onset and development of obesity and some accompanying comorbidities. Epigenetic mechanisms, such as DNA methylation, are putatively involved in the regulation of the circadian clock system. The aim of this study was to investigate the influence of a weight loss intervention based on an energy-controlled Mediterranean dietary pattern in the methylation levels of 3 clock genes, BMAL1, CLOCK, and NR1D1, and the association between the methylation levels and changes induced in the serum lipid profile with the weight loss treatment. The study sample enrolled 61 women (body mass index = 28.6 ± 3.4 kg/m(2); age: 42.2 ± 11.4 years), who followed a nutritional program based on a Mediterranean dietary pattern. DNA was isolated from whole blood obtained at the beginning and end point. Methylation levels at different CpG sites of BMAL1, CLOCK, and NR1D1 were analyzed by Sequenom's MassArray. The energy-restricted intervention modified the methylation levels of different CpG sites in BMAL1 (CpGs 5, 6, 7, 9, 11, and 18) and NR1D1 (CpGs 1, 10, 17, 18, 19, and 22). Changes in cytosine methylation in the CpG 5 to 9 region of BMAL1 with the intervention positively correlated with the eveningness profile (p = 0.019). The baseline methylation of the CpG 5 to 9 region in BMAL1 positively correlated with energy (p = 0.047) and carbohydrate (p = 0.017) intake and negatively correlated with the effect of the weight loss intervention on total cholesterol (p = 0.032) and low-density lipoprotein cholesterol (p = 0.005). Similar significant and positive correlations were found between changes in methylation levels in the CpG 5 to 9 region of BMAL1 due to the intervention and changes in serum lipids (p < 0.05). This research describes apparently for the first time an association between changes in the methylation of the BMAL1 gene with the intervention and the effects of a weight loss intervention on blood lipids levels. © 2016 The Author(s).

The importance of a large sample cohort for studies on modifier genes influencing disease severity in FAP patients.

PubMed

Talseth-Palmer, Bente A; Wijnen, Juul T; Andreassen, Eva K; Barker, Daniel; Jagmohan-Changur, Shantie; Tops, Carli M; Meldrum, Cliff; Spigelman, Allan; Hes, Frederik J; Van Wezel, Tom; Vasen, Hans Fa; Scott, Rodney J

2013-12-29

Familial adenomatous polyposis (FAP) is usually characterised by the appearance of hundreds-to-thousands of adenomas throughout the colon and rectum and if left untreated the condition will develop into CRC with close to 100% penetrance. Germline mutations in the APC gene, which plays an integral role in the Wnt-signalling pathway, have been found to be responsible for 70-90% of FAP cases. Several studies suggest that modifier genes may play an important role in the development of CRC and possible modifiers for FAP have been suggested. Interestingly, a study has found that SNPs within ATP5A1 is associated with raised levels of ATP5A1 expression and high expression levels may facilitate CRC development. We aimed to determine if SNPs in ATP5A1 modify the risk of developing CRC/adenomas in FAP patients. Genomic DNA from 139 Australian FAP patients with a germline APC mutation underwent genotyping at the Australian Genome Research Facility (AGRF) utilising iPLEX GOLD chemistry with Sequenom MassArray on an Autoflex Spectrometer for 16 SNPs in the ATP5A1 gene. Association between ages of diagnosis/risk of CRC/adenomas was tested with Kaplan-Meier estimator analysis, logistic regression and cox proportional hazard regression. An association between age of diagnosis of CRC and genotypes was observed for SNP rs2578189 (p = 0.0014), with individuals harbouring the variant genotype developing CRC 29 years earlier than individuals harbouring the wildtype genotype. Individuals harbouring the variant genotype of SNP rs2578189 were also at increased risk of CRC (HR = 13.79, 95% CI = 2.36-80.64, p = 0.004). We used an independent Dutch FAP cohort (n = 427) to validate our results; no association between SNP rs2578189 and CRC was observed. These results highlight the difficulties in studying a disease that has a high degree of intervention and also emphasize the importance of large sample sizes when searching for modifier genes in patients with an inherited predisposition to disease. To fully determine if there are genetic modifiers of disease in FAP we would encourage people that are interested in collaborating in future studies into the role of modifier genes in disease expression in FAP to join forces.

Promoter methylation assay of SASH1 gene in hepatocellular carcinoma.

PubMed

Peng, Liu; Wei, He; Liren, Li

2014-01-01

To analyse the relationship between the expression of SASH1 and its methylation level in human hepatocellular carcinoma. Expression levels of SASH1 were examined with real-time PCR (RT-PCR) in tissues and cells, and methylation analysis was performed with MassArray. The expression levels of SASH1 were strongly reduced in liver cancer tissues compared with adjacent normal tissues. Quantitative methylation analysis by MassArray revealed different CpG sites in SASH1 promoter shared similar methylation pattern between liver cancer tissues and adjacent normal tissues and the CpG sites of significant difference in methylation level were found as follows: CpG_3, CpG_17, CpG_21.22, CpG_25, CpG_26.27, CpG_28, CpG_34.35.36 and CpG_51.52. Moreover, 5-aza-2'-deoxycytidine treatment of Hep-G2 cell line caused significant elevation of SASH1 mRNA. Based on these data, we propose that increase of DNA methylation degree in the promoter region of SASH1 gene, particularly CpG_26.27 sites, possibly repressed SASH1 expression in liver cancer.

Promoter methylation assay of SASH1 gene in breast cancer.

PubMed

Sheyu, Lin; Hui, Liu; Junyu, Zhang; Jiawei, Xu; Honglian, Wang; Qing, Sang; Hengwei, Zhang; Xuhui, Guo; Qinghe, Xing; Lin, He

2013-01-01

To analyze the relationship between the expression of SASH1 and its methylation level of SASH1 gene promoter in human breast cancer. Expression levels of SASH1 were examined in breast cancer tissues and adjacent normal tissues with immunohistochemistry and with real time PCR (RT-PCR) methylation analysis was performed with MassArray. Immunohistochemistry showed that SASH1 expression was strongly reduced in breast cancer compared with adjacent normal tissues. Quantitative methylation analysis by MassArray revealed that CpG sites in SASH1 promoter shared similar methylation pattern in tumor tissue and adjacent normal tissue. The CpG sites with significant difference in methylation level were CpG_26.27 and CpG_54.55. Moreover, 5-aza-2'-deoxycytidine (5-Aza-dc) treatment of tumor cell line MDA-MB-231 caused significant elevation of SASH1 mRNA. Based on these data, we propose that increase of DNA methylation level in the promoter region of gene SASH1, particularly CpG_26.27 or CpG_54.55 sites, possibly repressed SASH1 expression in breast cancer.

Association analysis of the SLC22A11 (organic anion transporter 4) and SLC22A12 (urate transporter 1) urate transporter locus with gout in New Zealand case-control sample sets reveals multiple ancestral-specific effects

PubMed Central

2013-01-01

Introduction There is inconsistent association between urate transporters SLC22A11 (organic anion transporter 4 (OAT4)) and SLC22A12 (urate transporter 1 (URAT1)) and risk of gout. New Zealand (NZ) Māori and Pacific Island people have higher serum urate and more severe gout than European people. The aim of this study was to test genetic variation across the SLC22A11/SLC22A12 locus for association with risk of gout in NZ sample sets. Methods A total of 12 single nucleotide polymorphism (SNP) variants in four haplotype blocks were genotyped using TaqMan® and Sequenom MassArray in 1003 gout cases and 1156 controls. All cases had gout according to the 1977 American Rheumatism Association criteria. Association analysis of single markers and haplotypes was performed using PLINK and Stata. Results A haplotype block 1 SNP (rs17299124) (upstream of SLC22A11) was associated with gout in less admixed Polynesian sample sets, but not European Caucasian (odds ratio; OR = 3.38, P = 6.1 × 10-4; OR = 0.91, P = 0.40, respectively) sample sets. A protective block 1 haplotype caused the rs17299124 association (OR = 0.28, P = 6.0 × 10-4). Within haplotype block 2 (SLC22A11) we could not replicate previous reports of association of rs2078267 with gout in European Caucasian (OR = 0.98, P = 0.82) sample sets, however this SNP was associated with gout in Polynesian (OR = 1.51, P = 0.022) sample sets. Within haplotype block 3 (including SLC22A12) analysis of haplotypes revealed a haplotype with trans-ancestral protective effects (OR = 0.80, P = 0.004), and a second haplotype conferring protection in less admixed Polynesian sample sets (OR = 0.63, P = 0.028) but risk in European Caucasian samples (OR = 1.33, P = 0.039). Conclusions Our analysis provides evidence for multiple ancestral-specific effects across the SLC22A11/SLC22A12 locus that presumably influence the activity of OAT4 and URAT1 and risk of gout. Further fine mapping of the association signal is needed using trans-ancestral re-sequence data. PMID:24360580

Multiplicative interaction of functional inflammasome genetic variants in determining the risk of gout.

PubMed

McKinney, Cushla; Stamp, Lisa K; Dalbeth, Nicola; Topless, Ruth K; Day, Richard O; Kannangara, Diluk Rw; Williams, Kenneth M; Janssen, Matthijs; Jansen, Timothy L; Joosten, Leo A; Radstake, Timothy R; Riches, Philip L; Tausche, Anne-Kathrin; Lioté, Frederic; So, Alexander; Merriman, Tony R

2015-10-13

The acute gout flare results from a localised self-limiting innate immune response to monosodium urate (MSU) crystals deposited in joints in hyperuricaemic individuals. Activation of the caspase recruitment domain-containing protein 8 (CARD8) NOD-like receptor pyrin-containing 3 (NLRP3) inflammasome by MSU crystals and production of mature interleukin-1β (IL-1β) is central to acute gouty arthritis. However very little is known about genetic control of the innate immune response involved in acute gouty arthritis. Therefore our aim was to test functional single nucleotide polymorphism (SNP) variants in the toll-like receptor (TLR)-inflammasome-IL-1β axis for association with gout. 1,494 gout cases of European and 863 gout cases of New Zealand (NZ) Polynesian (Māori and Pacific Island) ancestry were included. Gout was diagnosed by the 1977 ARA gout classification criteria. There were 1,030 Polynesian controls and 10,942 European controls including from the publicly-available Atherosclerosis Risk in Communities (ARIC) and Framingham Heart (FHS) studies. The ten SNPs were either genotyped by Sequenom MassArray or by Affymetrix SNP array or imputed in the ARIC and FHS datasets. Allelic association was done by logistic regression adjusting by age and sex with European and Polynesian data combined by meta-analysis. Sample sets were pooled for multiplicative interaction analysis, which was also adjusted by sample set. Eleven SNPs were tested in the TLR2, CD14, IL1B, CARD8, NLRP3, MYD88, P2RX7, DAPK1 and TNXIP genes. Nominally significant (P < 0.05) associations with gout were detected at CARD8 rs2043211 (OR = 1.12, P = 0.007), IL1B rs1143623 (OR = 1.10, P = 0.020) and CD14 rs2569190 (OR = 1.08; P = 0.036). There was significant multiplicative interaction between CARD8 and IL1B (P = 0.005), with the IL1B risk genotype amplifying the risk effect of CARD8. There is evidence for association of gout with functional variants in CARD8, IL1B and CD14. The gout-associated allele of IL1B increases expression of IL-1β - the multiplicative interaction with CARD8 would be consistent with a synergy of greater inflammasome activity (resulting from reduced CARD8) combined with higher levels of pre-IL-1β expression leading to increased production of mature IL-1β in gout.

Single-nucleotide polymorphism discovery in Leptographium longiclavatum, a mountain pine beetle-associated symbiotic fungus, using whole-genome resequencing.

PubMed

Ojeda, Dario I; Dhillon, Braham; Tsui, Clement K M; Hamelin, Richard C

2014-03-01

Single-nucleotide polymorphisms (SNPs) are rapidly becoming the standard markers in population genomics studies; however, their use in nonmodel organisms is limited due to the lack of cost-effective approaches to uncover genome-wide variation, and the large number of individuals needed in the screening process to reduce ascertainment bias. To discover SNPs for population genomics studies in the fungal symbionts of the mountain pine beetle (MPB), we developed a road map to discover SNPs and to produce a genotyping platform. We undertook a whole-genome sequencing approach of Leptographium longiclavatum in combination with available genomics resources of another MPB symbiont, Grosmannia clavigera. We sequenced 71 individuals pooled into four groups using the Illumina sequencing technology. We generated between 27 and 30 million reads of 75 bp that resulted in a total of 1, 181 contigs longer than 2 kb and an assembled genome size of 28.9 Mb (N50 = 48 kb, average depth = 125x). A total of 9052 proteins were annotated, and between 9531 and 17,266 SNPs were identified in the four pools. A subset of 206 genes (containing 574 SNPs, 11% false positives) was used to develop a genotyping platform for this species. Using this roadmap, we developed a genotyping assay with a total of 147 SNPs located in 121 genes using the Illumina(®) Sequenom iPLEX Gold. Our preliminary genotyping (success rate = 85%) of 304 individuals from 36 populations supports the utility of this approach for population genomics studies in other MPB fungal symbionts and other fungal nonmodel species. © 2013 John Wiley & Sons Ltd.

Use of Sequenom Sample ID Plus® SNP Genotyping in Identification of FFPE Tumor Samples

PubMed Central

Miller, Jessica K.; Buchner, Nicholas; Timms, Lee; Tam, Shirley; Luo, Xuemei; Brown, Andrew M. K.; Pasternack, Danielle; Bristow, Robert G.; Fraser, Michael; Boutros, Paul C.; McPherson, John D.

2014-01-01

Short tandem repeat (STR) analysis, such as the AmpFlSTR® Identifiler® Plus kit, is a standard, PCR-based human genotyping method used in the field of forensics. Misidentification of cell line and tissue DNA can be costly if not detected early; therefore it is necessary to have quality control measures such as STR profiling in place. A major issue in large-scale research studies involving archival formalin-fixed paraffin embedded (FFPE) tissues is that varying levels of DNA degradation can result in failure to correctly identify samples using STR genotyping. PCR amplification of STRs of several hundred base pairs is not always possible when DNA is degraded. The Sample ID Plus® panel from Sequenom allows for human DNA identification and authentication using SNP genotyping. In comparison to lengthy STR amplicons, this multiplexing PCR assay requires amplification of only 76–139 base pairs, and utilizes 47 SNPs to discriminate between individual samples. In this study, we evaluated both STR and SNP genotyping methods of sample identification, with a focus on paired FFPE tumor/normal DNA samples intended for next-generation sequencing (NGS). The ability to successfully validate the identity of FFPE samples can enable cost savings by reducing rework. PMID:24551080

Use of Sequenom sample ID Plus® SNP genotyping in identification of FFPE tumor samples.

PubMed

Miller, Jessica K; Buchner, Nicholas; Timms, Lee; Tam, Shirley; Luo, Xuemei; Brown, Andrew M K; Pasternack, Danielle; Bristow, Robert G; Fraser, Michael; Boutros, Paul C; McPherson, John D

2014-01-01

Short tandem repeat (STR) analysis, such as the AmpFlSTR® Identifiler® Plus kit, is a standard, PCR-based human genotyping method used in the field of forensics. Misidentification of cell line and tissue DNA can be costly if not detected early; therefore it is necessary to have quality control measures such as STR profiling in place. A major issue in large-scale research studies involving archival formalin-fixed paraffin embedded (FFPE) tissues is that varying levels of DNA degradation can result in failure to correctly identify samples using STR genotyping. PCR amplification of STRs of several hundred base pairs is not always possible when DNA is degraded. The Sample ID Plus® panel from Sequenom allows for human DNA identification and authentication using SNP genotyping. In comparison to lengthy STR amplicons, this multiplexing PCR assay requires amplification of only 76-139 base pairs, and utilizes 47 SNPs to discriminate between individual samples. In this study, we evaluated both STR and SNP genotyping methods of sample identification, with a focus on paired FFPE tumor/normal DNA samples intended for next-generation sequencing (NGS). The ability to successfully validate the identity of FFPE samples can enable cost savings by reducing rework.

Correlation between polymorphism of FTO gene and type 2 diabetes mellitus in Uygur people from northwest China.

PubMed

Xiao, Shan; Zeng, Xiaoyun; Quan, Li; Zhu, Jun

2015-01-01

To explore the correlation between FTO (fat mass and obesity associated) gene, which is associated with 3 single nucleotide polymorphisms (SNP) of fat mass and obesity, type 2 diabetes and body mass index (BMI) in the Uygur population in northwest China. A total of 849 Uygur patients with type 2 diabetes mellitus were selected from the hospitalized patients in the First Affiliated Hospital of Xinjiang Medical University, the First People's Hospital of Kashi and the hospitals in the Turpan areas. At the same time, 873 cases of healthy persons who conducted a medical checkup in the physical examination centre of the above hospitals were enrolled as controls. The present investigation used the case-control research method, and physical examination and biochemical index determination were carried out. The Sequenom MassARRAY technology was employed in the detection of 3 SNP loci of the FTO gene. The representative population of each SNP in the control group was analyzed by Hardy-Weinberg law. The differences of each clinical parameter in the two groups were analyzed by t-test analysis. The differences of genotype and allele of each SNP in the two groups were analyzed by χ(2) test. BMI, waistline (WL), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), total cholesterol (TC), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the type 2 diabetes group were higher than those in the control group, while the high density lipoprotein (HDL) and low density lipoprotein (LDL) were lower than those of the control group; 2. The allele frequency of A of rs8050136 and rs9939609 in the type 2 diabetes mellitus group was higher than that of the control group. The BMI of the whole population and type 2 diabetes group with genotype C/A+A/A of rs8050136 was higher than that in C/C group, and the BMI with genotype T/A+A/A of rs9939609 was higher than that in group T/T. Stratification was conducted on BMI according to the normal, overweight and obesity criteria. There were significant differences in the distribution of genotype frequency of rs9939609 in the type 2 diabetes group and the control group of the normal BMI group. Single nucleotide mutation of rs7195539 in FTO gene may be a protective factor against the Uygur type 2 diabetes. Single nucleotide mutations of rs8050136 and rs9939609 may be associated with the Uygur type 2 diabetes and obesity, with A as a potential risk allele. The gene polymorphism of rs8050136 may correlate with type 2 diabetes mellitus through the function of BMI, while the correlation between rs9939609 gene polymorphism and type 2 diabetes is not depending from BMI.

UCP2 and UCP3 variants and gene-environment interaction associated with prediabetes and T2DM in a rural population: a case control study in China.

PubMed

Su, Meifang; Chen, Xiaoying; Chen, Yue; Wang, Congyun; Li, Songtao; Ying, Xuhua; Xiao, Tian; Wang, Na; Jiang, Qingwu; Fu, Chaowei

2018-03-12

There are disparities for the association between uncoupling proteins (UCP) and type 2 diabetes (T2DM). The study was to examine the associations of genetic variants of UCP2 and UCP3 with prediabetes and T2DM in a rural Chinese population. A population-based case-control study of 397 adults with T2DM, 394 with prediabetes and 409 with normal glucose tolerance (NGT) was carried out in 2014 in a rural community in eastern China. Three groups were identified through a community survey and the prediabetes and NGT groups were frequently matched by age and gender with the T2DM group and they were not relatives of T2DM subjects. With r 2  ≥ 0.8 and minor allele frequency (MAF) ≥0.05 for tag single nucleotide polymorphisms (SNPs) with potential function, three (rs660339, rs45560234 and rs643064) and six (rs7930460, rs15763, rs647126, rs1800849, rs3781907 and rs1685356) SNPs were selected respectively for UCP2 and UCP3 and genotyped in real time using the MassARRAY system (Sequenom; USA). The haplotypes, gene-environmental interaction and association between genetic variants of UCP2 and UCP3 and prediabetes or T2DM were explored. There were no significant differences in age and sex among three study groups. After the adjustment for possible covariates, the A allele of rs1800849 in UCP3 was significantly associated with prediabetes (aOR AA vs GG  = 1.68, 95% CI: 1.02-2.78), and the association was also significant under the recessive model (aOR AA vs GA + GG  = 1.64, 95% CI: 1.02-2.66). Also, rs15763 was found to be marginally significantly associated with T2DM under dominant model (OR GA + AA vs GG  = 0.73, 95% CI: 0.52-1.03, P = 0.072). No haplotype was significantly associated with prediabetes or T2DM. Multiplicative interactions for rs660339-overweight on T2DM were observed. In addition, the AA genotype of rs660339 was associated with an increased risk of T2DM in overweight subjects (OR = 1.48, 95%CI: 0.87-2.52) but with a decreased risk in those with normal weight (OR = 0.54, 95%CI: 0.28-1.05). Rs1800849 in UCP3 was significantly associated with prediabetes. Overweight might modify the effects of rs660339 of UCP2 on T2DM.

Gene variations in sex hormone pathways and the risk of testicular germ cell tumour: a case-parent triad study in a Norwegian-Swedish population.

PubMed

Kristiansen, W; Andreassen, K E; Karlsson, R; Aschim, E L; Bremnes, R M; Dahl, O; Fosså, S D; Klepp, O; Langberg, C W; Solberg, A; Tretli, S; Adami, H-O; Wiklund, F; Grotmol, T; Haugen, T B

2012-05-01

Testicular germ cell tumour (TGCT) is the most common cancer in young men, and an imbalance between the estrogen and androgen levels in utero is hypothesized to influence TGCT risk. Thus, polymorphisms in genes involved in the action of sex hormones may contribute to variability in an individual's susceptibility to TGCT. We conducted a Norwegian-Swedish case-parent study. A total of 105 single-nucleotide polymorphisms (SNPs) in 20 sex hormone pathway genes were genotyped using Sequenom MassArray iPLEX Gold, in 831 complete triads and 474 dyads. To increase the statistical power, the analysis was expanded to include 712 case singletons and 3922 Swedish controls, thus including triads, dyads and the case-control samples in a single test for association. Analysis for allelic associations was performed with the UNPHASED program, using a likelihood-based association test for nuclear families with missing data, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. False discovery rate (FDR) was used to adjust for multiple testing. Five genetic variants across the ESR2 gene [encoding estrogen receptor beta (ERβ)] were statistically significantly associated with the risk of TGCT. In the case-parent analysis, the markers rs12434245 and rs10137185 were associated with a reduced risk of TGCT (OR = 0.66 and 0.72, respectively; both FDRs <5%), whereas rs2978381 and rs12435857 were associated with an increased risk of TGCT (OR = 1.21 and 1.19, respectively; both FDRs <5%). In the combined case-parent/case-control analysis, rs12435857 and rs10146204 were associated with an increased risk of TGCT (OR = 1.15 and 1.13, respectively; both FDRs <5%), whereas rs10137185 was associated with a reduced risk of TGCT (OR = 0.79, FDR <5%). In addition, we found that three genetic variants in CYP19A1 (encoding aromatase) were statistically significantly associated with the risk of TGCT in the case-parent analysis. The T alleles of the rs2414099, rs8025374 and rs3751592 SNPs were associated with an increased risk of TGCT (OR = 1.30, 1.30 and 1.21, respectively; all FDRs <5%). We found no statistically significant differences in allelic effect estimates between parental inherited genetic variation in the sex hormone pathways and TGCT risk in the offspring, and no evidence of heterogeneity between seminomas and non-seminomas, or between the Norwegian and the Swedish population, in any of the SNPs examined. Our findings provide support for ERβ and aromatase being implicated in the aetiology of TGCT. Exploring the functional role of the TGCT risk-associated SNPs will further elucidate the biological mechanisms involved.

Analysis of genetic polymorphisms in skeletal Class I crowding.

PubMed

Ting, Tung Yuen; Wong, Ricky Wing Kit; Rabie, A Bakr M

2011-07-01

Dental crowding is a problem for both adolescents and adults in modern society. The purpose of this research was to identify single nucleotide polymorphisms (SNPs) responsible for crowding in subjects with skeletal Class I relationships. The case subjects consisted of healthy Chinese people living in Hong Kong with skeletal Class I relationships and at least 5 mm of crowding in either arch. The control subjects met the same requirements but lacked crowding or spacing. SNP genotyping was performed on the MassARRAY platform. The chi-square test was used to compare genotype and allele type distributions between the case and the control groups. Logistic regression was used to calculate odds ratios with 95% confidence intervals, and the effects of age and sex for each SNP. Analyses of linkage disequilibrium and haplotype associations between SNPs were performed with software. Five SNPs were found to be significantly different in genotype or allele type distributions. SNP rs372024 was significantly associated with crowding (P = 0.004). Two SNPs, rs3764746 and rs3795170, on the EDA gene were found to be associated marginally. SNPs rs1005464 and rs15705 also exhibited marginal association with crowding. The effects of associated SNPs remained significant after adjustments for age and sex factors. This study suggests an association for the genes EDA and XEDAR in dental crowding in the Hong Kong Chinese population. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Quantitative mutant analysis of viral quasispecies by chip-based matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry

PubMed Central

Amexis, Georgios; Oeth, Paul; Abel, Kenneth; Ivshina, Anna; Pelloquin, Francois; Cantor, Charles R.; Braun, Andreas; Chumakov, Konstantin

2001-01-01

RNA viruses exist as quasispecies, heterogeneous and dynamic mixtures of mutants having one or more consensus sequences. An adequate description of the genomic structure of such viral populations must include the consensus sequence(s) plus a quantitative assessment of sequence heterogeneities. For example, in quality control of live attenuated viral vaccines, the presence of even small quantities of mutants or revertants may indicate incomplete or unstable attenuation that may influence vaccine safety. Previously, we demonstrated the monitoring of oral poliovirus vaccine with the use of mutant analysis by PCR and restriction enzyme cleavage (MAPREC). In this report, we investigate genetic variation in live attenuated mumps virus vaccine by using both MAPREC and a platform (DNA MassArray) based on matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Mumps vaccines prepared from the Jeryl Lynn strain typically contain at least two distinct viral substrains, JL1 and JL2, which have been characterized by full length sequencing. We report the development of assays for characterizing sequence variants in these substrains and demonstrate their use in quantitative analysis of substrains and sequence variations in mixed virus cultures and mumps vaccines. The results obtained from both the MAPREC and MALDI-TOF methods showed excellent correlation. This suggests the potential utility of MALDI-TOF for routine quality control of live viral vaccines and for assessment of genetic stability and quantitative monitoring of genetic changes in other RNA viruses of clinical interest. PMID:11593021

Multilocus analysis reveals three candidate genes for Chinese migraine susceptibility.

PubMed

An, X-K; Fang, J; Yu, Z-Z; Lin, Q; Lu, C-X; Qu, H-L; Ma, Q-L

2017-08-01

Several genome-wide association studies (GWASs) in Caucasian populations have identified 12 loci that are significantly associated with migraine. More evidence suggests that serotonin receptors are also involved in migraine pathophysiology. In the present study, a case-control study was conducted in a cohort of 581 migraine cases and 533 ethnically matched controls among a Chinese population. Eighteen polymorphisms from serotonin receptors and GWASs were selected, and genotyping was performed using a Sequenom MALDI-TOF mass spectrometry iPLEX platform. The genotypic and allelic distributions of MEF2D rs2274316 and ASTN2 rs6478241 were significantly different between migraine patients and controls. Univariate and multivariate analysis revealed significant associations of polymorphisms in the MEF2D and ASTN2 genes with migraine susceptibility. MEF2D, PRDM16 and ASTN2 were also found to be associated with migraine without aura (MO) and migraine with family history. And, MEF2D and ASTN2 also served as genetic risk factors for the migraine without family history. The generalized multifactor dimensionality reduction analysis identified that MEF2D and HTR2E constituted the two-factor interaction model. Our study suggests that the MEF2D, PRDM16 and ASTN2 genes from GWAS are associated with migraine susceptibility, especially MO, among Chinese patients. It appears that there is no association with serotonin receptor related genes. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Clinical features and treatment outcome of non-small cell lung cancer (NSCLC) patients with uncommon or complex epidermal growth factor receptor (EGFR) mutations

PubMed Central

Fassan, Matteo; Indraccolo, Stefano; Calabrese, Fiorella; Favaretto, Adolfo; Bonanno, Laura; Polo, Valentina; Zago, Giulia; Lunardi, Francesca; Attili, Ilaria; Pavan, Alberto; Rugge, Massimo; Guarneri, Valentina; Conte, PierFranco; Pasello, Giulia

2017-01-01

Introduction Tyrosine-kinase inhibitors (TKIs) represent the best treatment for advanced non-small cell lung cancer (NSCLC) with common exon 19 deletion or exon 21 epidermal growth factor receptor mutation (EGFRm). This is an observational study investigating epidemiology, clinical features and treatment outcome of NSCLC cases harbouring rare/complex EGFRm. Results Among 764 non-squamous NSCLC cases with known EGFRm status, 26(3.4%) harboured rare/complex EGFRm. Patients receiving first-line TKIs (N = 17) achieved median Progression Free Survival (PFS) and Overall Survival (OS) of 53 (IC 95%, 2–105) and 84 (CI 95%, 27–141) weeks respectively, without significant covariate impact. Response Rate and Disease Control Rate (DCR) were 47% and 65%, respectively. Uncommon exon 19 mutations achieved longer OS and PFS and higher DCR compared with exon 18 and 20 mutations. No additional gene mutation was discovered by MassARRAY analysis. TKIs were globally well tolerated. Materials and methods A retrospective review of advanced non-squamous NSCLC harbouring rare/complex EGFRm referred to our Center between 2010 and 2015 was performed. Additional molecular pathways disregulation was explored in selected cases, through MassARRAY analysis. Conclusions Peculiar clinical features and lower TKIs sensitivity of uncommon/complex compared with common EGFRm were shown. Exon 19 EGFRm achieved the best TKIs treatment outcome, while the optimal treatment of exon 18 and 20 mutations should be further clarified. PMID:28427238

Associations of Genetic Variants at Nongenic Susceptibility Loci with Breast Cancer Risk and Heterogeneity by Tumor Subtype in Southern Han Chinese Women

PubMed Central

Liang, Huiying; Li, Hong; Yang, Xuexi; Chen, Lujia; Zhu, Anna; Sun, Minying; Ye, Changsheng; Li, Ming

2016-01-01

Current understanding of cancer genomes is mainly “gene centric.” However, GWAS have identified some nongenic breast cancer susceptibility loci. Validation studies showed inconsistent results among different populations. To further explore this inconsistency and to investigate associations by intrinsic subtype (Luminal-A, Luminal-B, ER−&PR−&HER2+, and triple negative) among Southern Han Chinese women, we genotyped five nongenic polymorphisms (2q35: rs13387042, 5p12: rs981782 and rs4415084, and 8q24: rs1562430 and rs13281615) using MassARRAY IPLEX platform in 609 patients and 882 controls. Significant associations with breast cancer were observed for rs13387042 and rs4415084 with OR (95% CI) per-allele 1.29 (1.00–1.66) and 0.83 (0.71–0.97), respectively. In subtype specific analysis, rs13387042 (per-allele adjusted OR = 1.36, 95% CI = 1.00–1.87) and rs4415084 (per-allele adjusted OR = 0.82, 95% CI = 0.66–1.00) showed slightly significant association with Luminal-A subtype; however, only rs13387042 was associated with ER−&PR−&HER2+ tumors (per-allele adjusted OR = 1.55, 95% CI = 1.00–2.40), and none of them were linked to Luminal-B and triple negative subtype. Collectively, nongenic SNPs were heterogeneous according to the intrinsic subtype. Further studies with larger datasets along with intrinsic subtype categorization should explore and confirm the role of these variants in increasing breast cancer risk. PMID:27022606

Filter Paper-based Nucleic Acid Storage in High-throughput Solid Tumor Genotyping.

PubMed

Stachler, Matthew; Jia, Yonghui; Sharaf, Nematullah; Wade, Jacqueline; Longtine, Janina; Garcia, Elizabeth; Sholl, Lynette M

2015-01-01

Molecular testing of tumors from formalin-fixed paraffin-embedded (FFPE) tissue blocks is central to clinical practice; however, it requires histology support and increases test turnaround time. Prospective fresh frozen tissue collection requires special handling, additional storage space, and may not be feasible for small specimens. Filter paper-based collection of tumor DNA reduces the need for histology support, requires little storage space, and preserves high-quality nucleic acid. We investigated the performance of tumor smears on filter paper in solid tumor genotyping, as compared with paired FFPE samples. Whatman FTA Micro Card (FTA preps) smears were prepared from 21 fresh tumor samples. A corresponding cytology smear was used to assess tumor cellularity and necrosis. DNA was isolated from FTA preps and FFPE core samples using automated methods and quantified using SYBR green dsDNA detection. Samples were genotyped for 471 mutations on a mass spectrophotometry-based platform (Sequenom). DNA concentrations from FTA preps and FFPE correlated for untreated carcinomas but not for mesenchymal tumors (Spearman σ=0.39 and σ=-0.1, respectively). Average DNA concentrations were lower from FTA preps as compared with FFPE, but DNA quality was higher with less fragmentation. Seventy-six percent of FTA preps and 86% of FFPE samples generated adequate DNA for genotyping. FTA preps tended to perform poorly for collection of DNA from pretreated carcinomas and mesenchymal neoplasms. Of the 16 paired DNA samples that were genotyped, 15 (94%) gave entirely concordant results. Filter paper-based sample preservation is a feasible alternative to FFPE for use in automated, high-throughput genotyping of carcinomas.

Associations Between Polymorphisms in the Glucocorticoid-Receptor Gene and Cardiovascular Risk Factors in a Chinese Population

PubMed Central

Yan, Yu-Xiang; Dong, Jing; Wu, Li-Juan; Shao, Shuang; Zhang, Jie; Zhang, Ling; Wang, Wei; He, Yan; Liu, You-Qin

2013-01-01

Background Glucocorticoid is an important regulator of energy homeostasis. Glucocorticoid receptor (GR) gene polymorphisms that contribute to variability in glucocorticoid sensitivity have been identified. We explored the associations of single-nucleotide polymorphisms (SNPs) of the GR gene with traditional cardiovascular risk factors in the Chinese Han population. Methods We recruited 762 consecutive adults who underwent a regular physical examination at Beijing Xuanwu Hospital. Blood pressure, glucose, lipid levels (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein [LDL] cholesterol and triglycerides), body mass index (BMI), and waist-to-hip ratio were measured. Fourteen tag SNPs and 5 functional SNPs were selected and genotyped using the high-throughput Sequenom genotyping platform. Differences between genotypes/alleles for each SNP were adjusted for sex and age and tested using a general linear model procedure. Various models of inheritance, including additive, dominant, and recessive, were tested. Results Among the 19 SNPs examined, 5 markers were associated with cardiovascular risk factors. The rs41423247 GG genotype and the rs7701443 AA genotype were associated with higher BMI and systolic blood pressure (P < 0.0004), and the rs17209251 GG genotype was associated with higher systolic blood pressure (P < 0.0004). Lower systolic blood pressure, total cholesterol, and LDL cholesterol were observed among rs10052957 A allele carriers (P < 0.0004), and lower plasma glucose and LDL-cholesterol concentrations were observed among rs2963156 TT carriers (P < 0.0004). Conclusions Polymorphism of the GR gene was associated with cardiovascular risk factors and may contribute to susceptibility to cardiovascular disease. PMID:23892712

Primary tumor location predicts poor clinical outcome with cetuximab in RAS wild-type metastatic colorectal cancer.

PubMed

Kim, Dalyong; Kim, Sun Young; Lee, Ji Sung; Hong, Yong Sang; Kim, Jeong Eun; Kim, Kyu-Pyo; Kim, Jihun; Jang, Se Jin; Yoon, Young-Kwang; Kim, Tae Won

2017-11-23

In metastatic colorectal cancer, the location of the primary tumor has been suggested to have biological significance. In this study, we investigated whether primary tumor location affects cetuximab efficacy in patients with RAS wild-type metastatic colorectal cancer. Genotyping by the SequenomMassARRAY technology platform (OncoMap) targeting KRAS, NRAS, PIK3CA, and BRAF was performed in tumors from 307 patients who had been given cetuximab as salvage treatment. Tumors with mutated RAS (KRAS or NRAS; n = 127) and those with multiple primary location (n = 10) were excluded. Right colon cancer was defined as a tumor located in the proximal part to splenic flexure. A total of 170 patients were included in the study (right versus left, 23 and 147, respectively). Patients with right colon cancer showed more mutated BRAF (39.1% vs. 5.4%), mutated PIK3CA (13% vs. 1.4%), poorly differentiated tumor (17.4% vs. 3.4%), and peritoneal involvement (26.1% vs. 8.8%) than those with left colon and rectal cancer. Right colon cancer showed poorer progression-free survival (2.0 vs.5.0 months, P = 0.002) and overall survival (4.1 months and 13.0 months, P < 0.001) than the left colon and rectal cancer. By multivariable analysis, BRAF mutation, right colon primary, poorly differentiated histology, and peritoneal involvement were associated with risk of death. In RAS wild-type colon cancer treated with cetuximab as salvage treatment, right colon primary was associated with poorer survival outcomes than left colon and rectal cancer.

Novel Genetic Variants of Sporadic Atrial Septal Defect (ASD) in a Chinese Population Identified by Whole-Exome Sequencing (WES)

PubMed Central

Liu, Yong; Cao, Yu; Li, Yaxiong; Lei, Dongyun; Li, Lin; Hou, Zong Liu; Han, Shen; Meng, Mingyao; Shi, Jianlin; Zhang, Yayong; Wang, Yi; Niu, Zhaoyi; Xie, Yanhua; Xiao, Benshan; Wang, Yuanfei; Li, Xiao; Yang, Lirong

2018-01-01

Background Recently, mutations in several genes have been described to be associated with sporadic ASD, but some genetic variants remain to be identified. The aim of this study was to use whole-exome sequencing (WES) combined with bioinformatics analysis to identify novel genetic variants in cases of sporadic congenital ASD, followed by validation by Sanger sequencing. Material/Methods Five Han patients with secundum ASD were recruited, and their tissue samples were analyzed by WES, followed by verification by Sanger sequencing of tissue and blood samples. Further evaluation using blood samples included 452 additional patients with sporadic secundum ASD (212 male and 240 female patients) and 519 healthy subjects (252 male and 267 female subjects) for further verification by a multiplexed MassARRAY system. Bioinformatic analyses were performed to identify novel genetic variants associated with sporadic ASD. Results From five patients with sporadic ASD, a total of 181,762 genomic variants in 33 exon loci, validated by Sanger sequencing, were selected and underwent MassARRAY analysis in 452 patients with ASD and 519 healthy subjects. Three loci with high mutation frequencies, the 138665410 FOXL2 gene variant, the 23862952 MYH6 gene variant, and the 71098693 HYDIN gene variant were found to be significantly associated with sporadic ASD (P<0.05); variants in FOXL2 and MYH6 were found in patients with isolated, sporadic ASD (P<5×10−4). Conclusions This was the first study that demonstrated variants in FOXL2 and HYDIN associated with sporadic ASD, and supported the use of WES and bioinformatics analysis to identify disease-associated mutations. PMID:29505555

Novel Genetic Variants of Sporadic Atrial Septal Defect (ASD) in a Chinese Population Identified by Whole-Exome Sequencing (WES).

PubMed

Liu, Yong; Cao, Yu; Li, Yaxiong; Lei, Dongyun; Li, Lin; Hou, Zong Liu; Han, Shen; Meng, Mingyao; Shi, Jianlin; Zhang, Yayong; Wang, Yi; Niu, Zhaoyi; Xie, Yanhua; Xiao, Benshan; Wang, Yuanfei; Li, Xiao; Yang, Lirong; Wang, Wenju; Jiang, Lihong

2018-03-05

BACKGROUND Recently, mutations in several genes have been described to be associated with sporadic ASD, but some genetic variants remain to be identified. The aim of this study was to use whole-exome sequencing (WES) combined with bioinformatics analysis to identify novel genetic variants in cases of sporadic congenital ASD, followed by validation by Sanger sequencing. MATERIAL AND METHODS Five Han patients with secundum ASD were recruited, and their tissue samples were analyzed by WES, followed by verification by Sanger sequencing of tissue and blood samples. Further evaluation using blood samples included 452 additional patients with sporadic secundum ASD (212 male and 240 female patients) and 519 healthy subjects (252 male and 267 female subjects) for further verification by a multiplexed MassARRAY system. Bioinformatic analyses were performed to identify novel genetic variants associated with sporadic ASD. RESULTS From five patients with sporadic ASD, a total of 181,762 genomic variants in 33 exon loci, validated by Sanger sequencing, were selected and underwent MassARRAY analysis in 452 patients with ASD and 519 healthy subjects. Three loci with high mutation frequencies, the 138665410 FOXL2 gene variant, the 23862952 MYH6 gene variant, and the 71098693 HYDIN gene variant were found to be significantly associated with sporadic ASD (P<0.05); variants in FOXL2 and MYH6 were found in patients with isolated, sporadic ASD (P<5×10^-4). CONCLUSIONS This was the first study that demonstrated variants in FOXL2 and HYDIN associated with sporadic ASD, and supported the use of WES and bioinformatics analysis to identify disease-associated mutations.

The suitability of small biopsy and cytology specimens for EGFR and other mutation testing in non-small cell lung cancer

PubMed Central

Wang, Shu; Yu, Bing; Ng, Chiu Chin; Mercorella, Belinda; Selinger, Christina I.; O’Toole, Sandra A.

2015-01-01

Background Patients with advanced non-small cell lung cancer (NSCLC) benefit from treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) when their tumor harbors an activating EGFR mutation. As the majority of NSCLC patients present with advanced disease, cytology and small biopsy specimens are frequently the only tissue available for mutation testing, but can pose challenges due to low tumor content. We aim to better define the suitability of these specimens for mutation testing. Methods NSCLC cases referred to our institution for mutation testing over a 15-month period were retrospectively reviewed. Specimens were tested for mutations including EGFR, KRAS, and BRAF, using a multiplex PCR assay (OncoCarta Panel v1.0) and analyzed on the Agena Bioscience MassARRAY platform. Results A total of 146 specimens were tested, comprising 53 (36.3%) resection specimens (including 28 lung resection specimens), 55 (37.7%) small biopsy specimens and 38 (26%) cytology specimens. Of 142 cases with sufficient DNA for mutation testing, EGFR mutations were detected in 31 specimens (21.8%), KRAS mutations in 31 specimens (21.8%) and BRAF mutations in three specimens (2.1%). There was no significant difference in the EGFR mutation rate between lung resection (10 of 28 cases; 35.7%), small biopsy (9 of 53 cases; 17%), and cytology specimens (8 of 36 cases; 22.2%). Conclusions Our results support the utility of small biopsy and cytology specimens for mutation testing. Careful evaluation of the adequacy of small specimens is required to minimize the risk of false negative or positive results. PMID:25870794

The role of DNA methylation in catechol-enhanced erythroid differentiation of K562 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Xiao-Fei; Wu, Xiao-Rong; Xue, Ming

2012-11-15

Catechol is one of phenolic metabolites of benzene in vivo. Catechol is also widely used in pharmaceutical and chemical industries. In addition, fruits, vegetables and cigarette smoke also contain catechol. Our precious study showed that several benzene metabolites (phenol, hydroquinone, and 1,2,4-benzenetriol) inhibited erythroid differentiation of K562 cells. In present study, the effect of catechol on erythroid differentiation of K562 cells was investigated. Moreover, to address the role of DNA methylation in catechol-induced effect on erythroid differentiation in K562 cells, methylation levels of erythroid-specific genes were analyzed by Quantitative MassARRAY methylation analysis platform. Benzidine staining showed that exposure to catecholmore » enhanced hemin-induced hemoglobin accumulation in K562 cells in concentration- and time-dependent manners. The mRNA expression of erythroid specific genes, including α-globin, β-globin, γ-globin, erythroid 5-aminolevulinate synthase, erythroid porphobilinogen deaminase, and transcription factor GATA-1 genes, showed a significant concentration-dependent increase in catechol-treated K562 cells. The exposure to catechol caused a decrease in DNA methylation levels at a few CpG sites in some erythroid specific genes including α-globin, β-globin and erythroid porphobilinogen deaminase genes. These results indicated that catechol improved erythroid differentiation potency of K562 cells at least partly via up-regulating transcription of some erythroid related genes, and suggested that inhibition of DNA methylation might be involved in up-regulated expression of some erythroid related genes. -- Highlights: ► Catechol enhanced hemin-induced hemoglobin accumulation. ► Exposure to catechol resulted in up-regulated expression of erythroid genes. ► Catechol reduced methylation levels at some CpG sites in erythroid genes.« less

Prevalence, Patterns, and Genetic Association Analysis of Modic Vertebral Endplate Changes.

PubMed

Kanna, Rishi Mugesh; Shanmuganathan, Rajasekaran; Rajagopalan, Veera Ranjani; Natesan, Senthil; Muthuraja, Raveendran; Cheung, Kenneth Man Chee; Chan, Danny; Kao, Patrick Yu Ping; Yee, Anita; Shetty, Ajoy Prasad

2017-08-01

A prospective genetic association study. The etiology of Modic changes (MCs) is unclear. Recently, the role of genetic factors in the etiology of MCs has been evaluated. However, studies with a larger patient subset are lacking, and candidate genes involved in other disc degeneration phenotypes have not been evaluated. We studied the prevalence of MCs and genetic association of 41 candidate genes in a large Indian cohort. MCs are vertebral endplate signal changes predominantly observed in the lumbar spine. A significant association between MCs and lumbar disc degeneration and nonspecific low back pain has been described, with the etiopathogenesis implicating various mechanical, infective, and biochemical factors. We studied 809 patients using 1.5-T magnetic resonance imaging to determine the prevalence, patterns, distribution, and type of lumbar MCs. Genetic association analysis of 71 single nucleotide polymorphisms (SNPs) of 41 candidate genes was performed based on the presence or absence of MCs. SNPs were genotyped using the Sequenome platform, and an association test was performed using PLINK software. The mean age of the study population (n=809) was 36.7±10.8 years. Based on the presence of MCs, the cohort was divided into 702 controls and 107 cases (prevalence, 13%). MCs were more commonly present in the lower (149/251, 59.4%) than in the upper (102/251, 40.6%) endplates. L4-5 endplates were the most commonly affected levels (30.7%). Type 2 MCs were the most commonly observed pattern (n=206, 82%). The rs2228570 SNP of VDR ( p =0.02) and rs17099008 SNP of MMP20 ( p =0.03) were significantly associated with MCs. Genetic polymorphisms of SNPs of VDR and MMP20 were significantly associated with MCs. Understanding the etiopathogenetic mechanisms of MCs is important for planning preventive and therapeutic strategies.

New evidence for involvement of ESR1 gene in susceptibility to Chinese migraine.

PubMed

An, Xingkai; Fang, Jie; Lin, Qing; Lu, Congxia; Ma, Qilin; Qu, Hongli

2017-01-01

Migraine is a common and disabling nervous system disease with a significant genetic predisposition. The sex hormones play an important role in the pathogenesis of migraine. However, the conclusions of the previous genetic relation studies are conflicting. The aim of this study is to determine whether variants in genes involved in estrogen receptor and estrogen hormone metabolism are related to Chinese migraine. By employing a case-control approach, 8 SNPs in the ESR1, ESR2, and CYP19A1 genes are studied in a cohort of 494 migraine cases and 533 controls. In addition, genotyping is performed using Sequenom MALDI-TOF mass spectrometry iPLEX platform. Univariate and multivariate analyses are carried out by logistic regression. The corresponding haplotypes are studied with the Haploview software and gene-gene interaction is assessed using the Generalized Multifactor Dimensionality Reduction (GMDR) analysis. There are significant differences in allelic distributions for rs2234693 and rs9340799 in ESR1 gene between patients with migraine and control subjects. Univariate logistic analysis shows that rs2234693 and rs9340799 are risk factors for migraine, but multivariate analysis reveals that only rs2234693 is significant associated with migraine. In the subgroup analysis, rs2234693 in ESR1 gene is found associated with menstrually related migraine. Further haplotypic analysis shows that rs2234693-rs9340799 TA haplotype serves as risk haplotype for migraine. The GMDR analysis identifies rs2234693 in ESR1 alone to be a crucial candidate in migraine susceptibility. This study is in agreement with the previous studies that variants in the ESR1 gene are associated with migraine suggesting that it plays a role in the migraine process.

Functional evaluation of genetic variants associated with endometriosis near GREB1.

PubMed

Fung, Jenny N; Holdsworth-Carson, Sarah J; Sapkota, Yadav; Zhao, Zhen Zhen; Jones, Lincoln; Girling, Jane E; Paiva, Premila; Healey, Martin; Nyholt, Dale R; Rogers, Peter A W; Montgomery, Grant W

2015-05-01

Do DNA variants in the growth regulation by estrogen in breast cancer 1 (GREB1) region regulate endometrial GREB1 expression and increase the risk of developing endometriosis in women? We identified new single nucleotide polymorphisms (SNPs) with strong association with endometriosis at the GREB1 locus although we did not detect altered GREB1 expression in endometriosis patients with defined genotypes. Genome-wide association studies have identified the GREB1 region on chromosome 2p25.1 for increasing endometriosis risk. The differential expression of GREB1 has also been reported by others in association with endometriosis disease phenotype. Fine mapping studies comprehensively evaluated SNPs within the GREB1 region in a large-scale data set (>2500 cases and >4000 controls). Publicly available bioinformatics tools were employed to functionally annotate SNPs showing the strongest association signal with endometriosis risk. Endometrial GREB1 mRNA and protein expression was studied with respect to phases of the menstrual cycle (n = 2-45 per cycle stage) and expression quantitative trait loci (eQTL) analysis for significant SNPs were undertaken for GREB1 [mRNA (n = 94) and protein (n = 44) in endometrium]. Participants in this study are females who provided blood and/or endometrial tissue samples in a hospital setting. The key SNPs were genotyped using Sequenom MassARRAY. The functional roles and regulatory annotations for identified SNPs are predicted by various publicly available bioinformatics tools. Endometrial GREB1 expression work employed qRT-PCR, western blotting and immunohistochemistry studies. Fine mapping results identified a number of SNPs showing stronger association (0.004 < P < 0.032) with endometriosis risk than the original GWAS SNP (rs13394619) (P = 0.034). Some of these SNPs were predicted to have functional roles, for example, interaction with transcription factor motifs. The haplotype (a combination of alleles) formed by the risk alleles from two common SNPs showed significant association (P = 0.026) with endometriosis and epistasis analysis showed no evidence for interaction between the two SNPs, suggesting an additive effect of SNPs on endometriosis risk. In normal human endometrium, GREB1 protein expression was altered depending on the cycle stage (significantly different in late proliferative versus late secretory, P < 0.05) and cell type (glandular epithelium, not stromal cells). However, GREB1 expression in endometriosis cases versus controls and eQTL analyses did not reveal any significant changes. In silico prediction tools are generally based on cell lines different to our tissue and disease of interest. Functional annotations drawn from these analyses should be considered with this limitation in mind. We identified cell-specific and hormone-specific changes in GREB1 protein expression. The lack of a significant difference observed following our GREB1 expression studies may be the result of moderate power on mixed cell populations in the endometrial tissue samples. This study further implicates the GREB1 region on chromosome 2p25.1 and the GREB1 gene with involvement in endometriosis risk. More detailed functional studies are required to determine the role of the novel GREB1 transcripts in endometriosis pathophysiology. Funding for this work was provided by NHMRC Project Grants APP1012245, APP1026033, APP1049472 and APP1046880. There are no competing interests. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

EZH2 and CD79B mutational status over time in B-cell non-Hodgkin lymphomas detected by high-throughput sequencing using minimal samples

PubMed Central

Saieg, Mauro Ajaj; Geddie, William R; Boerner, Scott L; Bailey, Denis; Crump, Michael; da Cunha Santos, Gilda

2013-01-01

BACKGROUND: Numerous genomic abnormalities in B-cell non-Hodgkin lymphomas (NHLs) have been revealed by novel high-throughput technologies, including recurrent mutations in EZH2 (enhancer of zeste homolog 2) and CD79B (B cell antigen receptor complex-associated protein beta chain) genes. This study sought to determine the evolution of the mutational status of EZH2 and CD79B over time in different samples from the same patient in a cohort of B-cell NHLs, through use of a customized multiplex mutation assay. METHODS: DNA that was extracted from cytological material stored on FTA cards as well as from additional specimens, including archived frozen and formalin-fixed histological specimens, archived stained smears, and cytospin preparations, were submitted to a multiplex mutation assay specifically designed for the detection of point mutations involving EZH2 and CD79B, using MassARRAY spectrometry followed by Sanger sequencing. RESULTS: All 121 samples from 80 B-cell NHL cases were successfully analyzed. Mutations in EZH2 (Y646) and CD79B (Y196) were detected in 13.2% and 8% of the samples, respectively, almost exclusively in follicular lymphomas and diffuse large B-cell lymphomas. In one-third of the positive cases, a wild type was detected in a different sample from the same patient during follow-up. CONCLUSIONS: Testing multiple minimal tissue samples using a high-throughput multiplex platform exponentially increases tissue availability for molecular analysis and might facilitate future studies of tumor progression and the related molecular events. Mutational status of EZH2 and CD79B may vary in B-cell NHL samples over time and support the concept that individualized therapy should be based on molecular findings at the time of treatment, rather than on results obtained from previous specimens. Cancer (Cancer Cytopathol) 2013;121:377–386. © 2013 American Cancer Society. PMID:23361872

Prevalence, Patterns, and Genetic Association Analysis of Modic Vertebral Endplate Changes

PubMed Central

Kanna, Rishi Mugesh; Rajagopalan, Veera Ranjani; Natesan, Senthil; Muthuraja, Raveendran; Cheung, Kenneth Man Chee; Chan, Danny; Kao, Patrick Yu Ping; Yee, Anita; Shetty, Ajoy Prasad

2017-01-01

Study Design A prospective genetic association study. Purpose The etiology of Modic changes (MCs) is unclear. Recently, the role of genetic factors in the etiology of MCs has been evaluated. However, studies with a larger patient subset are lacking, and candidate genes involved in other disc degeneration phenotypes have not been evaluated. We studied the prevalence of MCs and genetic association of 41 candidate genes in a large Indian cohort. Overview of Literature MCs are vertebral endplate signal changes predominantly observed in the lumbar spine. A significant association between MCs and lumbar disc degeneration and nonspecific low back pain has been described, with the etiopathogenesis implicating various mechanical, infective, and biochemical factors. Methods We studied 809 patients using 1.5-T magnetic resonance imaging to determine the prevalence, patterns, distribution, and type of lumbar MCs. Genetic association analysis of 71 single nucleotide polymorphisms (SNPs) of 41 candidate genes was performed based on the presence or absence of MCs. SNPs were genotyped using the Sequenome platform, and an association test was performed using PLINK software. Results The mean age of the study population (n=809) was 36.7±10.8 years. Based on the presence of MCs, the cohort was divided into 702 controls and 107 cases (prevalence, 13%). MCs were more commonly present in the lower (149/251, 59.4%) than in the upper (102/251, 40.6%) endplates. L4–5 endplates were the most commonly affected levels (30.7%). Type 2 MCs were the most commonly observed pattern (n=206, 82%). The rs2228570 SNP of VDR (p=0.02) and rs17099008 SNP of MMP20 (p=0.03) were significantly associated with MCs. Conclusions Genetic polymorphisms of SNPs of VDR and MMP20 were significantly associated with MCs. Understanding the etiopathogenetic mechanisms of MCs is important for planning preventive and therapeutic strategies. PMID:28874978

Linkage Analysis in Autoimmune Addison's Disease: NFATC1 as a Potential Novel Susceptibility Locus.

PubMed

Mitchell, Anna L; Bøe Wolff, Anette; MacArthur, Katie; Weaver, Jolanta U; Vaidya, Bijay; Erichsen, Martina M; Darlay, Rebecca; Husebye, Eystein S; Cordell, Heather J; Pearce, Simon H S

2015-01-01

Autoimmune Addison's disease (AAD) is a rare, highly heritable autoimmune endocrinopathy. It is possible that there may be some highly penetrant variants which confer disease susceptibility that have yet to be discovered. DNA samples from 23 multiplex AAD pedigrees from the UK and Norway (50 cases, 67 controls) were genotyped on the Affymetrix SNP 6.0 array. Linkage analysis was performed using Merlin. EMMAX was used to carry out a genome-wide association analysis comparing the familial AAD cases to 2706 UK WTCCC controls. To explore some of the linkage findings further, a replication study was performed by genotyping 64 SNPs in two of the four linked regions (chromosomes 7 and 18), on the Sequenom iPlex platform in three European AAD case-control cohorts (1097 cases, 1117 controls). The data were analysed using a meta-analysis approach. In a parametric analysis, applying a rare dominant model, loci on chromosomes 7, 9 and 18 had LOD scores >2.8. In a non-parametric analysis, a locus corresponding to the HLA region on chromosome 6, known to be associated with AAD, had a LOD score >3.0. In the genome-wide association analysis, a SNP cluster on chromosome 2 and a pair of SNPs on chromosome 6 were associated with AAD (P <5x10-7). A meta-analysis of the replication study data demonstrated that three chromosome 18 SNPs were associated with AAD, including a non-synonymous variant in the NFATC1 gene. This linkage study has implicated a number of novel chromosomal regions in the pathogenesis of AAD in multiplex AAD families and adds further support to the role of HLA in AAD. The genome-wide association analysis has also identified a region of interest on chromosome 2. A replication study has demonstrated that the NFATC1 gene is worthy of future investigation, however each of the regions identified require further, systematic analysis.

ROCK2 and MYLK variants under hypobaric hypoxic environment of high altitude associate with high altitude pulmonary edema and adaptation

PubMed Central

Pandey, Priyanka; Mohammad, Ghulam; Singh, Yogendra; Qadar Pasha, MA

2015-01-01

Objective To date, a major class of kinases, serine–threonine kinase, has been scantly investigated in stress-induced rare, fatal (if not treated early), and morbid disorder, high altitude pulmonary edema (HAPE). This study examined three major serine–threonine kinases, ROCK2, MYLK, and JNK1, along with six other genes, tyrosine hydroxylase, G-protein subunits GNA11 and GNB3, and alpha1 adrenergic receptor isoforms 1A, 1B, and 1D as candidate gene markers of HAPE and adaptation. Methods For this, 57 variants across these nine genes were genotyped in HAPE patients (n=225), HAPE controls (n=210), and highlanders (n=259) by Sequenom MS (TOF)-based MassARRAY® platform using iPLEX™ Gold technology. In addition, to study the gene expression, quantitative real-time polymerase chain reaction was performed in human peripheral blood mononuclear cells of the three study groups. Results A significant association was observed for C allele (ROCK2 single-nucleotide polymorphism, rs10929728) with HAPE (P=0.03) and C, T, and A alleles (MYLK single-nucleotide polymorphisms, rs11717814, rs40305, and rs820336) with both HAPE and adaptation (P=0.001, P=0.006, and P=0.02, respectively). ROCK2 88 kb GGGTTGGT haplotype was associated with lower risk of HAPE (P=0.0009). MYLK 7 kb haplotype CTA, composed of variant alleles, was associated with higher risk of HAPE (P=0.0006) and lower association with adaptation (P=1E–06), whereas haplotype GCG, composed of wild-type alleles, was associated with lower risk of HAPE (P=0.001) and higher association with adaptation (P=1E–06). Haplotype–haplotype and gene–gene interactions demonstrated a correlation in working of ROCK2 and MYLK. Conclusion The data suggest the association of ROCK2 with HAPE and MYLK with HAPE and adaptation in Indian population. The outcome has provided new insights into the physiology of HAPE and adaptation. PMID:26586960

Genome-wide DNA methylation profiling in infants born to gestational diabetes mellitus.

PubMed

Weng, Xiaoling; Liu, Fatao; Zhang, Hong; Kan, Mengyuan; Wang, Ting; Dong, Mingyue; Liu, Yun

2018-03-26

Offspring exposed to gestational diabetes mellitus (GDM) are at a high risk for metabolic diseases. The mechanisms behind the association between offspring exposed to GDM in utero and an increased risk of health consequences later in life remain unclear. The aim of this study was to clarify the changes in methylation levels in the foetuses of women with GDM and to explore the possible mechanisms linking maternal GDM with a high risk of metabolic diseases in offspring later in life. A genome-wide comparative methylome analysis on the umbilical cord blood of infants born to 30 women with GDM and 33 women with normal pregnancy was performed using Infinium HumanMethylation 450 BeadChip assays. A quantitative methylation analysis of 18 CpG dinucleotides was verified in the validation umbilical cord blood samples from 102 newborns exposed to GDM and 103 newborns who experienced normal pregnancy by MassARRAY EpiTYPER. A total of 4485 differentially methylated sites (DMSs), including 2150 hypermethylated sites and 2335 hypomethylated sites, with a mean β-value difference of >0.05, were identified by the 450k array. Good agreement was observed between the massarray validation data and the 450k array data (R 2 > 0.99; P < 0.0001). Thirty-seven CpGs (representing 20 genes) with a β-value difference of >0.15 between the GDM and healthy groups were identified and showed potential as clinical biomarkers for GDM. "hsa04940: Type I diabetes mellitus" was the most significant Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, with a P-value = 3.20E-07 and 1.36E-02 in the hypermethylated and hypomethylated genepathway enrichment analyses, respectively. In the Gene Ontology (GO) pathway analyses, immune MHC-related pathways and neuron development-related pathways were significantly enriched. Our results suggest that GDM has epigenetic effects on genes that are preferentially involved in the Type I diabetes mellitus pathway, immune MHC (major histocompatibility complex)-related pathways and neuron development-related pathways, with consequences on fetal growth and development, and provide supportive evidence that DNA methylation is involved in fetal metabolic programming. Copyright © 2018. Published by Elsevier B.V.

Somatic profiling of the epidermal growth factor receptor pathway in tumours from patients with advanced colorectal cancer, treated with chemotherapy ± cetuximab

PubMed Central

Smith, Christopher G.; Fisher, David; Claes, Bart; Maughan, Timothy S.; Idziaszczyk, Shelley; Peuteman, Gilian; Harris, Rebecca; James, Michelle D.; Meade, Angela; Jasani, Bharat; Adams, Richard A.; Kenny, Sarah; Kaplan, Richard; Lambrechts, Diether; Cheadle, Jeremy P.

2013-01-01

Purpose To study the somatic molecular profile of the epidermal growth factor receptor (EGFR) pathway in advanced CRC (aCRC), its relationship to prognosis, the site of the primary and metastases, and response to cetuximab. Experimental Design We used Sequenom and Pyrosequencing for high-throughput somatic profiling the EGFR pathway in 1,976 tumours from patients with aCRC from the COIN trial (oxaliplatin and fluoropyrimidine chemotherapy ±cetuximab). Correlations between mutations, clinico-pathological, response and survival data were carried out. Results Sequenom and Pyrosequencing had 99.0% (9961/10063) genotype concordance. We identified thirteen different KRAS mutations in 42.3% of aCRCs, two BRAF mutations in 9.0%, four NRAS mutations in 3.6% and five PIK3CA mutations in 12.7%. 4.2% of aCRCs had microsatellite instability (MSI). KRAS and PIK3CA exon 9, but not exon 20, mutations co-occurred (P=8.9×10−4) as did MSI and BRAF mutations (P=5.3×10−10). KRAS mutations were associated with right colon cancers (P=5.2×10−5) and BRAF mutations with right (P=7.2×10−5) and transverse colon (P=9.8×10−6) cancers. KRAS mutations were associated with lung-only metastases (P=2.3×10−4), BRAF mutations with peritoneal (P=9.2×10−4) and nodal-only (P=3.7×10−5) metastases, and MSI (BRAFWT) with nodal-only metastases (P=2.9×10−4). MSI (BRAFWT) was associated with worse survival (HR=1.89, 95% CI 1.30-2.76, P=8.5×10−4). No mutations, subsets of mutations, or MSI-status were associated with response to cetuximab. Conclusions Our data support a functional co-operation between KRAS and PIK3CA in colorectal tumourigenesis and link somatic profiles to the sites of metastases. MSI was associated with poor prognosis in advanced disease, and no individual somatic profile was associated with response to cetuximab in COIN. PMID:23741067

Mass spectrometry: a revolution in clinical microbiology?

PubMed

Lavigne, Jean-Philippe; Espinal, Paula; Dunyach-Remy, Catherine; Messad, Nourredine; Pantel, Alix; Sotto, Albert

2013-02-01

Recently, different bacteriological laboratory interventions that decrease reporting time have been developed. These promising new broad-based techniques have merit, based on their ability to identify rapidly many bacteria, organisms difficult to grow or newly emerging strains, as well as their capacity to track disease transmission. The benefit of rapid reporting of identification and/or resistance of bacteria can greatly impact patient outcomes, with an improvement in the use of antibiotics, in the reduction of the emergence of multidrug resistant bacteria and in mortality rates. Different techniques revolve around mass spectrometry (MS) technology: matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), PCR combined with electrospray ionization-mass spectrometry (PCR/ESIMS), iPLEX MassArray system and other new evolutions combining different techniques. This report emphasizes the (r)evolution of these technologies in clinical microbiology.

Cordblood-Based High-Throughput Screening for Deafness Gene of 646 Newborns in Jinan Area of China

PubMed Central

Li, Shou-Xia; Chen, Ding-Li; Zhao, Su-Bin; Guo, Li-Li; Feng, Hai-Qin; Zhang, Xiao-Fang; Ping, Li-Li; Yang, Zhi-Ming; Sun, Cai-Xia

2015-01-01

Objectives Infants with slight/mild or late-onset hearing impairment might be missed in universal newborn hearing screening (UNHS). We identified the mutation hot spot of common deaf gene in the newborns in Jinan area population by screening the mutation spot with neonate cord blood, in order to make clear whether the neonate cord blood for screening is feasible. Methods Six hundred and forty-six newborns were subjected to both UNHS and genetic screening for deafness by using neonate cord blood. The newborn genetic screening targeted four deafness-associated genes, which were commonly found in the Chinese population including gap junction beta-2 protein (GJB2), gap junction beta-3 protein (GJB3), solute carrier family 26 member 4 (SLC26A4), and mtDNA 12S rRNA. The most common 20 spot mutations in 4 deaf genes were detected by MassARRAY iPLEX platform and mitochondrial 12S rRNA A1555G and C1494T mutations were sequenced using Sanger sequencing. Results Among the 646 newborns, 635 cases passed the UNHS and the other 11 cases (1.7%) did not. Of the 11 failures, two cases were found to carry homozygous GJB2 p.R143W pathogenic mutation, one case was found to have heterozygous GJB2 235delC mutation, and another one case carried heterozygous GJB3 p.R180X pathogenic mutation. Six hundred and thirty-five babies passed the newborn hearing screening, in which 25 babies were identified to carry pathogenic mutations, including 12 heterozygotes (1.9%) for GJB2 235delC, eight heterozygotes (1.3%) for SLC26A4 IVS7-2A>G, one heterozygote (0.2%) for p.R409H, two homozygotes (0.3%) for m.1494C>T, and two homozygotes (0.3%) for m.1555A>G. Conclusion Newborn genetic screening through the umbilical cord blood for common deafness-associated mutations may identify carriers sensitive to aminoglycoside antibiotic, and can effectively prevent or delay hearing loss occurs. PMID:26330914

Genetic Polymorphisms of Glutathione S-Transferase P1 (GSTP1) and the Incidence of Anti-Tuberculosis Drug-Induced Hepatotoxicity.

PubMed

Wu, Shouquan; Wang, You-Juan; Tang, Xiaoyan; Wang, Yu; Wu, Jingcan; Ji, Guiyi; Zhang, Miaomiao; Chen, Guo; Liu, Qianqian; Sandford, Andrew J; He, Jian-Qing

2016-01-01

Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is one of the most common adverse effects associated with tuberculosis (TB) therapy. Animal studies have demonstrated important roles of glutathione S-transferases in the prevention of chemical-induced hepatotoxicity. The aim of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) of glutathione S-transferase P1 (GSTP1) and ATDH in TB patients. We used two independent samples for this genetic association study. In the initial prospective study, 322 newly diagnosed TB patients were followed up for three months after initiating anti-TB therapy. In an independent retrospective study, 115 ATDH patients and 116 patients without ATDH were selected to verify the results of the prospective study. Tag-SNPs of GSTP1 were genotyped either with the MassARRAY platform or the improved multiple ligase detection reaction (iMLDR) method. The associations between SNPs and ATDH were analyzed by logistic regression analysis adjusting for confounding factors. Of the 322 patients recruited in the prospective cohort, 35 were excluded during the 3 months of follow-up, and 30 were diagnosed with ATDH and were considered as the ATDH group. The remaining 257 subjects without ATDH were considered as the non-ATDH group. After correction for potential confounding factors, significant differences were found for rs1695 (A>G) under an allelic model (OR = 3.876, 95%CI: 1.258011.905; P = 0.018). In the retrospective study, rs1695 allele A also had a higher risk of ATDH (OR = 2.10, 95%CI: 1.17-3.76; P = 0.012). We only found rs4147581AA genotype under a dominant model was related to ATDH in the prospective study (OR = 2.578, 95%CI: 1.076-6.173; P = 0.034). This is the first study to suggest that GSTP1 genotyping can be an important tool for identifying patients who are susceptible to ATDH. This result should be verified in independent large sample studies and also in other ethnic populations.

Study of the association of 17 lipid-related gene polymorphisms with coronary heart disease

PubMed Central

Wu, Nan; Liu, Guili; Huang, Yi; Liao, Qi; Han, Liyuan; Ye, Huandan; Duan, Shiwei; Chen, Xiaomin

2018-01-01

Objective Blood lipids are well-known risk factors for coronary heart disease (CHD). The aim of this study was to explore the association between 17 lipid-related gene polymorphisms and CHD. Methods The current study examined with 784 CHD cases and 739 non-CHD controls. Genotyping was performed on the MassARRAY iPLEX® assay platform. Results Our analyses revealed a significant association of APOE rs7259620 with CHD (genotype: χ2=6.353, df=2, p=0.042; allele: χ2=5.05, df=1, p=0.025; recessive model: χ2=5.57, df=1, p=0.018). A further gender-based subgroup analysis revealed significant associations of APOE rs7259620 and PPAP2B rs72664392 with CHD in males (genotype: χ2=8.379, df=2, p=0.015; allele: χ2=5.190, df=1, p=0.023; recessive model: χ2=19.3, df=1, p<0.0001) and females (genotype: χ2=9.878, df=2, p=0.007), respectively. Subsequent breakdown analysis by age showed that CETP rs4783961, MLXIPL rs35493868, and PON2 rs12704796 were significantly associated with CHD among individuals younger than 55 years of age (CETP rs4783961: χ2=8.966, df=1, p=0.011 by genotype; MLXIPL rs35493868: χ2=4.87, df=1, p=0.027 by allele; χ2=4.88, df=1, p=0.027 by dominant model; PON2 rs12704796: χ2=6.511, df=2, p=0.039 by genotype; χ2=6.210, df=1, p=0.013 by allele; χ2=5.03, df=1, p=0.025 by dominant model). Significant allelic association was observed between LEPR rs656451 and CHD among individuals older than 65 years of age (χ2=4.410, df=1, p=0.036). Conclusion Our study revealed significant associations of APOE, PPAP2B, CETP, MLXIPL, PON2, and LEPR gene polymorphisms with CHD among the Han Chinese. PMID:29848931

Combined study of genetic and epigenetic biomarker risperidone treatment efficacy in Chinese Han schizophrenia patients

PubMed Central

Shi, Y; Li, M; Song, C; Xu, Q; Huo, R; Shen, L; Xing, Q; Cui, D; Li, W; Zhao, J; He, L; Qin, S

2017-01-01

Nowadays, risperidone is an atypical antipsychotic drug that has been increasingly used for treatment and maintenance therapy in schizophrenia. However, partially affected by genetic or environmental factors, there is significant difference in treatment outcomes among patients. In this study, we aimed to interpret the difference between good and poor responders treated with risperidone in both genetic and epigenetic levels in 288 mainland Chinese patients. We recruited a Henan cohort including 98 patients as initial discovery group and then confirmed our results in Shanghai cohort. In genetic studies, we found 10 candidate single-nucleotide polymorphisms (SNPs) and 2 rare variants in Henan cohort by next-generation sequencing of 100 risperidone-response-related genes. After replication in Shanghai cohort by massarray platform, ultimately, rs6706232 and rs4818 were significantly associated with risperidone response in the two cohort meta-analysis (P=0.024 and 0.04, respectively). Besides, we also selected another reported 17 candidate SNPs associated with risperidone drug response to replicate in our mainland Chinese samples, while, we found no significant SNPs after Bonferroni correction. In epigenetic studies, we investigated the methylation status in promoters or gene-coding region of risperidone drug response-related genes including CYP3A4, CYP2D6, ABCB1, HTR2A, DRD2. Totally we found seven significant CpG sites in the meta-analysis with Bonferroni-corrected PCYP3A4_CpG_-36=0.0014, PCYP3A4_CpG_-258=0.0013, PCYP3A4_CpG_-296=0.0014, PCYP3A4_CpG_-367:-372:-374=0.028, PCYP2D6_CpG_193=0.012, PCYP2D6_CpG_242:244:250=0.00076 and PCYP2D6_CpG_284=0.034, respectively. As genetic and epigenetic factors may interactively affect drug response, we finally carried out a multivariant interaction analysis with multifactor dimensionality reduction and discovered a significant four-locus model (CYP3A4_CpG_-82:-86 +rs6280+rs1800497+rs6265, P=0.038) affecting drug response. These findings could partially explain different risperidone response outcome in Chinese population in a systematic level. PMID:28696411

Quantitative analysis of low-density SNP data for parentage assignment and estimation of family contributions to pooled samples.

PubMed

Henshall, John M; Dierens, Leanne; Sellars, Melony J

2014-09-02

While much attention has focused on the development of high-density single nucleotide polymorphism (SNP) assays, the costs of developing and running low-density assays have fallen dramatically. This makes it feasible to develop and apply SNP assays for agricultural species beyond the major livestock species. Although low-cost low-density assays may not have the accuracy of the high-density assays widely used in human and livestock species, we show that when combined with statistical analysis approaches that use quantitative instead of discrete genotypes, their utility may be improved. The data used in this study are from a 63-SNP marker Sequenom® iPLEX Platinum panel for the Black Tiger shrimp, for which high-density SNP assays are not currently available. For quantitative genotypes that could be estimated, in 5% of cases the most likely genotype for an individual at a SNP had a probability of less than 0.99. Matrix formulations of maximum likelihood equations for parentage assignment were developed for the quantitative genotypes and also for discrete genotypes perturbed by an assumed error term. Assignment rates that were based on maximum likelihood with quantitative genotypes were similar to those based on maximum likelihood with perturbed genotypes but, for more than 50% of cases, the two methods resulted in individuals being assigned to different families. Treating genotypes as quantitative values allows the same analysis framework to be used for pooled samples of DNA from multiple individuals. Resulting correlations between allele frequency estimates from pooled DNA and individual samples were consistently greater than 0.90, and as high as 0.97 for some pools. Estimates of family contributions to the pools based on quantitative genotypes in pooled DNA had a correlation of 0.85 with estimates of contributions from DNA-derived pedigree. Even with low numbers of SNPs of variable quality, parentage testing and family assignment from pooled samples are sufficiently accurate to provide useful information for a breeding program. Treating genotypes as quantitative values is an alternative to perturbing genotypes using an assumed error distribution, but can produce very different results. An understanding of the distribution of the error is required for SNP genotyping platforms.

Genomic characterization of explant tumorgraft models derived from fresh patient tumor tissue

PubMed Central

2012-01-01

Background There is resurgence within drug and biomarker development communities for the use of primary tumorgraft models as improved predictors of patient tumor response to novel therapeutic strategies. Despite perceived advantages over cell line derived xenograft models, there is limited data comparing the genotype and phenotype of tumorgrafts to the donor patient tumor, limiting the determination of molecular relevance of the tumorgraft model. This report directly compares the genomic characteristics of patient tumors and the derived tumorgraft models, including gene expression, and oncogenic mutation status. Methods Fresh tumor tissues from 182 cancer patients were implanted subcutaneously into immune-compromised mice for the development of primary patient tumorgraft models. Histological assessment was performed on both patient tumors and the resulting tumorgraft models. Somatic mutations in key oncogenes and gene expression levels of resulting tumorgrafts were compared to the matched patient tumors using the OncoCarta (Sequenom, San Diego, CA) and human gene microarray (Affymetrix, Santa Clara, CA) platforms respectively. The genomic stability of the established tumorgrafts was assessed across serial in vivo generations in a representative subset of models. The genomes of patient tumors that formed tumorgrafts were compared to those that did not to identify the possible molecular basis to successful engraftment or rejection. Results Fresh tumor tissues from 182 cancer patients were implanted into immune-compromised mice with forty-nine tumorgraft models that have been successfully established, exhibiting strong histological and genomic fidelity to the originating patient tumors. Comparison of the transcriptomes and oncogenic mutations between the tumorgrafts and the matched patient tumors were found to be stable across four tumorgraft generations. Not only did the various tumors retain the differentiation pattern, but supporting stromal elements were preserved. Those genes down-regulated specifically in tumorgrafts were enriched in biological pathways involved in host immune response, consistent with the immune deficiency status of the host. Patient tumors that successfully formed tumorgrafts were enriched for cell signaling, cell cycle, and cytoskeleton pathways and exhibited evidence of reduced immunogenicity. Conclusions The preservation of the patient’s tumor genomic profile and tumor microenvironment supports the view that primary patient tumorgrafts provide a relevant model to support the translation of new therapeutic strategies and personalized medicine approaches in oncology. PMID:22709571

Association of SNP rs1867277 in FOXE1 Gene and Cleft Lip with or without Cleft Palate in a Han Chinese Population.

PubMed

Xie, Liang; Deng, Ying; Yuan, Yumei; Tan, Xiong; Liu, Lijun; Li, Nana; Deng, Changfei; Liu, Hanmin; Dai, Li

2018-04-01

The genetic factors causing cleft lip with or without cleft palate (CL ± P) are still unclear. The SNPs in FOXE1 gene were associated with CL ± P. However, the results have been inconsistent. We explored the associations of four SNPs in FOXE1 gene and CL ± P by a family based study. 128 children with CL ± P and their parents were recruited. rs3758249 and rs1867277 were genotyped by high-resolution melting curve (HRM) method, whereas rs1443434 and rs907577 were genotyped by Sequenom MassARRAY® method. The software PLINK, FBAT and FAMHAP were used for analyzing data. rs1867277 was associated with CL ± P (P m = 0.0395). The patients were divided into two subgroups, individuals with cleft lip only and persons with cleft lip and palate. There were no associations in subgroup analyses. We confirmed the association of FOXE1 gene and CL ± P by a family based study. For the first time, rs1867277 was significantly associated with CL ± P.

A 3'UTR polymorphism of IL-6R is associated with Chinese pediatric tuberculosis.

PubMed

Shen, Chen; Qi, Hui; Sun, Lin; Xiao, Jing; Yin, Qing-qin; Jiao, Wei-wei; Wu, Xi-rong; Tian, Jian-ling; Han, Rui; Shen, A-dong

2014-01-01

IL-6 is a proinflammatory cytokine that plays a critical role in host defense against tuberculosis (TB). Genetic polymorphisms of IL-6 and its receptor IL-6R had been discussed in adult TB recently. However, their role in pediatric TB is still unclear. Due to the obvious differences in TB pathophysiology in children, which may also reflect differences in genetic background, further association studies in pediatric populations are needed. A case-control study was carried out in a Chinese pediatric population including 353 TB patients and 400 healthy controls. Tag-SNPs of IL-6 and IL-6R genes were selected by Haploview software, genotyped using MassArray, and analyzed statistically. One polymorphism, rs2229238, in the 3'UTR region of IL-6R was observed to be associated with increased resistance to TB (adjusted P = 0.03). The rs2229238 T allele contributed to a reduced risk to TB in recessive heritable model (OR, 0.53; 95% CI, 0.35-0.78). By tag-SNP genotyping based case-control study, we identified a genetic polymorphism in the IL-6R 3'UTR that regulates host resistance to pediatric TB in a Chinese population.

Aberrant expression and DNA methylation of lipid metabolism genes in PCOS: a new insight into its pathogenesis.

PubMed

Pan, Jie-Xue; Tan, Ya-Jing; Wang, Fang-Fang; Hou, Ning-Ning; Xiang, Yu-Qian; Zhang, Jun-Yu; Liu, Ye; Qu, Fan; Meng, Qing; Xu, Jian; Sheng, Jian-Zhong; Huang, He-Feng

2018-01-01

Polycystic ovary syndrome (PCOS), whose etiology remains uncertain, is a highly heterogenous and genetically complex endocrine disorder. The aim of this study was to identify differentially expressed genes (DEGs) in granulosa cells (GCs) from PCOS patients and make epigenetic insights into the pathogenesis of PCOS. Included in this study were 110 women with PCOS and 119 women with normal ovulatory cycles undergoing in vitro fertilization acting as the control group. RNA-seq identified 92 DEGs unique to PCOS GCs in comparison with the control group. Bioinformatic analysis indicated that synthesis of lipids and steroids was activated in PCOS GCs. 5-Methylcytosine analysis demonstrated that there was an approximate 25% reduction in global DNA methylation of GCs in PCOS women (4.44 ± 0.65%) compared with the controls (6.07 ± 0.72%; P  < 0.05). Using MassArray EpiTYPER quantitative DNA methylation analysis, we also found hypomethylation of several gene promoters related to lipid and steroid synthesis, which might result in the aberrant expression of these genes. Our results suggest that hypomethylated genes related to the synthesis of lipid and steroid may dysregulate expression of these genes and promote synthesis of steroid hormones including androgen, which could partially explain mechanisms of hyperandrogenism in PCOS.

Distribution of gene mutations in sporadic congenital cataract in a Han Chinese population

PubMed Central

Li, Dan; Wang, Siying; Ye, Hongfei; Tang, Yating; Qiu, Xiaodi; Fan, Qi; Rong, Xianfang; Liu, Xin; Chen, Yuhong; Yang, Jin

2016-01-01

Purpose This study aimed to investigate the genetic effects underlying non-familial sporadic congenital cataract (SCC). Methods We collected DNA samples from 74 patients with SCC and 20 patients with traumatic cataract (TC) in an age-matched group and performed genomic sequencing of 61 lens-related genes with target region capture and next-generation sequencing (NGS). The suspected SCC variants were validated with MassARRAY and Sanger sequencing. DNA samples from 103 healthy subjects were used as additional controls in the confirmation examination. Results By filtering against common variants in public databases and those associated with TC cases, we identified 23 SCC-specific variants in 17 genes from 19 patients, which were predicted to be functional. These mutations were further confirmed by examination of the 103 healthy controls. Among the mutated genes, CRYBB3 had the highest mutation frequency with mutations detected four times in four patients, followed by EPHA2, NHS, and WDR36, the mutation of which were detected two times in two patients. We observed that the four patients with CRYBB3 mutations had three different cataract phenotypes. Conclusions From this study, we concluded the clinical and genetic heterogeneity of SCC. This is the first study to report broad spectrum genotyping for patients with SCC. PMID:27307692

TIMP-2 SNPs rs7342880 and rs4789936 are linked to risk of knee osteoarthritis in the Chinese Han Population

PubMed Central

Jin, Tianbo; Wang, Jihong; Fan, Dongsheng; Hao, Zengtao; Jing, Shangfei; Han, ChaoQian; Du, Jieli; Jiang, Dong; Wen, Shuzheng; Wang, Jianzhong

2017-01-01

This study aimed to investigate whether functional polymorphisms in the tissue inhibitors of metalloproteinase-2 (TIMP-2) gene are associated with susceptibility to knee osteoarthritis (OA) in the Chinese Han population. Six TIMP-2 single nucleotide polymorphisms (SNPs) were assayed using MassARRAY in 300 patients clinically and radiographically diagnosed with knee OA and in 428 controls. Allelic and genotypic frequencies were compared between groups. Logistic regression adjusting for age and gender was used to estimate risk associations between specific genotypes and knee OA by computing odds ratios (ORs) and 95% confidence intervals (95% CIs). We found that allele “A” in rs7342880 was significantly associated with increased risk of knee OA (OR = 1.44, 95%CI = 1.09-1.91, p = 0.035). In addition, in the over-dominant model, rs4789936 correlated with reduced risk of knee OA, adjusting for age and gender (OR = 0.69, 95%CI = 0.49-0.98, p = 0.036). Finally, rs7342880 correlated with increased risk of knee OA in females. This study provides evidence that TIMP-2 is a knee OA susceptibility gene in the Chinese population and a potential diagnostic and preventive marker for the disease. PMID:27901480

Identification and validation of loss of function variants in clinical contexts.

PubMed

Lescai, Francesco; Marasco, Elena; Bacchelli, Chiara; Stanier, Philip; Mantovani, Vilma; Beales, Philip

2014-01-01

The choice of an appropriate variant calling pipeline for exome sequencing data is becoming increasingly more important in translational medicine projects and clinical contexts. Within GOSgene, which facilitates genetic analysis as part of a joint effort of the University College London and the Great Ormond Street Hospital, we aimed to optimize a variant calling pipeline suitable for our clinical context. We implemented the GATK/Queue framework and evaluated the performance of its two callers: the classical UnifiedGenotyper and the new variant discovery tool HaplotypeCaller. We performed an experimental validation of the loss-of-function (LoF) variants called by the two methods using Sequenom technology. UnifiedGenotyper showed a total validation rate of 97.6% for LoF single-nucleotide polymorphisms (SNPs) and 92.0% for insertions or deletions (INDELs), whereas HaplotypeCaller was 91.7% for SNPs and 55.9% for INDELs. We confirm that GATK/Queue is a reliable pipeline in translational medicine and clinical context. We conclude that in our working environment, UnifiedGenotyper is the caller of choice, being an accurate method, with a high validation rate of error-prone calls like LoF variants. We finally highlight the importance of experimental validation, especially for INDELs, as part of a standard pipeline in clinical environments.

Factors affecting levels of circulating cell-free fetal DNA in maternal plasma and their implications for noninvasive prenatal testing.

PubMed

Kinnings, Sarah L; Geis, Jennifer A; Almasri, Eyad; Wang, Huiquan; Guan, Xiaojun; McCullough, Ron M; Bombard, Allan T; Saldivar, Juan-Sebastian; Oeth, Paul; Deciu, Cosmin

2015-08-01

Sufficient fetal DNA in a maternal plasma sample is required for accurate aneuploidy detection via noninvasive prenatal testing, thus highlighting a need to understand the factors affecting fetal fraction. The MaterniT21™ PLUS test uses massively parallel sequencing to analyze cell-free fetal DNA in maternal plasma and detect chromosomal abnormalities. We assess the impact of a variety of factors, both maternal and fetal, on the fetal fraction across a large number of samples processed by Sequenom Laboratories. The rate of increase in fetal fraction with increasing gestational age varies across the duration of the testing period and is also influenced by fetal aneuploidy status. Maternal weight trends inversely with fetal fraction, and we find no added benefit from analyzing body mass index or blood volume instead of weight. Strong correlations exist between fetal fractions from aliquots taken from the same patient at the same blood draw and also at different blood draws. While a number of factors trend with fetal fraction across the cohort as a whole, they are not the sole determinants of fetal fraction. In this study, the variability for any one patient does not appear large enough to justify postponing testing to a later gestational age. © 2015 John Wiley & Sons, Ltd.

Genetic polymorphism of matrix metalloproteinase-1 and coronary artery disease susceptibility: a case-control study in a Han Chinese population.

PubMed

Qintao, Cui; Yan, Li; Changhong, Duan; Xiaoliang, Guo; Xiaochen, Liu

2014-12-01

Coronary artery disease (CAD) receives intensive research due to its high incidence and severe impact on the quality of life. One member of the matrix metalloproteinases (MMPs), MMP-1, has been reported to be associated with CAD. To identify the markers contributing to the genetic susceptibility to CAD, nine single-nucleotide polymorphisms (rs1799750, rs498186, rs475007, rs514921, rs494379, rs996999, rs2071232, rs1938901, and rs2239008) throughout the MMP-1 gene were genotyped using MALDI-TOF within the MassARRAY system, and the allele and genotype distributions were compared between 438 healthy controls and 411 patients with CAD from a Chinese Han population. The analysis revealed a weak association between the rs1799750 (in the promoter region) genotype distribution and CAD (p=0.022). An increased risk of CAD was significantly associated with the 2G allele of rs1799750 (p=0.005, odds ratio=1.329, 95% confidence interval=1.090-1.620, after Bonferroni corrections). Strong linkage disequilibrium was observed in three blocks (D'>0.9). Significantly more C-2G (rs498186-rs1799750) haplotypes (p=0.001 after Bonferroni corrections) were found in CAD subjects. These findings point to a role for the polymorphism in the MMP-1 promoter in CAD among a Han Chinese population and may be informative for future genetic or biological studies on CAD.

Genetic variations of MMP9 gene and intracerebral hemorrhage susceptibility: a case-control study in Chinese Han population.

PubMed

Yang, Jie; Wu, Bo; Lin, Sen; Zhou, Junshan; Li, Yingbin; Dong, Wei; Arima, Hisatomi; Zhang, Chanfei; Liu, Yukai; Liu, Ming

2014-06-15

To investigate the association between genetic variations of matrix metalloproteinase 9 (MMP9) gene and intracerebral hemorrhage (ICH) susceptibility in Chinese Han population. The clinical data and peripheral blood samples from the patients with ICH and hypertension, and controlled subjects with hypertension only, were collected. MassARRAY Analyzer was used to genotype the tagger single nucleotide polymorphism (SNP) of MMP9 gene. Haploview4.2 and Unphased3.1.7 were employed to construct haplotypes and to analyze the association between genetic variations (alleles, genotypes and haplotypes) of MMP9 gene and ICH susceptibility. 181 patients with ICH and hypertension, and 197 patients with hypertension only, were recruited between Sep 2009 and Oct 2010. Patients in the ICH group were younger (61.80 ± 13.27 vs. 72.44 ± 12.71 years, p<0.05). Other conventional risk factors between the ICH and control groups were similar. There were 6 Tagger SNPs and 4 haplotypes of MMP9 gene in our sample population. Our logistical regression analysis showed that there were no significant associations between genetic variations of the MPP9 gene and ICH susceptibility (all p>0.05). The genetic variations of MMP9 gene were not significantly associated with ICH susceptibility in the Chinese Han population. Copyright © 2014 Elsevier B.V. All rights reserved.

Pharmacogenomics of platinum-based chemotherapy response in NSCLC: a genotyping study and a pooled analysis

PubMed Central

Chen, Juan; Wang, Zhan; Zou, Ting; Cui, Jiajia; Yin, Jiye; Zheng, Wei; Jiang, Wuzhong; Zhou, Honghao; Liu, Zhaoqian

2016-01-01

Published data showed inconsistent results about associations of extensively studied polymorphisms with platinum-based chemotherapy response. Our study aimed to provide reliable conclusions of these associations by detecting genotypes of the SNPs in a larger sample size and summarizing a comprehensive pooled analysis. 13 SNPs in 8 genes were genotyped in 1024 NSCLC patients by SequenomMassARRAY. 39 published studies and our study were included in meta-analysis. Patients with GA or GG genotypes of XRCC1 G1196 had better response than AA genotype carriers (Genotyping study: OR = 0.72, 95%CI: 0.53-0.96, P = 0.028; Meta-analysis: OR = 0.74, 95%CI: 0.62-0.89, P = 0.001). Patients carrying CT or TT genotypes of XRCC1 C580T could be more sensitive to platinum-based chemotherapy compared to patients with CC genotype (OR = 0.54, 95%CI: 0.37-0.80, P = 0.002). CC genotype of XRCC3 C18067T carriers showed more resistance to platinum-based chemotherapy when compared to those with CT or TT genotypes (OR = 0.69, 95%CI: 0.52-0.91, P = 0.009). Our study indicated that XRCC1 G1196A/C580T and XRCC3 C18067T should be paid attention for personalized platinum-based chemotherapy in NSCLC patients. PMID:27248474

ABO blood group and chronic pancreatitis risk in the NAPS2 cohort.

PubMed

Greer, Julia B; LaRusch, Jessica; Brand, Randall E; O'Connell, Michael R; Yadav, Dhiraj; Whitcomb, David C

2011-11-01

A risk association has been observed between non-O blood groups and pancreatic adenocarcinoma. Chronic pancreatitis also increases risk for pancreatic cancer, raising questions as to whether non-O blood groups are a risk for chronic pancreatitis and whether the pathophysiologic pathways are linked. Our goal was to determine whether ABO blood group may affect the risk of chronic pancreatitis. The study cohort included chronic pancreatitis patients (n = 499) and healthy controls (n = 631) from the North American Pancreatitis Study 2 study. Genotyping was performed using Sequenom assay of rs8176746 A/C and rs505922 C/T to classify participants into ABO blood groups. O blood group was nonsignificantly more common among cases (44.7% vs 42.0%; P = 0.36), particularly among cases with alcohol-related chronic pancreatitis (49.3% vs 42%; P = 0.060). Alcoholic patients without coexisting high-risk PRSS1, CFTR, or SPINK1 variants had a significant overrepresentation of O blood type when compared with controls (odds ratio, 1.54; 95% confidence interval, 1.09-2.17; P = 0.01). A, B, and AB blood groups were not associated with a greater likelihood of having chronic pancreatitis and may decrease the risk of chronic pancreatitis in individuals who are very heavy drinkers. These results suggest that the mechanism linking non-O blood type with pancreatic pathology is specific to carcinogenesis.

Maternal adversities during pregnancy and cord blood oxytocin receptor (OXTR) DNA methylation

PubMed Central

Unternaehrer, Eva; Bolten, Margarete; Nast, Irina; Staehli, Simon; Meyer, Andrea H.; Dempster, Emma; Hellhammer, Dirk H.; Lieb, Roselind

2016-01-01

The aim of this study was to investigate whether maternal adversities and cortisol levels during pregnancy predict cord blood DNA methylation of the oxytocin receptor (OXTR). We collected cord blood of 39 babies born to mothers participating in a cross-sectional study (N = 100) conducted in Basel, Switzerland (2007–10). Mothers completed the Inventory of Life Events (second trimester: T2), the Edinburgh Postnatal Depression Scale (EPDS, third trimester: T3), the Trier Inventory of Chronic Stress (TICS-K, 1–3 weeks postpartum) and provided saliva samples (T2, T3) for maternal cortisol profiles, as computed by the area under the curve with respect to ground (AUCg) or increase (AUCi) for the cortisol awakening response (CAR) and for diurnal cortisol profiles (DAY). OXTR DNA methylation was quantified using Sequenom EpiTYPER. The number of stressful life events (P = 0.032), EPDS score (P = 0.007) and cortisol AUCgs at T2 (CAR: P = 0.020; DAY: P = 0.024) were negatively associated with OXTR DNA methylation. Our findings suggest that distinct prenatal adversities predict decreased DNA methylation in a gene that is relevant for childbirth, maternal behavior and wellbeing of mother and offspring. If a reduced OXTR methylation increases OXTR expression, our findings could suggest an epigenetic adaptation to an adverse early environment. PMID:27107296

Identification of Genes Promoting Skin Youthfulness by Genome-Wide Association Study

PubMed Central

Chang, Anne L.S.; Atzmon, Gil; Bergman, Aviv; Brugmann, Samantha; Atwood, Scott X; Chang, Howard Y; Barzilai, Nir

2014-01-01

To identify genes that promote facial skin youthfulness (SY), a genome-wide association study on an Ashkenazi Jewish discovery group (n=428) was performed using Affymetrix 6.0 Single-Nucleotide Polymorphism (SNP) Array. After SNP quality controls, 901,470 SNPs remained for analysis. The eigenstrat method showed no stratification. Cases and controls were identified by global facial skin aging severity including intrinsic and extrinsic parameters. Linear regression adjusted for age and gender, with no significant differences in smoking history, body mass index, menopausal status, or personal or family history of centenarians. Six SNPs met the Bonferroni threshold with Pallele<10−8; two of these six had Pgenotype<10−8. Quantitative trait loci mapping confirmed linkage disequilibrium. The six SNPs were interrogated by MassARRAY in a replication group (n=436) with confirmation of rs6975107, an intronic region of KCND2 (potassium voltage-gated channel, Shal-related family member 2) (Pgenotype=0.023). A second replication group (n=371) confirmed rs318125, downstream of DIAPH2 (diaphanous homolog 2 (Drosophila)) (Pallele=0.010, Pgenotype=0.002) and rs7616661, downstream of EDEM1 (ER degradation enhancer, mannosidase α-like 1) (Pgenotype=0.042). DIAPH2 has been associated with premature ovarian insufficiency, an aging phenotype in humans. EDEM1 associates with lifespan in animal models, although not humans. KCND2 is expressed in human skin, but has not been associated with aging. These genes represent new candidate genes to study the molecular basis of healthy skin aging. PMID:24037343

DNA methylome profiling of maternal peripheral blood and placentas reveal potential fetal DNA markers for non-invasive prenatal testing.

PubMed

Xiang, Yuqian; Zhang, Junyu; Li, Qiaoli; Zhou, Xinyao; Wang, Teng; Xu, Mingqing; Xia, Shihui; Xing, Qinghe; Wang, Lei; He, Lin; Zhao, Xinzhi

2014-09-01

Utilizing epigenetic (DNA methylation) differences to differentiate between maternal peripheral blood (PBL) and fetal (placental) DNA has been a promising strategy for non-invasive prenatal testing (NIPT). However, the differentially methylated regions (DMRs) have yet to be fully ascertained. In the present study, we performed genome-wide comparative methylome analysis between maternal PBL and placental DNA from pregnancies of first trimester by methylated DNA immunoprecipitation-sequencing (MeDIP-Seq) and Infinium HumanMethylation450 BeadChip assays. A total of 36 931 DMRs and 45 804 differentially methylated sites (DMSs) covering the whole genome, exclusive of the Y chromosome, were identified via MeDIP-Seq and Infinium 450k array, respectively, of which 3759 sites in 2188 regions were confirmed by both methods. Not only did we find the previously reported potential fetal DNA markers in our identified DMRs/DMSs but also we verified fully the identified DMRs/DMSs in the validation round by MassARRAY EpiTYPER. The screened potential fetal DNA markers may be used for NIPT on aneuploidies and other chromosomal diseases, such as cri du chat syndrome and velo-cardio-facial syndrome. In addition, these potential markers may have application in the early diagnosis of placental dysfunction, such as pre-eclampsia. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

DNA methylation profile distinguishes clear cell sarcoma of the kidney from other pediatric renal tumors.

PubMed

Ueno, Hitomi; Okita, Hajime; Akimoto, Shingo; Kobayashi, Kenichiro; Nakabayashi, Kazuhiko; Hata, Kenichiro; Fujimoto, Junichiro; Hata, Jun-Ichi; Fukuzawa, Masahiro; Kiyokawa, Nobutaka

2013-01-01

A number of specific, distinct neoplastic entities occur in the pediatric kidney, including Wilms' tumor, clear cell sarcoma of the kidney (CCSK), congenital mesoblastic nephroma (CMN), rhabdoid tumor of the kidney (RTK), and the Ewing's sarcoma family of tumors (ESFT). By employing DNA methylation profiling using Illumina Infinium HumanMethylation27, we analyzed the epigenetic characteristics of the sarcomas including CCSK, RTK, and ESFT in comparison with those of the non-neoplastic kidney (NK), and these tumors exhibited distinct DNA methylation profiles in a tumor-type-specific manner. CCSK is the most frequently hypermethylated, but least frequently hypomethylated, at CpG sites among these sarcomas, and exhibited 490 hypermethylated and 46 hypomethylated CpG sites in compared with NK. We further validated the results by MassARRAY, and revealed that a combination of four genes was sufficient for the DNA methylation profile-based differentiation of these tumors by clustering analysis. Furthermore, THBS1 CpG sites were found to be specifically hypermethylated in CCSK and, thus, the DNA methylation status of these THBS1 sites alone was sufficient for the distinction of CCSK from other pediatric renal tumors, including Wilms' tumor and CMN. Moreover, combined bisulfite restriction analysis could be applied for the detection of hypermethylation of a THBS1 CpG site. Besides the biological significance in the pathogenesis, the DNA methylation profile should be useful for the differential diagnosis of pediatric renal tumors.

Copy number variants and genetic polymorphisms in TBX21, GATA3, Rorc, Foxp3 and susceptibility to Behcet's disease and Vogt-Koyanagi-Harada syndrome.

PubMed

Liao, Dan; Hou, Shengping; Zhang, Jun; Fang, Jing; Liu, Yunjia; Bai, Lin; Cao, Qingfeng; Kijlstra, Aize; Yang, Peizeng

2015-04-15

This study aimed to investigate the role of genetic variants including single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) of TBX21, GATA3, Rorc and Foxp3 genes in Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population. Genotyping of 25 SNPs was performed by iPLEX system (Sequenom) or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). TaqMan real time PCR was used to assess CNVs. The expression of Rorc and Foxp3 were examined by real-time PCR and cytokine production was measured by ELISA. High Rorc CNV was associated with the susceptibility to BD (P = 8.99 × 10(-8), OR = 3.0), and low Foxp3 CNV predisposed to BD in female patients (P = 1.92 × 10(-5), OR = 3.1). CNVs for the investigated genes were not altered in VKH syndrome. Further functional studies demonstrated that the relative mRNA expression levels of Rorc were increased in individuals with high Rorc copy number, but not for Foxp3. Increased production of IL-1β and IL-6 was found in individuals carrying a high CNV of Rorc. Our study showed that high CNVs of Rorc and low CNVs of Foxp3 confer risk for BD but not for VKH syndrome. The tested 25 SNPs in TBX21, GATA3, Rorc and Foxp3 did not associate with BD and VKH syndrome.

Serum Brain-Derived Neurotrophic Factor is Related to Platelet Reactivity but not to Genetic Polymorphisms within BDNF Encoding Gene in Patients with Type 2 Diabetes.

PubMed

Eyileten, Ceren; Zaremba, Małgorzata; Janicki, Piotr K; Rosiak, Marek; Cudna, Agnieszka; Kapłon-Cieślicka, Agnieszka; Opolski, Grzegorz; Filipiak, Krzysztof J; Kosior, Dariusz A; Mirowska-Guzel, Dagmara; Postula, Marek

2016-01-07

The aim of this study was to investigate the association between serum concentrations of the brain-derived neurotrophic factor (BDNF), platelet reactivity and inflammatory markers, as well as its association with BDNF encoding gene variants in type 2 diabetic patients (T2DM) during acetylsalicylic acid (ASA) therapy. This retrospective, open-label study enrolled 91 patients. Serum BDNF, genotype variants, hematological, biochemical, and inflammatory markers were measured. Blood samples were taken in the morning 2-3 h after the last ASA dose. The BDNF genotypes for selected variants were analyzed by use of the iPLEX Sequenom assay. In multivariate linear regression analysis, CADP-CT >74 sec (p<0.001) and sP-selectin concentration (p=0.03) were predictive of high serum BDNF. In multivariate logistic regression analysis, CADP-CT >74 sec (p=0.02) and IL-6 concentration (p=0.03) were risk factors for serum BDNF above the median. Non-significant differences were observed between intronic SNP rs925946, missense SNP rs6265, and intronic SNP rs4923463 allelic groups and BDNF concentrations in the investigated cohort. Chronic inflammatory condition and enhanced immune system are associated with the production of BDNF, which may be why the serum BDNF level in T2DM patients with high platelet reactivity was higher compared to subjects with normal platelet reactivity in this study.

Association of polyunsaturated fatty acids in breast milk with fatty acid desaturase gene polymorphisms among Chinese lactating mothers.

PubMed

Ding, Zhen; Liu, Guo-Liang; Li, Xiang; Chen, Xue-Yan; Wu, Yi-Xia; Cui, Can-Can; Zhang, Xi; Yang, Guang; Xie, Lin

2016-06-01

The fatty acid desaturase (FADS) controls polyunsaturated fatty acid (PUFA) synthesis in human tissues and breast milk. Evaluate the influence of 10 single nucleotide polymorphisms (SNPs) and various haplotypes in the FADS gene cluster (FADS1, FADS2, FADS3) on PUFA concentration in the breast milk of 209 healthy Chinese women. PUFA concentrations were measured in breast milk using gas chromatography and genotyping was performed using the Sequenom Mass Array system. A SNP (rs1535) and 2-locus haplotypes (rs3834458-rs1535, rs1535-rs174575) in the FADS2 gene were associated with concentrations of γ-linoleic acid (GLA) and arachidonic acid (AA) in breast milk. Likewise, in the FADS1 gene, a 2-locus constructed haplotype (rs174547-rs174553) also affected GLA and AA concentration (P<0.05 for all). Minor allele carriers of the SNP and haplotypes described above had lower concentrations of GLA and AA. In the FADS2 gene, the 3-locus haplotype rs3834458-rs1535-rs174575, significantly affected concentrations of GLA but not AA. Pairwise comparison showed that individuals major homozygous for the SNP rs1000778 in the FADS3 gene had lower concentrations of ALA and linoleic acid (LA) in their breast milk. Polymorphisms in the FADS gene cluster influence PUFA concentrations in the breast milk of Chinese Han lactating women. Copyright © 2016 Elsevier Ltd. All rights reserved.

Maternal adversities during pregnancy and cord blood oxytocin receptor (OXTR) DNA methylation.

PubMed

Unternaehrer, Eva; Bolten, Margarete; Nast, Irina; Staehli, Simon; Meyer, Andrea H; Dempster, Emma; Hellhammer, Dirk H; Lieb, Roselind; Meinlschmidt, Gunther

2016-09-01

The aim of this study was to investigate whether maternal adversities and cortisol levels during pregnancy predict cord blood DNA methylation of the oxytocin receptor (OXTR). We collected cord blood of 39 babies born to mothers participating in a cross-sectional study (N = 100) conducted in Basel, Switzerland (2007-10). Mothers completed the Inventory of Life Events (second trimester: T2), the Edinburgh Postnatal Depression Scale (EPDS, third trimester: T3), the Trier Inventory of Chronic Stress (TICS-K, 1-3 weeks postpartum) and provided saliva samples (T2, T3) for maternal cortisol profiles, as computed by the area under the curve with respect to ground (AUCg) or increase (AUCi) for the cortisol awakening response (CAR) and for diurnal cortisol profiles (DAY). OXTR DNA methylation was quantified using Sequenom EpiTYPER. The number of stressful life events (P = 0.032), EPDS score (P = 0.007) and cortisol AUCgs at T2 (CAR: P = 0.020; DAY: P = 0.024) were negatively associated with OXTR DNA methylation. Our findings suggest that distinct prenatal adversities predict decreased DNA methylation in a gene that is relevant for childbirth, maternal behavior and wellbeing of mother and offspring. If a reduced OXTR methylation increases OXTR expression, our findings could suggest an epigenetic adaptation to an adverse early environment. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Dynamic changes in DNA methylation of stress-associated genes (OXTR, BDNF ) after acute psychosocial stress.

PubMed

Unternaehrer, E; Luers, P; Mill, J; Dempster, E; Meyer, A H; Staehli, S; Lieb, R; Hellhammer, D H; Meinlschmidt, G

2012-08-14

Environmentally induced epigenetic alterations are related to mental health. We investigated quantitative DNA methylation status before and after an acute psychosocial stressor in two stress-related genes: oxytocin receptor (OXTR) and brain-derived neurotrophic factor (BDNF ). The cross sectional study took place at the Division of Theoretical and Clinical Psychobiology, University of Trier, Germany and was conducted from February to August 2009. We included 83 participants aged 61-67 years. Thereof, 76 participants completed the full study procedure consisting of blood sampling before (pre-stress), 10 min after (post-stress) and 90 min after (follow-up) the Trier social stress test. We assessed quantitative DNA methylation of whole-blood cells using Sequenom EpiTYPER. Methylation status differed between sampling times in one target sequence of OXTR (P<0.001): methylation increased from pre- to post-stress (P=0.009) and decreased from post-stress to follow-up (P<0.001). This decrease was also found in a second target sequence of OXTR (P=0.034), where it lost statistical significance when blood cell count was statistically controlled. We did not detect any time-associated differences in methylation status of the examined BDNF region. The results suggest a dynamic regulation of DNA methylation in OXTR-which may in part reflect changes in blood cell composition-but not BDNF after acute psychosocial stress. This may enhance the understanding of how psychosocial events alter DNA methylation and could provide new insights into the etiology of mental disorders.

SMAD3 Is Upregulated in Human Osteoarthritic Cartilage Independent of the Promoter DNA Methylation.

PubMed

Aref-Eshghi, Erfan; Liu, Ming; Razavi-Lopez, Seyd Babak; Hirasawa, Kensuke; Harper, Patricia E; Martin, Glynn; Furey, Andrew; Green, Roger; Sun, Guang; Rahman, Proton; Zhai, Guangju

2016-02-01

To compare SMAD3 gene expression between human osteoarthritic and healthy cartilage and to examine whether expression is regulated by the promoter DNA methylation of the gene. Human cartilage samples were collected from patients undergoing total hip/knee joint replacement surgery due to primary osteoarthritis (OA), and from patients with hip fractures as controls. DNA/RNA was extracted from the cartilage tissues. Real-time quantitative PCR was performed to measure gene expression, and Sequenom EpiTyper was used to assay DNA methylation. Mann-Whitney test was used to compare the methylation and expression levels between OA cases and controls. Spearman rank correlation coefficient was calculated to examine the association between the methylation and gene expression. A total of 58 patients with OA (36 women, 22 men; mean age 64 ± 9 yrs) and 55 controls (43 women, 12 men; mean age 79 ± 10 yrs) were studied. SMAD3 expression was on average 83% higher in OA cartilage than in controls (p = 0.0005). No difference was observed for DNA methylation levels in the SMAD3 promoter region between OA cases and controls. No correlation was found between SMAD3 expression and promoter DNA methylation. Our study demonstrates that SMAD3 is significantly overexpressed in OA. This overexpression cannot be explained by DNA methylation in the promoter region. The results suggest that the transforming growth factor-β/SMAD3 pathway may be overactivated in OA cartilage and has potential in developing targeted therapies for OA.

Population, genetic, and antigenic diversity of the apicomplexan Eimeria tenella and their relevance to vaccine development

PubMed Central

Blake, Damer P.; Clark, Emily L.; Macdonald, Sarah E.; Thenmozhi, Venkatachalam; Kundu, Krishnendu; Garg, Rajat; Jatau, Isa D.; Ayoade, Simeon; Kawahara, Fumiya; Moftah, Abdalgader; Reid, Adam James; Adebambo, Ayotunde O.; Álvarez Zapata, Ramón; Srinivasa Rao, Arni S. R.; Thangaraj, Kumarasamy; Banerjee, Partha S.; Dhinakar-Raj, G.; Raman, M.; Tomley, Fiona M.

2015-01-01

The phylum Apicomplexa includes serious pathogens of humans and animals. Understanding the distribution and population structure of these protozoan parasites is of fundamental importance to explain disease epidemiology and develop sustainable controls. Predicting the likely efficacy and longevity of subunit vaccines in field populations relies on knowledge of relevant preexisting antigenic diversity, population structure, the likelihood of coinfection by genetically distinct strains, and the efficiency of cross-fertilization. All four of these factors have been investigated for Plasmodium species parasites, revealing both clonal and panmictic population structures with exceptional polymorphism associated with immunoprotective antigens such as apical membrane antigen 1 (AMA1). For the coccidian Toxoplasma gondii only genomic diversity and population structure have been defined in depth so far; for the closely related Eimeria species, all four variables are currently unknown. Using Eimeria tenella, a major cause of the enteric disease coccidiosis, which exerts a profound effect on chicken productivity and welfare, we determined population structure, genotype distribution, and likelihood of cross-fertilization during coinfection and also investigated the extent of naturally occurring antigenic diversity for the E. tenella AMA1 homolog. Using genome-wide Sequenom SNP-based haplotyping, targeted sequencing, and single-cell genotyping, we show that in this coccidian the functionality of EtAMA1 appears to outweigh immune evasion. This result is in direct contrast to the situation in Plasmodium and most likely is underpinned by the biology of the direct and acute coccidian life cycle in the definitive host. PMID:26354122

Variants in the ATM-CHEK2-BRCA1 axis determine genetic predisposition and clinical presentation of papillary thyroid carcinoma.

PubMed

Wójcicka, Anna; Czetwertyńska, Małgorzata; Świerniak, Michał; Długosińska, Joanna; Maciąg, Monika; Czajka, Agnieszka; Dymecka, Kinga; Kubiak, Anna; Kot, Adam; Płoski, Rafał; de la Chapelle, Albert; Jażdżewski, Krystian

2014-06-01

The risk of developing papillary thyroid carcinoma (PTC), the most frequent form of thyroid malignancy, is elevated up to 8.6-fold in first-degree relatives of PTC patients. The familial risk could be explained by high-penetrance mutations in yet unidentified genes, or polygenic action of low-penetrance alleles. Since the DNA-damaging exposure to ionizing radiation is a known risk factor for thyroid cancer, polymorphisms in DNA repair genes are likely to affect this risk. In a search for low-penetrance susceptibility alleles we employed Sequenom technology to genotype deleterious polymorphisms in ATM, CHEK2, and BRCA1 in 1,781 PTC patients and 2,081 healthy controls. As a result of the study, we identified CHEK2 rs17879961 (OR = 2.2, P = 2.37e-10) and BRCA1 rs16941 (odds ratio [OR] = 1.16, P = 0.005) as risk alleles for PTC. The ATM rs1801516 variant modifies the risk associated with the BRCA1 variant by 0.78 (P = 0.02). Both the ATM and BRCA1 variants modify the impact of male gender on clinical variables: T status (P = 0.007), N status (P = 0.05), and stage (P = 0.035). Our findings implicate an important role of variants in the ATM- CHEK2- BRCA1 axis in modification of the genetic predisposition to PTC and its clinical manifestations. Copyright © 2014 Wiley Periodicals, Inc.

Floor Plans Engine Removal Platform, Hold Down Arm Platform, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Floor Plans - Engine Removal Platform, Hold Down Arm Platform, Hydraulic Equipment Platforms, Isometric Cutaway of Engine Removal Platform, Isometric Cutaway of Hold Down Arm Platform, Isometric Cutaway of Hydraulic Platforms and Engine Support System Access - Marshall Space Flight Center, Saturn V S-IC Static Test Facility, West Test Area, Huntsville, Madison County, AL

30 CFR 250.909 - What is the Platform Verification Program?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 2 2011-07-01 2011-07-01 false What is the Platform Verification Program? 250... Platforms and Structures Platform Verification Program § 250.909 What is the Platform Verification Program? The Platform Verification Program is the MMS approval process for ensuring that floating platforms...

Correlation of interactions between NOS3 polymorphisms and oxygen therapy with retinopathy of prematurity susceptibility

PubMed Central

Yu, Chunhong; Yi, Jinglin; Yin, Xiaolong; Deng, Yan; Liao, Yujun; Li, Xiaobing

2015-01-01

Aim: This study was aimed to detect the correlation of nitric oxide synthase 3 (NOS3) gene polymorphisms (T-786C and G894T) and retinopathy of prematurity (ROP) susceptibility. Interaction between NOS3 gene polymorphisms and the duration of oxygen therapy was also explored in ROP babies. Methods: Genotypes of NOS3 gene polymorphisms were genotyped by MassArray method. Hardy-Weinberg equilibrium (HWE) was used to calculate the representativeness of the cases and controls. Crossover analysis was utilized to explore the gene environment interactions. Relative risk of ROP was presented by odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs). Results: Among the subject features, oxygen therapy had obvious difference between case and control groups (P<0.05). There existed significant association between-786C allele and ROP susceptibility (P=0.049, OR=0.669, 95% CI=0.447-0.999). Genotypes of T-786C polymorphism and genotypes and alleles of G894T polymorphism did not related to the susceptibility of ROP. Interactions were existed between NOS3 gene polymorphisms and oxygen therapy duration. When the duration of oxygen therapy was less than 17 days, both -786CC genotype and 894GT genotype were correlated with ROP susceptibility (P=0.020, OR=0.115, 95% CI=0.014-0.960; P=0.011, OR=0.294, 95% CI=0.100-0.784). Conclusion: -786C allele might have a protective effect for ROP. Interactions of -786CC and 894GT genotype with oxygen therapy duration (less than 17 days) were both protection factors of ROP. PMID:26823875

Interleukin gene polymorphisms in Chinese Han population with breast cancer, a case-control study.

PubMed

Zuo, Xiaoxiao; Li, Miao; Yang, Ya; Liang, Tiansong; Yang, Hongyao; Zhao, Xinhan; Yang, Daoke

2018-04-06

Cytokines are known as important regulators of the cancer involved in inflammatory and immunological responses. This fact and plethora of gene polymorphism data prompted us to investigate IL1 gene polymorphisms in breast cancer (BC) patients. Totally, 530 patients with BC and 628 healthy control women were studied. The genetic polymorphisms for IL1 were analyzed by Massarray Sequencing method. Three single nucleotide polymorphisms (SNPs) identified in IL1B, IL1R1 gene are thought to influence breast cancer risk. The results of the association between IL-1B, IL1R1 polymorphisms and breast cancer risk have significant. We found that the variant TT genotype of rs10490571 was associated with a significantly increased breast cancer risk (TT vs. CC: OR = 2.82, 95% CI = 1.12-7.08, P = 0.047 for the codominant model). For rs16944 (AG vs. GG: OR = 0.60, 95% CI = 0.41-0.90, P = 0.034 for the codominant model) and rs1143623 (CG vs. CC: OR = 0.65, 95% CI = 0.45-0.94, P = 0.023 for the codominant model) have significant associations were found in genetic models. In conclusion, the present analysis suggests a correlation of polymorphic markers within the IL-1 gene locus with the risk in developing breast cancer. Taken together with our finding that IL1B, IL1R1 gene three SNP are also associated with the risk for the disease, we suggest that inflammation via innate and adaptive immunity contributes to multifactorial hereditary predisposition to pathogenesis of the breast cancer.

The influence of aging on the methylation status of brain-derived neurotrophic factor gene in blood.

PubMed

Ihara, Kazushige; Fuchikami, Manabu; Hashizume, Masahiro; Okada, Satoshi; Kawai, Hisashi; Obuchi, Shuichi; Hirano, Hirohiko; Fujiwara, Yoshinori; Hachisu, Mitsugu; Hongyong, Kim; Morinobu, Shigeru

2018-06-28

Brain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of psychiatric disorders in adults and elderly individuals, and as a result, the DNA methylation (DNAm) of the BDNF gene in peripheral tissues including blood has been extensively examined to develop a useful biomarker for psychiatric disorders. However, studies to date have not previously investigated the effect of age on DNAm of the BDNF gene in blood. In this context, we measured DNAm of 39 CpG units in the CpG island at the promoter of exon I of the BDNF gene. We analyzed genomic DNA from peripheral blood of 105 health Japanese women 20 to 80 years of age to identify aging-associated change in DNAm of the BDNF gene. In addition, we examined the relationship between total MMSE scores, numbers of stressful life events, and serum BDNF levels on DNAm of the BDNF gene. The DNAm rate at each CpG unit was measured using a MassArray ® system (Agena Bioscience), and serum BDNF levels were measured by ELISA. There was a significant correlation between DNAm and age in 13 CpGs. However, there was no significant correlation between DNAm and total MMSE scores, numbers of life events, or serum BDNF levels. Despite the small number of subjects and the inclusion of only female subjects, our results suggest that DNAm of 13 CpGs of the BDNF gene may be an appropriate biomarker for aging and useful for predicting increased susceptibility to age-related psychiatric disorders. © 2018 John Wiley & Sons, Ltd.

Polymorphisms of the ghrelin/obestatin gene and ghrelin levels in Chinese children with short stature.

PubMed

Zou, Chao Chun; Huang, Ke; Liang, Li; Zhao, Zheng Yan

2008-07-01

To investigate the role of ghrelin and polymorphisms of ghrelin/obestatin gene in children with short stature. A total of 117 GH deficient (GHD) and 81 idiopathic short stature (ISS) children were studied. The controls consisted of 125 age and gender-matched healthy children. The Arg51Gln, Leu72Met and Gln90Leu polymorphisms were genotyped using MassArray and total plasma ghrelin was measured by radioimmunoassay. In this study, the frequency of the Arg51Gln polymorphism was very low (0% in controls and 1.0% in patients). The frequency of the Gln90Leu polymorphism was 1.6% in controls and 0.5% in patients, respectively. Higher frequencies of Leu72Met (34.4% in controls and 39.9% in patients) and Met72Met genotypes (4.0% in controls and 2.0% in patients) were found. The differences in the Arg51Gln, Leu72Met or Gln90Leu genotypes and allele frequencies between patients and controls were not significant. Also, there were no significant differences in the Leu72Met genotypes and allele frequencies between GHD and ISS subgroups. There were no significant differences in clinical characteristics and biochemistry markers (including ghrelin levels) among the different genotypes of Leu72Met. However, plasma ghrelin levels in the GHD group were significantly lower than those of controls (P = 0.001). These results suggest that ghrelin may have a role in GH secretion and controlling growth. Lower ghrelin levels, but not ghrelin/obestatin polymorphism, might contribute to GHD.

Exposure to meat-derived carcinogens and bulky DNA adduct levels in normal-appearing colon mucosa.

PubMed

Ho, Vikki; Brunetti, Vanessa; Peacock, Sarah; Massey, Thomas E; Godschalk, Roger W L; van Schooten, Frederik J; Ashbury, Janet E; Vanner, Stephen J; King, Will D

2017-09-01

Meat consumption is a risk factor for colorectal cancer. This research investigated the relationship between meat-derived carcinogen exposure and bulky DNA adduct levels, a biomarker of DNA damage, in colon mucosa. Least squares regression was used to examine the relationship between meat-derived carcinogen exposure (PhIP and meat mutagenicity) and bulky DNA adduct levels in normal-appearing colon tissue measured using 32 P-postlabelling among 202 patients undergoing a screening colonoscopy. Gene-diet interactions between carcinogen exposure and genetic factors relevant to biotransformation and DNA repair were also examined. Genotyping was conducting using the MassARRAY ® iPLEX ® Gold SNP Genotyping assay. PhIP and higher meat mutagenicity exposures were not associated with levels of bulky DNA adducts in colon mucosa. The XPC polymorphism (rs2228001) was found to associate with bulky DNA adduct levels, whereby genotypes conferring lower DNA repair activity were associated with higher DNA adduct levels than the normal activity genotype. Among individuals with genotypes associated with lower DNA repair (XPD, rs13181 and rs1799179) or detoxification activity (GSTP1, rs1695), higher PhIP or meat mutagenicity exposures were associated with higher DNA adduct levels. Significant interactions between the XPC polymorphism (rs2228000) and both dietary PhIP and meat mutagenicity on DNA adduct levels was observed, but associations were inconsistent with the a priori hypothesized direction of effect. Exposure to meat-derived carcinogens may be associated with increased DNA damage occurring directly in the colon among genetically susceptible individuals. Copyright © 2017 Elsevier B.V. All rights reserved.

Functional polymorphisms of circadian negative feedback regulation genes are associated with clinical outcome in hepatocellular carcinoma patients receiving radical resection.

PubMed

Zhang, Zhaohui; Ma, Fei; Zhou, Feng; Chen, Yibing; Wang, Xiaoyan; Zhang, Hongxin; Zhu, Yong; Bi, Jianwei; Zhang, Yiguan

2014-12-01

Previous studies have demonstrated that circadian negative feedback loop genes play an important role in the development and progression of many cancers. However, the associations between single-nucleotide polymorphisms (SNPs) in these genes and the clinical outcomes of hepatocellular carcinoma (HCC) after surgical resection have not been studied so far. Thirteen functional SNPs in circadian genes were genotyped using the Sequenom iPLEX genotyping system in a cohort of 489 Chinese HCC patients who received radical resection. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the prognosis analysis. Cumulative effect analysis and survival tree analysis were used for the multiple SNPs analysis. Four individual SNPs, including rs3027178 in PER1, rs228669 and rs2640908 in PER3 and rs3809236 in CRY1, were significantly associated with overall survival (OS) of HCC patients, and three SNPs, including rs3027178 in PER1, rs228729 in PER3 and rs3809236 in CRY1, were significantly associated with recurrence-free survival (RFS). Moreover, we observed a cumulative effect of significant SNPs on OS and RFS (P for trend < 0.001 for both). Survival tree analysis indicated that wild genotype of rs228729 in PER3 was the primary risk factor contributing to HCC patients' RFS. Our study suggests that the polymorphisms in circadian negative feedback loop genes may serve as independent prognostic biomarkers in predicting clinical outcomes for HCC patients who received radical resection. Further studies with different ethnicities are needed to validate our findings and generalize its clinical utility.

Sarcomeric gene mutations in sudden infant death syndrome (SIDS).

PubMed

Brion, Maria; Allegue, Catarina; Santori, Montserrat; Gil, Rocio; Blanco-Verea, Alejandro; Haas, Cordula; Bartsch, Christine; Poster, Simone; Madea, Burkhard; Campuzano, Oscar; Brugada, Ramon; Carracedo, Angel

2012-06-10

In developed countries, sudden infant death syndrome (SIDS) represents the most prevalent cause of death in children between 1 month and 1 year of age. SIDS is a diagnosis of exclusion, a negative autopsy which requires the absence of structural organ disease. Although investigators have confirmed that a significant percentage of SIDS cases are actually channelopathies, no data have been made available as to whether other sudden cardiac death-associated diseases, such as hypertrophic cardiomyopathy (HCM), could be responsible for some cases of SIDS. The presence of a genetic mutation in the sarcomeric protein usually affects the force of contraction of the myocyte, whose weakness is compensated with progressive hypertrophy and disarray. However, it is unclear whether in the most incipient forms, that is, first years of life, the lack of these phenotypes still confers a risk of arrhythmogenesis. The main goal of the present study is to wonder whether genetic defects in the sarcomeric proteins, previously associated with HCM, could be responsible for SIDS. We have analysed 286 SIDS cases for the most common genes implicated in HCM in adults. A total of 680 mutations localised in 16 genes were analysed by semi-automated matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDITOF-MS) using the Sequenom MassARRAY(®) System. Ten subjects with completely normal hearts showed mutated alleles at nine of the genetic variants analysed, and one additional novel mutation was detected by conventional sequencing. Therefore, a genetic mutation associated with HCM may cause sudden cardiac death in the absence of an identifiable phenotype. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Haplotypes of heparin-binding epidermal-growth-factor-like growth factor gene are associated with pre-eclampsia.

PubMed

Harendra, Galhenagey Gayani; Jayasekara, Rohan W; Dissanayake, Vajira H W

2012-01-01

Heparin-binding epidermal-growth-factor-like growth factor (HBEGF) plays an important role in placentation, including impaired placentation, the primary defect seen in pre-eclampsia. We carried out a case-control disease-association study to examine the association of single nucleotide polymorphisms (SNP) in the HBEGF gene and haplotypes defined by them with pre-eclampsia in a Sinhalese population in Sri Lanka. A total of 175 women with pre-eclampsia and 171 matched normotensive controls were genotyped for six SNP selected in silico as having putative functional effects using mass array Sequenom iplex methodology and a newly designed polymerase chain reaction-restriction fragment length polymorphism assay. The individual SNP were not associated with pre-eclampsia. The haplotypes defined by them, however, showed both predisposing (rs13385T,rs2074613G,rs2237076G,rs2074611C,rs4150196A,rs1862176A; odds ratio,1.65; 95% confidence interval1.04-2.60; P=0.032) and protective (rs13385C,rs2074613G,rs2237076A,rs2074611C,rs4150196A,rs1862176A; odds ratio,0.20; 95% confidence interval, 0.04-0.89; P=0.034) effects. These results confirm that polymorphisms in the HGEGF gene are associated with pre-eclampsia. The haplotypes are likely to exert their effects through the numerous transcription regulation factors binding to the polymorphic sites, namely GATA-1, GATA-3, MZF-1 and AML-1a. © 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.

Metastatic thyroid carcinoma without identifiable primary tumor within the thyroid gland: a retrospective study of a rare phenomenon.

PubMed

Xu, Bin; Scognamiglio, Theresa; Cohen, Perry R; Prasad, Manju L; Hasanovic, Adnan; Tuttle, Robert Michael; Katabi, Nora; Ghossein, Ronald A

2017-07-01

Metastatic papillary thyroid carcinoma (PTC) without an identifiable primary tumor despite extensive microscopic examination of the thyroid gland is a rare but true phenomenon.We retrieved 7 of such cases and described in detail the clinical and pathologic features of these tumors. BRAF V600E immunohistochemistry and Sequenom molecular profile were conducted in selected cases. All patients harbored metastatic disease in the central (n=3), lateral (n=3), or both neck compartments (n=1). The histotype of the metastatic disease was PTC (n=5), poorly differentiated thyroid carcinoma in association with a PTC columnar variant (n=1), and anaplastic thyroid carcinoma in association with a PTC tall cell variant (n=1). Fibrosis was present in the thyroid of 5 patients. All patients with PTC were alive without evidence of recurrence. The 76-year-old patient with poorly differentiated thyroid carcinoma did not recur and died of unknown causes. Finally, the patient with anaplastic thyroid carcinoma was alive with distant metastasis at last follow-up. The median follow-up for this cohort was 2.2years (range, 0.8-17). BRAF V600E was detected in 4 of 6 cases by immunohistochemistry. In conclusion, metastatic nodal disease without identifiable thyroid primary is a rare but real phenomenon of unknown mechanisms. Although most tumors are low grade and well differentiated, aggressive behavior due to poorly differentiated or anaplastic carcinoma can happen. Most cases are BRAF V600E -positive thyroid tumors. A papillary carcinoma phenotype is found in all reported cases. Copyright © 2017 Elsevier Inc. All rights reserved.

30 CFR 250.911 - If my platform is subject to the Platform Verification Program, what must I do?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 2 2012-07-01 2012-07-01 false If my platform is subject to the Platform Verification Program, what must I do? 250.911 Section 250.911 Mineral Resources BUREAU OF SAFETY AND... CONTINENTAL SHELF Platforms and Structures Platform Verification Program § 250.911 If my platform is subject...

30 CFR 250.911 - If my platform is subject to the Platform Verification Program, what must I do?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 2 2013-07-01 2013-07-01 false If my platform is subject to the Platform Verification Program, what must I do? 250.911 Section 250.911 Mineral Resources BUREAU OF SAFETY AND... CONTINENTAL SHELF Platforms and Structures Platform Verification Program § 250.911 If my platform is subject...

30 CFR 250.911 - If my platform is subject to the Platform Verification Program, what must I do?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 2 2014-07-01 2014-07-01 false If my platform is subject to the Platform Verification Program, what must I do? 250.911 Section 250.911 Mineral Resources BUREAU OF SAFETY AND... CONTINENTAL SHELF Platforms and Structures Platform Verification Program § 250.911 If my platform is subject...

Assessment of the cPAS-based BGISEQ-500 platform for metagenomic sequencing.

PubMed

Fang, Chao; Zhong, Huanzi; Lin, Yuxiang; Chen, Bing; Han, Mo; Ren, Huahui; Lu, Haorong; Luber, Jacob M; Xia, Min; Li, Wangsheng; Stein, Shayna; Xu, Xun; Zhang, Wenwei; Drmanac, Radoje; Wang, Jian; Yang, Huanming; Hammarström, Lennart; Kostic, Aleksandar D; Kristiansen, Karsten; Li, Junhua

2018-03-01

More extensive use of metagenomic shotgun sequencing in microbiome research relies on the development of high-throughput, cost-effective sequencing. Here we present a comprehensive evaluation of the performance of the new high-throughput sequencing platform BGISEQ-500 for metagenomic shotgun sequencing and compare its performance with that of 2 Illumina platforms. Using fecal samples from 20 healthy individuals, we evaluated the intra-platform reproducibility for metagenomic sequencing on the BGISEQ-500 platform in a setup comprising 8 library replicates and 8 sequencing replicates. Cross-platform consistency was evaluated by comparing 20 pairwise replicates on the BGISEQ-500 platform vs the Illumina HiSeq 2000 platform and the Illumina HiSeq 4000 platform. In addition, we compared the performance of the 2 Illumina platforms against each other. By a newly developed overall accuracy quality control method, an average of 82.45 million high-quality reads (96.06% of raw reads) per sample, with 90.56% of bases scoring Q30 and above, was obtained using the BGISEQ-500 platform. Quantitative analyses revealed extremely high reproducibility between BGISEQ-500 intra-platform replicates. Cross-platform replicates differed slightly more than intra-platform replicates, yet a high consistency was observed. Only a low percentage (2.02%-3.25%) of genes exhibited significant differences in relative abundance comparing the BGISEQ-500 and HiSeq platforms, with a bias toward genes with higher GC content being enriched on the HiSeq platforms. Our study provides the first set of performance metrics for human gut metagenomic sequencing data using BGISEQ-500. The high accuracy and technical reproducibility confirm the applicability of the new platform for metagenomic studies, though caution is still warranted when combining metagenomic data from different platforms.

30 CFR 250.909 - What is the Platform Verification Program?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What is the Platform Verification Program? 250... Verification Program § 250.909 What is the Platform Verification Program? The Platform Verification Program is the MMS approval process for ensuring that floating platforms; platforms of a new or unique design...

30 CFR 250.904 - What is the Platform Approval Program?

Code of Federal Regulations, 2011 CFR

2011-07-01

... these requirements will satisfy MMS criteria for approval of fixed platforms of a proven design that... approval for a floating platform; a platform of unique design; or a platform being installed in deepwater (> 400 ft.) or a frontier area, you must also meet the requirements of the Platform Verification Program...

Floor Plans Rolling Platform, Tech Systems Platform, and Load ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Floor Plans - Rolling Platform, Tech Systems Platform, and Load Platform Plans - Marshall Space Flight Center, F-1 Engine Static Test Stand, On Route 565 between Huntsville and Decatur, Huntsville, Madison County, AL

Statistical analysis of an RNA titration series evaluates microarray precision and sensitivity on a whole-array basis

PubMed Central

Holloway, Andrew J; Oshlack, Alicia; Diyagama, Dileepa S; Bowtell, David DL; Smyth, Gordon K

2006-01-01

Background Concerns are often raised about the accuracy of microarray technologies and the degree of cross-platform agreement, but there are yet no methods which can unambiguously evaluate precision and sensitivity for these technologies on a whole-array basis. Results A methodology is described for evaluating the precision and sensitivity of whole-genome gene expression technologies such as microarrays. The method consists of an easy-to-construct titration series of RNA samples and an associated statistical analysis using non-linear regression. The method evaluates the precision and responsiveness of each microarray platform on a whole-array basis, i.e., using all the probes, without the need to match probes across platforms. An experiment is conducted to assess and compare four widely used microarray platforms. All four platforms are shown to have satisfactory precision but the commercial platforms are superior for resolving differential expression for genes at lower expression levels. The effective precision of the two-color platforms is improved by allowing for probe-specific dye-effects in the statistical model. The methodology is used to compare three data extraction algorithms for the Affymetrix platforms, demonstrating poor performance for the commonly used proprietary algorithm relative to the other algorithms. For probes which can be matched across platforms, the cross-platform variability is decomposed into within-platform and between-platform components, showing that platform disagreement is almost entirely systematic rather than due to measurement variability. Conclusion The results demonstrate good precision and sensitivity for all the platforms, but highlight the need for improved probe annotation. They quantify the extent to which cross-platform measures can be expected to be less accurate than within-platform comparisons for predicting disease progression or outcome. PMID:17118209

View from second floor platform looking up at subsequent platforms. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

View from second floor platform looking up at subsequent platforms. Note the Shuttle assembly outlined by the platform edges. - Marshall Space Flight Center, Saturn V Dynamic Test Facility, East Test Area, Huntsville, Madison County, AL

PR-PR: Cross-Platform Laboratory Automation System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Linshiz, G; Stawski, N; Goyal, G

To enable protocol standardization, sharing, and efficient implementation across laboratory automation platforms, we have further developed the PR-PR open-source high-level biology-friendly robot programming language as a cross-platform laboratory automation system. Beyond liquid-handling robotics, PR-PR now supports microfluidic and microscopy platforms, as well as protocol translation into human languages, such as English. While the same set of basic PR-PR commands and features are available for each supported platform, the underlying optimization and translation modules vary from platform to platform. Here, we describe these further developments to PR-PR, and demonstrate the experimental implementation and validation of PR-PR protocols for combinatorial modified Goldenmore » Gate DNA assembly across liquid-handling robotic, microfluidic, and manual platforms. To further test PR-PR cross-platform performance, we then implement and assess PR-PR protocols for Kunkel DNA mutagenesis and hierarchical Gibson DNA assembly for microfluidic and manual platforms.« less

Turbine blade and non-integral platform with pin attachment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campbell, Christian X; Eng, Darryl; Marra, John J

Platforms (36, 38) span between turbine blades (23, 24, 25) on a disk (32). Each platform may be individually mounted to the disk by a pin attachment (42). Each platform (36) may have a rotationally rearward edge portion (50) that underlies a forward portion (45) of the adjacent platform (38). This limits centrifugal bending of the rearward portion of the platform, and provides coolant sealing. The rotationally forward edge (44A, 44B) of the platform overlies a seal element (51) on the pressure side (28) of the forwardly adjacent blade, and does not underlie a shelf on that blade. The pinmore » attachment allows radial mounting of each platform onto the disk via tilting (60) of the platform during mounting to provide mounting clearance for the rotationally rearward edge portion (50). This facilitates quick platform replacement without blade removal.« less

Turbine blade and non-integral platform with pin attachment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campbell, Christian Xavier; Eng, Darryl; Marra, John J.

2016-08-02

Platforms (36, 38) span between turbine blades (23, 24, 25) on a disk (32). Each platform may be individually mounted to the disk by a pin attachment (42). Each platform (36) may have a rotationally rearward edge portion (50) that underlies a forward portion (45) of the adjacent platform (38). This limits centrifugal bending of the rearward portion of the platform, and provides coolant sealing. The rotationally forward edge (44A, 44B) of the platform overlies a seal element (51) on the pressure side (28) of the forwardly adjacent blade, and does not underlie a shelf on that blade. The pinmore » attachment allows radial mounting of each platform onto the disk via tilting (60) of the platform during mounting to provide mounting clearance for the rotationally rearward edge portion (50). This facilitates quick platform replacement without blade removal.« less

PR-PR: cross-platform laboratory automation system.

PubMed

Linshiz, Gregory; Stawski, Nina; Goyal, Garima; Bi, Changhao; Poust, Sean; Sharma, Monica; Mutalik, Vivek; Keasling, Jay D; Hillson, Nathan J

2014-08-15

To enable protocol standardization, sharing, and efficient implementation across laboratory automation platforms, we have further developed the PR-PR open-source high-level biology-friendly robot programming language as a cross-platform laboratory automation system. Beyond liquid-handling robotics, PR-PR now supports microfluidic and microscopy platforms, as well as protocol translation into human languages, such as English. While the same set of basic PR-PR commands and features are available for each supported platform, the underlying optimization and translation modules vary from platform to platform. Here, we describe these further developments to PR-PR, and demonstrate the experimental implementation and validation of PR-PR protocols for combinatorial modified Golden Gate DNA assembly across liquid-handling robotic, microfluidic, and manual platforms. To further test PR-PR cross-platform performance, we then implement and assess PR-PR protocols for Kunkel DNA mutagenesis and hierarchical Gibson DNA assembly for microfluidic and manual platforms.

Implementation and performance test of cloud platform based on Hadoop

NASA Astrophysics Data System (ADS)

Xu, Jingxian; Guo, Jianhong; Ren, Chunlan

2018-01-01

Hadoop, as an open source project for the Apache foundation, is a distributed computing framework that deals with large amounts of data and has been widely used in the Internet industry. Therefore, it is meaningful to study the implementation of Hadoop platform and the performance of test platform. The purpose of this subject is to study the method of building Hadoop platform and to study the performance of test platform. This paper presents a method to implement Hadoop platform and a test platform performance method. Experimental results show that the proposed test performance method is effective and it can detect the performance of Hadoop platform.

Automated Platform Management System Scheduling

NASA Technical Reports Server (NTRS)

Hull, Larry G.

1990-01-01

The Platform Management System was established to coordinate the operation of platform systems and instruments. The management functions are split between ground and space components. Since platforms are to be out of contact with the ground more than the manned base, the on-board functions are required to be more autonomous than those of the manned base. Under this concept, automated replanning and rescheduling, including on-board real-time schedule maintenance and schedule repair, are required to effectively and efficiently meet Space Station Freedom mission goals. In a FY88 study, we developed several promising alternatives for automated platform planning and scheduling. We recommended both a specific alternative and a phased approach to automated platform resource scheduling. Our recommended alternative was based upon use of exactly the same scheduling engine in both ground and space components of the platform management system. Our phased approach recommendation was based upon evolutionary development of the platform. In the past year, we developed platform scheduler requirements and implemented a rapid prototype of a baseline platform scheduler. Presently we are rehosting this platform scheduler rapid prototype and integrating the scheduler prototype into two Goddard Space Flight Center testbeds, as the ground scheduler in the Scheduling Concepts, Architectures, and Networks Testbed and as the on-board scheduler in the Platform Management System Testbed. Using these testbeds, we will investigate rescheduling issues, evaluate operational performance and enhance the platform scheduler prototype to demonstrate our evolutionary approach to automated platform scheduling. The work described in this paper was performed prior to Space Station Freedom rephasing, transfer of platform responsibility to Code E, and other recently discussed changes. We neither speculate on these changes nor attempt to predict the impact of the final decisions. As a consequence some of our work and results may be outdated when this paper is published.

Platform options for the Space Station program

NASA Technical Reports Server (NTRS)

Mangano, M. J.; Rowley, R. W.

1986-01-01

Platforms for polar and 28.5 deg orbits were studied to determine the platform requirements and characteristics necessary to support the science objectives. Large platforms supporting the Earth-Observing System (EOS) were initially studied. Co-orbiting platforms were derived from these designs. Because cost estimates indicated that the large platform approach was likely to be too expensive, require several launches, and generally be excessively complex, studies of small platforms were undertaken. Results of these studies show the small platform approach to be technically feasible at lower overall cost. All designs maximized hardware inheritance from the Space Station program to reduce costs. Science objectives as defined at the time of these studies are largely achievable.

Geostationary platform systems concepts definition study. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

1980-01-01

The results of a geostationary platform concept analysis are summarized. Mission and payloads definition, concept selection, the requirements of an experimental platform, supporting research and technology, and the Space Transportation System interface requirements are addressed. It is concluded that platforms represent a logical extension of current trends toward larger, more complex, multifrequency satellites. Geostationary platforms offer significant cost savings compared to individual satellites, with the majority of these economies being realized with single Shuttle launched platforms. Further cost savings can be realized, however, by having larger platforms. Platforms accommodating communications equipment that operates at multiple frequencies and which provide larger scale frequency reuse through the use of large aperture multibeam antennas and onboard switching maximize the useful capacity of the orbital arc and frequency spectrum. Projections of market demand indicate that such conservation measures are clearly essential if orderly growth is to be provided for. In addition, it is pointed out that a NASA experimental platform is required to demonstrate the technologies necessary for operational geostationary platforms of the 1990's.

Composite airfoil assembly

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garcia-Crespo, Andres Jose

A composite blade assembly for mounting on a turbine wheel includes a ceramic airfoil and an airfoil platform. The ceramic airfoil is formed with an airfoil portion, a blade shank portion and a blade dovetail tang. The metal platform includes a platform shank and a radially inner platform dovetail. The ceramic airfoil is captured within the metal platform, such that in use, the ceramic airfoil is held within the turbine wheel independent of the metal platform.

Drowned carbonate platforms in the Huon Gulf, Papua New Guinea

NASA Astrophysics Data System (ADS)

Webster, Jody M.; Wallace, Laura; Silver, Eli; Applegate, Bruce; Potts, Donald; Braga, Juan Carlos; Riker-Coleman, Kristin; Gallup, Christina

2004-11-01

The western Huon Gulf, Papua New Guinea, is an actively subsiding foreland basin dominated by drowned carbonate platforms. We investigated these platforms using new high-resolution multibeam, side-scan sonar and seismic data, combined with submersible observations and previously published radiometric and sedimentary facies data. The data reveal 14 distinct drowned carbonate platforms and numerous pinnacles/banks that increase in age (˜20-450 kyr) and depth (0.1-2.5 km) NE toward the Ramu-Markham Trench. Superimposed on this overall downward flexing of the platforms toward the trench is a systematic tilting of the deep platforms 15 m/km toward the NW and the shallow platforms 2 m/km toward the SE. This may reflect the encroaching thrust load from the NW (Finisterre Range) and spatial variations in the flexural rigidity of the underlying basement. The drowned platforms form a complex system of promontories and reentrants, with abundant pinnacles and banks preserved at similar depths seaward of the main platforms. This configuration closely mimics the present-day Huon coastline and its seaward islands fringed by modern coral reefs. The platforms retain structural, morphologic, and sedimentary facies evidence of primary platform growth, drowning, and subsequent backstepping, despite some lateral erosion of the platform margins (<100 m slope defacement) by mass wasting. Both platforms and pinnacles are composite features containing multiple terrace levels and notches, corresponding to multiple phases of growth, emergence, and drowning in response to rapid climatic and sea level changes during the evolution of each structure. On the basis of all observational and numerical modeling data, we propose a chronology for the initiation, growth, and drowning of the 14 platforms. Over shorter timescales (≤100 kyr) the rate and amplitude of eustatic sea level changes are critical in controlling initiation, growth, drowning or subaerial exposure, subsequent reinitiation, and final drowning of the platforms. However, continued tectonic subsidence and basement substrate morphology influence the overall backstepping geometry and subsequent tilting of the platforms over longer timescales (≥100-500 kyr).

30 CFR 250.913 - When must I resubmit Platform Verification Program plans?

Code of Federal Regulations, 2011 CFR

2011-07-01

... CONTINENTAL SHELF Platforms and Structures Platform Verification Program § 250.913 When must I resubmit Platform Verification Program plans? (a) You must resubmit any design verification, fabrication... 30 Mineral Resources 2 2011-07-01 2011-07-01 false When must I resubmit Platform Verification...

Evolutionary space platform concept study. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

1982-01-01

The Evolutionary Space Platform Concept Study encompassed a 10 month effort to define, evaluate and compare approaches and concepts for evolving unmanned and manned capability platforms beyond the current Space Platform concepts to an evolutionary goal of establishing a permanent manned presence in space. Areas addressed included: special emphasis trade studies on the current unmanned concept, assessment of manned platform concepts, and utility analysis of a manned platform for defense related missions.

Study on key technologies of vehicle networking system platform for electric automobiles based on micro-service

NASA Astrophysics Data System (ADS)

Ye, Fei

2018-04-01

With the rapid increase of electric automobiles and charging piles, the elastic expansion and online rapid upgrade were required for the vehicle networking system platform (system platform for short). At present, it is difficult to meet the operation needs due to the traditional huge rock architecture used by the system platform. This paper studied the system platform technology architecture based on "cloud platform +micro-service" to obtain a new generation of vehicle networking system platform with the combination of elastic expansion and application, thus significantly improving the service operation ability of system.

Carboxylate platform: the MixAlco process part 1: comparison of three biomass conversion platforms.

PubMed

Holtzapple, Mark T; Granda, Cesar B

2009-05-01

To convert biomass to liquid fuels, three platforms are compared: thermochemical, sugar, and carboxylate. To create a common basis, each platform is fed "ideal biomass," which contains polysaccharides (68.3%) and lignin (31.7%). This ratio is typical of hardwood biomass and was selected so that when gasified and converted to hydrogen, the lignin has sufficient energy to produce ethanol from the carboxylic acids produced by the carboxylate platform. Using balanced chemical reactions, the theoretical yield and energy efficiency were determined for each platform. For all platforms, the ethanol yield can be increased by 71% to 107% by supplying external hydrogen produced from other sources (e.g., solar, wind, nuclear, fossil fuels). The alcohols can be converted to alkanes with a modest loss of energy efficiency (3 to 5 percentage points). Of the three platforms considered, the carboxylate platform has demonstrated the highest product yields.

A Novel Polymorphism in the Promoter of the CYP4A11 Gene Is Associated with Susceptibility to Coronary Artery Disease

PubMed Central

Sirotina, Svetlana; Ponomarenko, Irina; Kharchenko, Alexander; Bykanova, Marina; Bocharova, Anna; Vagaytseva, Kseniya; Solodilova, Maria

2018-01-01

Enzymes CYP4A11 and CYP4F2 are involved in biosynthesis of vasoactive 20-hydroxyeicosatetraenoic acid and may contribute to pathogenesis of coronary artery disease (CAD). We investigated whether polymorphisms of the CYP4A11 and CYP4F2 genes are associated with the risk of CAD in Russian population. DNA samples from 1323 unrelated subjects (637 angiographically confirmed CAD patients and 686 age- and sex-matched healthy individuals) were genotyped for polymorphisms rs3890011, rs9332978, and rs9333029 of CYP4A11 and rs3093098 and rs1558139 of CYP4F2 by using the Mass-ARRAY 4 system. SNPs rs3890011 and rs9332978 of CYP4A11 were associated with increased risk of CAD in women: OR = 1.26, 95% CI: 1.02–1.57, P = 0.004, and Q = 0.01 and OR = 1.45, 95% CI: 1.13–1.87, P = 0.004, and Q = 0.01, respectively. Haplotype G-C-A of CYP4A11 was associated with increased risk of CAD (adjusted OR = 1.41, 95% CI: 1.12–1.78, and P = 0.0036). Epistatic interactions were found between rs9332978 of CYP4A11 and rs1558139 of CYP4F2 (P interaction = 0.025). In silico analysis allowed identifying that SNP rs9332978 is located at a binding site for multiple transcription factors; many of them are known to regulate the pathways involved in the pathogenesis of CAD. This is the first study in Europeans that reported association between polymorphism rs9332978 of CYP4A11 and susceptibility to coronary artery disease. PMID:29484037

The use of FTA cards for preserving unfixed cytological material for high-throughput molecular analysis.

PubMed

Saieg, Mauro Ajaj; Geddie, William R; Boerner, Scott L; Liu, Ni; Tsao, Ming; Zhang, Tong; Kamel-Reid, Suzanne; da Cunha Santos, Gilda

2012-06-25

Novel high-throughput molecular technologies have made the collection and storage of cells and small tissue specimens a critical issue. The FTA card provides an alternative to cryopreservation for biobanking fresh unfixed cells. The current study compared the quality and integrity of the DNA obtained from 2 types of FTA cards (Classic and Elute) using 2 different extraction protocols ("Classic" and "Elute") and assessed the feasibility of performing multiplex mutational screening using fine-needle aspiration (FNA) biopsy samples. Residual material from 42 FNA biopsies was collected in the cards (21 Classic and 21 Elute cards). DNA was extracted using the Classic protocol for Classic cards and both protocols for Elute cards. Polymerase chain reaction for p53 (1.5 kilobase) and CARD11 (500 base pair) was performed to assess DNA integrity. Successful p53 amplification was achieved in 95.2% of the samples from the Classic cards and in 80.9% of the samples from the Elute cards using the Classic protocol and 28.5% using the Elute protocol (P = .001). All samples (both cards) could be amplified for CARD11. There was no significant difference in the DNA concentration or 260/280 purity ratio when the 2 types of cards were compared. Five samples were also successfully analyzed by multiplex MassARRAY spectrometry, with a mutation in KRAS found in 1 case. High molecular weight DNA was extracted from the cards in sufficient amounts and quality to perform high-throughput multiplex mutation assays. The results of the current study also suggest that FTA Classic cards preserve better DNA integrity for molecular applications compared with the FTA Elute cards. Copyright © 2012 American Cancer Society.

Identification of carbapenem-resistant Pseudomonas aeruginosa in selected hospitals of the Gulf Cooperation Council States: dominance of high-risk clones in the region.

PubMed

Zowawi, Hosam M; Syrmis, Melanie W; Kidd, Timothy J; Balkhy, Hanan H; Walsh, Timothy R; Al Johani, Sameera M; Al Jindan, Reem Y; Alfaresi, Mubarak; Ibrahim, Emad; Al-Jardani, Amina; Al Salman, Jameela; Dashti, Ali A; Sidjabat, Hanna E; Baz, Omar; Trembizki, Ella; Whiley, David M; Paterson, David L

2018-04-17

The molecular epidemiology and resistance mechanisms of carbapenem-resistant Pseudomonas aeruginosa (CRPA) were determined in hospitals in the countries of the Gulf Cooperation Council (GCC), namely, Saudi Arabia, the United Arab Emirates, Oman, Qatar, Bahrain and Kuwait. Isolates were screened for common carbapenem-resistance genes by PCR. Relatedness between isolates was assessed using previously described genotyping methods: an informative-single nucleotide polymorphism MassARRAY iPLEX assay (iPLEX20SNP) and the enterobacterial repetitive intergenic consensus (ERIC)-PCR assay, with selected isolates being subjected to multilocus sequence typing (MLST). Ninety-five non-repetitive isolates that were found to be resistant to carbapenems were subjected to further investigation.Results/Key findings. The most prevalent carbapenemase-encoding gene, blaVIM-type, was found in 37/95 (39 %) isolates, while only 1 isolate (from UAE) was found to have blaIMP-type. None of the CRPA were found to have blaNDM-type or blaKPC-type. We found a total of 14 sequence type (ST) clusters, with 4 of these clusters being observed in more than 1 country. Several clusters belonged to the previously recognized internationally disseminated high-risk clones ST357, ST235, ST111, ST233 and ST654. We also found the less predominant ST316, ST308 and ST823 clones, and novel MLST types (ST2010, ST2011, ST2012 and ST2013), in our collection. Overall our data show that 'high-risk' CRPA clones are now detected in the region and highlight the need for strategies to limit further spread of such organisms, including enhanced surveillance, infection control precautions and further promotion of antibiotic stewardship programmes.

Analysis of the expression level and methylation of tumor protein p53, phosphatase and tensin homolog and mutS homolog 2 in N-methyl-N-nitrosourea-induced thymic lymphoma in C57BL/6 mice.

PubMed

Huo, Xueyun; Li, Zhenkun; Zhang, Shuangyue; Li, Changlong; Guo, Meng; Lu, Jing; Lv, Jianyi; Du, Xiaoyan; Chen, Zhenwen

2017-10-01

Tumorigenesis is often caused by somatic mutation or epigenetic changes in genes that regulate aspects of cell death, proliferation and survival. Although the functions of multiple tumor suppressor genes have been well studied in isolation, how these genes cooperate during the progression of a single tumor remains unclear in numerous cases. The present study used N-methyl-N-nitrosourea (MNU), one of the most potent mutagenic nitrosourea compounds, to induce thymic lymphoma in C57BL/6J mice. Subsequently, the protein expression levels of phosphatase and tensin homolog (PTEN), transformation protein 53 and mutS homolog 2 (MSH2) were evaluated concomitantly in the thymus, liver, kidney and spleen of MNU-treated mice by western blotting. To determine whether changes in expression level were due to aberrant epigenetic regulation, the present study further examined the methylation status of each gene by MassARRAY analysis. During the tumorigenesis process of an MNU-induced single thymic lymphoma, the expression level of PTEN was revealed to be reduced in thymic lymphoma samples but not in normal or non-tumor thymus tissue samples. Furthermore, a marked reduction of P53 expression levels were demonstrated in thymic lymphomas and spleens with a metastatic tumor. Conversely, MSH2 upregulation was identified only in liver, kidney, and spleen samples that were infiltrated by thymic lymphoma cells. Furthermore, the present study revealed that a number of 5'-C-phosphate-G-3' sites located in the promoter of aberrantly expressed genes had significantly altered methylation statuses. These results improve the understanding of the course of mutagen-induced cancer, and highlight that epigenetic regulation may serve an important function in cancer.

Impact of Genetic Polymorphisms on 6-Thioguanine Nucleotide Levels and Toxicity in Pediatric Patients with IBD Treated with Azathioprine.

PubMed

Lee, Mi-Na; Kang, Ben; Choi, So Yoon; Kim, Mi Jin; Woo, Sook Young; Kim, Jong-Won; Choe, Yon Ho; Lee, Soo-Youn

2015-12-01

Thiopurine-related toxicity results in discontinuation of therapy in up to 30% of patients with inflammatory bowel disease. Although thiopurine S-methyltransferase (TPMT) is implicated in toxicity, not all toxicity can be attributed to TPMT polymorphisms. We investigated the effects of polymorphisms of genes involved in thiopurine and folate metabolism pathways on 6-thioguanine nucleotide levels and toxicity. Retrospective clinical data and blood samples were collected from 132 pediatric patients with inflammatory bowel disease treated with azathioprine. Eighty-seven genetic polymorphisms of 30 genes were screened using the MassARRAY system, and 70 polymorphisms of 28 genes were selected for further analysis. TPMT genotype (P < 0.001), concurrent use of mesalazine (P = 0.006), ABCC5 (rs2293001) (P < 0.001), ITPA (rs2236206 and rs8362) (P = 0.010 and P = 0.003), and ABCB1 (rs2032582) (P = 0.028) were all associated with the ratio of 6-thioguanine nucleotides to azathioprine dose. ADK (rs10824095) (P = 0.004, odds ratio [OR] = 6.220), SLC29A1 (rs747199) (P = 0.016, OR = 5.681), and TYMS (rs34743033) (P = 0.045, OR = 3.846) were associated with neutropenia. ABCC1 (rs2074087) (P = 0.022, OR = 3.406), IMPDH1 (rs2278294) (P = 0.027, OR = 0.276), and IMPDH2 (rs11706052) (P = 0.034, OR = 3.639) had a significant impact on lymphopenia. This study describes genetic polymorphisms in genes whose products may affect pharmacokinetics and which may predict the relative likelihood of benefit or risk from thiopurine treatment. These findings may serve as a basis for personalized thiopurine therapy in pediatric patients with inflammatory bowel disease, although our data need to be validated in further studies.

Replication of type 2 diabetes candidate genes variations in three geographically unrelated Indian population groups.

PubMed

Ali, Shafat; Chopra, Rupali; Manvati, Siddharth; Singh, Yoginder Pal; Kaul, Nabodita; Behura, Anita; Mahajan, Ankit; Sehajpal, Prabodh; Gupta, Subash; Dhar, Manoj K; Chainy, Gagan B N; Bhanwer, Amarjit S; Sharma, Swarkar; Bamezai, Rameshwar N K

2013-01-01

Type 2 diabetes (T2D) is a syndrome of multiple metabolic disorders and is genetically heterogeneous. India comprises one of the largest global populations with highest number of reported type 2 diabetes cases. However, limited information about T2D associated loci is available for Indian populations. It is, therefore, pertinent to evaluate the previously associated candidates as well as identify novel genetic variations in Indian populations to understand the extent of genetic heterogeneity. We chose to do a cost effective high-throughput mass-array genotyping and studied the candidate gene variations associated with T2D in literature. In this case-control candidate genes association study, 91 SNPs from 55 candidate genes have been analyzed in three geographically independent population groups from India. We report the genetic variants in five candidate genes: TCF7L2, HHEX, ENPP1, IDE and FTO, are significantly associated (after Bonferroni correction, p<5.5E-04) with T2D susceptibility in combined population. Interestingly, SNP rs7903146 of the TCF7L2 gene passed the genome wide significance threshold (combined P value = 2.05E-08) in the studied populations. We also observed the association of rs7903146 with blood glucose (fasting and postprandial) levels, supporting the role of TCF7L2 gene in blood glucose homeostasis. Further, we noted that the moderate risk provided by the independently associated loci in combined population with Odds Ratio (OR)<1.38 increased to OR = 2.44, (95%CI = 1.67-3.59) when the risk providing genotypes of TCF7L2, HHEX, ENPP1 and FTO genes were combined, suggesting the importance of gene-gene interactions evaluation in complex disorders like T2D.

Interleukin gene polymorphisms in Chinese Han population with breast cancer, a case-control study

PubMed Central

Yang, Ya; Liang, Tiansong; Yang, Hongyao; Zhao, Xinhan; Yang, Daoke

2018-01-01

Cytokines are known as important regulators of the cancer involved in inflammatory and immunological responses. This fact and plethora of gene polymorphism data prompted us to investigate IL1 gene polymorphisms in breast cancer (BC) patients. Totally, 530 patients with BC and 628 healthy control women were studied. The genetic polymorphisms for IL1 were analyzed by Massarray Sequencing method. Three single nucleotide polymorphisms (SNPs) identified in IL1B, IL1R1 gene are thought to influence breast cancer risk. The results of the association between IL-1B, IL1R1 polymorphisms and breast cancer risk have significant. We found that the variant TT genotype of rs10490571 was associated with a significantly increased breast cancer risk (TT vs. CC: OR = 2.82, 95% CI = 1.12–7.08, P = 0.047 for the codominant model). For rs16944 (AG vs. GG: OR = 0.60, 95% CI = 0.41–0.90, P = 0.034 for the codominant model) and rs1143623 (CG vs. CC: OR = 0.65, 95% CI = 0.45–0.94, P = 0.023 for the codominant model) have significant associations were found in genetic models. In conclusion, the present analysis suggests a correlation of polymorphic markers within the IL-1 gene locus with the risk in developing breast cancer. Taken together with our finding that IL1B, IL1R1 gene three SNP are also associated with the risk for the disease, we suggest that inflammation via innate and adaptive immunity contributes to multifactorial hereditary predisposition to pathogenesis of the breast cancer. PMID:29719585

Association of NOS1 gene polymorphisms with cerebral palsy in a Han Chinese population: a case-control study.

PubMed

Yu, Ting; Xia, Lei; Bi, Dan; Wang, Yangong; Shang, Qing; Zhu, Dengna; Song, Juan; Wang, Yong; Wang, Xiaoyang; Zhu, Changlian; Xing, Qinghe

2018-06-25

Cerebral palsy (CP) is the leading cause of motor disability in children; however, its pathogenesis is unknown in most cases. Growing evidence suggests that Nitric oxide synthase 1 (NOS1) is involved in neural development and neurologic diseases. The purpose of this study was to determine whether genetic variants of NOS1 contribute to CP susceptibility in a Han Chinese population. A case-control study involving 652 CP patients and 636 healthy controls was conducted. Six SNPs in the NOS1 gene (rs3782219, rs6490121, rs2293054, rs10774909, rs3741475, and rs2682826) were selected, and the MassARRAY typing technique was applied for genotyping. Data analysis was conducted using SHEsis online software, and multiple test corrections were performed using SNPSpD online software. There were no significant differences in genotype and allele frequencies between patients and controls for the SNPs except rs6490121, which deviated from Hardy-Weinberg equilibrium and was excluded from further analyses. Subgroup analysis revealed differences in genotype frequencies between the CP with neonatal encephalopathy group (CP + NE) and control group for rs10774909, rs3741475, and rs2682826 (after SNPSpD correction, p = 0.004, 0.012, and 0.002, respectively). The T allele of NOS1 SNP rs3782219 was negatively associated with spastic quadriplegia (OR = 0.742, 95% CI = 0.600-0.918, after SNPSpD correction, p = 0.023). There were no differences in allele or genotype frequencies between CP subgroups and controls for the other genetic polymorphisms. NOS1 is associated with CP + NE and spastic quadriplegia, suggesting that NOS1 is likely involved in the pathogenesis of CP and that it is a potential therapeutic target for treatment of cerebral injury.

Genetic Variations of COL4A1 Gene and Intracerebral Hemorrhage Outcome: A Cohort Study in a Chinese Han Population.

PubMed

Xia, Chao; Lin, Sen; Yang, Jie; He, Sha; Li, Hao; Liu, Ming; You, Chao

2018-05-01

To investigate the relationship between single nucleotide polymorphisms or haplotypes of COL4A1 gene and the outcome of intracerebral hemorrhage (ICH). In our study, 181 patients with hypertensive ICH were enrolled and followed up at 3 and 6 months. Outcome data included any cause of death and disability. Genomic DNA was extracted by DNA extraction kit, and the 6 single nucleotide polymorphism genotyping of the COL4A1 gene was detected through MassARRAY Analyzer. Unphased 3.1.4 and SPSS 19.0 were used to analyze the association between alleles, genotypes, and haplotypes of the COL4A1 gene and the outcomes of ICH. Of the 181 patients with hypertensive ICH, 12 were lost in follow-up, which accounted for 6.6%. Our association analysis showed that the rs532625 AA genotype of the COL4A1 gene may increase risk of disability at 3 months; the rs532625 A allele and AA genotype were association factors of the risk of disability at 6 months; the rs532625 AA genotype was an association factor of the risk of death/disability at 6 months. After adjusting for gender, age, coma, and severe neurologic deficits, only the rs532625 AA genotype was independently associated with the risk of disability at 3 and 6 months and the risk of death/disability at 6 months. Our study found that the rs532625 AA genotype in the COL4A1 gene was independently associated with the risk of disability at 3 and 6 months and death/disability at 6 months in a Chinese Han population. These conclusions need to be verified in future studies with larger samples. Copyright © 2018 Elsevier Inc. All rights reserved.

Replication of Type 2 Diabetes Candidate Genes Variations in Three Geographically Unrelated Indian Population Groups

PubMed Central

Ali, Shafat; Chopra, Rupali; Manvati, Siddharth; Mahajan, Ankit; Sehajpal, Prabodh; Gupta, Subash; Dhar, Manoj K.; Chainy, Gagan B. N.; Bhanwer, Amarjit S.; Sharma, Swarkar; Bamezai, Rameshwar N. K.

2013-01-01

Type 2 diabetes (T2D) is a syndrome of multiple metabolic disorders and is genetically heterogeneous. India comprises one of the largest global populations with highest number of reported type 2 diabetes cases. However, limited information about T2D associated loci is available for Indian populations. It is, therefore, pertinent to evaluate the previously associated candidates as well as identify novel genetic variations in Indian populations to understand the extent of genetic heterogeneity. We chose to do a cost effective high-throughput mass-array genotyping and studied the candidate gene variations associated with T2D in literature. In this case-control candidate genes association study, 91 SNPs from 55 candidate genes have been analyzed in three geographically independent population groups from India. We report the genetic variants in five candidate genes: TCF7L2, HHEX, ENPP1, IDE and FTO, are significantly associated (after Bonferroni correction, p<5.5E−04) with T2D susceptibility in combined population. Interestingly, SNP rs7903146 of the TCF7L2 gene passed the genome wide significance threshold (combined P value = 2.05E−08) in the studied populations. We also observed the association of rs7903146 with blood glucose (fasting and postprandial) levels, supporting the role of TCF7L2 gene in blood glucose homeostasis. Further, we noted that the moderate risk provided by the independently associated loci in combined population with Odds Ratio (OR)<1.38 increased to OR = 2.44, (95%CI = 1.67–3.59) when the risk providing genotypes of TCF7L2, HHEX, ENPP1 and FTO genes were combined, suggesting the importance of gene-gene interactions evaluation in complex disorders like T2D. PMID:23527042

36 h fasting of young men influences adipose tissue DNA methylation of LEP and ADIPOQ in a birth weight-dependent manner.

PubMed

Hjort, Line; Jørgensen, Sine W; Gillberg, Linn; Hall, Elin; Brøns, Charlotte; Frystyk, Jan; Vaag, Allan A; Ling, Charlotte

2017-01-01

Subjects born with low birth weight (LBW) display a more energy-conserving response to fasting compared with normal birth weight (NBW) subjects. However, the molecular mechanisms explaining these metabolic differences remain unknown. Environmental influences may dynamically affect epigenetic marks, also in postnatal life. Here, we aimed to study the effects of short-term fasting on leptin ( LEP ) and adiponectin ( ADIPOQ ) DNA methylation and gene expression in subcutaneous adipose tissue (SAT) from subjects with LBW and NBW. Twenty-one young LBW men and 18 matched NBW controls were studied during 36 h fasting. Eight subjects from each group completed a control study (overnight fast). We analyzed SAT LEP and ADIPOQ methylation (Epityper MassARRAY), gene expression (q-PCR), and adipokine plasma levels. After overnight fast (control study), LEP and ADIPOQ DNA methylation levels were higher in LBW compared to those in NBW subjects ( p  ≤ 0.03) and increased with 36 h fasting in NBW subjects only ( p  ≤ 0.06). Both LEP and ADIPOQ methylation levels were positively associated with total body fat percentage ( p  ≤ 0.05). Plasma leptin levels were higher in LBW versus NBW subjects after overnight fasting ( p  = 0.04) and decreased more than threefold in both groups after 36 h fasting ( p  ≤ 0.0001). This is the first study to demonstrate that fasting induces changes in DNA methylation. This was shown in LEP and ADIPOQ promoters in SAT among NBW but not LBW subjects. The altered epigenetic flexibility in LBW subjects might contribute to their differential response to fasting, adipokine levels, and increased risk of metabolic disease.

Associations of polymorphisms in circadian genes with abdominal obesity in Chinese adult population.

PubMed

Ye, Ding; Cai, Shaofang; Jiang, Xiyi; Ding, Ye; Chen, Kun; Fan, Chunhong; Jin, Mingjuan

2016-09-01

Circadian rhythm, which is controlled by circadian genes, regulates metabolic balance including the circulating levels of glucose, fatty acids, triglycerides, various hormones and so on. The study aimed to investigate the impact of potential polymorphisms in circadian genes on abdominal obesity among Chinese Han adults. A total of 260 cases with abdominal obesity and 260 controls were recruited by individual matching. Demographic characteristics and lifestyle information were collected by a validated questionnaire, and anthropometric parameters was measured by physical examination. Twenty-three single nucleotide polymorphisms (SNPs) in three circadian genes, CLOCK, CRY1 and CRY2, were genotyped by MassArray technique. Five SNPs significantly deviated from Hardy-Weinberg equilibrium (HWE) among controls, so eighteen SNPs were taken into logistic regression analysis. Independently, CLOCK rs10002541 (CC genotype vs. TT genotype: OR: 0.45, 95% CI: 0.23-0.86), CLOCK rs6850524 (CC genotype vs. GG genotype: OR: 0.50, 95% CI: 0.25-0.99) and CRY1 rs10861688 (TT genotype vs. CC genotype: OR: 0.50, 95% CI: 0.25-0.97) were negatively associated with the risk of abdominal obesity. Haplotype analysis showed that the haplotypes of CG and TG for CLOCK rs10002541 and rs4864546 had significant associations with abdominal obesity. Compared with the carriers of TA, those of CG were observed to have a lower risk (OR: 0.74, 95% CI: 0.56-0.99) of abdominal obesity, and those of TG presented a higher risk (OR: 1.70, 95% CI: 1.03-2.81). Our findings suggest that CLOCK and CRY1 polymorphisms might be involved in individual susceptibility to abdominal obesity in Chinese Han population. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

DNA methylation array analysis identifies breast cancer associated RPTOR, MGRN1 and RAPSN hypomethylation in peripheral blood DNA.

PubMed

Tang, Qiuqiong; Holland-Letz, Tim; Slynko, Alla; Cuk, Katarina; Marme, Frederik; Schott, Sarah; Heil, Jörg; Qu, Bin; Golatta, Michael; Bewerunge-Hudler, Melanie; Sutter, Christian; Surowy, Harald; Wappenschmidt, Barbara; Schmutzler, Rita; Hoth, Markus; Bugert, Peter; Bartram, Claus R; Sohn, Christof; Schneeweiss, Andreas; Yang, Rongxi; Burwinkel, Barbara

2016-09-27

DNA methylation changes in peripheral blood DNA have been shown to be associated with solid tumors. We sought to identify methylation alterations in whole blood DNA that are associated with breast cancer (BC). Epigenome-wide DNA methylation profiling on blood DNA from BC cases and healthy controls was performed by applying Infinium HumanMethylation450K BeadChips. Promising CpG sites were selected and validated in three independent larger sample cohorts via MassARRAY EpiTyper assays. CpG sites located in three genes (cg06418238 in RPTOR, cg00736299 in MGRN1 and cg27466532 in RAPSN), which showed significant hypomethylation in BC patients compared to healthy controls in the discovery cohort (p < 1.00 x 10-6) were selected and successfully validated in three independent cohorts (validation I, n =211; validation II, n=378; validation III, n=520). The observed methylation differences are likely not cell-type specific, as the differences were only seen in whole blood, but not in specific sub cell-types of leucocytes. Moreover, we observed in quartile analysis that women in the lower methylation quartiles of these three loci had higher ORs than women in the higher quartiles. The combined AUC of three loci was 0.79 (95%CI 0.73-0.85) in validation cohort I, and was 0.60 (95%CI 0.54-0.66) and 0.62 (95%CI 0.57-0.67) in validation cohort II and III, respectively. Our study suggests that hypomethylation of CpG sites in RPTOR, MGRN1 and RAPSN in blood is associated with BC and might serve as blood-based marker supplements for BC if these could be verified in prospective studies.

Relationship Between Final Performance and Block Times with the Traditional and the New Starting Platforms with A Back Plate in International Swimming Championship 50-M and 100-M Freestyle Events

PubMed Central

Garcia-Hermoso, Antonio; Escalante, Yolanda; Arellano, Raul; Navarro, Fernando; Domínguez, Ana M.; Saavedra, Jose M.

2013-01-01

The purpose of this study was to investigate the association between block time and final performance for each sex in 50-m and 100-m individual freestyle, distinguishing between classification (1st to 3rd, 4th to 8th, 9th to 16th) and type of starting platform (old and new) in international competitions. Twenty-six international competitions covering a 13-year period (2000-2012) were analysed retrospectively. The data corresponded to a total of 1657 swimmers’ competition histories. A two-way ANOVA (sex x classification) was performed for each event and starting platform with the Bonferroni post-hoc test, and another two-way ANOVA for sex and starting platform (sex x starting platform). Pearson’s simple correlation coefficient was used to determine correlations between the block time and the final performance. Finally, a simple linear regression analysis was done between the final time and the block time for each sex and platform. The men had shorter starting block times than the women in both events and from both platforms. For 50-m event, medalists had shorter block times than semi- finalists with the old starting platforms. Block times were directly related to performance with the old starting platforms. With the new starting platforms, however, the relationship was inverse, notably in the women’s 50-m event. The block time was related for final performance in the men’s 50- m event with the old starting platform, but with the new platform it was critical only for the women’s 50-m event. Key Points The men had shorter block times than the women in both events and with both platforms. For both distances, the swimmers had shorter block times in their starts from the new starting platform with a back plate than with the old platform. For the 50-m event with the old starting platform, the medalists had shorter block times than the semi-finalists. The new starting platform block time was only determinant in the women’s 50-m event. In order to improve performance, specific training with the new platform with a back plate should be considered. PMID:24421729

Floating production platforms and their applications in the development of oil and gas fields in the South China Sea

NASA Astrophysics Data System (ADS)

Zhang, Dagang; Chen, Yongjun; Zhang, Tianyu

2014-03-01

This paper studies the current available options for floating production platforms in developing deepwater oil fields and the potential development models of future oil and gas exploration in the South China Sea. A detailed review of current deepwater platforms worldwide was performed through the examples of industry projects, and the pros and cons of each platform are discussed. Four types of platforms are currently used for the deepwater development: tension leg platform, Spar, semi-submersible platform, and the floating production system offloading. Among these, the TLP and Spar can be used for dry tree applications, and have gained popularity in recent years. The dry tree application enables the extension of the drilling application for fixed platforms into floating systems, and greatly reduces the cost and complexity of the subsea operation. Newly built wet tree semi-submersible production platforms for ultra deepwater are also getting their application, mainly due to the much needed payload for deepwater making the conversion of the old drilling semi-submersible platforms impossible. These platforms have been used in different fields around the world for different environments; each has its own advantages and disadvantages. There are many challenges with the successful use of these floating platforms. A lot of lessons have been learned and extensive experience accumulated through the many project applications. Key technologies are being reviewed for the successful use of floating platforms for field development, and potential future development needs are being discussed. Some of the technologies and experience of platform applications can be well used for the development of the South China Sea oil and gas field.

Impacts from Partial Removal of Decommissioned Oil and Gas Platforms on Fish Biomass and Production on the Remaining Platform Structure and Surrounding Shell Mounds.

PubMed

Claisse, Jeremy T; Pondella, Daniel J; Love, Milton; Zahn, Laurel A; Williams, Chelsea M; Bull, Ann S

2015-01-01

When oil and gas platforms become obsolete they go through a decommissioning process. This may include partial removal (from the surface to 26 m depth) or complete removal of the platform structure. While complete removal would likely eliminate most of the existing fish biomass and associated secondary production, we find that the potential impacts of partial removal would likely be limited on all but one platform off the coast of California. On average 80% of fish biomass and 86% of secondary fish production would be retained after partial removal, with above 90% retention expected for both metrics on many platforms. Partial removal would likely result in the loss of fish biomass and production for species typically found residing in the shallow portions of the platform structure. However, these fishes generally represent a small proportion of the fishes associated with these platforms. More characteristic of platform fauna are the primarily deeper-dwelling rockfishes (genus Sebastes). "Shell mounds" are biogenic reefs that surround some of these platforms resulting from an accumulation of mollusk shells that have fallen from the shallow areas of the platforms mostly above the depth of partial removal. We found that shell mounds are moderately productive fish habitats, similar to or greater than natural rocky reefs in the region at comparable depths. The complexity and areal extent of these biogenic habitats, and the associated fish biomass and production, will likely be reduced after either partial or complete platform removal. Habitat augmentation by placing the partially removed platform superstructure or some other additional habitat enrichment material (e.g., rock boulders) on the seafloor adjacent to the base of partially removed platforms provides additional options to enhance fish production, potentially mitigating reductions in shell mound habitat.

30 CFR 250.904 - What is the Platform Approval Program?

Code of Federal Regulations, 2010 CFR

2010-07-01

... criteria for approval of fixed platforms of a proven design that will be placed in the shallow water areas... of unique design; or a platform being installed in deepwater (> 400 ft.) or a frontier area, you must also meet the requirements of the Platform Verification Program. The requirements of the Platform...

30 CFR 250.912 - What plans must I submit under the Platform Verification Program?

Code of Federal Regulations, 2012 CFR

2012-07-01

... and major members of concrete-gravity and steel-gravity structures; (2) For jacket and floating... Platforms and Structures Platform Verification Program § 250.912 What plans must I submit under the Platform Verification Program? If your platform, associated structure, or major modification meets the criteria in § 250...

30 CFR 250.912 - What plans must I submit under the Platform Verification Program?

Code of Federal Regulations, 2013 CFR

2013-07-01

... and major members of concrete-gravity and steel-gravity structures; (2) For jacket and floating... Platforms and Structures Platform Verification Program § 250.912 What plans must I submit under the Platform Verification Program? If your platform, associated structure, or major modification meets the criteria in § 250...

30 CFR 250.912 - What plans must I submit under the Platform Verification Program?

Code of Federal Regulations, 2014 CFR

2014-07-01

... and major members of concrete-gravity and steel-gravity structures; (2) For jacket and floating... Platforms and Structures Platform Verification Program § 250.912 What plans must I submit under the Platform Verification Program? If your platform, associated structure, or major modification meets the criteria in § 250...

Studying the Effectiveness of an Online Language Learning Platform in China

ERIC Educational Resources Information Center

Baker, Ryan; Wang, Feng; Ma, Zhenjun; Ma, Wei; Zheng, Shiyue

2018-01-01

In this paper we evaluate the effectiveness of an adaptive online learning platform, designed to support Chinese students in learning the English language. The adaptive platform is studied in three studies, where the experimental platform is compared to an alternate, non-adaptive platform, with random assignment to conditions (the adaptive…

Genetic variations in IDH gene as prognosis predictors in TACE-treated hepatocellular carcinoma patients.

PubMed

Zhang, Huiqing; Guo, Xu; Dai, Jingyao; Wu, Yousheng; Ge, Naijian; Yang, Yefa; Ji, Jiansong; Zhang, Hongxin

2014-11-01

Metabolic reprogramming is an important hallmark of cancer cells, including the alterations of activity and expression in tricarboxylic acid (TCA) cycle key enzymes. Previous studies have reported the associations between tumor formation and three core enzymes involved in the TCA cycle. However, the association between functional single nucleotide polymorphisms (SNPs) in one of TCA cycle key gene isocitrate dehydrogenase (IDH) and the overall survival of hepatocellular carcinoma (HCC) patients treated with transcatheter arterial chemoembolization (TACE) has never been investigated. Five functional SNPs in IDH1 and IDH2 genes were genotyped using the Sequenom iPLEX genotyping system in a cohort of 419 unresectable Chinese HCC patients treated with TACE. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the prognosis analysis. We found that SNPs rs12478635 in IDH1 and rs11632348 in IDH2 gene exhibited significant associations with death risk in HCC patients in the dominant model (HR 1.33; 95 % CI 1.02-1.73; P = 0.037) and in recessive model (HR 1.87; 95 % CI 1.27-2.75; P = 0.001), respectively. Moreover, we observed a cumulative effect of these two SNPs on HCC overall survival, indicating a significant trend of death risk increase with increasing number of unfavorable genotypes (P for trend = 0.001). Additionally, our data suggest that unfavorable genotypes of two SNPs may be used as an independent prognostic marker in those with advanced stage and patients with serum AFP <200 μg/L. Our results for the first time suggest that IDH gene polymorphisms may serve as an independent prognostic marker for HCC patients treated with TACE.

No association between apolipoprotein E or N-acetyltransferase 2 gene polymorphisms and age-related hearing loss.

PubMed

Dawes, Piers; Platt, Hazel; Horan, Michael; Ollier, William; Munro, Kevin; Pendleton, Neil; Payton, Antony

2015-01-01

Age-related hearing loss has a genetic component, but there have been limited genetic studies in this field. Both N-acetyltransferase 2 and apolipoprotein E genes have previously been associated. However, these studies have either used small sample sizes, examined a limited number of polymorphisms, or have produced conflicting results. Here we use a haplotype tagging approach to determine association with age-related hearing loss and investigate epistasis between these two genes. Candidate gene association study of a continuous phenotype. We investigated haplotype tagging single nucleotide polymorphisms in the N-acetyltransferase 2 gene and the presence/absence of the apolipoprotein E ε4 allele for association with age-related hearing loss in a cohort of 265 Caucasian elderly volunteers from Greater Manchester, United Kingdom. Hearing phenotypes were generated using principal component analysis of the hearing threshold levels for the better ear (severity, slope, and concavity). Genotype data for the N-acetyltransferase 2 gene was obtained from existing genome-wide association study data from the Illumina 610-Quadv1 chip. Apolipoprotein E genotyping was performed using Sequenom technology. Linear regression analysis was performed using Plink and Stata software. No significant associations (P value, > 0.05) were observed between the N-acetyltransferase 2 or apolipoprotein E gene polymorphisms and any hearing factor. No significant association was observed for epistasis analysis of apolipoprotein E ε4 and the N-acetyltransferase 2 single nucleotide polymorphism rs1799930 (NAT2*6A). We found no evidence to support that either N-acetyltransferase 2 or apolipoprotein E gene polymorphisms are associated with age-related hearing loss in a cohort of 265 elderly volunteers. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

The role of functionally defective rare germline variants of sialic acid acetylesterase in autoimmune Addison's disease

PubMed Central

Gan, Earn H; MacArthur, Katie; Mitchell, Anna L; Pearce, Simon H S

2012-01-01

Background Autoimmune Addison's disease (AAD) is a rare condition with a complex genetic basis. A panel of rare and functionally defective genetic variants in the sialic acid acetylesterase (SIAE) gene has recently been implicated in several common autoimmune conditions. We performed a case–control study to determine whether these rare variants are associated with a rarer condition, AAD. Method We analysed nine SIAE gene variants (W48X, M89V, C196F, C226G, R230W, T312M, Y349C, F404S and R479C) in a United Kingdom cohort of 378 AAD subjects and 387 healthy controls. All samples were genotyped using Sequenom iPlex chemistry to characterise primer extension products. Results A heterozygous rare allele at codon 312 (312*M) was found in one AAD patient (0.13%) but was not detected in the healthy controls. The commoner, functionally recessive variant at codon 89 (89*V) was found to be homozygous in two AAD patients but was only found in the heterozygous state in controls. Taking into account all nine alleles examined, 4/378 (1.06%) AAD patients and 1/387 (0.25%) healthy controls carried the defective SIAE alleles, with a calculated odds ratio of 4.13 (95% CI 0.44–97.45, two-tailed P value 0.212, NS). Conclusion We demonstrated the presence of 89*V homozygotes and the 312*M rare allele in the AAD cohort, but overall, our analysis does not support a role for rare variants in SIAE in the pathogenesis of AAD. However, the relatively small collection of AAD patients limits the power to exclude a small effect. PMID:23011869

Polymorphisms of EpCAM gene and prognosis for non-small-cell lung cancer in Han Chinese

PubMed Central

Yang, Yuefan; Fei, Fei; Song, Yang; Li, Xiaofei; Zhang, Zhipei; Fei, Zhou; Su, Haichuan; Wan, Shaogui

2014-01-01

The epithelial cell adhesion molecule (EpCAM) is overexpressed in a wide variety of human cancers and is associated with patient prognosis, including those with lung cancer. However, the association of single nucleotide polymorphisms (SNPs) in the EpCAM gene with the prognosis for non-small-cell lung cancer (NSCLC) patients has never been investigated. We evaluated the association between two SNPs, rs1126497 and rs1421, in the EpCAM gene and clinical outcomes in a Chinese cohort of 506 NSCLC patients. The SNPs were genotyped using the Sequenom iPLEX genotyping system. Multivariate Cox proportional hazards model and Kaplan–Meier curves were used to assess the association of EpCAM gene genotypes with the prognosis of NSCLC. We found that the non-synonymous SNP rs1126497 was significantly associated with survival. Compared with the CC genotype, the CT+TT genotype was a risk factor for both death (hazard ratio, 1.40; 95% confidence interval [CI], 1.02–1.94; P = 0.040) and recurrence (hazard ratio, 1.34; 95% CI, 1.02–1.77; P = 0.039). However, the SNP rs1421 did not show any significant effect on patient prognosis. Instead, the AG+GG genotype in rs1421 was significantly associated with early T stages (T1/T2) when compared with the AA genotype (odds ratio for late stage = 0.65; 95% CI, 0.44–0.96, P = 0.029). Further stratified analysis showed notable modulating effects of clinical characteristics on the associations between variant genotypes of rs1126497 and NSCLC outcomes. In conclusion, our study indicated that the non-synonymous SNP rs1126497 may be a potential prognostic marker for NSCLC patients. PMID:24304228

Association Analysis of the Ephrin-B2 Gene in African-Americans with End-Stage Renal Disease

PubMed Central

Hicks, Pamela J.; Staten, Jennifer L.; Palmer, Nicholette D.; Langefeld, Carl D.; Ziegler, Julie T.; Keene, Keith L.; Sale, Michele M.; Bowden, Donald W.; Freedman, Barry I.

2008-01-01

Background Genome scans in African-Americans with end-stage renal disease (ESRD) identified linkage on chromosome 13q33 in the region containing the ephrin-B2 ligand (EFNB2) genes. Interactions between the ephrin-B2 receptor and ephrin-B2 ligand play essential roles in renal angiogenesis, blood vessel maturation, and kidney disease. Methods The EFNB2 gene was evaluated as a positional candidate for non-diabetic and diabetic ESRD susceptibility in 1,071 unrelated African-American subjects; 316 with non-diabetic etiologies of ESRD, 394 with type 2 diabetes-associated ESRD and 361 healthy controls. Single nucleotide polymorphism (SNP) genotyping was performed on the Sequenom Mass Array System. Statistical analyses were computed using Dandelion version 1.26, Snpaddmix version 1.4 and Haploview version 3.32. Results Twenty-eight HapMap tag SNPs were genotyped spanning the 39 kilobases (kb) of the EFNB2 coding region, with average spacing of 1.43 kb. Analysis of 710 ESRD patient samples and 361 controls provided no evidence of single SNP associations in either diabetic or non-diabetic ESRD; although nominal evidence of association with all-cause ESRD was observed with a two SNP (p = 0.022) and three SNP (p = 0.023) haplotype, both containing SNPs rs7490924 and rs2391335 in intron 1. Conclusions Although an attractive positional candidate gene, polymorphisms in the EFNB2 gene do not appear to contribute in a substantial way to non-diabetic, diabetic or all-cause ESRD susceptibility in African-Americans. Additional genes within the chromosome 13q33 linkage interval are likely contributors to African-American non-diabetic ESRD. PMID:18580054

Prenatal maternal immune activation causes epigenetic differences in adolescent mouse brain

PubMed Central

Basil, P; Li, Q; Dempster, E L; Mill, J; Sham, P-C; Wong, C C Y; McAlonan, G M

2014-01-01

Epigenetic processes such as DNA methylation have been implicated in the pathophysiology of neurodevelopmental disorders including schizophrenia and autism. Epigenetic changes can be induced by environmental exposures such as inflammation. Here we tested the hypothesis that prenatal inflammation, a recognized risk factor for schizophrenia and related neurodevelopmental conditions, alters DNA methylation in key brain regions linked to schizophrenia, namely the dopamine rich striatum and endocrine regulatory centre, the hypothalamus. DNA methylation across highly repetitive elements (long interspersed element 1 (LINE1) and intracisternal A-particles (IAPs)) were used to proxy global DNA methylation. We also investigated the Mecp2 gene because it regulates transcription of LINE1 and has a known association with neurodevelopmental disorders. Brain tissue was harvested from 6 week old offspring of mice exposed to the viral analog PolyI:C or saline on gestation day 9. We used Sequenom EpiTYPER assay to quantitatively analyze differences in DNA methylation at IAPs, LINE1 elements and the promoter region of Mecp2. In the hypothalamus, prenatal exposure to PolyI:C caused significant global DNA hypomethylation (t=2.44, P=0.019, PolyI:C mean 69.67%, saline mean 70.19%), especially in females, and significant hypomethylation of the promoter region of Mecp2, (t=3.32, P=0.002; PolyI:C mean 26.57%, saline mean 34.63%). IAP methylation was unaltered. DNA methylation in the striatum was not significantly altered. This study provides the first experimental evidence that exposure to inflammation during prenatal life is associated with epigenetic changes, including Mecp2 promoter hypomethylation. This suggests that environmental and genetic risk factors associated with neurodevelopmental disorders may act upon similar pathways. This is important because epigenetic changes are potentially modifiable and their investigation may open new avenues for treatment. PMID:25180573

DNA mismatch repair gene polymorphisms affect survival in pancreatic cancer.

PubMed

Dong, Xiaoqun; Li, Yanan; Hess, Kenneth R; Abbruzzese, James L; Li, Donghui

2011-01-01

DNA mismatch repair (MMR) maintains genomic stability and mediates cellular response to DNA damage. We aim to demonstrate whether MMR genetic variants affect overall survival (OS) in pancreatic cancer. Using the Sequenom method in genomic DNA, we retrospectively genotyped 102 single-nucleotide polymorphisms (SNPs) of 13 MMR genes from 706 patients with pancreatic adenocarcinoma seen at The University of Texas MD Anderson Cancer Center. Association between genotype and OS was evaluated using multivariable Cox proportional hazard regression models. At a false discovery rate of 1% (p ≤ .0015), 15 SNPs of EXO1, MLH1, MSH2, MSH3, MSH6, PMS2, PMS2L3, TP73, and TREX1 in patients with localized disease (n = 333) and 6 SNPs of MSH3, MSH6, and TP73 in patients with locally advanced or metastatic disease (n = 373) were significantly associated with OS. In multivariable Cox proportional hazard regression models, SNPs of EXO1, MSH2, MSH3, PMS2L3, and TP73 in patients with localized disease, MSH2, MSH3, MSH6, and TP73 in patients with locally advanced or metastatic disease, and EXO1, MGMT, MSH2, MSH3, MSH6, PMS2L3, and TP73 in all patients remained significant predictors for OS (p ≤ .0015) after adjusting for all clinical predictors and all SNPs with p ≤ .0015 in single-locus analysis. Sixteen haplotypes of EXO1, MLH1, MSH2, MSH3, MSH6, PMS2, PMS2L3, RECQL, TP73, and TREX1 significantly correlated with OS in all patients (p ≤ .001). MMR gene variants may have potential value as prognostic markers for OS in pancreatic cancer patients.

Genome-wide DNA methylation analysis of pseudohypoparathyroidism patients with GNAS imprinting defects.

PubMed

Rochtus, Anne; Martin-Trujillo, Alejandro; Izzi, Benedetta; Elli, Francesca; Garin, Intza; Linglart, Agnes; Mantovani, Giovanna; Perez de Nanclares, Guiomar; Thiele, Suzanne; Decallonne, Brigitte; Van Geet, Chris; Monk, David; Freson, Kathleen

2016-01-01

Pseudohypoparathyroidism (PHP) is caused by (epi)genetic defects in the imprinted GNAS cluster. Current classification of PHP patients is hampered by clinical and molecular diagnostic overlaps. The European Consortium for the study of PHP designed a genome-wide methylation study to improve molecular diagnosis. The HumanMethylation 450K BeadChip was used to analyze genome-wide methylation in 24 PHP patients with parathyroid hormone resistance and 20 age- and gender-matched controls. Patients were previously diagnosed with GNAS-specific differentially methylated regions (DMRs) and include 6 patients with known STX16 deletion (PHP(Δstx16)) and 18 without deletion (PHP(neg)). The array demonstrated that PHP patients do not show DNA methylation differences at the whole-genome level. Unsupervised clustering of GNAS-specific DMRs divides PHP(Δstx16) versus PHP(neg) patients. Interestingly, in contrast to the notion that all PHP patients share methylation defects in the A/B DMR while only PHP(Δstx16) patients have normal NESP, GNAS-AS1 and XL methylation, we found a novel DMR (named GNAS-AS2) in the GNAS-AS1 region that is significantly different in both PHP(Δstx16) and PHP(neg), as validated by Sequenom EpiTYPER in a larger PHP cohort. The analysis of 58 DMRs revealed that 8/18 PHP(neg) and 1/6 PHP(Δstx16) patients have multi-locus methylation defects. Validation was performed for FANCC and SVOPL DMRs. This is the first genome-wide methylation study for PHP patients that confirmed that GNAS is the most significant DMR, and the presence of STX16 deletion divides PHP patients in two groups. Moreover, a novel GNAS-AS2 DMR affects all PHP patients, and PHP patients seem sensitive to multi-locus methylation defects.

Variant in the RFWD3 gene associated with PATN1, a modifier of leopard complex spotting.

PubMed

Holl, H M; Brooks, S A; Archer, S; Brown, K; Malvick, J; Penedo, M C T; Bellone, R R

2016-02-01

Leopard complex spotting (LP), the result of an incompletely dominant mutation in TRPM1, produces a collection of unique depigmentation patterns in the horse. Although the LP mutation allows for expression of the various patterns, other loci are responsible for modification of the extent of white. Pedigree analysis of families segregating for high levels of patterning indicated a single dominant gene, named Pattern-1 (PATN1), as a major modifier of LP. Linkage analysis in two half-sibling families segregating for PATN1 identified a 15-Mb region on ECA3p that warranted further investigation. Whole transcriptome sequencing of skin samples from horses with and without the PATN1 allele was performed to identify genic SNPs for fine mapping. Two Sequenom assays were utilized to genotype 192 individuals from five LP-carrying breeds. The initial panel highlighted a 1.6-Mb region without a clear candidate gene. In the second round of fine mapping, SNP ECA3:23 658 447T>G in the 3'-UTR of RING finger and WD repeat domain 3 (RFWD3) reached a significance level of P = 1.063 × 10(-39). Sequencing of RFWD3 did not identify any coding polymorphisms specific to PATN1 horses. Genotyping of the RFWD3 3'-UTR SNP in 54 additional LP animals and 327 horses from nine breeds not segregating for LP further supported the association (P = 4.17 × 10(-115)). This variant is a strong candidate for PATN1 and may be particularly useful for LP breeders to select for high levels of white patterning. © 2015 Stichting International Foundation for Animal Genetics.

Platform C North Installation

NASA Image and Video Library

2016-11-10

A heavy-lift crane lifts the second half of the C-level work platforms, C north, for NASA’s Space Launch System (SLS) rocket, high up from the transfer aisle of the Vehicle Assembly Building (VAB) at NASA's Kennedy Space Center in Florida. The C platform will be moved into High Bay 3 for installation on the north side of High Bay 3. The C platforms are the eighth of 10 levels of work platforms that will surround and provide access to the SLS rocket and Orion spacecraft for Exploration Mission 1. In view below Platform C are several of the previously installed platforms. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to VAB High Bay 3, including installation of the new work platforms, to prepare for NASA’s Journey to Mars.

Carbonate Platform Development and Stromatolite Morphogenesis: Constraints on Environmental and Biological Evolution

NASA Technical Reports Server (NTRS)

Grotzinger, John P.

2003-01-01

Work has been completed on the digital mapping of a terminal Proterozoic reef complex in Namibia. This complex formed an isolated carbonate platform developed downdip on a carbonate ramp of the Nama Group. The stratigraphic evolution of the platform was digitally reconstructed from an extensive dataset that was compiled by using digital surveying technologies. The platform comprises three accommodation cycles in which each subsequent cycle experienced progressively greater influence of a long-term accommodation increase. Aggradation and progradation during the first cycle resulted in a flat, uniform, sheet-like platform. The coarsening and shallowing-upward sequence representing the first cycle is dominated by columnar stromatolitic thrombolites and massive dolostones with interbedded mudstone-grainstone at the base of the sequence grading into cross-bedded dolostones. The second cycle features aggradation, formation of a distinct margin containing thrombolite mounds and domes, and the development of a bucket geometry. Columnar stromatolitic thrombolites dominate the platform interior. The final stage of platform development shows a deepening trend with initial aggradation and formation of well-bedded, thin deposits in the interior and mound development at the margins. While the interior drowned, the platform margin kept up with rising sea level and a complex pinnacle reef formed containing fused and coalesced thrombolite mounds flanked by bioclastic grainstones (containing Cloudina and Namacalathus fossils) and collapse breccias. A set of isolated large thrombolite mounds flanked by shales indicate the final stage of the carbonate platform. During a progressive increase in accommodation, a flat-topped isolated carbonate platform becomes aerially less extensive by either backstepping or formation of smaller pinnacles or a combination of both. The overall geometric evolution of the studied platform from flat-topped to bucket with elevated margins is recorded in many Proterozoic and Phanerozoic isolated carbonate platforms with similar dimensions. The terminal Proterozoic, microbial-dominated, isolated carbonate platform of this study clearly illustrates that the answer to accommodation changes was already familiar among carbonate platforms before the dawn of metazoan-dominated platforms.

Analysis of Human Plasma Metabolites across Different Liquid Chromatography - Mass Spectrometry Platforms: Cross-platform Transferable Chemical Signatures

PubMed Central

Telu, Kelly H.; Yan, Xinjian; Wallace, William E.; Stein, Stephen E.; Simón-Manso, Yamil

2016-01-01

RATIONALE The metabolite profiling of a NIST plasma Standard Reference Material (SRM 1950) on different LC-MS platforms showed significant differences. Although these findings suggest caution when interpreting metabolomics results, the degree of overlap of both profiles allowed us to use tandem mass spectral libraries of recurrent spectra to evaluate to what extent these results are transferable across platforms and to develop cross-platform chemical signatures. METHODS Non-targeted global metabolite profiles of SRM 1950 were obtained on different LC-MS platforms using reversed phase chromatography and different chromatographic scales (nano, conventional and UHPLC). The data processing and the metabolite differential analysis were carried out using publically available (XCMS), proprietary (Mass Profiler Professional) and in-house software (NIST pipeline). RESULTS Repeatability and intermediate precision showed that the non-targeted SRM 1950 profiling was highly reproducible when working on the same platform (RSD < 2%); however, substantial differences were found in the LC-MS patterns originating on different platforms or even using different chromatographic scales (conventional HPLC, UHPLC and nanoLC) on the same platform. A substantial degree of overlap (common molecular features) was also found. A procedure to generate consistent chemical signatures using tandem mass spectral libraries of recurrent spectra is proposed. CONLUSIONS Different platforms rendered significantly different metabolite profiles, but the results were highly reproducible when working within one platform. Tandem mass spectral libraries of recurrent spectra are proposed to evaluate the degree of transferability of chemical signatures generated on different platforms. Chemical signatures based on our procedure are most likely cross-platform transferable. PMID:26842580

Autonomous self-organizing resource manager for multiple networked platforms

NASA Astrophysics Data System (ADS)

Smith, James F., III

2002-08-01

A fuzzy logic based expert system for resource management has been developed that automatically allocates electronic attack (EA) resources in real-time over many dissimilar autonomous naval platforms defending their group against attackers. The platforms can be very general, e.g., ships, planes, robots, land based facilities, etc. Potential foes the platforms deal with can also be general. This paper provides an overview of the resource manager including the four fuzzy decision trees that make up the resource manager; the fuzzy EA model; genetic algorithm based optimization; co-evolutionary data mining through gaming; and mathematical, computational and hardware based validation. Methods of automatically designing new multi-platform EA techniques are considered. The expert system runs on each defending platform rendering it an autonomous system requiring no human intervention. There is no commanding platform. Instead the platforms work cooperatively as a function of battlespace geometry; sensor data such as range, bearing, ID, uncertainty measures for sensor output; intelligence reports; etc. Computational experiments will show the defending networked platform's ability to self- organize. The platforms' ability to self-organize is illustrated through the output of the scenario generator, a software package that automates the underlying data mining problem and creates a computer movie of the platforms' interaction for evaluation.

Analysis of the Motion Control Methods for Stratospheric Balloon-Borne Gondola Platform

NASA Astrophysics Data System (ADS)

Wang, H. H.; Yuan, Z. H.; Wu, J.

2006-10-01

At present, gondola platform is one of the stratospheric balloon-borne platforms being in research focus at home and overseas. Comparing to other stratospheric balloon-borne platforms, such as airship platform, gondola platform has advantages of higher stability, rapid in motion regulation and lower energy cost but disadvantages of less supporting capacity and be incapable of fixation. While all platforms have the same goal of keeping them at accurate angle and right pose for the requirements of instruments and objects installed in the platforms, when platforms rotate round the ground level perpendicular. That is accomplishing motion control. But, platform control system has factors of low damper, excessive and uncertain disturbances by the reason of its being hung over balloon in the air, it is hard to achieve the desired control precision because platform is ease to deviate its benchmark motion. Thus, in the controlling procedure in order to get higher precision, it is crucial to perceive the platform's swing synchronously and rapidly, and restrain the influence of disturbances effectively, keep the platform's pose steadily. Furthermore, while the platform in the air regard control center in the ground as reference object, it is ultimate to select a appropriate reference frame and work out the coordinates and implement the adjustment by the PC104 controller. This paper introduces the methods of the motion control based on stratospheric balloon-borne gondola platform. Firstly, this paper compares the characteristic of the flywheel and CMG and specifies the key methods of obtaining two significant states which are 'orientation stability' state and 'orientation tracking' state for platform motion control procedure using CMG as the control actuator. These two states reduce the deviation amplitude of rotation and swing of gondola's motion relative to original motion due to stratospheric intense atmosphere disturbance. We define it as the first procedure. In next procedure, we use the transfer matrix of earth reference frame to geographic reference frame to transform the data measured by the magnetic orientation sensors and the gyroscope to the space orientations, then the PC104 controller use the space orientations value as feedback to complete revises.

UAH/NASA Workshop on Space Science Platform

NASA Technical Reports Server (NTRS)

Wu, S. T. (Editor); Morgan, S. (Editor)

1978-01-01

The scientific user requirements for a space science platform were defined. The potential user benefits, technological implications and cost of space platforms were examined. Cost effectiveness of the platforms' capabilities were also examined.

77 FR 32644 - Medical Devices; Exemption From Premarket Notification: Wheelchair Elevator

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-01

... elevator devices commonly known as inclined platform lifts and vertical platform lifts. These devices are... inclined platform lifts and vertical platform lifts), classified under 21 CFR 890.3930. IV. Comments...

Platform C Installation

NASA Image and Video Library

2016-10-19

A heavy-lift crane lowers the first half of the C-level work platforms, C south, for NASA’s Space Launch System (SLS) rocket, for installation on the south side of High Bay 3 in the Vehicle Assembly Building (VAB) at NASA’s Kennedy Space Center in Florida. The C platforms are the eighth of 10 levels of work platforms that will surround and provide access to the SLS rocket and Orion spacecraft for Exploration Mission 1. In view below Platform C are several of the previously installed platforms. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to VAB High Bay 3, including installation of the new work platforms, to prepare for NASA’s Journey to Mars.

Assembly Platform For Use In Outer Space

NASA Technical Reports Server (NTRS)

Rao, Niranjan S.; Buddington, Patricia A.

1995-01-01

Report describes conceptual platform or framework for use in assembling other structures and spacecraft in outer space. Consists of three fixed structural beams comprising central beam and two cross beams. Robotic manipulators spaced apart on platform to provide telerobotic operation of platform by either space-station or ground crews. Platform and attached vehicles function synergistically to achieve maximum performance for intended purposes.

What Counts as Writing? An Examination of Students' Use of Social Media Platforms as Alternative Authoring Paths

ERIC Educational Resources Information Center

Stewart, Olivia Grace

2017-01-01

In this article-style dissertation, I explore how students used digital technologies, specifically three social media platforms, as multimodal writing platforms while creating a digital portfolio in a senior English class. These platforms are 1) Weebly pages: a website building platform, 2) Weebly Blogs: a feature of Weebly, and 3) Instagram: a…

Geostationary platform systems concepts definition study. Volume 2: Technical, book 1

NASA Technical Reports Server (NTRS)

1980-01-01

The initial selection and definition of operational geostationary platform concepts is discussed. Candidate geostationary platform missions and payloads were identified from COMSAT, Aerospace, and NASA studies. These missions and payloads were cataloged; classified with to communications, military, or scientific uses; screened for application and compatibility with geostationary platforms; and analyzed to identify platform requirements. Two platform locations were then selected (Western Hemisphere - 110 deg W, and Atlantic - 15 deg W), and payloads allocated based on nominal and high traffic models. Trade studies were performed leading to recommendation of selected concepts. Of 30 Orbit Transfer Vehicle (0TV) configuration and operating mode options identified, 18 viable candidates compatible with the operational geostationary platform missions were selected for analysis. Each was considered using four platform operational modes - 8 or 16 year life, and serviced or nonserviced, providing a total of 72 OTV/platform-mode options. For final trade study concept selection, a cost program was developed considering payload and platform costs and weight; transportation unit and total costs for the shuttle and OTV; and operational costs such as assembly or construction time, mating time, and loiter time. Servicing costs were added for final analysis and recommended selection.

Development and Validation of an Interactive Internet Platform for Older People: The Healthy Ageing Through Internet Counselling in the Elderly Study.

PubMed

Jongstra, Susan; Beishuizen, Cathrien; Andrieu, Sandrine; Barbera, Mariagnese; van Dorp, Matthijs; van de Groep, Bram; Guillemont, Juliette; Mangialasche, Francesca; van Middelaar, Tessa; Moll van Charante, Eric; Soininen, Hilkka; Kivipelto, Miia; Richard, Edo

2017-02-01

A myriad of Web-based applications on self-management have been developed, but few focus on older people. In the face of global aging, older people form an important target population for cardiovascular prevention. This article describes the full development of an interactive Internet platform for older people, which was designed for the Healthy Ageing Through Internet Counselling in the Elderly (HATICE) study. We provide recommendations to design senior-friendly Web-based applications for a new approach to multicomponent cardiovascular prevention. The development of the platform followed five phases: (1) conceptual framework; (2) platform concept and functional design; (3) platform building (software and content); (4) testing and pilot study; and (5) final product. We performed a meta-analysis, reviewed guidelines for cardiovascular diseases, and consulted end users, experts, and software developers to create the platform concept and content. The software was built in iterative cycles. In the pilot study, 41 people aged ≥65 years used the platform for 8 weeks. Participants used the interactive features of the platform and appreciated the coach support. During all phases adjustments were made to incorporate all improvements from the previous phases. The final platform is a personal, secured, and interactive platform supported by a coach. When carefully designed, an interactive Internet platform is acceptable and feasible for use by older people with basic computer skills. To improve acceptability by older people, we recommend involving the end users in the process of development, to personalize the platform and to combine the application with human support. The interactive HATICE platform will be tested for efficacy in a multinational randomized controlled trial (ISRCTN48151589).

Analysis of human plasma metabolites across different liquid chromatography/mass spectrometry platforms: Cross-platform transferable chemical signatures.

PubMed

Telu, Kelly H; Yan, Xinjian; Wallace, William E; Stein, Stephen E; Simón-Manso, Yamil

2016-03-15

The metabolite profiling of a NIST plasma Standard Reference Material (SRM 1950) on different liquid chromatography/mass spectrometry (LC/MS) platforms showed significant differences. Although these findings suggest caution when interpreting metabolomics results, the degree of overlap of both profiles allowed us to use tandem mass spectral libraries of recurrent spectra to evaluate to what extent these results are transferable across platforms and to develop cross-platform chemical signatures. Non-targeted global metabolite profiles of SRM 1950 were obtained on different LC/MS platforms using reversed-phase chromatography and different chromatographic scales (conventional HPLC, UHPLC and nanoLC). The data processing and the metabolite differential analysis were carried out using publically available (XCMS), proprietary (Mass Profiler Professional) and in-house software (NIST pipeline). Repeatability and intermediate precision showed that the non-targeted SRM 1950 profiling was highly reproducible when working on the same platform (relative standard deviation (RSD) <2%); however, substantial differences were found in the LC/MS patterns originating on different platforms or even using different chromatographic scales (conventional HPLC, UHPLC and nanoLC) on the same platform. A substantial degree of overlap (common molecular features) was also found. A procedure to generate consistent chemical signatures using tandem mass spectral libraries of recurrent spectra is proposed. Different platforms rendered significantly different metabolite profiles, but the results were highly reproducible when working within one platform. Tandem mass spectral libraries of recurrent spectra are proposed to evaluate the degree of transferability of chemical signatures generated on different platforms. Chemical signatures based on our procedure are most likely cross-platform transferable. Published in 2016. This article is a U.S. Government work and is in the public domain in the USA.

Potential Fish Production Impacts from Partial Removal of Decommissioned Oil and Gas Platforms off the Coast of California

NASA Astrophysics Data System (ADS)

Claisse, J.; Pondella, D.; Love, M.; Zahn, L.; Williams, C.; Bull, A. S.

2016-02-01

When oil and gas platforms become obsolete they go through a decommissioning process. This may include partial removal (from the surface to 26 m depth) or complete removal of the platform structure. While complete removal would likely eliminate most of the existing fish biomass and associated secondary production, we find that the potential impacts of partial removal would likely be limited on all but one platform off the coast of California. On average 80% of fish biomass and 86% of secondary fish production would be retained after partial removal, with above 90% retention expected for both metrics on many platforms. Partial removal would likely result in the loss of fish biomass and production for species typically found residing in the shallow portions of the platform structure. However, these fishes generally represent a small proportion of the fishes associated with these platforms. More characteristic of platform fauna are the primarily deeper-dwelling rockfishes (genus Sebastes). "Shell mounds" are biogenic reefs that surround some of these platforms resulting from an accumulation of mollusk shells that have fallen from the shallow areas of the platforms mostly above the depth of partial removal. We found that shell mounds are moderately productive fish habitats, similar to or greater than natural rocky reefs in the region at comparable depths. The complexity and areal extent of these biogenic habitats, and the associated fish biomass and production, will likely be reduced after either partial or complete platform removal. Habitat augmentation by placing the partially removed platform superstructure or some other additional habitat enrichment material (e.g., rock boulders) on the seafloor adjacent to the base of partially removed platforms provides additional options to enhance fish production, potentially mitigating reductions in shell mound habitat.

Advanced propulsion for LEO and GEO platforms

NASA Technical Reports Server (NTRS)

Sovey, James S.; Pidgeon, David J.

1990-01-01

Mission requirements and mass savings applicable to specific low earth orbit and geostationary earth orbit platforms using three highly developed propulsion systems are described. Advanced hypergolic bipropellant thrusters and hydrazine arcjets can provide about 11 percent additional instrument payload to 14,000 kg LEO platforms. By using electric propulsion on a 8,000 kg class GEO platform, mass savings in excess of 15 percent of the beginning-of-life platform mass are obtained. Effects of large, advanced technology solar arrays and antennas on platform propulsion requirements are also discussed.

System for damping vibrations in a turbine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roberts, III, Herbert Chidsey; Johnson, Curtis Alan; Taxacher, Glenn Curtis

2015-11-24

A system for damping vibrations in a turbine includes a first rotating blade having a first ceramic airfoil, a first ceramic platform connected to the first ceramic airfoil, and a first root connected to the first ceramic platform. A second rotating blade adjacent to the first rotating blade includes a second ceramic airfoil, a second ceramic platform connected to the second ceramic airfoil, and a second root connected to the second ceramic platform. A non-metallic platform damper has a first position in simultaneous contact with the first and second ceramic platforms.

Urban search mobile platform modeling in hindered access conditions

NASA Astrophysics Data System (ADS)

Barankova, I. I.; Mikhailova, U. V.; Kalugina, O. B.; Barankov, V. V.

2018-05-01

The article explores the control system simulation and the design of the experimental model of the rescue robot mobile platform. The functional interface, a structural functional diagram of the mobile platform control unit, and a functional control scheme for the mobile platform of secure robot were modeled. The task of design a mobile platform for urban searching in hindered access conditions is realized through the use of a mechanical basis with a chassis and crawler drive, a warning device, human heat sensors and a microcontroller based on Arduino platforms.

Gesture therapy: an upper limb virtual reality-based motor rehabilitation platform.

PubMed

Sucar, Luis Enrique; Orihuela-Espina, Felipe; Velazquez, Roger Luis; Reinkensmeyer, David J; Leder, Ronald; Hernández-Franco, Jorge

2014-05-01

Virtual reality platforms capable of assisting rehabilitation must provide support for rehabilitation principles: promote repetition, task oriented training, appropriate feedback, and a motivating environment. As such, development of these platforms is a complex process which has not yet reached maturity. This paper presents our efforts to contribute to this field, presenting Gesture Therapy, a virtual reality-based platform for rehabilitation of the upper limb. We describe the system architecture and main features of the platform and provide preliminary evidence of the feasibility of the platform in its current status.

Coverage Bias and Sensitivity of Variant Calling for Four Whole-genome Sequencing Technologies

PubMed Central

Lasitschka, Bärbel; Jones, David; Northcott, Paul; Hutter, Barbara; Jäger, Natalie; Kool, Marcel; Taylor, Michael; Lichter, Peter; Pfister, Stefan; Wolf, Stephan; Brors, Benedikt; Eils, Roland

2013-01-01

The emergence of high-throughput, next-generation sequencing technologies has dramatically altered the way we assess genomes in population genetics and in cancer genomics. Currently, there are four commonly used whole-genome sequencing platforms on the market: Illumina’s HiSeq2000, Life Technologies’ SOLiD 4 and its completely redesigned 5500xl SOLiD, and Complete Genomics’ technology. A number of earlier studies have compared a subset of those sequencing platforms or compared those platforms with Sanger sequencing, which is prohibitively expensive for whole genome studies. Here we present a detailed comparison of the performance of all currently available whole genome sequencing platforms, especially regarding their ability to call SNVs and to evenly cover the genome and specific genomic regions. Unlike earlier studies, we base our comparison on four different samples, allowing us to assess the between-sample variation of the platforms. We find a pronounced GC bias in GC-rich regions for Life Technologies’ platforms, with Complete Genomics performing best here, while we see the least bias in GC-poor regions for HiSeq2000 and 5500xl. HiSeq2000 gives the most uniform coverage and displays the least sample-to-sample variation. In contrast, Complete Genomics exhibits by far the smallest fraction of bases not covered, while the SOLiD platforms reveal remarkable shortcomings, especially in covering CpG islands. When comparing the performance of the four platforms for calling SNPs, HiSeq2000 and Complete Genomics achieve the highest sensitivity, while the SOLiD platforms show the lowest false positive rate. Finally, we find that integrating sequencing data from different platforms offers the potential to combine the strengths of different technologies. In summary, our results detail the strengths and weaknesses of all four whole-genome sequencing platforms. It indicates application areas that call for a specific sequencing platform and disallow other platforms. This helps to identify the proper sequencing platform for whole genome studies with different application scopes. PMID:23776689

Impacts from Partial Removal of Decommissioned Oil and Gas Platforms on Fish Biomass and Production on the Remaining Platform Structure and Surrounding Shell Mounds

PubMed Central

Claisse, Jeremy T.; Pondella, Daniel J.; Love, Milton; Zahn, Laurel A.; Williams, Chelsea M.; Bull, Ann S.

2015-01-01

When oil and gas platforms become obsolete they go through a decommissioning process. This may include partial removal (from the surface to 26 m depth) or complete removal of the platform structure. While complete removal would likely eliminate most of the existing fish biomass and associated secondary production, we find that the potential impacts of partial removal would likely be limited on all but one platform off the coast of California. On average 80% of fish biomass and 86% of secondary fish production would be retained after partial removal, with above 90% retention expected for both metrics on many platforms. Partial removal would likely result in the loss of fish biomass and production for species typically found residing in the shallow portions of the platform structure. However, these fishes generally represent a small proportion of the fishes associated with these platforms. More characteristic of platform fauna are the primarily deeper-dwelling rockfishes (genus Sebastes). “Shell mounds” are biogenic reefs that surround some of these platforms resulting from an accumulation of mollusk shells that have fallen from the shallow areas of the platforms mostly above the depth of partial removal. We found that shell mounds are moderately productive fish habitats, similar to or greater than natural rocky reefs in the region at comparable depths. The complexity and areal extent of these biogenic habitats, and the associated fish biomass and production, will likely be reduced after either partial or complete platform removal. Habitat augmentation by placing the partially removed platform superstructure or some other additional habitat enrichment material (e.g., rock boulders) on the seafloor adjacent to the base of partially removed platforms provides additional options to enhance fish production, potentially mitigating reductions in shell mound habitat. PMID:26332384

Marine communities on oil platforms in Gabon, West Africa: high biodiversity oases in a low biodiversity environment.

PubMed

Friedlander, Alan M; Ballesteros, Enric; Fay, Michael; Sala, Enric

2014-01-01

The marine biodiversity of Gabon, West Africa has not been well studied and is largely unknown. Our examination of marine communities associated with oil platforms in Gabon is the first scientific investigation of these structures and highlights the unique ecosystems associated with them. A number of species previously unknown to Gabonese waters were recorded during our surveys on these platforms. Clear distinctions in benthic communities were observed between older, larger platforms in the north and newer platforms to the south or closer to shore. The former were dominated by a solitary cup coral, Tubastraea sp., whereas the latter were dominated by the barnacle Megabalanus tintinnabulum, but with more diverse benthic assemblages compared to the northerly platforms. Previous work documented the presence of limited zooxanthellated scleractinian corals on natural rocky substrate in Gabon but none were recorded on platforms. Total estimated fish biomass on these platforms exceeded one ton at some locations and was dominated by barracuda (Sphyraena spp.), jacks (Carangids), and rainbow runner (Elagatis bipinnulata). Thirty-four percent of fish species observed on these platforms are new records for Gabon and 6% are new to tropical West Africa. Fish assemblages closely associated with platforms had distinct amphi-Atlantic affinities and platforms likely extend the distribution of these species into coastal West Africa. At least one potential invasive species, the snowflake coral (Carijoa riisei), was observed on the platforms. Oil platforms may act as stepping stones, increasing regional biodiversity and production but they may also be vectors for invasive species. Gabon is a world leader in terrestrial conservation with a network of protected areas covering >10% of the country. Oil exploration and biodiversity conservation currently co-exist in terrestrial and freshwater ecosystems in Gabon. Efforts to increase marine protection in Gabon may benefit by including oil platforms in the marine protected area design process.

Floor Plans Level 15 Load Platform, Level 17 Lower ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Floor Plans - Level 15 Load Platform, Level 17 Lower Platform, Level 22 and Upper Platform, and Level 27 - Marshall Space Flight Center, Saturn V S-IC Static Test Facility, West Test Area, Huntsville, Madison County, AL

Design and control of multifunctional sorting and training platform based on PLC control

NASA Astrophysics Data System (ADS)

Wan, Hongqiang; Ge, Shuai; Han, Peiying; Li, Fancong; Zhang, Simiao

2018-05-01

Electromechanical integration, as a multi-disciplinary subject, has been paid much attention by universities and is widely used in the automation production of enterprises. Aiming at the problem of the lack of control among enterprises and the lack of training among colleges and universities, this paper presents a design of multifunctional sorting training platform based on PLC control. Firstly, the structure of the platform is determined and three-dimensional modeling is done. Then design the platform's aerodynamic control and electrical control. Finally, realize the platform sorting function through PLC programming and configuration software development. The training platform can be used to design the practical training experiment, which has a strong advance and pertinence in the electromechanical integration teaching. At the same time, the platform makes full use of modular thinking to make the sorting modules more flexible. Compared with the traditional training platform, its teaching effect is more significant.

Turbine engine airfoil and platform assembly

DOEpatents

Campbell, Christian X [Oviedo, FL; James, Allister W [Chuluota, FL; Morrison, Jay A [Oviedo, FL

2012-07-31

A turbine airfoil (22A) is formed by a first process using a first material. A platform (30A) is formed by a second process using a second material that may be different from the first material. The platform (30A) is assembled around a shank (23A) of the airfoil. One or more pins (36A) extend from the platform into holes (28) in the shank (23A). The platform may be formed in two portions (32A, 34A) and placed around the shank, enclosing it. The two platform portions may be bonded to each other. Alternately, the platform (30B) may be cast around the shank (23B) using a metal alloy with better castability than that of the blade and shank, which may be specialized for thermal tolerance. The pins (36A-36D) or holes for them do not extend to an outer surface (31) of the platform, avoiding stress concentrations.

Improvement in the amine glass platform by bubbling method for a DNA microarray

PubMed Central

Jee, Seung Hyun; Kim, Jong Won; Lee, Ji Hyeong; Yoon, Young Soo

2015-01-01

A glass platform with high sensitivity for sexually transmitted diseases microarray is described here. An amino-silane-based self-assembled monolayer was coated on the surface of a glass platform using a novel bubbling method. The optimized surface of the glass platform had highly uniform surface modifications using this method, as well as improved hybridization properties with capture probes in the DNA microarray. On the basis of these results, the improved glass platform serves as a highly reliable and optimal material for the DNA microarray. Moreover, in this study, we demonstrated that our glass platform, manufactured by utilizing the bubbling method, had higher uniformity, shorter processing time, lower background signal, and higher spot signal than the platforms manufactured by the general dipping method. The DNA microarray manufactured with a glass platform prepared using bubbling method can be used as a clinical diagnostic tool. PMID:26468293

Improvement in the amine glass platform by bubbling method for a DNA microarray.

PubMed

Jee, Seung Hyun; Kim, Jong Won; Lee, Ji Hyeong; Yoon, Young Soo

2015-01-01

A glass platform with high sensitivity for sexually transmitted diseases microarray is described here. An amino-silane-based self-assembled monolayer was coated on the surface of a glass platform using a novel bubbling method. The optimized surface of the glass platform had highly uniform surface modifications using this method, as well as improved hybridization properties with capture probes in the DNA microarray. On the basis of these results, the improved glass platform serves as a highly reliable and optimal material for the DNA microarray. Moreover, in this study, we demonstrated that our glass platform, manufactured by utilizing the bubbling method, had higher uniformity, shorter processing time, lower background signal, and higher spot signal than the platforms manufactured by the general dipping method. The DNA microarray manufactured with a glass platform prepared using bubbling method can be used as a clinical diagnostic tool.

Risk Management of P2P Internet Financing Service Platform

NASA Astrophysics Data System (ADS)

Yalei, Li

2017-09-01

Since 2005, the world’s first P2P Internet financing service platform Zopa in UK was introduced, in the development of “Internet +” trend, P2P Internet financing service platform has been developed rapidly. In 2007, China’s first P2P platform “filming loan” was established, marking the P2P Internet financing service platform to enter China and the rapid development. At the same time, China’s P2P Internet financing service platform also appeared in different forms of risk. This paper focuses on the analysis of the causes of risk of P2P Internet financing service platform and the performance of risk management process. It provides a solution to the Internet risk management plan, and explains the risk management system of the whole P2P Internet financing service platform and the future development direction.

Cretaceous tropical carbonate platform changes used as paleoclimatic and paleoceanic indicators: the three lower Cretaceous platform crises

NASA Astrophysics Data System (ADS)

Arnaud-Vanneau, A.; Vrielynck, B.

2009-04-01

Carbonate platform sediments are of biogenic origin. More commonly the bioclasts are fragments of shells and skeletons. The bioclastic composition of a limestone may reflect the nature of biota inhabiting the area and a carbonate platform can be estimated as a living factory, which reflects the prevailing ecological factors. The rate of carbonate production is highest in the tropics, in oligotrophic environments, and in the photic zone. The rate of carbonate production varies greatly with temperature and nutrient input. Three types of biotic carbonate platform can be distinguished. The highest carbonate production is linked to oligotrophic carbonate platform characterized by the presence of assemblages with hermatypic corals. This type of platform is developed in shallow marine environment, nutrient poor water and warm tropical sea. A less efficient production of carbonate platform is related to mesotrophic environments in cooler and/or deeper water and associated to nutrient flux with, sometime, detrital input. The biota includes red algae, solitary coral and branching ahermatypic corals, common bryozoans, crinoids and echinoids. The less productive carbonate platform is the eutrophic muddy platform where the mud is due to the intense bacterial activity, probably related to strong nutrient flux. All changes of type of carbonate platform can be related to climatic and oceanic changes. Three platform crises occurred during lower Cretaceous time. They are followed by important turnover of microfauna (large benthic foraminifers) and microflora (marine algae). They start with the demise of the previous oligotrophic platform, they continue with oceanic perturbations, expression of which was the widespread deposition of organic-rich sediments, well expressed during Late Aptian/Albian and Cenomanian Turonian boundary and the replacement of previous oligotrophic platforms by mesotrophic to eutrophic platforms. The first crisis occurred during Valanginian and Hauterivian time and is related to the opening of the North Atlantic and the neocimerian tectonic phase. It could be linked to cooling periods. Geographically, the warm oligotrophic tropical carbonate platforms of the northern Tethyan margin migrated towards the equator from more than 500kms. The Upper Valanginian-Hauterivian mesotrophic to eutrophic carbonate platforms are muddier and microbially dominated (algal mats, oolites). 60% of benthic foraminifers living in carbonate platform became extinct. The second crisis occurred during Late Aptian to Albian time. It is coeval to the increasing plate movement and the opening of the central Atlantic Ocean. It is linked to massive detrital input on both margins of the Tethys. Tropical carbonate platform are mostly mesotrophic to eutrophic with abundance of opportunistic species such as Orbitolina, which took advantage of abundance of clastic grains. 50% of benthic foraminifers living in carbonate platform became extinct. The last crisis coincides with the Cenomanian-Turonian boundary. This period corresponds to a rapid northward movement of Africa and Spain and the opening of the North-South Atlantic connection. At the boundary we note the disappearance of organisms such as large benthic foraminifers, corals and rudists, which had a symbiotic relationship with green algae. More than 90% of large benthic foraminifers living in carbonate platform became extinct, but this extinction is not available for small size benthic foraminifers, which had not symbiosis.

Mobility platform coupling device and method for coupling mobility platforms

DOEpatents

Shirey, David L.; Hayward, David R.; Buttz, James H.

2002-01-01

A coupling device for connecting a first mobility platform to a second mobility platform in tandem. An example mobility platform is a robot. The coupling device has a loose link mode for normal steering conditions and a locking position, tight link mode for navigation across difficult terrain and across obstacles, for traversing chasms, and for navigating with a reduced footprint in tight steering conditions.

Stabilized floating platforms

DOEpatents

Thomas, David G.

1976-01-01

The subject invention is directed to a floating platform for supporting nuclear reactors and the like at selected offshore sites. The platform is provided with a stabilizer mechanism which significantly reduces the effects of wave action upon the platform and which comprises a pair of relatively small floats attached by rigid booms to the platform at locations spaced therefrom for reducing wave pitch, acceleration, and the resonance period of the wave.

Earth observing system instrument pointing control modeling for polar orbiting platforms

NASA Technical Reports Server (NTRS)

Briggs, H. C.; Kia, T.; Mccabe, S. A.; Bell, C. E.

1987-01-01

An approach to instrument pointing control performance assessment for large multi-instrument platforms is described. First, instrument pointing requirements and reference platform control systems for the Eos Polar Platforms are reviewed. Performance modeling tools including NASTRAN models of two large platforms, a modal selection procedure utilizing a balanced realization method, and reduced order platform models with core and instrument pointing control loops added are then described. Time history simulations of instrument pointing and stability performance in response to commanded slewing of adjacent instruments demonstrates the limits of tolerable slew activity. Simplified models of rigid body responses are also developed for comparison. Instrument pointing control methods required in addition to the core platform control system to meet instrument pointing requirements are considered.

Specification Patent Management for Web Application Platform Ecosystem

NASA Astrophysics Data System (ADS)

Fukami, Yoshiaki; Isshiki, Masao; Takeda, Hideaki; Ohmukai, Ikki; Kokuryo, Jiro

Diversified usage of web applications has encouraged disintegration of web platform into management of identification and applications. Users make use of various kinds of data linked to their identity with multiple applications on certain social web platforms such as Facebook or MySpace. There has emerged competition among web application platforms. Platformers can design relationship with developers by controlling patent of their own specification and adopt open technologies developed external organizations. Platformers choose a way to open according to feature of the specification and their position. Patent management of specification come to be a key success factor to build competitive web application platforms. Each way to attract external developers such as standardization, open source has not discussed and analyzed all together.

Platform C North Installation

NASA Image and Video Library

2016-11-10

A heavy-lift crane lowers the second half of the C-level work platforms, C north, for NASA’s Space Launch System (SLS) rocket, into High Bay 3 of the Vehicle Assembly Building (VAB) at NASA's Kennedy Space Center in Florida. The C platform will be installed on the north side of High Bay 3. In view below are several of the previously installed levels of platforms. The C platforms are the eighth of 10 levels of work platforms that will surround and provide access to the SLS rocket and Orion spacecraft for Exploration Mission 1. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to VAB High Bay 3, including installation of the new work platforms, to prepare for NASA’s Journey to Mars.

Geostationary platform systems concepts definition study. Volume 2A: Appendixes, book 1

NASA Technical Reports Server (NTRS)

1980-01-01

Appendixes addressing various aspects of a geostationary platform concepts definition study are given. Communication platform traffic requirements, video conferencing forecast, intersatellite link capacity requirements, link budgets, payload data, payload assignments, and platform synthesis are addressed.

A multiple pointing-mount control strategy for space platforms

NASA Technical Reports Server (NTRS)

Johnson, C. D.

1992-01-01

A new disturbance-adaptive control strategy for multiple pointing-mount space platforms is proposed and illustrated by consideration of a simplified 3-link dynamic model of a multiple pointing-mount space platform. Simulation results demonstrate the effectiveness of the new platform control strategy. The simulation results also reveal a system 'destabilization phenomena' that can occur if the set of individual platform-mounted experiment controllers are 'too responsive.'

Remote platform power conserving system

NASA Technical Reports Server (NTRS)

Kurvin, C. W. (Inventor)

1974-01-01

A system is described where an unattended receiver and transmitter equipped data collection platform is interrogated by a substantially polar orbiting satellite. The method and apparatus involve physically representing the orbit of the satellite and the spin of the planetary body with timers, and using these representations to turn on the platform's receiver only when the satellite should be in radio range of the platform, whereby battery power at the platform is conserved.

Feasibility of Floating Platform Systems for Wind Turbines: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Musial, W.; Butterfield, S.; Boone, A.

This paper provides a general technical description of several types of floating platforms for wind turbines. Platform topologies are classified into multiple- or single-turbine floaters and by mooring method. Platforms using catenary mooring systems are contrasted to vertical mooring systems and the advantages and disadvantages are discussed. Specific anchor types are described in detail. A rough cost comparison is performed for two different platform architectures using a generic 5-MW wind turbine. One platform is a Dutch study of a tri-floater platform using a catenary mooring system, and the other is a mono-column tension-leg platform developed at the National Renewable Energymore » Laboratory. Cost estimates showed that single unit production cost is $7.1 M for the Dutch tri-floater, and $6.5 M for the NREL TLP concept. However, value engineering, multiple unit series production, and platform/turbine system optimization can lower the unit platform costs to $4.26 M and $2.88 M, respectively, with significant potential to reduce cost further with system optimization. These foundation costs are within the range necessary to bring the cost of energy down to the DOE target range of $0.05/kWh for large-scale deployment of offshore floating wind turbines.« less

Scoping review and evaluation of SMS/text messaging platforms for mHealth projects or clinical interventions.

PubMed

Iribarren, Sarah J; Brown, William; Giguere, Rebecca; Stone, Patricia; Schnall, Rebecca; Staggers, Nancy; Carballo-Diéguez, Alex

2017-05-01

Mobile technology supporting text messaging interventions (TMIs) continues to evolve, presenting challenges for researchers and healthcare professionals who need to choose software solutions to best meet their program needs. The objective of this review was to systematically identify and compare text messaging platforms and to summarize their advantages and disadvantages as described in peer-reviewed literature. A scoping review was conducted using four steps: 1) identify currently available platforms through online searches and in mHealth repositories; 2) expand evaluation criteria of an mHealth mobile messaging toolkit and integrate prior user experiences as researchers; 3) evaluate each platform's functions and features based on the expanded criteria and a vendor survey; and 4) assess the documentation of platform use in the peer-review literature. Platforms meeting inclusion criteria were assessed independently by three reviewers and discussed until consensus was reached. The PRISMA guidelines were followed to report findings. Of the 1041 potentially relevant search results, 27 platforms met inclusion criteria. Most were excluded because they were not platforms (e.g., guides, toolkits, reports, or SMS gateways). Of the 27 platforms, only 12 were identified in existing mHealth repositories, 10 from Google searches, while five were found in both. The expanded evaluation criteria included 22 items. Results indicate no uniform presentation of platform features and functions, often making these difficult to discern. Fourteen of the platforms were reported as open source, 10 focused on health care and 16 were tailored to meet needs of low resource settings (not mutually exclusive). Fifteen platforms had do-it-yourself setup (programming not required) while the remainder required coding/programming skills or setups could be built to specification by the vendor. Frequently described features included data security and access to the platform via cloud-based systems. Pay structures and reported targeted end-users varied. Peer-reviewed publications listed only 6 of the 27 platforms across 21 publications. The majority of these articles reported the name of the platform used but did not describe advantages or disadvantages. Searching for and comparing mHealth platforms for TMIs remains a challenge. The results of this review can serve as a resource for researchers and healthcare professionals wanting to integrate TMIs into health interventions. Steps to identify, compare and assess advantages and disadvantages are outlined for consideration. Expanded evaluation criteria can be used by future researchers. Continued and more comprehensive platform tools should be integrated into mHealth repositories. Detailed descriptions of platform advantages and disadvantages are needed when mHealth researchers publish findings to expand the body of research on TMI tools for healthcare. Standardized descriptions and features are recommended for vendor sites. Copyright © 2017 Elsevier B.V. All rights reserved.

The Effects of Anthropogenic Structures on Habitat Connectivity and the Potential Spread of Non-Native Invertebrate Species in the Offshore Environment.

PubMed

Simons, Rachel D; Page, Henry M; Zaleski, Susan; Miller, Robert; Dugan, Jenifer E; Schroeder, Donna M; Doheny, Brandon

2016-01-01

Offshore structures provide habitat that could facilitate species range expansions and the introduction of non-native species into new geographic areas. Surveys of assemblages of seven offshore oil and gas platforms in the Santa Barbara Channel revealed a change in distribution of the non-native sessile invertebrate Watersipora subtorquata, a bryozoan with a planktonic larval duration (PLD) of 24 hours or less, from one platform in 2001 to four platforms in 2013. We use a three-dimensional biophysical model to assess whether larval dispersal via currents from harbors to platforms and among platforms is a plausible mechanism to explain the change in distribution of Watersipora and to predict potential spread to other platforms in the future. Hull fouling is another possible mechanism to explain the change in distribution of Watersipora. We find that larval dispersal via currents could account for the increase in distribution of Watersipora from one to four platforms and that Watersipora is unlikely to spread from these four platforms to additional platforms through larval dispersal. Our results also suggest that larvae with PLDs of 24 hours or less released from offshore platforms can attain much greater dispersal distances than larvae with PLDs of 24 hours or less released from nearshore habitat. We hypothesize that the enhanced dispersal distance of larvae released from offshore platforms is driven by a combination of the offshore hydrodynamic environment, larval behavior, and larval release above the seafloor.

Influence of platform switching on bone-level alterations: a three-year randomized clinical trial.

PubMed

Enkling, N; Jöhren, P; Katsoulis, J; Bayer, S; Jervøe-Storm, P-M; Mericske-Stern, R; Jepsen, S

2013-12-01

The concept of platform switching has been introduced to implant dentistry based on clinical observations of reduced peri-implant crestal bone loss. However, published data are controversial, and most studies are limited to 12 months. The aim of the present randomized clinical trial was to test the hypothesis that platform switching has a positive impact on crestal bone-level changes after 3 years. Two implants with a diameter of 4 mm were inserted crestally in the posterior mandible of 25 patients. The intraindividual allocation of platform switching (3.3-mm platform) and the standard implant (4-mm platform) was randomized. After 3 months of submerged healing, single-tooth crowns were cemented. Patients were followed up at short intervals for monitoring of healing and oral hygiene. Statistical analysis for the influence of time and platform type on bone levels employed the Brunner-Langer model. At 3 years, the mean radiographic peri-implant bone loss was 0.69 ± 0.43 mm (platform switching) and 0.74 ± 0.57 mm (standard platform). The mean intraindividual difference was 0.05 ± 0.58 mm (95% confidence interval: -0.19, 0.29). Crestal bone-level alteration depended on time (p < .001) but not on platform type (p = .363). The present randomized clinical trial could not confirm the hypothesis of a reduced peri-implant crestal bone loss, when implants had been restored according to the concept of platform switching.

Measurement of baseline and orientation between distributed aerospace platforms.

PubMed

Wang, Wen-Qin

2013-01-01

Distributed platforms play an important role in aerospace remote sensing, radar navigation, and wireless communication applications. However, besides the requirement of high accurate time and frequency synchronization for coherent signal processing, the baseline between the transmitting platform and receiving platform and the orientation of platform towards each other during data recording must be measured in real time. In this paper, we propose an improved pulsed duplex microwave ranging approach, which allows determining the spatial baseline and orientation between distributed aerospace platforms by the proposed high-precision time-interval estimation method. This approach is novel in the sense that it cancels the effect of oscillator frequency synchronization errors due to separate oscillators that are used in the platforms. Several performance specifications are also discussed. The effectiveness of the approach is verified by simulation results.

Mechanically latchable tiltable platform for forming micromirrors and micromirror arrays

DOEpatents

Garcia, Ernest J [Albuquerque, NM; Polosky, Marc A [Tijeras, NM; Sleefe, Gerard E [Cedar Crest, NM

2006-12-12

A microelectromechanical (MEM) apparatus is disclosed which includes a platform that can be electrostatically tilted from being parallel to a substrate on which the platform to being tilted at an angle of 1 20 degrees with respect to the substrate. Once the platform has been tilted to a maximum angle of tilt, the platform can be locked in position using an electrostatically-operable latching mechanism which engages a tab protruding below the platform. The platform has a light-reflective upper surface which can be optionally coated to provide an enhanced reflectivity and form a micromirror. An array of such micromirrors can be formed on a common substrate for applications including optical switching (e.g. for fiber optic communications), optical information processing, image projection displays or non-volatile optical memories.

Platform C Installation

NASA Image and Video Library

2016-10-19

A heavy-lift crane lifts the first half of the C-level work platforms, C south, for NASA’s Space Launch System (SLS) rocket, up from the transfer aisle floor of the Vehicle Assembly Building (VAB) at NASA’s Kennedy Space Center in Florida. Large Tandemloc bars have been attached to the platform to keep it level during lifting and installation. The C platform will be installed on the south side of High Bay 3. The C platforms are the eighth of 10 levels of work platforms that will surround and provide access to the SLS rocket and Orion spacecraft for Exploration Mission 1. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to VAB High Bay 3, including installation of the new work platforms, to prepare for NASA’s Journey to Mars.

Digital image analysis of Ki67 proliferation index in breast cancer using virtual dual staining on whole tissue sections: clinical validation and inter-platform agreement.

PubMed

Koopman, Timco; Buikema, Henk J; Hollema, Harry; de Bock, Geertruida H; van der Vegt, Bert

2018-05-01

The Ki67 proliferation index is a prognostic and predictive marker in breast cancer. Manual scoring is prone to inter- and intra-observer variability. The aims of this study were to clinically validate digital image analysis (DIA) of Ki67 using virtual dual staining (VDS) on whole tissue sections and to assess inter-platform agreement between two independent DIA platforms. Serial whole tissue sections of 154 consecutive invasive breast carcinomas were stained for Ki67 and cytokeratin 8/18 with immunohistochemistry in a clinical setting. Ki67 proliferation index was determined using two independent DIA platforms, implementing VDS to identify tumor tissue. Manual Ki67 score was determined using a standardized manual counting protocol. Inter-observer agreement between manual and DIA scores and inter-platform agreement between both DIA platforms were determined and calculated using Spearman's correlation coefficients. Correlations and agreement were assessed with scatterplots and Bland-Altman plots. Spearman's correlation coefficients were 0.94 (p < 0.001) for inter-observer agreement between manual counting and platform A, 0.93 (p < 0.001) between manual counting and platform B, and 0.96 (p < 0.001) for inter-platform agreement. Scatterplots and Bland-Altman plots revealed no skewness within specific data ranges. In the few cases with ≥ 10% difference between manual counting and DIA, results by both platforms were similar. DIA using VDS is an accurate method to determine the Ki67 proliferation index in breast cancer, as an alternative to manual scoring of whole sections in clinical practice. Inter-platform agreement between two different DIA platforms was excellent, suggesting vendor-independent clinical implementability.

Helicopter flight simulation motion platform requirements

NASA Astrophysics Data System (ADS)

Schroeder, Jeffery Allyn

Flight simulators attempt to reproduce in-flight pilot-vehicle behavior on the ground. This reproduction is challenging for helicopter simulators, as the pilot is often inextricably dependent on external cues for pilot-vehicle stabilization. One important simulator cue is platform motion; however, its required fidelity is unknown. To determine the required motion fidelity, several unique experiments were performed. A large displacement motion platform was used that allowed pilots to fly tasks with matched motion and visual cues. Then, the platform motion was modified to give cues varying from full motion to no motion. Several key results were found. First, lateral and vertical translational platform cues had significant effects on fidelity. Their presence improved performance and reduced pilot workload. Second, yaw and roll rotational platform cues were not as important as the translational platform cues. In particular, the yaw rotational motion platform cue did not appear at all useful in improving performance or reducing workload. Third, when the lateral translational platform cue was combined with visual yaw rotational cues, pilots believed the platform was rotating when it was not. Thus, simulator systems can be made more efficient by proper combination of platform and visual cues. Fourth, motion fidelity specifications were revised that now provide simulator users with a better prediction of motion fidelity based upon the frequency responses of their motion control laws. Fifth, vertical platform motion affected pilot estimates of steady-state altitude during altitude repositionings. This refutes the view that pilots estimate altitude and altitude rate in simulation solely from visual cues. Finally, the combined results led to a general method for configuring helicopter motion systems and for developing simulator tasks that more likely represent actual flight. The overall results can serve as a guide to future simulator designers and to today's operators.

Reduction of Tribocorrosion Products When using the Platform-Switching Concept.

PubMed

Alrabeah, G O; Knowles, J C; Petridis, H

2018-03-01

The reduced marginal bone loss observed when using the platform-switching concept may be the result of reduced amounts of tribocorrosion products released to the peri-implant tissues. Therefore, the purpose of this study was to compare the tribocorrosion product release from various platform-matched and platform-switched implant-abutment couplings under cyclic loading. Forty-eight titanium implants were coupled with pure titanium, gold alloy, cobalt-chrome alloy, and zirconia abutments forming either platform-switched or platform-matched groups ( n = 6). The specimens were subjected to cyclic occlusal forces in a wet acidic environment for 24 h followed by static aqueous immersion for 6 d. The amount of metal ions released was measured using inductively coupled plasma mass spectrometry. Microscopic evaluations were performed pre- and postimmersion under scanning electron microscope (SEM) equipped with energy-dispersive spectroscopy X-ray for corrosion assessment at the interface and wear particle characterization. All platform-switched groups showed less metal ion release compared with their platform-matched counterparts within each abutment material group ( P < 0.001). Implants connected to platform-matched cobalt-chrome abutments demonstrated the highest total mean metal ion release (218 ppb), while the least total mean ion release (11 ppb) was observed in the implants connected to platform-switched titanium abutments ( P ≤ 0.001). Titanium was released from all test groups, with its highest mean release (108 ppb) observed in the implants connected to platform-matched gold abutments ( P < 0.001). SEM images showed surface tribocorrosion features such as pitting and bands of fretting scars. Wear particles were mostly titanium, ranging from submicron to 48 µm in length. The platform-matched groups demonstrated a higher amount of metal ion release and more surface damage. These findings highlight the positive effect of the platform-switching concept in the reduction of tribocorrosion products released from dental implants, which consequently may minimize the adverse tissue reactions that lead to peri-implant bone loss.

Low-cost bioanalysis on paper-based and its hybrid microfluidic platforms.

PubMed

Dou, Maowei; Sanjay, Sharma Timilsina; Benhabib, Merwan; Xu, Feng; Li, XiuJun

2015-12-01

Low-cost assays have broad applications ranging from human health diagnostics and food safety inspection to environmental analysis. Hence, low-cost assays are especially attractive for rural areas and developing countries, where financial resources are limited. Recently, paper-based microfluidic devices have emerged as a low-cost platform which greatly accelerates the point of care (POC) analysis in low-resource settings. This paper reviews recent advances of low-cost bioanalysis on paper-based microfluidic platforms, including fully paper-based and paper hybrid microfluidic platforms. In this review paper, we first summarized the fabrication techniques of fully paper-based microfluidic platforms, followed with their applications in human health diagnostics and food safety analysis. Then we highlighted paper hybrid microfluidic platforms and their applications, because hybrid platforms could draw benefits from multiple device substrates. Finally, we discussed the current limitations and perspective trends of paper-based microfluidic platforms for low-cost assays. Copyright © 2015 Elsevier B.V. All rights reserved.

Usability studies on e-learning platforms: Preliminary study in USM

NASA Astrophysics Data System (ADS)

Emang, Devinna Win Anak Boniface; Lukman, Raja Nurul Izzati Raja; Kamarulzaman, Muhammad Izzat Syafiq; Zaaba, Zarul Fitri

2017-10-01

This paper explores the end-users' experienced in regards to the usability issues in E-learning platform. An online survey utilising 116 participants were conducted to investigate the end-users understanding and satisfaction on E-learning platform in the Universiti Sains Malaysia (USM). The results indicates that mainly students still experiencing significant challenges in E-learning platform in regards to accessibility, technical terminologies and functionality. On the other hand, the 10 heuristic guideline is chosen to be a referral point to compare five E-learning platforms in order to assess each performance on regards to the usability criteria. Overall, USM E-learning platform can be considered in a good shape. However, there are more works to be done to improve the delivery system of the E-learning if it would like to sustain for a long period of time. Although the result is at the preliminary stage, it provides useful insights to improve the E-learning platform as one of the most popular education platform in Malaysia.

A web-based online collaboration platform for formulating engineering design projects

NASA Astrophysics Data System (ADS)

Varikuti, Sainath

Effective communication and collaboration among students, faculty and industrial sponsors play a vital role while formulating and solving engineering design projects. With the advent in the web technology, online platforms and systems have been proposed to facilitate interactions and collaboration among different stakeholders in the context of senior design projects. However, there are noticeable gaps in the literature with respect to understanding the effects of online collaboration platforms for formulating engineering design projects. Most of the existing literature is focused on exploring the utility of online platforms on activities after the problem is defined and teams are formed. Also, there is a lack of mechanisms and tools to guide the project formation phase in senior design projects, which makes it challenging for students and faculty to collaboratively develop and refine project ideas and to establish appropriate teams. In this thesis a web-based online collaboration platform is designed and implemented to share, discuss and obtain feedback on project ideas and to facilitate collaboration among students and faculty prior to the start of the semester. The goal of this thesis is to understand the impact of an online collaboration platform for formulating engineering design projects, and how a web-based online collaboration platform affects the amount of interactions among stakeholders during the early phases of design process. A survey measuring the amount of interactions among students and faculty is administered. Initial findings show a marked improvement in the students' ability to share project ideas and form teams with other students and faculty. Students found the online platform simple to use. The suggestions for improving the tool generally included features that were not necessarily design specific, indicating that the underlying concept of this collaborative platform provides a strong basis and can be extended for future online platforms. Although the platform was designed to promote collaboration, adoption of the collaborative platform by students and faculty has been slow. While the platform appears to be very useful for collaboration, more time is required for it to be widely used by all the stakeholders and to fully convert from email communication to the use of the online collaboration platform.

The pitfalls of platform comparison: DNA copy number array technologies assessed

PubMed Central

2009-01-01

Background The accurate and high resolution mapping of DNA copy number aberrations has become an important tool by which to gain insight into the mechanisms of tumourigenesis. There are various commercially available platforms for such studies, but there remains no general consensus as to the optimal platform. There have been several previous platform comparison studies, but they have either described older technologies, used less-complex samples, or have not addressed the issue of the inherent biases in such comparisons. Here we describe a systematic comparison of data from four leading microarray technologies (the Affymetrix Genome-wide SNP 5.0 array, Agilent High-Density CGH Human 244A array, Illumina HumanCNV370-Duo DNA Analysis BeadChip, and the Nimblegen 385 K oligonucleotide array). We compare samples derived from primary breast tumours and their corresponding matched normals, well-established cancer cell lines, and HapMap individuals. By careful consideration and avoidance of potential sources of bias, we aim to provide a fair assessment of platform performance. Results By performing a theoretical assessment of the reproducibility, noise, and sensitivity of each platform, notable differences were revealed. Nimblegen exhibited between-replicate array variances an order of magnitude greater than the other three platforms, with Agilent slightly outperforming the others, and a comparison of self-self hybridizations revealed similar patterns. An assessment of the single probe power revealed that Agilent exhibits the highest sensitivity. Additionally, we performed an in-depth visual assessment of the ability of each platform to detect aberrations of varying sizes. As expected, all platforms were able to identify large aberrations in a robust manner. However, some focal amplifications and deletions were only detected in a subset of the platforms. Conclusion Although there are substantial differences in the design, density, and number of replicate probes, the comparison indicates a generally high level of concordance between platforms, despite differences in the reproducibility, noise, and sensitivity. In general, Agilent tended to be the best aCGH platform and Affymetrix, the superior SNP-CGH platform, but for specific decisions the results described herein provide a guide for platform selection and study design, and the dataset a resource for more tailored comparisons. PMID:19995423

Selection and optimization of mooring cables on floating platform for special purposes

NASA Astrophysics Data System (ADS)

Ma, Guang-ying; Yao, Yun-long; Zhao, Chen-yao

2017-08-01

This paper studied a new type of assembled marine floating platform for special purposes. The selection and optimization of mooring cables on the floating platform are studied. By using ANSYS AQWA software, the hydrodynamic model of the platform was established to calculate the time history response of the platform motion under complex water environments, such as wind, wave, current and mooring. On this basis, motion response and cable tension were calculated with different cable mooring states under the designed environmental load. Finally, the best mooring scheme to meet the cable strength requirements was proposed, which can lower the motion amplitude of the platform effectively.

Platform C Installation

NASA Image and Video Library

2016-10-19

Inside the Vehicle Assembly Building at NASA’s Kennedy Space Center in Florida, construction workers assist with the installation of the first half of the C-level work platforms, C south, for NASA’s Space Launch System (SLS) rocket. The large bolts that hold the platform in place on the south wall are being secured. The C platforms are the eighth of 10 levels of work platforms that will surround and provide access to the SLS rocket and Orion spacecraft for Exploration Mission 1. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to VAB High Bay 3, including installation of the new work platforms, to prepare for NASA’s Journey to Mars.

Platform C Installation

NASA Image and Video Library

2016-10-19

Inside the Vehicle Assembly Building at NASA’s Kennedy Space Center in Florida, the first half of the C-level work platforms, C south, for NASA’s Space Launch System (SLS) rocket, has been installed on the south side of the high bay. In view below are several levels of previously installed platforms. The C platforms are the eighth of 10 levels of work platforms that will surround and provide access to the SLS rocket and Orion spacecraft for Exploration Mission 1. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to VAB High Bay 3, including installation of the new work platforms, to prepare for NASA’s Journey to Mars.

Geosynchronous platform definition study. Volume 5: Geosynchronous platform synthesis

NASA Technical Reports Server (NTRS)

1973-01-01

The development is described of the platform configurations, support subsystems, mission equipment, and servicing concepts. A common support module is developed; subsystem concepts are traded off; data relay, TDRS, earth observational, astro-physics, and advanced navigation and traffic control mission equipment concepts are postulated; and ancillary equipment required for delivery and on-orbit servicing interfaces with geosynchronous platforms is grossly defined. The general approach was to develop a platform concept capable of evolving through three on-orbit servicing modes: remote, EVA, and shirtsleeve. The definition of the equipment is to the assembly level. Weight, power, and volumetric data are compiled for all the platforms.

A survey on platforms for big data analytics.

PubMed

Singh, Dilpreet; Reddy, Chandan K

The primary purpose of this paper is to provide an in-depth analysis of different platforms available for performing big data analytics. This paper surveys different hardware platforms available for big data analytics and assesses the advantages and drawbacks of each of these platforms based on various metrics such as scalability, data I/O rate, fault tolerance, real-time processing, data size supported and iterative task support. In addition to the hardware, a detailed description of the software frameworks used within each of these platforms is also discussed along with their strengths and drawbacks. Some of the critical characteristics described here can potentially aid the readers in making an informed decision about the right choice of platforms depending on their computational needs. Using a star ratings table, a rigorous qualitative comparison between different platforms is also discussed for each of the six characteristics that are critical for the algorithms of big data analytics. In order to provide more insights into the effectiveness of each of the platform in the context of big data analytics, specific implementation level details of the widely used k-means clustering algorithm on various platforms are also described in the form pseudocode.

Helicopter Flight Simulation Motion Platform Requirements

NASA Technical Reports Server (NTRS)

Schroeder, Jeffery Allyn

1999-01-01

To determine motion fidelity requirements, a series of piloted simulations was performed. Several key results were found. First, lateral and vertical translational platform cues had significant effects on fidelity. Their presence improved performance and reduced pilot workload. Second, yaw and roll rotational platform cues were not as important as the translational platform cues. In particular, the yaw rotational motion platform cue did not appear at all useful in improving performance or reducing workload. Third, when the lateral translational platform cue was combined with visual yaw rotational cues, pilots believed the platform was rotating when it was not. Thus, simulator systems can be made more efficient by proper combination of platform and visual cues. Fourth, motion fidelity specifications were revised that now provide simulator users with a better prediction of motion fidelity based upon the frequency responses of their motion control laws. Fifth, vertical platform motion affected pilot estimates of steady-state altitude during altitude repositioning. Finally, the combined results led to a general method for configuring helicopter motion systems and for developing simulator tasks that more likely represent actual flight. The overall results can serve as a guide to future simulator designers and to today's operators.

Unsupervised detection of salt marsh platforms: a topographic method

NASA Astrophysics Data System (ADS)

Goodwin, Guillaume C. H.; Mudd, Simon M.; Clubb, Fiona J.

2018-03-01

Salt marshes filter pollutants, protect coastlines against storm surges, and sequester carbon, yet are under threat from sea level rise and anthropogenic modification. The sustained existence of the salt marsh ecosystem depends on the topographic evolution of marsh platforms. Quantifying marsh platform topography is vital for improving the management of these valuable landscapes. The determination of platform boundaries currently relies on supervised classification methods requiring near-infrared data to detect vegetation, or demands labour-intensive field surveys and digitisation. We propose a novel, unsupervised method to reproducibly isolate salt marsh scarps and platforms from a digital elevation model (DEM), referred to as Topographic Identification of Platforms (TIP). Field observations and numerical models show that salt marshes mature into subhorizontal platforms delineated by subvertical scarps. Based on this premise, we identify scarps as lines of local maxima on a slope raster, then fill landmasses from the scarps upward, thus isolating mature marsh platforms. We test the TIP method using lidar-derived DEMs from six salt marshes in England with varying tidal ranges and geometries, for which topographic platforms were manually isolated from tidal flats. Agreement between manual and unsupervised classification exceeds 94 % for DEM resolutions of 1 m, with all but one site maintaining an accuracy superior to 90 % for resolutions up to 3 m. For resolutions of 1 m, platforms detected with the TIP method are comparable in surface area to digitised platforms and have similar elevation distributions. We also find that our method allows for the accurate detection of local block failures as small as 3 times the DEM resolution. Detailed inspection reveals that although tidal creeks were digitised as part of the marsh platform, unsupervised classification categorises them as part of the tidal flat, causing an increase in false negatives and overall platform perimeter. This suggests our method may benefit from combination with existing creek detection algorithms. Fallen blocks and high tidal flat portions, associated with potential pioneer zones, can also lead to differences between our method and supervised mapping. Although pioneer zones prove difficult to classify using a topographic method, we suggest that these transition areas should be considered when analysing erosion and accretion processes, particularly in the case of incipient marsh platforms. Ultimately, we have shown that unsupervised classification of marsh platforms from high-resolution topography is possible and sufficient to monitor and analyse topographic evolution.

30 CFR 250.609 - Well-workover structures on fixed platforms.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Well-workover structures on fixed platforms. 250.609 Section 250.609 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR... consideration the corrosion protection, age of the platform, and previous stresses to the platform. ...

The Case for Spacecrime: The Rise of Crime and Piracy in the Space Domain

DTIC Science & Technology

2013-06-01

resulted in generally outdated hardware with limited capabilities.21 More recent hardware platforms such as Arduino, BeagleBone, Raspberry Pi and others...www.citizensinspace.org; Arduino platform, http://www.arduino.cc; Beaglebone platform, http://www.beagleboard.org; Raspberry Pi platform, http

Orbiter processing facility: Access platforms Kennedy Space Center, Florida, from challenge to achievement

NASA Technical Reports Server (NTRS)

Haratunian, M.

1985-01-01

A system of access platforms and equipment within the space shuttle orbiter processing facility at Kennedy Space Center is described. The design challenges of the platforms, including clearance envelopes, load criteria, and movement, are discussed. Various applications of moveable platforms are considered.

78 FR 70935 - Notice of Availability of the Environmental Protection Agency's 2011 Emissions Modeling Platform

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-27

... alternative data sets. II. Information Available for Public Comment The 2011 Emissions Modeling Platform... Assessment. The EPA has placed key information related to the 2011 emissions modeling platform into the... the Environmental Protection Agency's 2011 Emissions Modeling Platform AGENCY: Environmental...

SERS diagnostic platforms, methods and systems microarrays, biosensors and biochips

DOEpatents

Vo-Dinh, Tuan [Knoxville, TN

2007-09-11

A Raman integrated sensor system for the detection of targets including biotargets includes at least one sampling platform, at least one receptor probe disposed on the sampling platform, and an integrated circuit detector system communicably connected to the receptor. The sampling platform is preferably a Raman active surface-enhanced scattering (SERS) platform, wherein the Raman sensor is a SERS sensor. The receptors can include at least one protein receptor and at least one nucleic acid receptor.

Hot air balloons fill gap in atmospheric and sensing platforms

NASA Astrophysics Data System (ADS)

Watson, Steven M.; Price, Russ

Eric Edgerton was having a problem he could not solve: how to noninvasively collect in situ incinerator plume data. So he called in the Air Force and learned about its Atmospheric and Sensor Test Platform program; its platform is a manned hot air balloon. Many investigators are discovering the advantages of hot air balloons as stable, inexpensive platforms for performing in situ atmospheric measurements. Some are also using remote sensing capabilities on the balloon platforms.

A review of simulation platforms in surgery of the temporal bone.

PubMed

Bhutta, M F

2016-10-01

Surgery of the temporal bone is a high-risk activity in an anatomically complex area. Simulation enables rehearsal of such surgery. The traditional simulation platform is the cadaveric temporal bone, but in recent years other simulation platforms have been created, including plastic and virtual reality platforms. To undertake a review of simulation platforms for temporal bone surgery, specifically assessing their educational value in terms of validity and in enabling transition to surgery. Systematic qualitative review. Search of the Pubmed, CINAHL, BEI and ERIC databases. Assessment of reported outcomes in terms of educational value. A total of 49 articles were included, covering cadaveric, animal, plastic and virtual simulation platforms. Cadaveric simulation is highly rated as an educational tool, but there may be a ceiling effect on educational outcomes after drilling 8-10 temporal bones. Animal models show significant anatomical variation from man. Plastic temporal bone models offer much potential, but at present lack sufficient anatomical or haptic validity. Similarly, virtual reality platforms lack sufficient anatomical or haptic validity, but with technological improvements they are advancing rapidly. At present, cadaveric simulation remains the best platform for training in temporal bone surgery. Technological advances enabling improved materials or modelling mean that in the future plastic or virtual platforms may become comparable to cadaveric platforms, and also offer additional functionality including patient-specific simulation from CT data. © 2015 John Wiley & Sons Ltd.

Reduction of matrix interferences in furnace atomic absorption with the L'vov Platform

USGS Publications Warehouse

Kaiser, M.L.; Koirtyohann, S.R.; Hinderberger, E.J.; Taylor, Howard E.

1981-01-01

Use of a modified L'vov Platform and ammonium phosphate as a matrix modifier greatly reduced matrix interferences in a commercial Massmann-type atomic absorption furnace. Platforms were readily fabricated from furnace tubes and, once positioned in the furnace, caused no inconvenience in operation. Two volatile elements (Pb, Cd), two of intermediate volatility (Co, Cr) and two which form stable oxides (Al, Sn) were tested in natural water and selected synthetic matrices. In every case for which there was a significant matrix effect during atomization from the tube wall, the platform and platform plus modifier gave improved performance. With lead, for example, an average ratio of 0.48 ?? 0.11 was found when the slope of the standard additions plot for six different natural water samples was compared to the slope of the standard working curve in dilute acid. The average slope ratio between the natural water matrices and the dilute acid matrix was 0.94 ?? 0.03 with the L'vov Platform and 0.96 ?? 0.03 with the platform and matrix modifier. In none of the cases studied did the use of the platform or platform plus modifier cause an interference problem where none existed while atomizing from the tube wall. An additional benefit of the platform was a factor of about two improvement in peak height precision. ?? 1981.

Comprehensive comparison of three commercial human whole-exome capture platforms.

PubMed

Asan; Xu, Yu; Jiang, Hui; Tyler-Smith, Chris; Xue, Yali; Jiang, Tao; Wang, Jiawei; Wu, Mingzhi; Liu, Xiao; Tian, Geng; Wang, Jun; Wang, Jian; Yang, Huangming; Zhang, Xiuqing

2011-09-28

Exome sequencing, which allows the global analysis of protein coding sequences in the human genome, has become an effective and affordable approach to detecting causative genetic mutations in diseases. Currently, there are several commercial human exome capture platforms; however, the relative performances of these have not been characterized sufficiently to know which is best for a particular study. We comprehensively compared three platforms: NimbleGen's Sequence Capture Array and SeqCap EZ, and Agilent's SureSelect. We assessed their performance in a variety of ways, including number of genes covered and capture efficacy. Differences that may impact on the choice of platform were that Agilent SureSelect covered approximately 1,100 more genes, while NimbleGen provided better flanking sequence capture. Although all three platforms achieved similar capture specificity of targeted regions, the NimbleGen platforms showed better uniformity of coverage and greater genotype sensitivity at 30- to 100-fold sequencing depth. All three platforms showed similar power in exome SNP calling, including medically relevant SNPs. Compared with genotyping and whole-genome sequencing data, the three platforms achieved a similar accuracy of genotype assignment and SNP detection. Importantly, all three platforms showed similar levels of reproducibility, GC bias and reference allele bias. We demonstrate key differences between the three platforms, particularly advantages of solutions over array capture and the importance of a large gene target set.

Scoping Review and Evaluation of SMS/text Messaging Platforms for mHealth Projects or Clinical Interventions

PubMed Central

Iribarren, Sarah; Brown, William; Giguere, Rebecca; Stone, Patricia; Schnall, Rebecca; Staggers, Nancy; Carballo-Diéguez, Alex

2017-01-01

Objectives Mobile technology supporting text messaging interventions (TMIs) continues to evolve, presenting challenges for researchers and healthcare professionals who need to choose software solutions to best meet their program needs. The objective of this review was to systematically identify and compare text messaging platforms and to summarize their advantages and disadvantages as described in peer-reviewed literature. Methods A scoping review was conducted using four steps: 1) identify currently available platforms through online searches and in mHealth repositories; 2) expand evaluation criteria of an mHealth mobile messaging toolkit and prior user experiences as researchers; 3) evaluate each platform’s functions and features based on the expanded criteria and a vendor survey; and 4) assess the documentation of platform use in the peer-review literature. Platforms meeting inclusion criteria were assessed independently by three reviewers and discussed until consensus was reached. The PRISMA guidelines were followed to report findings. Results Of the 1041 potentially relevant search results, 27 platforms met inclusion criteria. Most were excluded because they were not platforms (e.g., guides, toolkits, reports, or SMS gateways). Of the 27 platforms, only 12 were identified in existing mHealth repositories, 10 from Google searches, while five were found in both. The expanded evaluation criteria included 22 items. Results indicate no uniform presentation of platform features and functions, often making these difficult to discern. Fourteen of the platforms were reported as open source, 10 focused on health care and 16 were tailored to meet needs of low resource settings (not mutually exclusive). Fifteen platforms had do-it-yourself setup (programming not required) while the remainder required coding/programming skills or setups could be built to specification by the vendor. Frequently described features included data security and access to the platform via cloud-based systems. Pay structures and reported targeted end-users varied. Peer-reviewed publications listed only 6 of the 27 platforms across 21 publications. The majority of these articles reported the name of the platform used but did not describe advantages or disadvantages. Conclusions Searching for and comparing mHealth platforms for TMIs remains a challenge. The results of this review can serve as a resource for researchers and healthcare professionals wanting to integrate TMIs into health interventions. Steps to identify, compare and assess advantages and disadvantages are outlined for consideration. Expanded evaluation criteria can be used by future researchers. Continued and more comprehensive platform tools should be integrated into mHealth repositories. Detailed descriptions of platform advantages and disadvantages are needed when mHealth researchers publish findings to expand the body of research on texting-based tools for healthcare. Standardized descriptions and features are recommended for vendor sites. PMID:28347445

A novel rotating experimental platform in a superconducting magnet.

PubMed

Chen, Da; Cao, Hui-Ling; Ye, Ya-Jing; Dong, Chen; Liu, Yong-Ming; Shang, Peng; Yin, Da-Chuan

2016-08-01

This paper introduces a novel platform designed to be used in a strong static magnetic field (in a superconducting magnet). The platform is a sample holder that rotates in the strong magnetic field. Any samples placed in the platform will rotate due to the rotation of the sample holder. With this platform, a number of experiments such as material processing, culture of biological systems, chemical reactions, or other processes can be carried out. In this report, we present some preliminary experiments (protein crystallization, cell culture, and seed germination) conducted using this platform. The experimental results showed that the platform can affect the processes, indicating that it provides a novel environment that has not been investigated before and that the effects of such an environment on many different physical, chemical, or biological processes can be potentially useful for applications in many fields.

Simulation of cooperating robot manipulators on a mobile platform

NASA Technical Reports Server (NTRS)

Murphy, Stephen H.; Wen, John Ting-Yung; Saridis, George N.

1991-01-01

The dynamic equations of motion are presented for two or more cooperating manipulators on a freely moving mobile platform. The system of cooperating robot manipulators forms a closed kinematic chain where the force of interaction must be included in the formulation of robot and platform dynamics. The formulation includes the full dynamic interactions from arms to platform and arm tip to arm tip, and the possible translation and rotation of the platform. The equations of motion are shown to be identical in structure to the fixed-platform cooperative manipulator dynamics. The number of DOFs of the system is sufficiently large to make recursive dynamic calculation methods potentially more efficient than closed-form solutions. A complete simulation with two 6-DOF manipulators of a free-floating platform is presented along a with a multiple-arm controller to position the common load.

Circular Bioassay Platforms for Applications in Microwave-Accelerated Techniques.

PubMed

Mohammed, Muzaffer; Clement, Travis C; Aslan, Kadir

2014-12-02

In this paper, we present the design of four different circular bioassay platforms, which are suitable for homogeneous microwave heating, using theoretical calculations (i.e., COMSOL™ multiphysics software). Circular bioassay platforms are constructed from poly(methyl methacrylate) (PMMA) for optical transparency between 400-800 nm, has multiple sample capacity (12, 16, 19 and 21 wells) and modified with silver nanoparticle films (SNFs) to be used in microwave-accelerated bioassays (MABs). In addition, a small monomode microwave cavity, which can be operated with an external microwave generator (100 W), for use with the bioassay platforms in MABs is also developed. Our design parameters for the circular bioassay platforms and monomode microwave cavity during microwave heating were: (i) temperature profiles, (ii) electric field distributions, (iii) location of the circular bioassay platforms inside the microwave cavity, and (iv) design and number of wells on the circular bioassay platforms. We have also carried out additional simulations to assess the use of circular bioassay platforms in a conventional kitchen microwave oven (e.g., 900 W). Our results show that the location of the circular bioassay platforms in the microwave cavity was predicted to have a significant effect on the homogeneous heating of these platforms. The 21-well circular bioassay platform design in our monomode microwave cavity was predicted to offer a homogeneous heating pattern, where inter-well temperature was observed to be in between 23.72-24.13°C and intra-well temperature difference was less than 0.21°C for 60 seconds of microwave heating, which was also verified experimentally.

Developing a Web Platform to Support a Community of Practice: A Mixed Methods Study in Pediatric Physiotherapy.

PubMed

Pratte, Gabrielle; Hurtubise, Karen; Rivard, Lisa; Berbari, Jade; Camden, Chantal

2018-01-01

Web platforms are increasingly used to support virtual interactions between members of communities of practice (CoP). However, little is known about how to develop these platforms to support the implementation of best practices for health care professionals. The aim of this article is to explore pediatric physiotherapists' (PTs) perspectives regarding the utility and usability of the characteristic of a web platform developed to support virtual communities of practice (vCoP). This study adopted an explanatory sequential mixed methods design. A web platform supporting the interactions of vCoP members was developed for PTs working with children with developmental coordination disorder. Specific strategies and features were created to support the effectiveness of the platform across three domains: social, information-quality, and system-quality factors. Quantitative data were collected from a cross-sectional survey (n = 41) after 5 months of access to the web platform. Descriptive statistics were calculated. Qualitative data were also collected from semistructured interviews (n = 9), which were coded, interpreted, and analyzed by using Boucher's Web Ergonomics Conceptual Framework. The utility of web platform characteristics targeting the three key domain factors were generally perceived positively by PTs. However, web platform usability issues were noted by PTs, including problems with navigation and information retrieval. Web platform aiming to support vCoP should be carefully developed to target potential users' needs. Whenever possible, users should co-construct the web platform with vCoP developers. Moreover, each of the developed characteristics (eg, newsletter, search function) should be evaluated in terms of utility and usability for the users.

Told through the wine: A liquid chromatography-mass spectrometry interplatform comparison reveals the influence of the global approach on the final annotated metabolites in non-targeted metabolomics.

PubMed

Díaz, Ramon; Gallart-Ayala, Hector; Sancho, Juan V; Nuñez, Oscar; Zamora, Tatiana; Martins, Claudia P B; Hernández, Félix; Hernández-Cassou, Santiago; Saurina, Javier; Checa, Antonio

2016-02-12

This work focuses on the influence of the selected LC-HRMS platform on the final annotated compounds in non-targeted metabolomics. Two platforms that differed in columns, mobile phases, gradients, chromatographs, mass spectrometers (Orbitrap [Platform#1] and Q-TOF [Platform#2]), data processing and marker selection protocols were compared. A total of 42 wines samples from three different protected denomination of origin (PDO) were analyzed. At the feature level, good (O)PLS-DA models were obtained for both platforms (Q(2)[Platform#1]=0.89, 0.83 and 0.72; Q(2)[Platform#2]=0.86, 0.86 and 0.77 for Penedes, Ribera del Duero and Rioja wines respectively) with 100% correctly classified samples in all cases. At the annotated metabolite level, platforms proposed 9 and 8 annotated metabolites respectively which were identified by matching standards or the MS/MS spectra of the compounds. At this stage, there was no coincidence among platforms regarding the suggested metabolites. When screened on the raw data, 6 and 5 of these compounds were detected on the other platform with a similar trend. Some of the detected metabolites showed complimentary information when integrated on biological pathways. Through the use of some examples at the annotated metabolite level, possible explanations of this initial divergence on the results are presented. This work shows the complications that may arise on the comparison of non-targeted metabolomics platforms even when metabolite focused approaches are used in the identification. Copyright © 2016 Elsevier B.V. All rights reserved.

Thiolene and SIFEL-based Microfluidic Platforms for Liquid-Liquid Extraction

PubMed Central

Goyal, Sachit; Desai, Amit V.; Lewis, Robert W.; Ranganathan, David R.; Li, Hairong; Zeng, Dexing; Reichert, David E.; Kenis, Paul J.A.

2014-01-01

Microfluidic platforms provide several advantages for liquid-liquid extraction (LLE) processes over conventional methods, for example with respect to lower consumption of solvents and enhanced extraction efficiencies due to the inherent shorter diffusional distances. Here, we report the development of polymer-based parallel-flow microfluidic platforms for LLE. To date, parallel-flow microfluidic platforms have predominantly been made out of silicon or glass due to their compatibility with most organic solvents used for LLE. Fabrication of silicon and glass-based LLE platforms typically requires extensive use of photolithography, plasma or laser-based etching, high temperature (anodic) bonding, and/or wet etching with KOH or HF solutions. In contrast, polymeric microfluidic platforms can be fabricated using less involved processes, typically photolithography in combination with replica molding, hot embossing, and/or bonding at much lower temperatures. Here we report the fabrication and testing of microfluidic LLE platforms comprised of thiolene or a perfluoropolyether-based material, SIFEL, where the choice of materials was mainly guided by the need for solvent compatibility and fabrication amenability. Suitable designs for polymer-based LLE platforms that maximize extraction efficiencies within the constraints of the fabrication methods and feasible operational conditions were obtained using analytical modeling. To optimize the performance of the polymer-based LLE platforms, we systematically studied the effect of surface functionalization and of microstructures on the stability of the liquid-liquid interface and on the ability to separate the phases. As demonstrative examples, we report (i) a thiolene-based platform to determine the lipophilicity of caffeine, and (ii) a SIFEL-based platform to extract radioactive copper from an acidic aqueous solution. PMID:25246730

Circular Bioassay Platforms for Applications in Microwave-Accelerated Techniques

PubMed Central

Mohammed, Muzaffer; Clement, Travis C.; Aslan, Kadir

2014-01-01

In this paper, we present the design of four different circular bioassay platforms, which are suitable for homogeneous microwave heating, using theoretical calculations (i.e., COMSOL™ multiphysics software). Circular bioassay platforms are constructed from poly(methyl methacrylate) (PMMA) for optical transparency between 400–800 nm, has multiple sample capacity (12, 16, 19 and 21 wells) and modified with silver nanoparticle films (SNFs) to be used in microwave-accelerated bioassays (MABs). In addition, a small monomode microwave cavity, which can be operated with an external microwave generator (100 W), for use with the bioassay platforms in MABs is also developed. Our design parameters for the circular bioassay platforms and monomode microwave cavity during microwave heating were: (i) temperature profiles, (ii) electric field distributions, (iii) location of the circular bioassay platforms inside the microwave cavity, and (iv) design and number of wells on the circular bioassay platforms. We have also carried out additional simulations to assess the use of circular bioassay platforms in a conventional kitchen microwave oven (e.g., 900 W). Our results show that the location of the circular bioassay platforms in the microwave cavity was predicted to have a significant effect on the homogeneous heating of these platforms. The 21-well circular bioassay platform design in our monomode microwave cavity was predicted to offer a homogeneous heating pattern, where inter-well temperature was observed to be in between 23.72–24.13°C and intra-well temperature difference was less than 0.21°C for 60 seconds of microwave heating, which was also verified experimentally. PMID:25568813

Unmanned Instrument Platform for Undersea Exploration

NASA Technical Reports Server (NTRS)

Paine, G.; Hansen, G. R.; Gulizia, R. W.; Paluzzi, P.

1984-01-01

Instruments accommodated on moving underwater platform. Towable underwater platform 3.2 meters long, 1.2 meters wide, 1.4 meters high and has mass of about 1,250 kilogram. Platform remotely operated and unmanned. Serves as test bed for development of ocean-measuring instruments and sonars at depths to 20,000 feet.

30 CFR 250.509 - Well-completion structures on fixed platforms.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Well-completion structures on fixed platforms. 250.509 Section 250.509 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR... consideration the corrosion protection, age of platform, and previous stresses to the platform. [53 FR 10690...

Defensive platform size and survivability. [Platform survivability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Canavan, Gregory H.

1988-06-01

This report discusses the survivability of space platforms, concentrating on space based kinetic energy interceptors. It evaluates the efficacy of hardening, maneuver, self-defense, and deception in extending the survivability of platforms of varying sizes to expected threats, concluding that they should be adequate in the near and mid terms.

77 FR 40302 - Department of the Treasury Acquisition Regulation; Internet Payment Platform

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-09

... Treasury Acquisition Regulation; Internet Payment Platform AGENCY: Office of the Procurement Executive... Treasury Acquisition Regulation (DTAR) to implement use of the Internet Payment Platform, a centralized... implement the Internet Payment Platform (IPP) no later than the end of fiscal year 2012; with all new...

30 CFR 250.913 - When must I resubmit Platform Verification Program plans?

Code of Federal Regulations, 2010 CFR

2010-07-01

... Structures Platform Verification Program § 250.913 When must I resubmit Platform Verification Program plans? (a) You must resubmit any design verification, fabrication verification, or installation verification... 30 Mineral Resources 2 2010-07-01 2010-07-01 false When must I resubmit Platform Verification...

Feasibility of observer system for determining orientation of balloon borne observational platforms

NASA Technical Reports Server (NTRS)

Nigro, N. J.; Gagliardi, J. C.

1982-01-01

The instantaneous orientation (i.e., the attitude) of the LACATE instrumentation platform with respect to a local vertical is discussed. An observer model for predicting the orientation of balloon-borne research platforms is described. Determination of the platform orientation as a function of time is addressed.

Plans: 3'/50 Cal. Gun Platform, Boat Deck House Top & ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Plans: 3'/50 Cal. Gun Platform, Boat Deck House Top & Fidley Top, Boat Deck, Radar Platform Lower, Pilot House Top, Navigation Bridge, Upper Bridge Deck, Poop Deck, Cargo Deck, Motor Boat Platform, Bridge Deck, Forecastle Deck, Upper Deck - Taluga, Suisun Bay Reserve Fleet, Benicia, Solano County, CA

User definition and mission requirements for unmanned airborne platforms, revised

NASA Technical Reports Server (NTRS)

Kuhner, M. B.; Mcdowell, J. R.

1979-01-01

The airborne measurement requirements of the scientific and applications experiment user community were assessed with respect to the suitability of proposed strawman airborne platforms. These platforms provide a spectrum of measurement capabilities supporting associated mission tradeoffs such as payload weight, operating altitude, range, duration, flight profile control, deployment flexibility, quick response, and recoverability. The results of the survey are used to examine whether the development of platforms is warranted and to determine platform system requirements as well as research and technology needs.

A multilevel control approach for a modular structured space platform

NASA Technical Reports Server (NTRS)

Chichester, F. D.; Borelli, M. T.

1981-01-01

A three axis mathematical representation of a modular assembled space platform consisting of interconnected discrete masses, including a deployable truss module, was derived for digital computer simulation. The platform attitude control system as developed to provide multilevel control utilizing the Gauss-Seidel second level formulation along with an extended form of linear quadratic regulator techniques. The objectives of the multilevel control are to decouple the space platform's spatial axes and to accommodate the modification of the platform's configuration for each of the decoupled axes.

Flexible, secure agent development framework

DOEpatents

Goldsmith,; Steven, Y [Rochester, MN

2009-04-07

While an agent generator is generating an intelligent agent, it can also evaluate the data processing platform on which it is executing, in order to assess a risk factor associated with operation of the agent generator on the data processing platform. The agent generator can retrieve from a location external to the data processing platform an open site that is configurable by the user, and load the open site into an agent substrate, thereby creating a development agent with code development capabilities. While an intelligent agent is executing a functional program on a data processing platform, it can also evaluate the data processing platform to assess a risk factor associated with performing the data processing function on the data processing platform.

Reactions of Standing Bipeds on Moving Platforms to Keep Their Balance May Increase the Amplitude of Oscillations of Platforms Satisfying Hooke’s Law

PubMed Central

Goldsztein, Guillermo H.

2016-01-01

Consider a person standing on a platform that oscillates laterally, i.e. to the right and left of the person. Assume the platform satisfies Hooke’s law. As the platform moves, the person reacts and moves its body attempting to keep its balance. We develop a simple model to study this phenomenon and show that the person, while attempting to keep its balance, may do positive work on the platform and increase the amplitude of its oscillations. The studies in this article are motivated by the oscillations in pedestrian bridges that are sometimes observed when large crowds cross them. PMID:27304857

Reactions of Standing Bipeds on Moving Platforms to Keep Their Balance May Increase the Amplitude of Oscillations of Platforms Satisfying Hooke's Law.

PubMed

Goldsztein, Guillermo H

2016-01-01

Consider a person standing on a platform that oscillates laterally, i.e. to the right and left of the person. Assume the platform satisfies Hooke's law. As the platform moves, the person reacts and moves its body attempting to keep its balance. We develop a simple model to study this phenomenon and show that the person, while attempting to keep its balance, may do positive work on the platform and increase the amplitude of its oscillations. The studies in this article are motivated by the oscillations in pedestrian bridges that are sometimes observed when large crowds cross them.

Platform C Installation

NASA Image and Video Library

2016-10-19

A heavy-lift crane lifts the first half of the C-level work platforms, C south, for NASA’s Space Launch System (SLS) rocket, high up from the transfer aisle floor of the Vehicle Assembly Building (VAB) at NASA’s Kennedy Space Center in Florida. The C platform will be installed on the south side of High Bay 3. The C platforms are the eighth of 10 levels of work platforms that will surround and provide access to the SLS rocket and Orion spacecraft for Exploration Mission 1. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to VAB High Bay 3, including installation of the new work platforms, to prepare for NASA’s Journey to Mars.

Platform C North Installation

NASA Image and Video Library

2016-11-10

A heavy-lift crane lifts the second half of the C-level work platforms, C north, for NASA’s Space Launch System (SLS) rocket, high up from the transfer aisle floor of the Vehicle Assembly Building (VAB) at NASA’s Kennedy Space Center in Florida. The C platform will be installed on the north side of High Bay 3. The C platforms are the eighth of 10 levels of work platforms that will surround and provide access to the SLS rocket and Orion spacecraft for Exploration Mission 1. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to VAB High Bay 3, including installation of the new work platforms, to prepare for NASA’s Journey to Mars.

Platform C Installation

NASA Image and Video Library

2016-10-19

A heavy-lift crane lifts the first half of the C-level work platforms, C south, for NASA’s Space Launch System (SLS) rocket, high up from the transfer aisle floor of the Vehicle Assembly Building (VAB) at NASA’s Kennedy Space Center in Florida. The C platform will be moved into High Bay 3 for installation on the south wall. The C platforms are the eighth of 10 levels of work platforms that will surround and provide access to the SLS rocket and Orion spacecraft for Exploration Mission 1. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to VAB High Bay 3, including installation of the new work platforms, to prepare for NASA’s Journey to Mars.

Platform C Installation

NASA Image and Video Library

2016-10-19

Inside the Vehicle Assembly Building at NASA’s Kennedy Space Center in Florida, a construction worker assist with the installation of the first half of the C-level work platforms, C south, for NASA’s Space Launch System (SLS) rocket. The large bolts that hold the platform in place on the south wall are being secured. The C platforms are the eighth of 10 levels of work platforms that will surround and provide access to the SLS rocket and Orion spacecraft for Exploration Mission 1. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to VAB High Bay 3, including installation of the new work platforms, to prepare for NASA’s Journey to Mars.

Platform C North Installation

NASA Image and Video Library

2016-11-10

A heavy-lift crane lifts the second half of the C-level work platforms, C north, for NASA’s Space Launch System (SLS) rocket, up from the transfer aisle floor of the Vehicle Assembly Building (VAB) at NASA’s Kennedy Space Center in Florida. The C platform will be installed on the north side of High Bay 3. The C platforms are the eighth of 10 levels of work platforms that will surround and provide access to the SLS rocket and Orion spacecraft for Exploration Mission 1. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to VAB High Bay 3, including installation of the new work platforms, to prepare for NASA’s Journey to Mars.

Platform C North Installation

NASA Image and Video Library

2016-11-10

A heavy-lift crane lifts the second half of the C-level work platforms, C north, for NASA’s Space Launch System (SLS) rocket, high up from the transfer aisle floor of the Vehicle Assembly Building (VAB) at NASA’s Kennedy Space Center in Florida. The C platform will be moved into High Bay 3 for installation on the north wall. The C platforms are the eighth of 10 levels of work platforms that will surround and provide access to the SLS rocket and Orion spacecraft for Exploration Mission 1. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to VAB High Bay 3, including installation of the new work platforms, to prepare for NASA’s Journey to Mars.

VAB Platform K(2) Lift & Install into Highbay 3

NASA Image and Video Library

2016-03-07

A 250-ton crane is used to lift the second half of the K-level work platforms for NASA’s Space Launch System (SLS) rocket high above the transfer aisle inside the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. The platform is being lifted up for transfer into High Bay 3 for installation. The platform will be secured about 86 feet above the VAB floor, on tower E of the high bay. The K work platforms will provide access to the SLS core stage and solid rocket boosters during processing and stacking operations on the mobile launcher. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to High Bay 3 to support processing of the SLS and Orion spacecraft. A total of 10 levels of new platforms, 20 platform halves altogether, will surround the SLS rocket and Orion spacecraft.

The development of optimal control laws for orbiting tethered platform systems

NASA Technical Reports Server (NTRS)

Bainum, P. M.; Woodard, S.; Juang, J.-N.

1986-01-01

A mathematical model of the open and closed loop in-orbit plane dynamics of a space platform-tethered-subsatellite system is developed. The system consists of a rigid platform from which an (assumed massless) tether is deploying (retrieving) a subsatellite from an attachment point which is, in general, offset from the platform's mass center. A Lagrangian formulation yields equations describing platform pitch, subsatellite tether-line swing, and varying tether length motions. These equations are linearized about the nominal station keeping motion. Control can be provided by both modulation of the tether tension level and by a momentum type platform-mounted device; system controllability depends on the presence of both control inputs. Stability criteria are developed in terms of the control law gains, the platform inertia ratio, and tether offset parameter. Control law gains are obtained based on linear quadratic regulator techniques. Typical transient responses of both the state and required control effort are presented.

The development of optimal control laws for orbiting tethered platform systems

NASA Technical Reports Server (NTRS)

Bainum, P. M.

1986-01-01

A mathematical model of the open and closed loop in orbit plane dynamics of a space platform-tethered-subsatellite system is developed. The system consists of a rigid platform from which an (assumed massless) tether is deploying (retrieving) a subsatellite from an attachment point which is, in general, offset from the platform's mass center. A Langrangian formulation yields equations describing platform pitch, subsatellite tetherline swing, and varying tether length motions. These equations are linearized about the nominal station keeping motion. Control can be provided by both modulation of the tether tension level and by a momentum type platform-mounted device; system controllability depends on the presence of both control inputs. Stability criteria are developed in terms of the control law gains, the platform inertia ratio, and tether offset parameter. Control law gains are obtained based on linear quadratic regulator techniques. Typical transient responses of both the state and required control effort are presented.

Evolutionary space platform concept study. Volume 2, part B: Manned space platform concepts

NASA Technical Reports Server (NTRS)

1982-01-01

Logical, cost-effective steps in the evolution of manned space platforms are investigated and assessed. Tasks included the analysis of requirements for a manned space platform, identifying alternative concepts, performing system analysis and definition of the concepts, comparing the concepts and performing programmatic analysis for a reference concept.

33 CFR 147.839 - Mad Dog Truss Spar Platform safety zone.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Mad Dog Truss Spar Platform... SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.839 Mad Dog Truss Spar Platform safety zone. (a) Description. Mad Dog Truss Spar Platform, Green Canyon 782 (GC 782), located at position...

33 CFR 147.839 - Mad Dog Truss Spar Platform safety zone.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Mad Dog Truss Spar Platform... SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.839 Mad Dog Truss Spar Platform safety zone. (a) Description. Mad Dog Truss Spar Platform, Green Canyon 782 (GC 782), located at position...

33 CFR 147.839 - Mad Dog Truss Spar Platform safety zone.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Mad Dog Truss Spar Platform... SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.839 Mad Dog Truss Spar Platform safety zone. (a) Description. Mad Dog Truss Spar Platform, Green Canyon 782 (GC 782), located at position...

46 CFR 163.002-21 - Approval tests.

Code of Federal Regulations, 2011 CFR

2011-10-01

... must not break or crack during these tests. (2) Platform strength. If the pilot hoist has a lift... deck interlock must prevent movement of the ladder or lift platform when the lever is activated. (4... of the hoist is placed on its ladder or lift platform. The ladder or lift platform is repeatedly...

33 CFR 147.839 - Mad Dog Truss Spar Platform safety zone.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Mad Dog Truss Spar Platform... SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.839 Mad Dog Truss Spar Platform safety zone. (a) Description. Mad Dog Truss Spar Platform, Green Canyon 782 (GC 782), located at position...

33 CFR 147.839 - Mad Dog Truss Spar Platform safety zone.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Mad Dog Truss Spar Platform... SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.839 Mad Dog Truss Spar Platform safety zone. (a) Description. Mad Dog Truss Spar Platform, Green Canyon 782 (GC 782), located at position...

Conditioned inhibition in the spatial domain.

PubMed

Sansa, J; Rodrigo, T; Santamaría, J J; Manteiga, R D; Chamizo, V D

2009-10-01

Using a variation on the standard procedure of conditioned inhibition (Trials A+ and AX-), rats (Rattus norvegicus) in a circular pool were trained to find a hidden platform that was located in a specific spatial position in relation to 2 individual landmarks (Trials A --> platform and B --> platform; Experiments 1a and 1b) and to 2 configurations of landmarks (Trials ABC --> platform and FGH --> platform; Experiment 2a). The rats also underwent inhibitory trials (Experiment 1: Trials AZ --> no platform; Experiment 2a: Trials CDE --> no platform) interspersed with these excitatory trials. In both experiments, subsequent test trials without the platform showed both a summation effect and retardation of excitatory conditioning, and in Experiment 2a rats learned to avoid the CDE quadrant over the course of the experiment. Two further experiments established that these results could not be attributed to any difference in salience between the conditioned inhibitors and the control stimuli. All these results contribute to the growing body of evidence consistent with the idea that there is a general mechanism of learning that is associative in nature. PsycINFO Database Record (c) 2009 APA, all rights reserved.

The GridEcon Platform: A Business Scenario Testbed for Commercial Cloud Services

NASA Astrophysics Data System (ADS)

Risch, Marcel; Altmann, Jörn; Guo, Li; Fleming, Alan; Courcoubetis, Costas

Within this paper, we present the GridEcon Platform, a testbed for designing and evaluating economics-aware services in a commercial Cloud computing setting. The Platform is based on the idea that the exact working of such services is difficult to predict in the context of a market and, therefore, an environment for evaluating its behavior in an emulated market is needed. To identify the components of the GridEcon Platform, a number of economics-aware services and their interactions have been envisioned. The two most important components of the platform are the Marketplace and the Workflow Engine. The Workflow Engine allows the simple composition of a market environment by describing the service interactions between economics-aware services. The Marketplace allows trading goods using different market mechanisms. The capabilities of these components of the GridEcon Platform in conjunction with the economics-aware services are described in this paper in detail. The validation of an implemented market mechanism and a capacity planning service using the GridEcon Platform also demonstrated the usefulness of the GridEcon Platform.

Sedimentological evolution of the Cretaceous carbonate platform of Chiapas (Mexico)

NASA Astrophysics Data System (ADS)

Cros, Pierre; Michaud, François; Fourcade, Eric; Fleury, Jean-Jacques

1998-07-01

The Cretaceous epicontinental carbonate platform of Chiapas (south-east of Mexico) extends along a 200 km NW-SE narrow strip, north of the Sierra Madre basement, from Ocozocoautla to Comitan. In the western and central domain, three stratigraphic sections of the Sierra Madre Formation (late Aptian to early Senonian) display well exposed facies sequences enabling broad facies correlations about: (1) The successive transgressive-regressive stages, (2) the different subsidence rates controlling the outer to inner platform environmental evolution, (3) the conditions of tectonically controlled partial platform drowning during Campanian-Maastrichtian. Three other sections through the eastern Maastrichtian carbonate platform area record the changes from limestone to dolomite during the Angostura Maastrichtian platform stage. This evolution of thickness and facies in the occidental domain of Piedra Parada and in the central domain of Guadalupe Victoria and Julian Grajales illustrates the settlement process of the carbonate platform and the general decreasing of the thickness of the Sierra Madre Formation from west to east. The eastern platform domain (Comitan) crops out extensively and enables new correlations along a south-north transect. The Sierra Madre Formation and Angostura Formation documents continuous carbonate platform sedimentation with foraminifers, rudists and dasycladacean algae during Campanian and Maastrichtian. These sections permit palaeogeographical comparisons of depositional conditions of the Mexican margin of the Maya block.

Evaluation of a new eLearning platform for distance teaching of microsurgery.

PubMed

Messaoudi, T; Bodin, F; Hidalgo Diaz, J J; Ichihara, S; Fikry, T; Lacreuse, I; Liverneaux, P; Facca, S

2015-06-01

Online learning (or eLearning) is in constant evolution in medicine. An analytical survey of the websites of eight academic societies and medical schools was carried out. These sites were evaluated against parameters that define the quality of an eLearning website, as well as the shareable content object reference model (SCORM) technical standards. All studied platforms were maintained by a webmaster and regularly updated. Only two platforms had teleconference opportunities, five had courses in PDF format, and four allowed online testing. Based on SCORM standards, only four platforms allowed direct access without a password. The content of all platforms was adaptable, interoperable and reusable. But their sustainability was difficult to assess. In parallel, we developed the first eLearning platform to be used as part of a university diploma in microsurgery in France. The platform was evaluated by students enrolled this diploma program. A satisfaction survey and platform evaluation showed that students were generally satisfied and had used the platform for microsurgery education, especially the seven students living abroad. ELearning for microsurgery allows the content to be continuously updated, makes for fewer classroom visits, provides easy remote access, and especially better training time management and cost savings in terms of travel and accommodations. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Survival and failure modes: platform-switching for internal and external hexagon cemented fixed dental prostheses.

PubMed

Anchieta, Rodolfo B; Machado, Lucas S; Hirata, Ronaldo; Coelho, Paulo G; Bonfante, Estevam A

2016-10-01

This study evaluated the probability of survival (reliability) of platform-switched fixed dental prostheses (FDPs) cemented on different implant-abutment connection designs. Eighty-four-three-unit FDPs (molar pontic) were cemented on abutments connected to two implants of external or internal hexagon connection. Four groups (n = 21 each) were established: external hexagon connection and regular platform (ERC); external hexagon connection and switched platform (ESC); internal hexagon and regular platform (IRC); and internal hexagon and switched platform (ISC). Prostheses were subjected to step-stress accelerated life testing in water. Weibull curves and probability of survival for a mission of 100,000 cycles at 400 N (two-sided 90% CI) were calculated. The beta values of 0.22, 0.48, 0.50, and 1.25 for groups ERC, ESC, IRC, and ISC, respectively, indicated a limited role of fatigue in damage accumulation, except for group ISC. Survival decreased for both platform-switched groups (ESC: 74%, and ISC: 59%) compared with the regular matching platform counterparts (ERC: 95%, and IRC: 98%). Characteristic strength was higher only for ERC compared with ESC, but not different between internal connections. Failures chiefly involved the abutment screw. Platform switching decreased the probability of survival of FDPs on both external and internal connections. The absence in loss of characteristic strength observed in internal hexagon connections favor their use compared with platform-switched external hexagon connections. © 2016 Eur J Oral Sci.

Using coral disease prevalence to assess the effects of concentrating tourism activities on offshore reefs in a tropical marine park.

PubMed

Lamb, Joleah B; Willis, Bette L

2011-10-01

Concentrating tourism activities can be an effective way to closely manage high-use parks and minimize the extent of the effects of visitors on plants and animals, although considerable investment in permanent tourism facilities may be required. On coral reefs, a variety of human-related disturbances have been associated with elevated levels of coral disease, but the effects of reef-based tourist facilities (e.g., permanent offshore visitor platforms) on coral health have not been assessed. In partnership with reef managers and the tourism industry, we tested the effectiveness of concentrating tourism activities as a strategy for managing tourism on coral reefs. We compared prevalence of brown band disease, white syndromes, black band disease, skeletal eroding band, and growth anomalies among reefs with and without permanent tourism platforms within the Great Barrier Reef Marine Park. Coral diseases were 15 times more prevalent at reefs with offshore tourism platforms than at nearby reefs without platforms. The maximum prevalence and maximum number of cases of each disease type were recorded at reefs with permanently moored tourism platforms. Diseases affected 10 coral genera from 7 families at reefs with platforms and 4 coral genera from 3 families at reefs without platforms. The greatest number of disease cases occurred within the spatially dominant acroporid corals, which exhibited 18-fold greater disease prevalence at reefs with platforms than at reefs without platforms. Neither the percent cover of acroporids nor overall coral cover differed significantly between reefs with and without platforms, which suggests that neither factor was responsible for the elevated levels of disease. Identifying how tourism activities and platforms facilitate coral disease in marine parks will help ensure ongoing conservation of coral assemblages and tourism. ©2011 Society for Conservation Biology.

Embedded-Based Graphics Processing Unit Cluster Platform for Multiple Sequence Alignments

PubMed Central

Wei, Jyh-Da; Cheng, Hui-Jun; Lin, Chun-Yuan; Ye, Jin; Yeh, Kuan-Yu

2017-01-01

High-end graphics processing units (GPUs), such as NVIDIA Tesla/Fermi/Kepler series cards with thousands of cores per chip, are widely applied to high-performance computing fields in a decade. These desktop GPU cards should be installed in personal computers/servers with desktop CPUs, and the cost and power consumption of constructing a GPU cluster platform are very high. In recent years, NVIDIA releases an embedded board, called Jetson Tegra K1 (TK1), which contains 4 ARM Cortex-A15 CPUs and 192 Compute Unified Device Architecture cores (belong to Kepler GPUs). Jetson Tegra K1 has several advantages, such as the low cost, low power consumption, and high applicability, and it has been applied into several specific applications. In our previous work, a bioinformatics platform with a single TK1 (STK platform) was constructed, and this previous work is also used to prove that the Web and mobile services can be implemented in the STK platform with a good cost-performance ratio by comparing a STK platform with the desktop CPU and GPU. In this work, an embedded-based GPU cluster platform will be constructed with multiple TK1s (MTK platform). Complex system installation and setup are necessary procedures at first. Then, 2 job assignment modes are designed for the MTK platform to provide services for users. Finally, ClustalW v2.0.11 and ClustalWtk will be ported to the MTK platform. The experimental results showed that the speedup ratios achieved 5.5 and 4.8 times for ClustalW v2.0.11 and ClustalWtk, respectively, by comparing 6 TK1s with a single TK1. The MTK platform is proven to be useful for multiple sequence alignments. PMID:28835734

The effect of platform switching on the levels of metal ion release from different implant–abutment couples

PubMed Central

Alrabeah, Ghada O; Knowles, Jonathan C; Petridis, Haralampos

2016-01-01

The improved peri-implant bone response demonstrated by platform switching may be the result of reduced amounts of metal ions released to the surrounding tissues. The aim of this study was to compare the levels of metal ions released from platform-matched and platform-switched implant–abutment couples as a result of accelerated corrosion. Thirty-six titanium alloy (Ti-6Al-4V) and cobalt–chrome alloy abutments were coupled with titanium cylinders forming either platform-switched or platform-matched groups (n=6). In addition, 18 unconnected samples served as controls. The specimens were subjected to accelerated corrosion by static immersion in 1% lactic acid for 1 week. The amount of metal ions ion of each test tube was measured using inductively coupled plasma mass spectrometry. Scanning electron microscope (SEM) images and energy dispersive spectroscopy X-ray analyses were performed pre- and post-immersion to assess corrosion at the interface. The platform-matched groups demonstrated higher ion release for vanadium, aluminium, cobalt, chrome, and molybdenum compared with the platform-switched groups (P<0.05). Titanium was the highest element to be released regardless of abutment size or connection (P<0.05). SEM images showed pitting corrosion prominent on the outer borders of the implant and abutment platform surfaces. In conclusion, implant–abutment couples underwent an active corrosion process resulting in metal ions release into the surrounding environment. The highest amount of metal ions released was recorded for the platform-matched groups, suggesting that platform-switching concept has a positive effect in reducing the levels of metal ion release from the implant–abutment couples. PMID:27357323

Embedded-Based Graphics Processing Unit Cluster Platform for Multiple Sequence Alignments.

PubMed

Wei, Jyh-Da; Cheng, Hui-Jun; Lin, Chun-Yuan; Ye, Jin; Yeh, Kuan-Yu

2017-01-01

High-end graphics processing units (GPUs), such as NVIDIA Tesla/Fermi/Kepler series cards with thousands of cores per chip, are widely applied to high-performance computing fields in a decade. These desktop GPU cards should be installed in personal computers/servers with desktop CPUs, and the cost and power consumption of constructing a GPU cluster platform are very high. In recent years, NVIDIA releases an embedded board, called Jetson Tegra K1 (TK1), which contains 4 ARM Cortex-A15 CPUs and 192 Compute Unified Device Architecture cores (belong to Kepler GPUs). Jetson Tegra K1 has several advantages, such as the low cost, low power consumption, and high applicability, and it has been applied into several specific applications. In our previous work, a bioinformatics platform with a single TK1 (STK platform) was constructed, and this previous work is also used to prove that the Web and mobile services can be implemented in the STK platform with a good cost-performance ratio by comparing a STK platform with the desktop CPU and GPU. In this work, an embedded-based GPU cluster platform will be constructed with multiple TK1s (MTK platform). Complex system installation and setup are necessary procedures at first. Then, 2 job assignment modes are designed for the MTK platform to provide services for users. Finally, ClustalW v2.0.11 and ClustalWtk will be ported to the MTK platform. The experimental results showed that the speedup ratios achieved 5.5 and 4.8 times for ClustalW v2.0.11 and ClustalWtk, respectively, by comparing 6 TK1s with a single TK1. The MTK platform is proven to be useful for multiple sequence alignments.

Overview of Next-generation Sequencing Platforms Used in Published Draft Plant Genomes in Light of Genotypization of Immortelle Plant (Helichrysium Arenarium)

PubMed Central

Hodzic, Jasin; Gurbeta, Lejla; Omanovic-Miklicanin, Enisa; Badnjevic, Almir

2017-01-01

Introduction: Major advancements in DNA sequencing methods introduced in the first decade of the new millennium initiated a rapid expansion of sequencing studies, which yielded a tremendous amount of DNA sequence data, including whole sequenced genomes of various species, including plants. A set of novel sequencing platforms, often collectively named as “next-generation sequencing” (NGS) completely transformed the life sciences, by allowing extensive throughput, while greatly reducing the necessary time, labor and cost of any sequencing endeavor. Purpose: of this paper is to present an overview NGS platforms used to produce the current compendium of published draft genomes of various plants, namely the Roche/454, ABI/SOLiD, and Solexa/Illumina, and to determine the most frequently used platform for the whole genome sequencing of plants in light of genotypization of immortelle plant. Materials and methods: 45 papers were selected (with 47 presented plant genome draft sequences), and utilized sequencing techniques and NGS platforms (Roche/454, ABI/SOLiD and Illumina/Solexa) in selected papers were determined. Subsequently, frequency of usage of each platform or combination of platforms was calculated. Results: Illumina/Solexa platforms are by used either as sole sequencing tool in 40.42% of published genomes, or in combination with other platforms - additional 48.94% of published genomes, followed by Roche/454 platforms, used in combination with traditional Sanger sequencing method (10.64%), and never as a sole tool. ABI/SOLiD was only used in combination with Illumina/Solexa and Roche/454 in 4.25% of publications. Conclusions: Illumina/Solexa platforms are by far most preferred by researchers, most probably due to most affordable sequencing costs. Taking into consideration the current economic situation in the Balkans region, Illumina Solexa is the best (if not the only) platform choice if the sequencing of immortelle plant (Helichrysium arenarium) is to be performed by the researchers in this region. PMID:28974852

The Doktabörse - an innovative online platform for research projects at the medical faculty of the LMU Munich.

PubMed

Nicolai, Leo; Gradel, Maximilian; Antón, Sofia; Pander, Tanja; Kalb, Anke; Köhler, Lisa; Fischer, Martin R; Dimitriadis, Konstantinos; von der Borch, Philip

2017-01-01

Introduction: One of the most important extracurricular aspects of medical studies in Germany is a research thesis completed by most students. This research project often times conveys relevant competencies for the physician's role as scientist. Nevertheless, the choice of the right project remains a challenge. Reasons for this are among others, missing structures for a comprehensive overview of research groups and their respective projects. Description of the project: We developed the online platform Doktabörse as an online marketplace for doctoral research projects. The platform enables authorized researchers to create working groups and upload, deactivate and change research projects within their institute. For interested students, a front end with integrated search function displays these projects in a structured and well-arranged way. In parallel, the Doktabörse provides for a comprehensive overview of research at the medical faculty. We evaluated Researchers' and students' use of the platform. Results: 96,6% of students participating in the evaluation (n=400) were in favor of a centralized research platform at the medical faculty. The platform grew at a steady pace and included 120 research groups in June 2016. The students appreciated the structure and design of the Doktabörse. Two thirds of all uploaded projects matched successfully with doctoral students via the platform and over 94% of researchers stated that they did not need technical assistance with uploading projects and handling the platform. Discussion : The Doktabörse represents an innovative and well accepted platform for doctoral research projects. The platform is perceived positively by researchers and students alike. However, students criticized limited extent and timeliness of offered projects. In addition, the platform serves as databank of research at the medical faculty of the LMU Munich. The future potential of this platform is to provide for an integrated management solution of doctoral thesis projects, possibly beyond the medical field and faculty.

The geomorphic effect of recent storms - Quantifying meso scale abrasion across a shore platform

NASA Astrophysics Data System (ADS)

Cullen, Niamh; Bourke, Mary; Naylor, Larissa

2017-04-01

Boulder abrasion trails (BATs) are lineations on the surface of rock platforms formed by the movement of traction-load clasts by waves. They have been observed on a variety of platform lithologies, including limestone, granite and basalt. Despite previous reporting of these features, the abrasion styles and geomorphic work done by boulder transport has not been quantified. We present the first quantitative measurement of shore platform erosion by boulder transport during extreme storms that occurred in the winter of 2015-2016. Following two storm events in 2016 we mapped and measured 33 individual BATs on a sandstone platform on the west coast of Ireland. The total (minimum) abraded surface area was 10m2. The total (minimum) volume of material abraded was 0.2m3. In order to test the efficacy of this process during non-storm conditions we conducted field experiments on the same platform. We identified two sites on the platform that were similar, but differed in their intertidal roughness. We installed an RBR solo wave pressure transducer (PT) at 0m OD at both locations to record wave data. We measured platform roughness, determined as the fractal dimension of the platform profiles at both sites. We deployed an array of boulders of known dimensions and mass, parallel to the shoreline at 0.5m intervals from the PTs. The experiments were conducted 1. during relatively calm conditions and 2. during higher energy conditions. Data was collected for one tidal cycle. Any boulder displacement distance and direction was measured and geomorphic effects were documented. We find that BATs are formed under a range of wave energy conditions. Our observations indicate that along the North Atlantic coastline, BATs can occur at a high frequency, only limited by sediment supply. Our data show that abrasion by boulder transport is a potentially significant geomorphological process acting to abrade platforms under contemporary climate conditions. In addition, our preliminary findings suggest that platform roughness exerts a strong influence on wave energy and potential boulder transport. We find that abrasion of the platform surface is a fundamentally important process which contributes to lowering of the platform surface over time.

Data Collection for Mental Health Studies Through Digital Platforms: Requirements and Design of a Prototype

PubMed Central

Triana Hoyos, Ana Maria; Alakörkkö, Tuomas; Kaski, Kimmo; Saramäki, Jari; Isometsä, Erkki; Darst, Richard K

2017-01-01

Background Mental and behavioral disorders are the main cause of disability worldwide. However, their diagnosis is challenging due to a lack of reliable biomarkers; current detection is based on structured clinical interviews which can be biased by the patient’s recall ability, affective state, changing in temporal frames, etc. While digital platforms have been introduced as a possible solution to this complex problem, there is little evidence on the extent of usability and usefulness of these platforms. Therefore, more studies where digital data is collected in larger scales are needed to collect scientific evidence on the capacities of these platforms. Most of the existing platforms for digital psychiatry studies are designed as monolithic systems for a certain type of study; publications from these studies focus on their results, rather than the design features of the data collection platform. Inevitably, more tools and platforms will emerge in the near future to fulfill the need for digital data collection for psychiatry. Currently little knowledge is available from existing digital platforms for future data collection platforms to build upon. Objective The objective of this work was to identify the most important features for designing a digital platform for data collection for mental health studies, and to demonstrate a prototype platform that we built based on these design features. Methods We worked closely in a multidisciplinary collaboration with psychiatrists, software developers, and data scientists and identified the key features which could guarantee short-term and long-term stability and usefulness of the platform from the designing stage to data collection and analysis of collected data. Results The key design features that we identified were flexibility of access control, flexibility of data sources, and first-order privacy protection. We also designed the prototype platform Non-Intrusive Individual Monitoring Architecture (Niima), where we implemented these key design features. We described why each of these features are important for digital data collection for psychiatry, gave examples of projects where Niima was used or is going to be used in the future, and demonstrated how incorporating these design principles opens new possibilities for studies. Conclusions The new methods of digital psychiatry are still immature and need further research. The design features we suggested are a first step to design platforms which can adapt to the upcoming requirements of digital psychiatry. PMID:28600276

Dynamic Gaming Platform (DGP)

DTIC Science & Technology

2009-04-01

GAMING PLATFORM (DGP) Lockheed Martin Corporation...YYYY) APR 09 2. REPORT TYPE Final 3. DATES COVERED (From - To) Jul 07 – Mar 09 4. TITLE AND SUBTITLE DYNAMIC GAMING PLATFORM (DGP) 5a...CMU Carnegie Mellon University DGP Dynamic Gaming Platform GA Genetic Algorithm IARPA Intelligence Advanced Research Projects Activity LM ATL Lockheed Martin Advanced Technology Laboratories PAINT ProActive INTelligence

49 CFR 571.403 - Standard No. 403; Platform lift systems for motor vehicles.

Code of Federal Regulations, 2012 CFR

2012-10-01

... relative to the platform surface. After removal of the load, the handrail must exhibit no permanent... 49 Transportation 6 2012-10-01 2012-10-01 false Standard No. 403; Platform lift systems for motor... STANDARDS Federal Motor Vehicle Safety Standards § 571.403 Standard No. 403; Platform lift systems for motor...

77 FR 20558 - Federal Motor Vehicle Safety Standards; Platform Lifts for Motor Vehicles; Platform Lift...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-05

... amendments to the Federal motor vehicle safety standards on platform lift systems for motor vehicles. The... [email protected] . For legal issues, you may contact David Jasinski, Office of the Chief Counsel, NCC... in the Federal Register a final rule establishing FMVSS No. 403, Platform lift systems for motor...

30 CFR 250.921 - How do I analyze my platform for cumulative fatigue?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false How do I analyze my platform for cumulative fatigue? 250.921 Section 250.921 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR... Inspection, Maintenance, and Assessment of Platforms § 250.921 How do I analyze my platform for cumulative...

33 CFR 147.809 - Mars Tension Leg Platform safety zone.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Mars Tension Leg Platform safety... SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.809 Mars Tension Leg Platform safety zone. (a) Description. The Mars Tension Leg Platform (Mars TLP) is located at position 28°10′10.29...

33 CFR 147.809 - Mars Tension Leg Platform safety zone.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Mars Tension Leg Platform safety... SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.809 Mars Tension Leg Platform safety zone. (a) Description. The Mars Tension Leg Platform (Mars TLP) is located at position 28°10′10.29...

33 CFR 147.809 - Mars Tension Leg Platform safety zone.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Mars Tension Leg Platform safety... SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.809 Mars Tension Leg Platform safety zone. (a) Description. The Mars Tension Leg Platform (Mars TLP) is located at position 28°10′10.29...

33 CFR 147.809 - Mars Tension Leg Platform safety zone.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Mars Tension Leg Platform safety... SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.809 Mars Tension Leg Platform safety zone. (a) Description. The Mars Tension Leg Platform (Mars TLP) is located at position 28°10′10.29...

33 CFR 147.809 - Mars Tension Leg Platform safety zone.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Mars Tension Leg Platform safety... SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.809 Mars Tension Leg Platform safety zone. (a) Description. The Mars Tension Leg Platform (Mars TLP) is located at position 28°10′10.29...

Development of a Web-Enabled Learning Platform for Geospatial Laboratories: Improving the Undergraduate Learning Experience

ERIC Educational Resources Information Center

Mui, Amy B.; Nelson, Sarah; Huang, Bruce; He, Yuhong; Wilson, Kathi

2015-01-01

This paper describes a web-enabled learning platform providing remote access to geospatial software that extends the learning experience outside of the laboratory setting. The platform was piloted in two undergraduate courses, and includes a software server, a data server, and remote student users. The platform was designed to improve the quality…

49 CFR 571.404 - Standard No. 404; Platform lift installations in motor vehicles.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 6 2010-10-01 2010-10-01 false Standard No. 404; Platform lift installations in... VEHICLE SAFETY STANDARDS Federal Motor Vehicle Safety Standards § 571.404 Standard No. 404; Platform lift... platform lifts used to assist persons with limited mobility in entering or leaving a vehicle. S2. Purpose...

49 CFR 571.404 - Standard No. 404; Platform lift installations in motor vehicles.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 6 2011-10-01 2011-10-01 false Standard No. 404; Platform lift installations in... VEHICLE SAFETY STANDARDS Federal Motor Vehicle Safety Standards § 571.404 Standard No. 404; Platform lift... platform lifts used to assist persons with limited mobility in entering or leaving a vehicle. S2. Purpose...

Geostationary Platforms Mission and Payload Requirements Study. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

1979-01-01

Time-phased missions and payloads for potential accommodation on geostationary platforms and the engineering requirements placed upon the platform housekeeping elements by selected payloads are identified. Optimum locations for geostationary platforms, potential missions and their characteristics, and potential user requirements were determined as well as the interface requirements between the missions and h the geostationary platform. A payload data book was prepared and antenna tradeoff studies were conducted. Payload missions are defined in terms of frequencies, power, beam patterns, interconnections, support requirements, and other characteristics.

Cross-platform learning: on the nature of children's learning from multiple media platforms.

PubMed

Fisch, Shalom M

2013-01-01

It is increasingly common for an educational media project to span several media platforms (e.g., TV, Web, hands-on materials), assuming that the benefits of learning from multiple media extend beyond those gained from one medium alone. Yet research typically has investigated learning from a single medium in isolation. This paper reviews several recent studies to explore cross-platform learning (i.e., learning from combined use of multiple media platforms) and how such learning compares to learning from one medium. The paper discusses unique benefits of cross-platform learning, a theoretical mechanism to explain how these benefits might arise, and questions for future research in this emerging field. Copyright © 2013 Wiley Periodicals, Inc., A Wiley Company.

Space assembly fixtures and aids

NASA Technical Reports Server (NTRS)

Bloom, K. A.; Lillenas, A. N.

1980-01-01

Concepts and requirements for assembly fixtures and aids necessary for the assembly and maintenance of spare platforms were studied. Emphasis was placed on erectable and deployable type structures with the shuttle orbiter as the assembly base. Both single and multiple orbiter flight cases for the platform assembly were considered. Applicable space platform assembly studies were reviewed to provide a data base for establishing the assembly fixture and aids design requirements, assembly constraints, and the development of representative design concepts. Conclusions indicated that fixture requirements will vary with platform size. Larger platforms will require translation relative to the orbiter RMS working volume. The installation of platform payloads and subsystems (e.g., utility distribution) must also be considered in the specification of assembly fixtures and aids.

Apparatus to position a microelectromechanical platform

DOEpatents

Miller, Samuel Lee; Rodgers, Murray Steven

2003-09-23

The present invention comprises a microelectromechanical positioner to achieve substantially translational positioning of a platform without rotational motion, thereby maintaining a constant angular orientation of the platform during movement. A linkage mechanism of the positioner can comprise parallelogram linkages to constrain the rotational motion of the platform. Such linkages further can comprise flexural hinges or other turning joints at the linkage pivots to eliminate the need for rubbing surfaces. A plurality of the linkage mechanisms can be used to enable translational motion of the platform with two degrees of freedom. A variety of means can be used to actuate the positioner. Independent actuation of the anchor links of the linkage mechanisms with rotary electrostatic actuators can be used to provide controlled translational movement of the platform.

Platform B North Installation

NASA Image and Video Library

2016-12-16

Construction workers wearing safety harnesses and tethered lines assist with the installation of the second half of the B-level work platforms, B north, for NASA’s Space Launch System (SLS) rocket, high up in the Vehicle Assembly Building (VAB) at NASA’s Kennedy Space Center in Florida. They are securing the large bolts that hold the platform securely in place on the north side of High Bay 3. The B platforms are the ninth of 10 levels of work platforms that will surround and provide access to the SLS rocket and Orion spacecraft for Exploration Mission 1. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to VAB High Bay 3, including installation of the new work platforms, to prepare for NASA’s Journey to Mars.

Design of a dynamic test platform for autonomous robot vision systems

NASA Technical Reports Server (NTRS)

Rich, G. C.

1980-01-01

The concept and design of a dynamic test platform for development and evluation of a robot vision system is discussed. The platform is to serve as a diagnostic and developmental tool for future work with the RPI Mars Rover's multi laser/multi detector vision system. The platform allows testing of the vision system while its attitude is varied, statically or periodically. The vision system is mounted on the test platform. It can then be subjected to a wide variety of simulated can thus be examined in a controlled, quantitative fashion. Defining and modeling Rover motions and designing the platform to emulate these motions are also discussed. Individual aspects of the design process are treated separately, as structural, driving linkages, and motors and transmissions.

Platform C North Installation

NASA Image and Video Library

2016-11-10

A heavy-lift crane lifts the second half of the C-level work platforms, C north, for NASA’s Space Launch System (SLS) rocket, high up from the transfer aisle of the Vehicle Assembly Building (VAB) at NASA's Kennedy Space Center in Florida. The C platform will be moved into High Bay 3 for installation on the north side of High Bay 3. The C platforms are the eighth of 10 levels of work platforms that will surround and provide access to the SLS rocket and Orion spacecraft for Exploration Mission 1. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to VAB High Bay 3, including installation of the new work platforms, to prepare for NASA’s Journey to Mars.

Platform B North Installation

NASA Image and Video Library

2016-12-16

A construction worker solders a section of steel during the installation of the second half of the B-level work platforms, B north, for NASA's Space Launch System (SLS) rocket, in High Bay 3 in the Vehicle Assembly Building (VAB) at NASA's Kennedy Space Center in Florida. Construction workers will secure the large bolts that hold the platform in place on the north wall. The B platforms are the ninth of 10 levels of work platforms that will surround and provide access to the SLS rocket and Orion spacecraft for Exploration Mission 1. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to VAB High Bay 3, including installation of the new work platforms, to prepare for NASA’s Journey to Mars.

Apparatus and method for materials processing utilizing a rotating magnetic field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muralidharan, Govindarajan; Angelini, Joseph A.; Murphy, Bart L.

An apparatus for materials processing utilizing a rotating magnetic field comprises a platform for supporting a specimen, and a plurality of magnets underlying the platform. The plurality of magnets are configured for rotation about an axis of rotation intersecting the platform. A heat source is disposed above the platform for heating the specimen during the rotation of the plurality of magnets. A method for materials processing utilizing a rotating magnetic field comprises providing a specimen on a platform overlying a plurality of magnets; rotating the plurality of magnets about an axis of rotation intersecting the platform, thereby applying a rotatingmore » magnetic field to the specimen; and, while rotating the plurality of magnets, heating the specimen to a desired temperature.« less

Development of a Modular Research Platform to Create Medical Observational Studies for Mobile Devices.

PubMed

Zens, Martin; Grotejohann, Birgit; Tassoni, Adrian; Duttenhoefer, Fabian; Südkamp, Norbert P; Niemeyer, Philipp

2017-05-23

Observational studies have proven to be a valuable resource in medical research, especially when performed on a large scale. Recently, mobile device-based observational studies have been discovered by an increasing number of researchers as a promising new source of information. However, the development and deployment of app-based studies is not trivial and requires profound programming skills. The aim of this project was to develop a modular online research platform that allows researchers to create medical studies for mobile devices without extensive programming skills. The platform approach for a modular research platform consists of three major components. A Web-based platform forms the researchers' main workplace. This platform communicates via a shared database with a platform independent mobile app. Furthermore, a separate Web-based login platform for physicians and other health care professionals is outlined and completes the concept. A prototype of the research platform has been developed and is currently in beta testing. Simple questionnaire studies can be created within minutes and published for testing purposes. Screenshots of an example study are provided, and the general working principle is displayed. In this project, we have created a basis for a novel research platform. The necessity and implications of a modular approach were displayed and an outline for future development given. International researchers are invited and encouraged to participate in this ongoing project. ©Martin Zens, Birgit Grotejohann, Adrian Tassoni, Fabian Duttenhoefer, Norbert P Südkamp, Philipp Niemeyer. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 23.05.2017.

Modern sediments and Pleistocene reefs from isolated carbonate platforms (Iles Eparses, SW Indian Ocean): A preliminary study

NASA Astrophysics Data System (ADS)

Jorry, Stéphan J.; Camoin, Gilbert F.; Jouet, Gwénaël; Roy, Pascal Le; Vella, Claude; Courgeon, Simon; Prat, Sophie; Fontanier, Christophe; Paumard, Victorien; Boulle, Julien; Caline, Bruno; Borgomano, Jean

2016-04-01

Isolated carbonate platforms occur throughout the geologic record, from Archean to present. Although the respective roles of tectonics, sediment supply and sea-level changes in the stratigraphical architecture of these systems are relatively well constrained, the details of the nature and controls on the variability of sedimentological patterns between and within individual geomorphologic units on platforms have been barely investigated. This study aims at describing and comparing geomorphological and sedimentological features of surficial sediments and fossil reefs from three isolated carbonate platforms located in the SW Indian Ocean (Glorieuses, Juan de Nova and Europa). These carbonate platforms are relatively small and lack continuous reef margins, which have developed only on windward sides. Field observations, petrographic characterization and grain-size analyses are used to illustrate the spatial patterns of sediment accumulation on these platforms. The internal parts of both Glorieuses and Juan de Nova platforms are blanketed by sand dunes with medium to coarse sands with numerous reef pinnacles. Skeletal components including coral, green algae, and benthic foraminifera fragments prevail in these sediments. Europa platform exhibits a similar skeletal assemblage dominated by coral fragments, with the absence of wave-driven sedimentary bodies. Fossil reefs from the Last interglacial (125,000 years BP) occur on the three platforms. At Glorieuses, a succession of drowned terraces detected on seismic lines is interpreted as reflecting the last deglacial sea-level rise initiated 20,000 years ago. These findings highlight the high potential of these platforms to study past sea-level changes and the related reef response, which remain poorly documented in the SW Indian Ocean.

A pilot study of surgical training using a virtual robotic surgery simulator.

PubMed

Tergas, Ana I; Sheth, Sangini B; Green, Isabel C; Giuntoli, Robert L; Winder, Abigail D; Fader, Amanda N

2013-01-01

Our objectives were to compare the utility of learning a suturing task on the virtual reality da Vinci Skills Simulator versus the da Vinci Surgical System dry laboratory platform and to assess user satisfaction among novice robotic surgeons. Medical trainees were enrolled prospectively; one group trained on the virtual reality simulator, and the other group trained on the da Vinci dry laboratory platform. Trainees received pretesting and post-testing on the dry laboratory platform. Participants then completed an anonymous online user experience and satisfaction survey. We enrolled 20 participants. Mean pretest completion times did not significantly differ between the 2 groups. Training with either platform was associated with a similar decrease in mean time to completion (simulator platform group, 64.9 seconds [P = .04]; dry laboratory platform group, 63.9 seconds [P < .01]). Most participants (58%) preferred the virtual reality platform. The majority found the training "definitely useful" in improving robotic surgical skills (mean, 4.6) and would attend future training sessions (mean, 4.5). Training on the virtual reality robotic simulator or the dry laboratory robotic surgery platform resulted in significant improvements in time to completion and economy of motion for novice robotic surgeons. Although there was a perception that both simulators improved performance, there was a preference for the virtual reality simulator. Benefits unique to the simulator platform include autonomy of use, computerized performance feedback, and ease of setup. These features may facilitate more efficient and sophisticated simulation training above that of the conventional dry laboratory platform, without loss of efficacy.

Mathematical analysis of the impact mechanism of information platform on agro-product supply chain and agro-product competitiveness

NASA Astrophysics Data System (ADS)

Jiang, Qi-Jie; Jin, Mao-Zhu; Ren, Pei-Yu

2017-04-01

How to optimize agro-product supply chain to promote its operating efficiency so as to enhance the competitiveness of regional agricultural products has posed a problem to academic circles, business circles and governments of various levels. One way to solve this problem is to introduce an information platform into the supply chain, which this essay focuses on. Firstly, a review of existing research findings concerning the agro-product competitiveness, agro-product supply chain (ASC) and information platform was given. Secondly, we constructed a mathematical model to analyze the impact of information platform on the bullwhip effect in ASC. Thirdly, another mathematical model was constructed to help compare and analyze the impact of information platform on information acquisition of members in ASC. The research results show that the implantation of information platform can mitigate the bullwhip effect in ASC, and members can determine order amount or production more close to the actual market demand. And also the information platform can reduce the time for members in ASC to get information from other members. Besides, information platform can help ASC to alleviate information asymmetry among upstream and downstream members. Furthermore, researches about the operating mechanism and pattern, technical feature and running structure of the information platform, along with their impacts on agro-product supply chain and the competitiveness of agricultural products need to be advanced.

30 CFR 56.7051 - Loose objects on the mast or drill platform.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Loose objects on the mast or drill platform. 56... Drilling and Rotary Jet Piercing Drilling § 56.7051 Loose objects on the mast or drill platform. To prevent injury to personnel, tools and other objects shall not be left loose on the mast or drill platform. ...

Strategies Used by Professors through Virtual Educational Platforms in Face-to-Face Classes: A View from the Chamilo Platform

ERIC Educational Resources Information Center

Valencia, Heriberto Gonzalez; Villota Enriquez, Jackeline Amparo; Agredo, Patricia Medina

2017-01-01

This study consisted in characterizing the strategies used by professors; implemented through virtual educational platforms. The context of this research were the classrooms of the Santiago de Cali University and the virtual space of the Chamilo virtual platform, where two professors from the Faculty of Education of the same university…

30 CFR 250.911 - If my platform is subject to the Platform Verification Program, what must I do?

Code of Federal Regulations, 2010 CFR

2010-07-01

... a project management timeline, Gantt Chart, that depicts when interim and final reports required by... 30 Mineral Resources 2 2010-07-01 2010-07-01 false If my platform is subject to the Platform Verification Program, what must I do? 250.911 Section 250.911 Mineral Resources MINERALS MANAGEMENT SERVICE...

30 CFR 56.7051 - Loose objects on the mast or drill platform.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Loose objects on the mast or drill platform. 56... Drilling and Rotary Jet Piercing Drilling § 56.7051 Loose objects on the mast or drill platform. To prevent injury to personnel, tools and other objects shall not be left loose on the mast or drill platform. ...

30 CFR 56.7051 - Loose objects on the mast or drill platform.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Loose objects on the mast or drill platform. 56... Drilling and Rotary Jet Piercing Drilling § 56.7051 Loose objects on the mast or drill platform. To prevent injury to personnel, tools and other objects shall not be left loose on the mast or drill platform. ...

Creating an Effective Multi-Domain Wide-Area Surveillance Platform to Enhance Border Security

DTIC Science & Technology

2008-03-01

SWOT ANALYSIS ........................................................................................43 I. ANALYSIS OF PROS AND CONS ...weaknesses and opportunities and SWOT analysis was also used to build pros and cons for the platform. All the interviewees liked unmanned platforms...because of the reduced night hour’s operations and SWOT analysis was also used to build pros and cons for the platform. All the interviewees really

46 CFR 160.027-7 - Pre-approval tests for alternate platform designs.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 6 2014-10-01 2014-10-01 false Pre-approval tests for alternate platform designs. 160... § 160.027-7 Pre-approval tests for alternate platform designs. (a) The tests in this section are for... deformation as a result of this test. (c) The float body must be supported so that the platform is suspended...

46 CFR 160.027-7 - Pre-approval tests for alternate platform designs.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 6 2011-10-01 2011-10-01 false Pre-approval tests for alternate platform designs. 160... § 160.027-7 Pre-approval tests for alternate platform designs. (a) The tests in this section are for... deformation as a result of this test. (c) The float body must be supported so that the platform is suspended...

46 CFR 160.027-7 - Pre-approval tests for alternate platform designs.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 6 2013-10-01 2013-10-01 false Pre-approval tests for alternate platform designs. 160... § 160.027-7 Pre-approval tests for alternate platform designs. (a) The tests in this section are for... deformation as a result of this test. (c) The float body must be supported so that the platform is suspended...

46 CFR 160.027-7 - Pre-approval tests for alternate platform designs.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 6 2010-10-01 2010-10-01 false Pre-approval tests for alternate platform designs. 160... § 160.027-7 Pre-approval tests for alternate platform designs. (a) The tests in this section are for... deformation as a result of this test. (c) The float body must be supported so that the platform is suspended...

46 CFR 160.027-7 - Pre-approval tests for alternate platform designs.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 6 2012-10-01 2012-10-01 false Pre-approval tests for alternate platform designs. 160... § 160.027-7 Pre-approval tests for alternate platform designs. (a) The tests in this section are for... deformation as a result of this test. (c) The float body must be supported so that the platform is suspended...

Electrostatically Driven Large Aperture Micro-Mirror Actuator Assemblies for High Fill-Factor, Agile Optical Phase Arrays

DTIC Science & Technology

2015-06-18

platform assembly 2, with micro-mirror platform deflection, measured on actuation side ( PFa ) and side opposite actuation (PFo...beam micro-mirror platform assembly 1; micro-mirror platform deflection, measured on actuation side ( PFa ) and side opposite actuation (PFo...side ( PFa ) and side opposite actuation (PFo) ........................................................ 106 xiv Figure 73: Graph of measured 10-beam

Development of a Web-Enabled Informatics Platform for Manipulation of Gene Expression Data

DTIC Science & Technology

2004-12-01

genomic platforms such as metabolomics and proteomics , and to federated databases for knowledge management. A successful SBIR Phase I completed...measurements that require sophisticated bioinformatic platforms for data archival, management, integration, and analysis if researchers are to derive...web-enabled bioinformatic platform consisting of a Laboratory Information Management System (LIMS), an Analysis Information Management System (AIMS

Information Management Platform for Data Analytics and Aggregation (IMPALA) System Design Document

NASA Technical Reports Server (NTRS)

Carnell, Andrew; Akinyelu, Akinyele

2016-01-01

The System Design document tracks the design activities that are performed to guide the integration, installation, verification, and acceptance testing of the IMPALA Platform. The inputs to the design document are derived from the activities recorded in Tasks 1 through 6 of the Statement of Work (SOW), with the proposed technical solution being the completion of Phase 1-A. With the documentation of the architecture of the IMPALA Platform and the installation steps taken, the SDD will be a living document, capturing the details about capability enhancements and system improvements to the IMPALA Platform to provide users in development of accurate and precise analytical models. The IMPALA Platform infrastructure team, data architecture team, system integration team, security management team, project manager, NASA data scientists and users are the intended audience of this document. The IMPALA Platform is an assembly of commercial-off-the-shelf (COTS) products installed on an Apache-Hadoop platform. User interface details for the COTS products will be sourced from the COTS tools vendor documentation. The SDD is a focused explanation of the inputs, design steps, and projected outcomes of every design activity for the IMPALA Platform through installation and validation.

Application of a Smartphone Metabolomics Platform to the Authentication of Schisandra sinensis.

PubMed

Kwon, Hyuk Nam; Phan, Hong-Duc; Xu, Wen Jun; Ko, Yoon-Joo; Park, Sunghyouk

2016-05-01

Herbal medicines have been used for a long time all around the world. Since the quality of herbal preparations depends on the source of herbal materials, there has been a strong need to develop methods to correctly identify the origin of materials. To develop a smartphone metabolomics platform as a simpler and low-cost alternative for the identification of herbal material source. Schisandra sinensis extracts from Korea and China were prepared. The visible spectra of all samples were measured by a smartphone spectrometer platform. This platform included all the necessary measures built-in for the metabolomics research: data acquisition, processing, chemometric analysis and visualisation of the results. The result of the smartphone metabolomics platform was compared to that of NMR-based metabolomics, suggesting the feasibility of smartphone platform in metabolomics research. The smartphone metabolomics platform gave similar results to the NMR method, showing good separation between Korean and Chinese materials and correct predictability for all test samples. With its accuracy and advantages of affordability, user-friendliness, and portability, the smartphone metabolomics platform could be applied to the authentication of other medicinal plants. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Geostationary platform systems concepts definition study. Volume 2: Technical, book 2

NASA Technical Reports Server (NTRS)

1980-01-01

A selected concept for a geostationary platform is defined in sufficient detail to identify requirements for supporting research and technology, space demonstrations, GFE interfaces, costs, and schedules. This system consists of six platforms in geostationary orbit (GEO) over the Western Hemisphere and six over the Atlantic, to satisfy the total payload set associated with the nominal traffic model. Each platform is delivered to low Earth orbit (LEO) in a single shuttle flight, already mated to its LEO to GEO transfer vehicle and ready for deployment and transfer to GEO. An alternative concept is looked at briefly for comparison of configuration and technology requirements. This alternative consists of two large platforms, one over the Western Hemisphere consisting of three docked modules, and one over the Atlantic (two docked modules), to satisfy a high traffic model. The modules are full length orbiter cargo bay payloads, mated at LEO to orbital transfer vehicles (OTVs) delivered in other shuttle flights, for transfer to GEO, rendezvous, and docking. A preliminary feasibility study of an experimental platform is also performed to demonstrate communications and platform technologies required for the operational platforms of the 1990s.

Implementation of Online Veterinary Hospital on Cloud Platform.

PubMed

Chen, Tzer-Shyong; Chen, Tzer-Long; Chung, Yu-Fang; Huang, Yao-Min; Chen, Tao-Chieh; Wang, Huihui; Wei, Wei

2016-06-01

Pet markets involve in great commercial possibilities, which boost thriving development of veterinary hospital businesses. The service tends to intensive competition and diversified channel environment. Information technology is integrated for developing the veterinary hospital cloud service platform. The platform contains not only pet medical services but veterinary hospital management and services. In the study, QR Code andcloud technology are applied to establish the veterinary hospital cloud service platform for pet search by labeling a pet's identification with QR Code. This technology can break the restriction on veterinary hospital inspection in different areas and allows veterinary hospitals receiving the medical records and information through the exclusive QR Code for more effective inspection. As an interactive platform, the veterinary hospital cloud service platform allows pet owners gaining the knowledge of pet diseases and healthcare. Moreover, pet owners can enquire and communicate with veterinarians through the platform. Also, veterinary hospitals can periodically send reminders of relevant points and introduce exclusive marketing information with the platform for promoting the service items and establishing individualized marketing. Consequently, veterinary hospitals can increase the profits by information share and create the best solution in such a competitive veterinary market with industry alliance.

Computing Platforms for Big Biological Data Analytics: Perspectives and Challenges.

PubMed

Yin, Zekun; Lan, Haidong; Tan, Guangming; Lu, Mian; Vasilakos, Athanasios V; Liu, Weiguo

2017-01-01

The last decade has witnessed an explosion in the amount of available biological sequence data, due to the rapid progress of high-throughput sequencing projects. However, the biological data amount is becoming so great that traditional data analysis platforms and methods can no longer meet the need to rapidly perform data analysis tasks in life sciences. As a result, both biologists and computer scientists are facing the challenge of gaining a profound insight into the deepest biological functions from big biological data. This in turn requires massive computational resources. Therefore, high performance computing (HPC) platforms are highly needed as well as efficient and scalable algorithms that can take advantage of these platforms. In this paper, we survey the state-of-the-art HPC platforms for big biological data analytics. We first list the characteristics of big biological data and popular computing platforms. Then we provide a taxonomy of different biological data analysis applications and a survey of the way they have been mapped onto various computing platforms. After that, we present a case study to compare the efficiency of different computing platforms for handling the classical biological sequence alignment problem. At last we discuss the open issues in big biological data analytics.

End effector with astronaut foot restraint

NASA Technical Reports Server (NTRS)

Monford, Leo G., Jr. (Inventor)

1991-01-01

The combination of a foot restraint platform designed primarily for use by an astronaut being rigidly and permanently attached to an end effector which is suitable for attachment to the manipulator arm of a remote manipulating system is described. The foot restraint platform is attached by a brace to the end effector at a location away from the grappling interface of the end effector. The platform comprises a support plate provided with a pair of stirrups for receiving the toe portion of an astronaut's boots when standing on the platform and a pair of heel retainers in the form of raised members which are fixed to the surface of the platform and located to provide abutment surfaces for abutting engagement with the heels of the astronaut's boots when his toes are in the stirrups. The heel retainers preclude a backward sliding movement of the feet on the platform and instead require a lifting of the heels in order to extract the feet. The brace for attaching the foot restraint platform to the end effector may include a pivot or swivel joint to permit various orientations of the platform with respect to the end effector.

Intra-Platform Repeatability and Inter-Platform Comparability of MicroRNA Microarray Technology

PubMed Central

Sato, Fumiaki; Tsuchiya, Soken; Terasawa, Kazuya; Tsujimoto, Gozoh

2009-01-01

Over the last decade, DNA microarray technology has provided a great contribution to the life sciences. The MicroArray Quality Control (MAQC) project demonstrated the way to analyze the expression microarray. Recently, microarray technology has been utilized to analyze a comprehensive microRNA expression profiling. Currently, several platforms of microRNA microarray chips are commercially available. Thus, we compared repeatability and comparability of five different microRNA microarray platforms (Agilent, Ambion, Exiqon, Invitrogen and Toray) using 309 microRNAs probes, and the Taqman microRNA system using 142 microRNA probes. This study demonstrated that microRNA microarray has high intra-platform repeatability and comparability to quantitative RT-PCR of microRNA. Among the five platforms, Agilent and Toray array showed relatively better performances than the others. However, the current lineup of commercially available microRNA microarray systems fails to show good inter-platform concordance, probably because of lack of an adequate normalization method and severe divergence in stringency of detection call criteria between different platforms. This study provided the basic information about the performance and the problems specific to the current microRNA microarray systems. PMID:19436744

Polymer-based platform for microfluidic systems

DOEpatents

Benett, William [Livermore, CA; Krulevitch, Peter [Pleasanton, CA; Maghribi, Mariam [Livermore, CA; Hamilton, Julie [Tracy, CA; Rose, Klint [Boston, MA; Wang, Amy W [Oakland, CA

2009-10-13

A method of forming a polymer-based microfluidic system platform using network building blocks selected from a set of interconnectable network building blocks, such as wire, pins, blocks, and interconnects. The selected building blocks are interconnectably assembled and fixedly positioned in precise positions in a mold cavity of a mold frame to construct a three-dimensional model construction of a microfluidic flow path network preferably having meso-scale dimensions. A hardenable liquid, such as poly (dimethylsiloxane) is then introduced into the mold cavity and hardened to form a platform structure as well as to mold the microfluidic flow path network having channels, reservoirs and ports. Pre-fabricated elbows, T's and other joints are used to interconnect various building block elements together. After hardening the liquid the building blocks are removed from the platform structure to make available the channels, cavities and ports within the platform structure. Microdevices may be embedded within the cast polymer-based platform, or bonded to the platform structure subsequent to molding, to create an integrated microfluidic system. In this manner, the new microfluidic platform is versatile and capable of quickly generating prototype systems, and could easily be adapted to a manufacturing setting.

Methods for multi-material stereolithography

DOEpatents

Wicker, Ryan [El Paso, TX; Medina, Francisco [El Paso, TX; Elkins, Christopher [Redwood City, CA

2011-06-14

Methods and systems of stereolithography for building cost-efficient and time-saving multi-material, multi-functional and multi-colored prototypes, models and devices configured for intermediate washing and curing/drying is disclosed including: laser(s), liquid and/or platform level sensing system(s), controllable optical system(s), moveable platform(s), elevator platform(s), recoating system(s) and at least one polymer retaining receptacle. Multiple polymer retaining receptacles may be arranged in a moveable apparatus, wherein each receptacle is adapted to actively/passively maintain a uniform, desired level of polymer by including a recoating device and a material fill/remove system. The platform is movably accessible to the polymer retaining receptacle(s), elevator mechanism(s) and washing and curing/drying area(s) which may be housed in a shielded enclosure(s). The elevator mechanism is configured to vertically traverse and rotate the platform, thus providing angled building, washing and curing/drying capabilities. A horizontal traversing mechanism may be included to facilitate manufacturing between components of SL cabinet(s) and/or alternative manufacturing technologies.

Benchmarking of dynamic simulation predictions in two software platforms using an upper limb musculoskeletal model

PubMed Central

Saul, Katherine R.; Hu, Xiao; Goehler, Craig M.; Vidt, Meghan E.; Daly, Melissa; Velisar, Anca; Murray, Wendy M.

2014-01-01

Several opensource or commercially available software platforms are widely used to develop dynamic simulations of movement. While computational approaches are conceptually similar across platforms, technical differences in implementation may influence output. We present a new upper limb dynamic model as a tool to evaluate potential differences in predictive behavior between platforms. We evaluated to what extent differences in technical implementations in popular simulation software environments result in differences in kinematic predictions for single and multijoint movements using EMG- and optimization-based approaches for deriving control signals. We illustrate the benchmarking comparison using SIMM-Dynamics Pipeline-SD/Fast and OpenSim platforms. The most substantial divergence results from differences in muscle model and actuator paths. This model is a valuable resource and is available for download by other researchers. The model, data, and simulation results presented here can be used by future researchers to benchmark other software platforms and software upgrades for these two platforms. PMID:24995410

Reconstructing the Avalon continent: Marginal to inner platform transition in the Cambrian of southern New Brunswick

USGS Publications Warehouse

Landing, E.

1996-01-01

A west to east, marginal to inner Avalonian platform transition, comparable to that in southeast Newfoundland and southern Britain, is present in the Cambrian of southern New Brunswick. The Saint John - Caton's Island - Hanford Brook area lay on the marginal platform, and its thick, uppermost Precambrian - lower Lower Cambrian is unconformably overlain by trilobite-bearing, upper Lower Cambrian. An inner platform remnant is preserved in the Cradle Brook outlier 60 km northeast of Saint John. In contrast to the marginal platform sequences, the Cradle Brook outlier has a very thin lower Lower Cambrian and has middle Lower Cambrian strata (Bonavista Group) not present on the marginal platform. The Cradle Brook Lower Cambrian closely resembles inner platform successions in eastern Massachusetts and Trinity and Placentia bays, southeast Newfoundland. A limestone with Camenella baltica Zone fossils on Cradle Brook seems to be the peritidal limestone cap of the subtrilobitic Lower Cambrian known in Avalonian North America (Fosters Point Formation) and England (Home Farm Member).

Integrated Spintronic Platforms for Biomolecular Recognition Detection

NASA Astrophysics Data System (ADS)

Martins, V. C.; Cardoso, F. A.; Loureiro, J.; Mercier, M.; Germano, J.; Cardoso, S.; Ferreira, R.; Fonseca, L. P.; Sousa, L.; Piedade, M. S.; Freitas, P. P.

2008-06-01

This paper covers recent developments in magnetoresistive based biochip platforms fabricated at INESC-MN, and their application to the detection and quantification of pathogenic waterborn microorganisms in water samples for human consumption. Such platforms are intended to give response to the increasing concern related to microbial contaminated water sources. The presented results concern the development of biological active DNA chips and protein chips and the demonstration of the detection capability of the present platforms. Two platforms are described, one including spintronic sensors only (spin-valve based or magnetic tunnel junction based), and the other, a fully scalable platform where each probe site consists of a MTJ in series with a thin film diode (TFD). Two microfluidic systems are described, for cell separation and concentration, and finally, the read out and control integrated electronics are described, allowing the realization of bioassays with a portable point of care unit. The present platforms already allow the detection of complementary biomolecular target recognition with 1 pM concentration.

A novel 3D bioprinted flexible and biocompatible hydrogel bioelectronic platform.

PubMed

Agarwala, Shweta; Lee, Jia Min; Ng, Wei Long; Layani, Michael; Yeong, Wai Yee; Magdassi, Shlomo

2018-04-15

Bioelectronics platforms are gaining widespread attention as they provide a template to study the interactions between biological species and electronics. Decoding the effect of the electrical signals on the cells and tissues holds the promise for treating the malignant tissue growth, regenerating organs and engineering new-age medical devices. This work is a step forward in this direction, where bio- and electronic materials co-exist on one platform without any need for post processing. We fabricate a freestanding and flexible hydrogel based platform using 3D bioprinting. The fabrication process is simple, easy and provides a flexible route to print materials with preferred shapes, size and spatial orientation. Through the design of interdigitated electrodes and heating coil, the platform can be tailored to print various circuits for different functionalities. The biocompatibility of the printed platform is tested using C2C12 murine myoblasts cell line. Furthermore, normal human dermal fibroblasts (primary cells) are also seeded on the platform to ascertain the compatibility. Copyright © 2017 Elsevier B.V. All rights reserved.

Benchmarking of dynamic simulation predictions in two software platforms using an upper limb musculoskeletal model.

PubMed

Saul, Katherine R; Hu, Xiao; Goehler, Craig M; Vidt, Meghan E; Daly, Melissa; Velisar, Anca; Murray, Wendy M

2015-01-01

Several opensource or commercially available software platforms are widely used to develop dynamic simulations of movement. While computational approaches are conceptually similar across platforms, technical differences in implementation may influence output. We present a new upper limb dynamic model as a tool to evaluate potential differences in predictive behavior between platforms. We evaluated to what extent differences in technical implementations in popular simulation software environments result in differences in kinematic predictions for single and multijoint movements using EMG- and optimization-based approaches for deriving control signals. We illustrate the benchmarking comparison using SIMM-Dynamics Pipeline-SD/Fast and OpenSim platforms. The most substantial divergence results from differences in muscle model and actuator paths. This model is a valuable resource and is available for download by other researchers. The model, data, and simulation results presented here can be used by future researchers to benchmark other software platforms and software upgrades for these two platforms.

The COMET Sleep Research Platform.

PubMed

Nichols, Deborah A; DeSalvo, Steven; Miller, Richard A; Jónsson, Darrell; Griffin, Kara S; Hyde, Pamela R; Walsh, James K; Kushida, Clete A

2014-01-01

The Comparative Outcomes Management with Electronic Data Technology (COMET) platform is extensible and designed for facilitating multicenter electronic clinical research. Our research goals were the following: (1) to conduct a comparative effectiveness trial (CET) for two obstructive sleep apnea treatments-positive airway pressure versus oral appliance therapy; and (2) to establish a new electronic network infrastructure that would support this study and other clinical research studies. The COMET platform was created to satisfy the needs of CET with a focus on creating a platform that provides comprehensive toolsets, multisite collaboration, and end-to-end data management. The platform also provides medical researchers the ability to visualize and interpret data using business intelligence (BI) tools. COMET is a research platform that is scalable and extensible, and which, in a future version, can accommodate big data sets and enable efficient and effective research across multiple studies and medical specialties. The COMET platform components were designed for an eventual move to a cloud computing infrastructure that enhances sustainability, overall cost effectiveness, and return on investment.

The COMET Sleep Research Platform

PubMed Central

Nichols, Deborah A.; DeSalvo, Steven; Miller, Richard A.; Jónsson, Darrell; Griffin, Kara S.; Hyde, Pamela R.; Walsh, James K.; Kushida, Clete A.

2014-01-01

Introduction: The Comparative Outcomes Management with Electronic Data Technology (COMET) platform is extensible and designed for facilitating multicenter electronic clinical research. Background: Our research goals were the following: (1) to conduct a comparative effectiveness trial (CET) for two obstructive sleep apnea treatments—positive airway pressure versus oral appliance therapy; and (2) to establish a new electronic network infrastructure that would support this study and other clinical research studies. Discussion: The COMET platform was created to satisfy the needs of CET with a focus on creating a platform that provides comprehensive toolsets, multisite collaboration, and end-to-end data management. The platform also provides medical researchers the ability to visualize and interpret data using business intelligence (BI) tools. Conclusion: COMET is a research platform that is scalable and extensible, and which, in a future version, can accommodate big data sets and enable efficient and effective research across multiple studies and medical specialties. The COMET platform components were designed for an eventual move to a cloud computing infrastructure that enhances sustainability, overall cost effectiveness, and return on investment. PMID:25848590

A comparative analysis of high-throughput platforms for validation of a circulating microRNA signature in diabetic retinopathy.

PubMed

Farr, Ryan J; Januszewski, Andrzej S; Joglekar, Mugdha V; Liang, Helena; McAulley, Annie K; Hewitt, Alex W; Thomas, Helen E; Loudovaris, Tom; Kay, Thomas W H; Jenkins, Alicia; Hardikar, Anandwardhan A

2015-06-02

MicroRNAs are now increasingly recognized as biomarkers of disease progression. Several quantitative real-time PCR (qPCR) platforms have been developed to determine the relative levels of microRNAs in biological fluids. We systematically compared the detection of cellular and circulating microRNA using a standard 96-well platform, a high-content microfluidics platform and two ultra-high content platforms. We used extensive analytical tools to compute inter- and intra-run variability and concordance measured using fidelity scoring, coefficient of variation and cluster analysis. We carried out unprejudiced next generation sequencing to identify a microRNA signature for Diabetic Retinopathy (DR) and systematically assessed the validation of this signature on clinical samples using each of the above four qPCR platforms. The results indicate that sensitivity to measure low copy number microRNAs is inversely related to qPCR reaction volume and that the choice of platform for microRNA biomarker validation should be made based on the abundance of miRNAs of interest.

Determination of current loads of floating platform for special purposes

NASA Astrophysics Data System (ADS)

Ma, Guang-ying; Yao, Yun-long; Zhao, Chen-yao

2017-08-01

This article studied a new floating offshore platform for special purposes, which was assembled by standard floating modules. The environmental load calculation of the platform is an important part of the research of the ocean platform, which has always been paid attention to by engineers. In addition to wave loads, the wind loads and current loads are also important environmental factors that affect the dynamic response of the offshore platform. The current loads on the bottom structure should not be ignored. By Fluent software, the hydrostatic conditions and external current loads of the platform were calculated in this paper. The coefficient which is independent of the current velocity, namely, current force coefficient, can be fitted through current loads, which can be used for the consequent hydrodynamic and mooring analyses.

VAB Platform K(2) Lift & Install into Highbay 3

NASA Image and Video Library

2016-03-07

Work is underway to secure the second half of the K-level work platforms for NASA’s Space Launch System (SLS) rocket in High Bay 3 inside the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. The platform is being secured into position on tower E, about 86 feet above the floor. The K work platforms will provide access to NASA's Space Launch System (SLS) core stage and solid rocket boosters during processing and stacking operations on the mobile launcher. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to High Bay 3 to support processing of the SLS and Orion spacecraft. A total of 10 levels of new platforms, 20 platform halves altogether, will surround the SLS rocket and Orion spacecraft.

VAB Platform K(2) Lift & Install into Highbay 3

NASA Image and Video Library

2016-03-07

A 250-ton crane is used to lower the second half of the K-level work platforms for NASA’s Space Launch System (SLS) rocket into High Bay 3 inside the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. The platform will be secured about 86 feet above the VAB floor, on tower E of the high bay. The K work platforms will provide access to the SLS core stage and solid rocket boosters during processing and stacking operations on the mobile launcher. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to High Bay 3 to support processing of the SLS and Orion spacecraft. A total of 10 levels of new platforms, 20 platform halves altogether, will surround the SLS rocket and Orion spacecraft.

eTRIKS platform: Conception and operation of a highly scalable cloud-based platform for translational research and applications development.

PubMed

Bussery, Justin; Denis, Leslie-Alexandre; Guillon, Benjamin; Liu, Pengfeï; Marchetti, Gino; Rahal, Ghita

2018-04-01

We describe the genesis, design and evolution of a computing platform designed and built to improve the success rate of biomedical translational research. The eTRIKS project platform was developed with the aim of building a platform that can securely host heterogeneous types of data and provide an optimal environment to run tranSMART analytical applications. Many types of data can now be hosted, including multi-OMICS data, preclinical laboratory data and clinical information, including longitudinal data sets. During the last two years, the platform has matured into a robust translational research knowledge management system that is able to host other data mining applications and support the development of new analytical tools. Copyright © 2018 Elsevier Ltd. All rights reserved.

Collegial Activity Learning between Heterogeneous Sensors.

PubMed

Feuz, Kyle D; Cook, Diane J

2017-11-01

Activity recognition algorithms have matured and become more ubiquitous in recent years. However, these algorithms are typically customized for a particular sensor platform. In this paper we introduce PECO, a Personalized activity ECOsystem, that transfers learned activity information seamlessly between sensor platforms in real time so that any available sensor can continue to track activities without requiring its own extensive labeled training data. We introduce a multi-view transfer learning algorithm that facilitates this information handoff between sensor platforms and provide theoretical performance bounds for the algorithm. In addition, we empirically evaluate PECO using datasets that utilize heterogeneous sensor platforms to perform activity recognition. These results indicate that not only can activity recognition algorithms transfer important information to new sensor platforms, but any number of platforms can work together as colleagues to boost performance.

The contribution of fiscal/financial decentralization to the debt expansion of the local financing platform

NASA Astrophysics Data System (ADS)

Huayang, Yin; Di, Zhou; Bing, Cui

2018-02-01

Using soft budget theory to explore the formation mechanism and the deep institutional incentive of the local financing platform debt expansion from the perspective of fiscal / financial decentralization, construct theoretical framework which explain the expansion of local debt financing platform and conduct an empirical test, the results showed that the higher the degree of fiscal decentralization, fiscal autonomy as a soft constraint body of local government the stronger, local financing platform debt scale is greater; the higher the degree of financial decentralization, local government and financial institutions have the higher autonomy with respect to the central, local financing platform debt scale is bigger; financial synergy degree is stronger, local government financial mutual supervision prompted the local government debt more transparency, local debt financing platform size is smaller.

Earth resources instrumentation for the Space Station Polar Platform

NASA Technical Reports Server (NTRS)

Donohoe, Martin J.; Vane, Deborah

1986-01-01

The spacecraft and payloads of the Space Station Polar Platform program are described in a brief overview. Present plans call for one platform in a descending morning-equator-crossing orbit at 824 km and two or three platforms in ascending afternoon-crossing orbits at 542-824 km. The components of the NASA Earth Observing System (EOS) and NOAA payloads are listed in tables and briefly characterized, and data-distribution requirements and the mission development schedule are discussed. A drawing of the platform, a graph showing the spectral coverage of the EOS instruments, and a glossary of acronyms are provided.

Demand Analysis of Logistics Information Matching Platform: A Survey from Highway Freight Market in Zhejiang Province

NASA Astrophysics Data System (ADS)

Chen, Daqiang; Shen, Xiahong; Tong, Bing; Zhu, Xiaoxiao; Feng, Tao

With the increasing competition in logistics industry and promotion of lower logistics costs requirements, the construction of logistics information matching platform for highway transportation plays an important role, and the accuracy of platform design is the key to successful operation or not. Based on survey results of logistics service providers, customers and regulation authorities to access to information and in-depth information demand analysis of logistics information matching platform for highway transportation in Zhejiang province, a survey analysis for framework of logistics information matching platform for highway transportation is provided.

Web Platform for Sharing Modeling Software in the Field of Nonlinear Optics

NASA Astrophysics Data System (ADS)

Dubenskaya, Julia; Kryukov, Alexander; Demichev, Andrey

2018-02-01

We describe the prototype of a Web platform intended for sharing software programs for computer modeling in the rapidly developing field of the nonlinear optics phenomena. The suggested platform is built on the top of the HUBZero open-source middleware. In addition to the basic HUBZero installation we added to our platform the capability to run Docker containers via an external application server and to send calculation programs to those containers for execution. The presented web platform provides a wide range of features and might be of benefit to nonlinear optics researchers.

Toward Ubiquitous Communication Platform for Emergency Medical Care

NASA Astrophysics Data System (ADS)

Ishibashi, Kenichi; Morishima, Naoto; Kanbara, Masayuki; Sunahara, Hideki; Imanishi, Masami

Interaction between emergency medical technicians (EMTs) and doctors is essential in emergency medical care. Doctors require diverse information related to a patient to provide efficient aid. In 2005, we started the Ikoma119 project and have developed a ubiquitous communication platform for emergency medical care called Mobile ER. Our platform, which is based on wireless internet technology, has such desirable properties as low-cost, location-independent service, and ease of service introduction. We provide an overview of our platform and describe the services that we have developed. We also discuss the remaining issues to realize our platform's actual operation.

Data Collection for Mental Health Studies Through Digital Platforms: Requirements and Design of a Prototype.

PubMed

Aledavood, Talayeh; Triana Hoyos, Ana Maria; Alakörkkö, Tuomas; Kaski, Kimmo; Saramäki, Jari; Isometsä, Erkki; Darst, Richard K

2017-06-09

Mental and behavioral disorders are the main cause of disability worldwide. However, their diagnosis is challenging due to a lack of reliable biomarkers; current detection is based on structured clinical interviews which can be biased by the patient's recall ability, affective state, changing in temporal frames, etc. While digital platforms have been introduced as a possible solution to this complex problem, there is little evidence on the extent of usability and usefulness of these platforms. Therefore, more studies where digital data is collected in larger scales are needed to collect scientific evidence on the capacities of these platforms. Most of the existing platforms for digital psychiatry studies are designed as monolithic systems for a certain type of study; publications from these studies focus on their results, rather than the design features of the data collection platform. Inevitably, more tools and platforms will emerge in the near future to fulfill the need for digital data collection for psychiatry. Currently little knowledge is available from existing digital platforms for future data collection platforms to build upon. The objective of this work was to identify the most important features for designing a digital platform for data collection for mental health studies, and to demonstrate a prototype platform that we built based on these design features. We worked closely in a multidisciplinary collaboration with psychiatrists, software developers, and data scientists and identified the key features which could guarantee short-term and long-term stability and usefulness of the platform from the designing stage to data collection and analysis of collected data. The key design features that we identified were flexibility of access control, flexibility of data sources, and first-order privacy protection. We also designed the prototype platform Non-Intrusive Individual Monitoring Architecture (Niima), where we implemented these key design features. We described why each of these features are important for digital data collection for psychiatry, gave examples of projects where Niima was used or is going to be used in the future, and demonstrated how incorporating these design principles opens new possibilities for studies. The new methods of digital psychiatry are still immature and need further research. The design features we suggested are a first step to design platforms which can adapt to the upcoming requirements of digital psychiatry. ©Talayeh Aledavood, Ana Maria Triana Hoyos, Tuomas Alakörkkö, Kimmo Kaski, Jari Saramäki, Erkki Isometsä, Richard K Darst. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 09.06.2017.

Treatment patterns in disease-modifying therapy for patients with multiple sclerosis in the United States.

PubMed

Bonafede, Machaon M; Johnson, Barbara H; Wenten, Madé; Watson, Crystal

2013-10-01

Patients with multiple sclerosis (MS) whose disease activity is inadequately controlled with a platform therapy (interferon beta or glatiramer acetate [GA]) may switch to another platform therapy or escalate therapy to natalizumab or fingolimod, which were approved in the US in 2006 and 2010, respectively. The objective of this study was to describe treatment patterns in patients with multiple sclerosis (MS) in the United States who were followed for 2 years after initiating a disease-modifying therapy (DMT). A retrospective observational cohort study was conducted to examine treatment patterns of initial DMT use (on initial therapy for 2 years with and without gaps of ≥ 60 days, medication switching, and discontinuation) among patients with MS who initiated a platform therapy (interferon-β or glatiramer acetate) or natalizumab between January 1, 2007, and September 30, 2009; the first DMT claim was the index. Eligible patients were identified in the MarketScan Commercial and Medicare Supplemental databases based on continuous enrollment for 6 months before (preindex period) and 24 months after their index date, with a diagnosis of MS and no claim for a previous DMT in the 6-month preindex period. Demographics at index and clinical characteristics during the preindex period were also analyzed. A total of 6181 MS patients were included, with 5735 (92.8%) starting on platform therapy. Natalizumab initiators were more likely to stay on index therapy (32.3% vs 16.9%, P < 0.001) and have fewer treatment gaps of ≥ 60 days (44.8% vs 55.3%, P < 0.001) compared with platform initiators. In addition, natalizumab initiators were less likely to switch treatment (13.9% vs 19.1%, P = 0.007) and took longer to switch (400.9 days vs 330.7 days, P < 0.001) compared with platform initiators. Nearly 79% of platform initiators who switched went to another platform therapy. Approximately two thirds of patients who switched to a third DMT (n = 130) switched to another platform therapy. A total of 9% of natalizumab and platform initiators discontinued DMT within the 2 years. Most MS patients initiating DMT started on platform therapy. Natalizumab initiators tended to stay on index therapy, have fewer treatment gaps, and switch less than platform initiators in the 2 years after treatment initiation. Switching between platform therapies is common despite evidence that MS patients on platform therapy may benefit from switching to natalizumab. © 2013 Elsevier HS Journals, Inc. All rights reserved.

Design, Analysis, Hybrid Testing and Orientation Control of a Floating Platform with Counter-Rotating Vertical-Axis Wind Turbines

NASA Astrophysics Data System (ADS)

Kanner, Samuel Adam Chinman

The design and operation of two counter-rotating vertical-axis wind turbines on a floating, semi-submersible platform is studied. The technology, called the Multiple Integrated and Synchronized Turbines (MIST) platform has the potential to reduce the cost of offshore wind energy per unit of installed capacity. Attached to the platform are closely-spaced, counter-rotating turbines, which can achieve a higher power density per planform area because of synergistic interaction effects. The purpose of the research is to control the orientation of the platform and rotational speeds of the turbines by modifying the energy absorbed by each of the generators of the turbines. To analyze the various aspects of the platform and wind turbines, the analysis is drawn from the fields of hydrodynamics, electromagnetics, aerodynamics and control theory. To study the hydrodynamics of the floating platform in incident monochromatic waves, potential theory is utilized, taking into account the slow-drift yaw motion of the platform. Steady, second-order moments that are spatially dependent (i.e., dependent on the platform's yaw orientation relative to the incident waves) are given special attention since there are no natural restoring yaw moment. The aerodynamics of the counter-rotating turbines are studied in collaboration with researchers at the UC Berkeley Mathematics Department using a high-order, implicit, large-eddy simulation. An element flipping technique is utilized to extend the method to a domain with counter-rotating turbines and the effects from the closely-spaced turbines is compared with existing experimental data. Hybrid testing techniques on a model platform are utilized to prove the controllability of the platform in lieu of a wind-wave tank. A 1:82 model-scale floating platform is fabricated and tested at the UC Berkeley Physical-Model Testing Facility. The vertical-axis wind turbines are simulated by spinning, controllable actuators that can be updated in real-time of the model scale. Under certain wind and wave headings, it is possible to control the orientation of the platform in regular waves to maximize the power output from the turbines. A time-domain numerical simulation tool is able to confirm some of the experimental findings, taking into account the decoupled properties of the slow-drift hydrodynamics and wind turbine aerodynamics. Future platform designs are discussed, including the French-based, pre-commercial design from Nenuphar Wind, called the TwinFloat, which is closely related to concepts examined in the thesis.

Characteristics of depositional environment and evolution of Upper Cretaceous Mishrif Formation, Halfaya Oil field, Iraq based on sedimentary microfacies analysis

NASA Astrophysics Data System (ADS)

Zhong, Yuan; Zhou, Lu; Tan, Xiucheng; Guo, Rui; Zhao, Limin; Li, Fei; Jin, Zhimin; Chen, Yantao

2018-04-01

As one of the most important carbonate targets in the Middle East, Upper Cretaceous Mishrif Formation has been highlighted for a long time. Although consensus has been reached on the overall sedimentary background, disputes still exist in understanding the sedimentary environment changes among sub-regions due to relatively limited research, rare outcrop, and incomplete drilled core, which hinders the analysis on sedimentary environment and thus the horizontal and vertical correlation. In this study, taking the Halfaya Oil Field as an example, the sedimentary microfacies analysis method was introduced to comprehensively characterize the cored interval of Mishrif Formation, including Single Layers MC1-1 to MA2. A total of 11 sedimentary microfacies are identified through system identification of sedimentary microfacies and environmental analysis, with reference to the standard microfacies classification in the rimmed carbonate platform. Then three kinds of environments are identified through microfacies assemblage analysis, namely restricted platform, open platform, and platform margin. Systematic analyses indicate that the deposits are mainly developed in the open platform and platform margin. Meanwhile, rock-electricity interpretation model is established according to the electricity response to cored intervals, and is then employed to interpret the uncored intervals, which finally helps build the sedimentary evolution pattern through horizontal and vertical correlation. It is proposed that the Single Layers MC1-1 to MB2-3 were deposited in the open platform featured by low water level, including sub-environments of low-energy shoal within platform and inter-shoal sea; Single Layers MB2-2 to MB1-2B were deposited in the open platform and platform margin, including sub-environments of high-energy shoal on the platform margin, low-energy shoal within platform, inter-shoal sea, and open sea; and Single Layers MB1-2A to MA2 were again deposited in the open platform with high water level, and the circumstance of open sea was dominant. The deposition of Single Layers MC1-1 to MA2 actually corresponded to a retrogradation-progradation process. Results of this study will not only provide significant guidance to the exploration and development of Mishrif Formation, Halfaya Oil Field, but also support that the theory of sedimentary environment correlation with adjacent areas is reliable.

ADMS Evaluation Platform

DOE Office of Scientific and Technical Information (OSTI.GOV)

2018-01-23

Deploying an ADMS or looking to optimize its value? NREL offers a low-cost, low-risk evaluation platform for assessing ADMS performance. The National Renewable Energy Laboratory (NREL) has developed a vendor-neutral advanced distribution management system (ADMS) evaluation platform and is expanding its capabilities. The platform uses actual grid-scale hardware, large-scale distribution system models, and advanced visualization to simulate realworld conditions for the most accurate ADMS evaluation and experimentation.

75 FR 55970 - Safety Zone; VERMILION 380A at Block 380 Outer Continental Shelf Fixed Platform in the Gulf of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-15

...-AA00 Safety Zone; VERMILION 380A at Block 380 Outer Continental Shelf Fixed Platform in the Gulf of... safety zone around VERMILION 380A, a fixed platform, at Block 380 in the Outer Continental Shelf, approximately 90 miles south of Vermilion Bay, Louisiana. The fixed platform is on fire and the safety zone is...

Floating sample-collection platform with stage-activated automatic water sampler for streams with large variation in stage

USGS Publications Warehouse

Tarte, Stephen R.; Schmidt, A.R.; Sullivan, Daniel J.

1992-01-01

A floating sample-collection platform is described for stream sites where the vertical or horizontal distance between the stream-sampling point and a safe location for the sampler exceed the suction head of the sampler. The platform allows continuous water sampling over the entire storm-runoff hydrogrpah. The platform was developed for a site in southern Illinois.

Single Landmark Learning in Rats: Sex Differences in a Navigation Task

ERIC Educational Resources Information Center

Forcano, L.; Santamaria, J.; Mackintosh, N. J.; Chamizo, V. D.

2009-01-01

In Experiments 1 and 2, rats were trained in a Morris pool to find a hidden platform located some distance away from a single landmark. Males learned to swim to the platform faster than females, but on test trials without the platform, males, unlike females, spent less time in the platform quadrant of the pool in the second half of each test trial…

An air quality emission inventory of offshore operations for the exploration and production of petroleum by the Mexican oil industry

NASA Astrophysics Data System (ADS)

Villasenor, R.; Magdaleno, M.; Quintanar, A.; Gallardo, J. C.; López, M. T.; Jurado, R.; Miranda, A.; Aguilar, M.; Melgarejo, L. A.; Palmerín, E.; Vallejo, C. J.; Barchet, W. R.

An air quality screening study was performed to assess the impacts of emissions from the offshore operations of the oil and gas exploration and production by Mexican industry in the Campeche Sound, which includes the states of Tabasco and Campeche in southeast Mexico. The major goal of this study was the compilation of an emission inventory (EI) for elevated, boom and ground level flares, processes, internal combustion engines and fugitive emissions. This inventory is so far the most comprehensive emission register that has ever been developed for the Mexican petroleum industry in this area. The EI considered 174 offshore platforms, the compression station at Atasta, and the Maritime Ports at Dos Bocas and Cayo Arcas. The offshore facilities identified as potential emitters in the area were the following: (1) trans-shipment stations, (2) a maritime floating port terminal, (3) drilling platforms, (4) crude oil recovering platforms, (5) crude oil production platforms, (6) linking platforms, (7) water injection platforms, (8) pumping platforms, (9) shelter platforms, (10) telecommunication platforms, (11) crude oil measurement platforms, and (12) flaring platforms. Crude oil storage tanks, helicopters and marine ship tankers were also considered to have an EI accurate enough for air quality regulations and mesoscale modeling of atmospheric pollutants. Historical ambient data measure at two onshore petroleum facilities were analyzed to measure air quality impacts on nearby inhabited coastal areas, and a source-receptor relationship for flares at the Ixtoc marine complex was performed to investigate health-based standards for offshore workers. A preliminary air quality model simulation was performed to observe the transport and dispersion patterns of SO 2, which is the main pollutant emitted from the offshore platforms. The meteorological wind and temperature fields were generated with CALMET, a diagnostic meteorological model that used surface observations and upper air soundings from a 4-day field campaign conducted in February of 1999. The CALMET meteorological output and the generated EI drove the transport and dispersion model, CALPUFF. Model results were compared with SO 2 measurements taken from the monitoring network at Dos Bocas.

EGFR mutation detection in ctDNA from NSCLC patient plasma: A cross-platform comparison of leading technologies to support the clinical development of AZD9291.

PubMed

Thress, Kenneth S; Brant, Roz; Carr, T Hedley; Dearden, Simon; Jenkins, Suzanne; Brown, Helen; Hammett, Tracey; Cantarini, Mireille; Barrett, J Carl

2015-12-01

To assess the ability of different technology platforms to detect epidermal growth factor receptor (EGFR) mutations, including T790M, from circulating tumor DNA (ctDNA) in advanced non-small cell lung cancer (NSCLC) patients. A comparison of multiple platforms for detecting EGFR mutations in plasma ctDNA was undertaken. Plasma samples were collected from patients entering the ongoing AURA trial (NCT01802632), investigating the safety, tolerability, and efficacy of AZD9291 in patients with EGFR-sensitizing mutation-positive NSCLC. Plasma was collected prior to AZD9291 dosing but following clinical progression on a previous EGFR-tyrosine kinase inhibitor (TKI). Extracted ctDNA was analyzed using two non-digital platforms (cobas(®) EGFR Mutation Test and therascreen™ EGFR amplification refractory mutation system assay) and two digital platforms (Droplet Digital™ PCR and BEAMing digital PCR [dPCR]). Preliminary assessment (38 samples) was conducted using all four platforms. For EGFR-TKI-sensitizing mutations, high sensitivity (78-100%) and specificity (93-100%) were observed using tissue as a non-reference standard. For the T790M mutation, the digital platforms outperformed the non-digital platforms. Subsequent assessment using 72 additional baseline plasma samples was conducted using the cobas(®) EGFR Mutation Test and BEAMing dPCR. The two platforms demonstrated high sensitivity (82-87%) and specificity (97%) for EGFR-sensitizing mutations. For the T790M mutation, the sensitivity and specificity were 73% and 67%, respectively, with the cobas(®) EGFR Mutation Test, and 81% and 58%, respectively, with BEAMing dPCR. Concordance between the platforms was >90%, showing that multiple platforms are capable of sensitive and specific detection of EGFR-TKI-sensitizing mutations from NSCLC patient plasma. The cobas(®) EGFR Mutation Test and BEAMing dPCR demonstrate a high sensitivity for T790M mutation detection. Genomic heterogeneity of T790M-mediated resistance may explain the reduced specificity observed with plasma-based detection of T790M mutations versus tissue. These data support the use of both platforms in the AZD9291 clinical development program. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Numerical analysis of seawater circulation in carbonate platforms: II. The dynamic interaction between geothermal and brine reflux circulation

USGS Publications Warehouse

Jones, G.D.; Whitaker, F.F.; Smart, P.L.; Sanford, W.E.

2004-01-01

Density-driven seawater circulation may occur in carbonate platforms due to geothermal heating and / or reflux of water of elevated salinity. In geothermal circulation lateral contrasts in temperature between seawater and platform groundwaters warmed by the geothermal heat flux result in upward convective flow, with colder seawater drawn into the platform at depth. With reflux circulation, platform-top waters concentrated by evaporation flow downward, displacing less dense underlying groundwaters. We have used a variable density groundwater flow model to examine the pattern, magnitude and interaction of these two different circulation mechanisms, for mesosaline platform-top waters (50???) and brines concentrated up to saturation with respect to gypsum (150???) and halite (246???). Geothermal circulation, most active around the platform margin, becomes restricted and eventually shut-off by reflux of brines from the platform interior towards the margin. The persistence of geothermal circulation is dependent on the rate of brine reflux, which is proportional to the concentration of platform-top brines and also critically dependent on the magnitude and distribution of permeability. Low permeability evaporites can severely restrict reflux whereas high permeability units in hydraulic continuity enhance brine transport. Reduction in permeability with depth and anisotropy of permeability (kv < < kh) focuses flow laterally in the shallow subsurface (<1 km), resulting in a horizontally elongated brine plume. Aquifer porosity and dispersivity are relatively minor controls on reflux. Platform brines can entrain surficial seawater when brine generating conditions cease but the platform-top remains submerged, a variant of reflux we term "latent reflux". Brines concentrated up to gypsum saturation have relatively long residence times of at least 100 times the duration of the reflux event. They thus represent a long-term control on post-reflux groundwater circulation, and consequently on the rates and spatial patterns of shallow burial diagenesis, such as dolomitization.

Carbonate-platform response to the Toarcian Oceanic Anoxic Event in the southern hemisphere: Implications for climatic change and biotic platform demise

NASA Astrophysics Data System (ADS)

Han, Zhong; Hu, Xiumian; Kemp, David B.; Li, Juan

2018-05-01

The Toarcian Oceanic Anoxic Event (T-OAE, ∼183 Ma) was a profound short-term environmental perturbation associated with the large-scale release of 13C-depleted carbon into the global ocean-atmosphere system, which resulted in a significant negative carbon-isotope excursion (CIE). The general lack of characteristic T-OAE records outside of the northern hemisphere means that the precise environmental effects and significance of this event are uncertain. Many biotic carbonate platforms of the northern hemisphere western Tethys drowned or shifted to non-skeletal platforms during the early Toarcian. However, southern hemisphere records of Toarcian carbonate platforms are rare, and thus the extent and significance of biotic platform demise during the T-OAE is unclear. Here we present high-resolution geochemical and sedimentological data across two Pliensbachian-Toarcian shallow-water carbonate-platform sections exposed in the Tibetan Himalaya. These sections were located paleogeographically on the open southeastern tropical Tethyan margin in the southern hemisphere. The T-OAE in the Tibetan Himalaya is marked by a negative CIE in organic matter. Our sedimentological analysis of the two sections reveals an abundance of storm deposits within the T-OAE interval, which emphasizes a close link between warming and tropical storms during the T-OAE event, in line with evidence recently provided from western Tethyan sections of the northern hemisphere. In addition, our analysis also reveals extensive biotic carbonate-platform demise by drowning or changing to non-skeletal carbonates coincident with the onset of the CIE. Taken together, our results suggest that rapid and pervasive seawater warming in response to carbon release likely played a significant role in sudden biotic carbonate platform demise, and suppression/postponement of biotic platform re-development along the whole tropical/subtropical Tethyan margin.

A large-scale superhydrophobic surface-enhanced Raman scattering (SERS) platform fabricated via capillary force lithography and assembly of Ag nanocubes for ultratrace molecular sensing.

PubMed

Tan, Joel Ming Rui; Ruan, Justina Jiexin; Lee, Hiang Kwee; Phang, In Yee; Ling, Xing Yi

2014-12-28

An analytical platform with an ultratrace detection limit in the atto-molar (aM) concentration range is vital for forensic, industrial and environmental sectors that handle scarce/highly toxic samples. Superhydrophobic surface-enhanced Raman scattering (SERS) platforms serve as ideal platforms to enhance detection sensitivity by reducing the random spreading of aqueous solution. However, the fabrication of superhydrophobic SERS platforms is generally limited due to the use of sophisticated and expensive protocols and/or suffers structural and signal inconsistency. Herein, we demonstrate a high-throughput fabrication of a stable and uniform superhydrophobic SERS platform for ultratrace molecular sensing. Large-area box-like micropatterns of the polymeric surface are first fabricated using capillary force lithography (CFL). Subsequently, plasmonic properties are incorporated into the patterned surfaces by decorating with Ag nanocubes using the Langmuir-Schaefer technique. To create a stable superhydrophobic SERS platform, an additional 25 nm Ag film is coated over the Ag nanocube-decorated patterned template followed by chemical functionalization with perfluorodecanethiol. Our resulting superhydrophobic SERS platform demonstrates excellent water-repellency with a static contact angle of 165° ± 9° and a consequent analyte concentration factor of 59-fold, as compared to its hydrophilic counterpart. By combining the analyte concentration effect of superhydrophobic surfaces with the intense electromagnetic "hot spots" of Ag nanocubes, our superhydrophobic SERS platform achieves an ultra-low detection limit of 10(-17) M (10 aM) for rhodamine 6G using just 4 μL of analyte solutions, corresponding to an analytical SERS enhancement factor of 10(13). Our fabrication protocol demonstrates a simple, cost- and time-effective approach for the large-scale fabrication of a superhydrophobic SERS platform for ultratrace molecular detection.

An Integrated Web-Based 3d Modeling and Visualization Platform to Support Sustainable Cities

NASA Astrophysics Data System (ADS)

Amirebrahimi, S.; Rajabifard, A.

2012-07-01

Sustainable Development is found as the key solution to preserve the sustainability of cities in oppose to ongoing population growth and its negative impacts. This is complex and requires a holistic and multidisciplinary decision making. Variety of stakeholders with different backgrounds also needs to be considered and involved. Numerous web-based modeling and visualization tools have been designed and developed to support this process. There have been some success stories; however, majority failed to bring a comprehensive platform to support different aspects of sustainable development. In this work, in the context of SDI and Land Administration, CSDILA Platform - a 3D visualization and modeling platform -was proposed which can be used to model and visualize different dimensions to facilitate the achievement of sustainability, in particular, in urban context. The methodology involved the design of a generic framework for development of an analytical and visualization tool over the web. CSDILA Platform was then implemented via number of technologies based on the guidelines provided by the framework. The platform has a modular structure and uses Service-Oriented Architecture (SOA). It is capable of managing spatial objects in a 4D data store and can flexibly incorporate a variety of developed models using the platform's API. Development scenarios can be modeled and tested using the analysis and modeling component in the platform and the results are visualized in seamless 3D environment. The platform was further tested using number of scenarios and showed promising results and potentials to serve a wider need. In this paper, the design process of the generic framework, the implementation of CSDILA Platform and technologies used, and also findings and future research directions will be presented and discussed.

Regional Patterns in Invertebrate Assemblages on Offshore Oil Platforms Along the Pacific Outer Continental Shelf

NASA Astrophysics Data System (ADS)

Zaleski, S.; Page, H. M.; Miller, R. J.; Doheny, B.; Dugan, J. E.; Schroeder, D. M.

2016-02-01

Twenty-seven oil and gas platforms are arrayed offshore California from north of Point Conception south to San Pedro Bay (a coastline distance of >300 km). To test the hypothesis that variability in the structure of sessile invertebrate communities on the platforms is associated with regional differences in sea surface temperature, we sampled space-holding invertebrate taxa photographically on 23 platforms and compared the composition and cover of invertebrates among and within regions using multivariate analyses. To explore temporal variability in invertebrate assemblages, we also compared the cover and composition of invertebrates on a subset of platforms in the Santa Barbara Channel (SBC) where data were collected over ten years previously. The composition of invertebrate assemblages differed significantly among regions, and was driven by variation in the relative abundance of certain anemone, bryozoan, tubiferous annelid, sponge, and bivalve taxa. The presence of non-native bryozoan and anemone taxa on some platforms in the south (San Pedro Bay) and southeast SBC contributed to the distinction of these assemblages from the others. Comparison of survey data on the subset of platforms in the SBC surveyed over ten years apart revealed little change in the cover of major space-holding taxa (e.g., anemones Metridium, Corynactis) across platforms, although there was an increase in cover of the non-native bryozoan Watersipora subtorquata between surveys. The existence of geographical patterns in the composition of platform invertebrate assemblages suggests that these assemblages may be useful as barometers of short and longer-term environmental change. For biogeographic transition zones, such as the SBC, monitoring of platform invertebrate assemblages could permit an evaluation of the concept that these zones are particularly susceptible to shifts in the composition of marine species driven by ocean climate.

Differences in energy expenditure for conventional and femtosecond-assisted cataract surgery using 2 different phacoemulsification systems.

PubMed

Yesilirmak, Nilufer; Diakonis, Vasilios F; Sise, Adam; Waren, Daniel P; Yoo, Sonia H; Donaldson, Kendall E

2017-01-01

To compare the mean cumulative dissipated energy (CDE) in patients having femtosecond laser-assisted or conventional phacoemulsification cataract surgery using 2 different phacoemulsification platforms. Bascom Palmer Eye Institute, Miami, Florida, USA. Prospective comparative nonrandomized clinical study. Consecutive patients were scheduled to have femtosecond laser-assisted cataract surgery with the Lensx laser or conventional phacoemulsification using an active-fluidics torsional platform (Centurion) or torsional platform (Infiniti). The mean CDE and cataract grade were recorded. The study comprised 570 eyes (570 patients). There was no statistically significant difference in mean age (P = .41, femtosecond group; P = .33, conventional group) or cataract grade (P = .78 and P = .45, respectively) between the active-fluidics and gravity-fluidics platforms. In femtosecond cases (145 eyes), the mean CDE (percent-seconds) was 5.18 ± 4.58 (SD) with active fluidics and 7.00 ± 6.85 with gravity fluidics; in conventional cases (425 eyes), the mean CDE was 7.77 ± 6.97 and 11.43 ± 9.12, respectively. In both femtosecond cases and conventional cases, the CDE was lower with the active-fluidics platform than with the gravity-fluidics platform (P = .029, femtosecond group; P < .001 conventional group). With both fluidics platforms, the mean CDE was significantly lower in the femtosecond group than in the conventional group (both P < .001). The active-fluidics phacoemulsification platform achieved lower CDE values than the gravity-fluidics platform for conventional cataract extraction. Femtosecond laser pretreatment with the active-fluidics platform further reduced CDE. Copyright © 2017 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Chromatography process development in the quality by design paradigm I: Establishing a high-throughput process development platform as a tool for estimating "characterization space" for an ion exchange chromatography step.

PubMed

Bhambure, R; Rathore, A S

2013-01-01

This article describes the development of a high-throughput process development (HTPD) platform for developing chromatography steps. An assessment of the platform as a tool for establishing the "characterization space" for an ion exchange chromatography step has been performed by using design of experiments. Case studies involving use of a biotech therapeutic, granulocyte colony-stimulating factor have been used to demonstrate the performance of the platform. We discuss the various challenges that arise when working at such small volumes along with the solutions that we propose to alleviate these challenges to make the HTPD data suitable for empirical modeling. Further, we have also validated the scalability of this platform by comparing the results from the HTPD platform (2 and 6 μL resin volumes) against those obtained at the traditional laboratory scale (resin volume, 0.5 mL). We find that after integration of the proposed correction factors, the HTPD platform is capable of performing the process optimization studies at 170-fold higher productivity. The platform is capable of providing semi-quantitative assessment of the effects of the various input parameters under consideration. We think that platform such as the one presented is an excellent tool for examining the "characterization space" and reducing the extensive experimentation at the traditional lab scale that is otherwise required for establishing the "design space." Thus, this platform will specifically aid in successful implementation of quality by design in biotech process development. This is especially significant in view of the constraints with respect to time and resources that the biopharma industry faces today. Copyright © 2013 American Institute of Chemical Engineers.

Lactulose:Mannitol Diagnostic Test by HPLC and LC-MSMS Platforms: Considerations for Field Studies of Intestinal Barrier Function and Environmental Enteropathy

PubMed Central

Lee, Gwenyth O.; Kosek, Peter; Lima, Aldo A.M.; Singh, Ravinder; Yori, Pablo P.; Olortegui, Maribel P.; Lamsam, Jesse L.; Oliveira, Domingos B.; Guerrant, Richard L.; Kosek, Margaret

2014-01-01

ABSTRACT Objectives: The lactulose:mannitol (L:M) diagnostic test is frequently used in field studies of environmental enteropathy (EE); however, heterogeneity in test administration and disaccharide measurement has limited the comparison of results between studies and populations. We aim to assess the agreement between L:M measurement between high-performance liquid chromatography with pulsed amperometric detection (HPLC-PAD) and liquid chromatography-tandem mass spectrometry (LC-MSMS) platforms. Methods: The L:M test was administered in a cohort of Peruvian infants considered at risk for EE. A total of 100 samples were tested for lactulose and mannitol at 3 independent laboratories: 1 running an HPLC-PAD platform and 2 running LC-MSMS platforms. Agreement between the platforms was estimated. Results: The Spearman correlation between the 2 LC-MSMS platforms was high (ρ ≥ 0.89) for mannitol, lactulose, and the L:M ratio. The correlation between the HPLC-PAD platform and LC-MSMS platform was ρ = 0.95 for mannitol, ρ = 0.70 for lactulose, and ρ = 0.43 for the L:M ratio. In addition, the HPLC-PAD platform overestimated the lowest disaccharide concentrations to the greatest degree. Conclusions: Given the large analyte concentration range, the improved accuracy of LC-MSMS has important consequences for the assessment of lactulose and mannitol following oral administration in populations at risk for EE. We recommend that researchers wishing to implement a dual-sugar test as part of a study of EE use an LC-MSMS platform to optimize the accuracy of results and increase comparability between studies. PMID:24941958

Floor Plans Fuel Tank Support, Fuel Platform, and LOX ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Floor Plans - Fuel Tank Support, Fuel Platform, and LOX Platform Plans - Marshall Space Flight Center, F-1 Engine Static Test Stand, On Route 565 between Huntsville and Decatur, Huntsville, Madison County, AL

Study on the E-commerce platform based on the agent

NASA Astrophysics Data System (ADS)

Fu, Ruixue; Qin, Lishuan; Gao, Yinmin

2011-10-01

To solve problem of dynamic integration in e-commerce, the Multi-Agent architecture of electronic commerce platform system based on Agent and Ontology has been introduced, which includes three major types of agent, Ontology and rule collection. In this architecture, service agent and rule are used to realize the business process reengineering, the reuse of software component, and agility of the electronic commerce platform. To illustrate the architecture, a simulation work has been done and the results imply that the architecture provides a very efficient method to design and implement the flexible, distributed, open and intelligent electronic commerce platform system to solve problem of dynamic integration in ecommerce. The objective of this paper is to illustrate the architecture of electronic commerce platform system, and the approach how Agent and Ontology support the electronic commerce platform system.

Micro-UAV tracking framework for EO exploitation

NASA Astrophysics Data System (ADS)

Browning, David; Wilhelm, Joe; Van Hook, Richard; Gallagher, John

2012-06-01

Historically, the Air Force's research into aerial platforms for sensing systems has focused on low-, mid-, and highaltitude platforms. Though these systems are likely to comprise the majority of the Air Force's assets for the foreseeable future, they have limitations. Specifically, these platforms, their sensor packages, and their data exploitation software are unsuited for close-quarter surveillance, such as in alleys and inside of buildings. Micro-UAVs have been gaining in popularity, especially non-fixed-wing platforms such as quad-rotors. These platforms are much more appropriate for confined spaces. However, the types of video exploitation techniques that can effectively be used are different from the typical nadir-looking aerial platform. This paper discusses the creation of a framework for testing existing and new video exploitation algorithms, as well as describes a sample micro-UAV-based tracker.

Designing an Online Social Support Platform Through Co-Creation with Seniors.

PubMed

Rochat, Jessica; Nap, Henk Herman; Ricci, Arnaud; Cornelisse, Lotte; Lukkien, Dirk; Lovis, Christian; Ehrler, Frédéric

2018-01-01

The high number of seniors that feels excluded of society highlights the necessity to promote active ageing. This intention can be supported through online platforms that encourage participation in social activities. The goal of the present study was to identify design principles of online support platforms for seniors through focus groups and to ideate the platform through co-creation sessions. The results show that a social platform for seniors must, among other, help to foster contact between users, and must provide services and meaningful activities. A first mock-up of the platform's design has been created based on the co-creation sessions and will be iteratively evaluated and enhanced in future studies in four countries across Europe. Our findings are in line with those of other studies demonstrating that seniors attach importance to trustworthiness and need to maintain social ties.

A new family of omnidirectional and holonomic wheeled platforms for mobile robots

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pin, F.G.; Killough, S.M.

1994-08-01

This paper presents the concepts for a new family of holonomic wheeled platforms that feature full omnidirectionality with simultaneous and independently controlled rotational and translational motion capabilities. The authors first present the orthogonal-wheels'' concept and the two major wheel assemblies on which these platforms are based. The authors then describe how a combination of these assemblies with appropriate control can be used to generate an omnidirectional capability for mobile robot platforms. Several alternative designs are considered, and their respective characteristics with respect to rotational and translational motion control are discussed. The design and control of a prototype platform developed tomore » test and demonstrate the proposed concepts is then described, and experimental results illustrating the full omnidirectionality of the platforms with decoupled rotational and translational degrees of freedom are presented.« less

Evaluating the enhancement and improvement of China's technology and financial services platform innovation strategy.

PubMed

Wu, Ching-Sung; Hu, Kuang-Hua; Chen, Fu-Hsiang

2016-01-01

The development of high-tech industry has been prosperous around the world in past decades, while technology and finance have already become the most significant issues in the information era. While high-tech firms are a major force behind a country's economic development, it requires a lot of money for the development process, as well as the financing difficulties for its potential problems, thus, how to evaluate and establish appropriate technology and financial services platforms innovation strategy has become one of the most critical and difficult issues. Moreover, how the chosen intertwined financial environment can be optimized in order that high-tech firms financing problems can be decided has seldom been addressed. Thus, this research aims to establish a technology and financial services platform innovation strategy improvement model, as based on the hybrid MADM model, which addresses the main causal factors and amended priorities in order to strengthen ongoing planning. A DEMATEL technique, as based on Analytic Network Process, as well as modified VIKOR, will be proposed for selecting and re-configuring the aspired technology and financial services platform. An empirical study, as based on China's technology and financial services platform innovation strategy, will be provided for verifying the effectiveness of this proposed methodology. Based on expert interviews, technology and financial services platforms innovation strategy improvement should be made in the following order: credit guarantee platform ( C )_credit rating platform ( B )_investment and finance platform ( A ).

Characteristics of train noise in above-ground and underground stations with side and island platforms

NASA Astrophysics Data System (ADS)

Shimokura, Ryota; Soeta, Yoshiharu

2011-04-01

Railway stations can be principally classified by their locations, i.e., above-ground or underground stations, and by their platform styles, i.e., side or island platforms. However, the effect of the architectural elements on the train noise in stations is not well understood. The aim of the present study is to determine the different acoustical characteristics of the train noise for each station style. The train noise was evaluated by (1) the A-weighted equivalent continuous sound pressure level ( LAeq), (2) the amplitude of the maximum peak of the interaural cross-correlation function (IACC), (3) the delay time ( τ1) and amplitude ( ϕ1) of the first maximum peak of the autocorrelation function. The IACC, τ1 and ϕ1 are related to the subjective diffuseness, pitch and pitch strength, respectively. Regarding the locations, the LAeq in the underground stations was 6.4 dB higher than that in the above-ground stations, and the pitch in the underground stations was higher and stronger. Regarding the platform styles, the LAeq on the side platforms was 3.3 dB higher than on the island platforms of the above-ground stations. For the underground stations, the LAeq on the island platforms was 3.3 dB higher than that on the side platforms when a train entered the station. The IACC on the island platforms of the above-ground stations was higher than that in the other stations.

Validation of the iPhone app using the force platform to estimate vertical jump height.

PubMed

Carlos-Vivas, Jorge; Martin-Martinez, Juan P; Hernandez-Mocholi, Miguel A; Perez-Gomez, Jorge

2018-03-01

Vertical jump performance has been evaluated with several devices: force platforms, contact mats, Vertec, accelerometers, infrared cameras and high-velocity cameras; however, the force platform is considered the gold standard for measuring vertical jump height. The purpose of this study was to validate an iPhone app called My Jump, that measures vertical jump height by comparing it with other methods that use the force platform to estimate vertical jump height, namely, vertical velocity at take-off and time in the air. A total of 40 sport sciences students (age 21.4±1.9 years) completed five countermovement jumps (CMJs) over a force platform. Thus, 200 CMJ heights were evaluated from the vertical velocity at take-off and the time in the air using the force platform, and from the time in the air with the My Jump mobile application. The height obtained was compared using the intraclass correlation coefficient (ICC). Correlation between APP and force platform using the time in the air was perfect (ICC=1.000, P<0.001). Correlation between APP and force platform using the vertical velocity at take-off was also very high (ICC=0.996, P<0.001), with an error margin of 0.78%. Therefore, these results showed that application, My Jump, is an appropriate method to evaluate the vertical jump performance; however, vertical jump height is slightly overestimated compared with that of the force platform.

Platform based design of EAP transducers in Danfoss PolyPower A/S

NASA Astrophysics Data System (ADS)

Sarban, Rahimullah; Gudlaugsson, Tómas V.

2013-04-01

Electroactive Polymer (EAP) has gained increasing focus, in research communities, in last two decades. Research within the field of EAP has, so far, been mainly focused on material improvements, characterization, modeling and developing demonstrators. As the EAP technology matures, the need for a new area of research namely product development emerges. Product development can be based on an isolated design and production for a single product or platform design where a product family is developed. In platform design the families of products exploits commonality of platform modules while satisfying a variety of different market segments. Platform based approach has the primary benefit of being cost efficient and short lead time to market when new products emerges. Products development based on EAP technology is challenging both technologically as well as from production and processing point of view. Both the technological and processing challenges need to be addressed before a successful implementation of EAP technology into products. Based on this need Danfoss PolyPower A/S has, in 2011, launched a EAP platform project in collaboration with three Danish universities and three commercial organizations. The aim of the project is to develop platform based designs and product family for the EAP components to be used in variety of applications. This paper presents the structure of the platform project as a whole and specifically the platform based designs of EAP transducers. The underlying technologies, essential for EAP transducers, are also presented. Conceptual design and solution for the concepts are presented as well.

OTEC platform configuration and integration study. Volume I. Systems engineering and integration. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

1978-04-01

The economic success of an Ocean Thermal Energy Conversion (OTEC) system is highly dependent on a platform which provides adequate support for the power system, accommodates reliably the cold water pipe, and is most cost effective. The results of a study conducted for the Department of Energy to assess six generic types of platforms to determine the most satisfactory platform for severl potential sites are presented. The six platform configurations are ship, circular barge, semi-submersible, Tuned Sphere, submersible, and spar. These represent directional and symmetric types of platforms which operate on the surface, at the interface, and submerged. The fivemore » sites for this study were primarily New Orleans, Keahole Point (Hawaii), Brazil, and secondarily Key West and Puerto Rico. Electrical transmission of energy by submarine cable is the planned form of energy transmission for all sites except Brazil, where chemical conversion is to be the method of transmission. This study is devoted to the platform (or ocean systems) of the OTEC plant which is chiefly comprised of the hull and structure, the seawater system, the position control system, and miscellaneous support/assembly systems. The principal elements in the work breakdown structure for the commercial plants are presented. The assessment of the six platform configurations was conducted utilizing a baseline plan (100-MW(e) (Net)) and site (New Orleans) with variations from the baseline to cover the range of interested platforms and sites.« less

Cooperative Search by UAV Teams: A Model Predictive Approach Using Dynamic Graphs

DTIC Science & Technology

2011-10-01

decentralized processing and control architecture. SLAMEM asset models accurately represent the Unicorn UAV platforms and other standard military platforms in...IMPLEMENTATION The CGBMPS algorithm has been successfully field-tested using both Unicorn [27] and Raven [20] UAV platforms. This section describes...the hardware-software system setup and implementation used for testing with Unicorns , Toyon’s UAV test platform. We also present some results from the

Trust and Decision Making: An Empirical Platform

DTIC Science & Technology

2008-06-01

13th ICCRTS “C2 for Complex Endeavors” Trust and Decision Making : An Empirical Platform Topic(s): Cognitive and Social Issues...and Decision Making : An Empirical Platform 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e...PERSON a. REPORT unclassified b. ABSTRACT unclassified c. THIS PAGE unclassified Trust and Decision Making : An Empirical Platform Dr. Joseph B

Bucket platform cooling scheme and related method

DOEpatents

Abuaf, Nesim; Barb, Kevin Joseph; Chopra, Sanjay; Kercher, David Max; Kellock, Iain Robertson; Lenahan, Dean Thomas; Nellian, Sankar; Starkweather, John Howard; Lupe, Douglas Arthur

2002-01-01

A turbine bucket includes an airfoil extending from a platform, having high and low pressure sides; a wheel mounting portion; a hollow shank portion located radially between the platform and the wheel mounting portion, the platform having an under surface. An impingement cooling plate is located in the hollow shank portion, spaced from the under surface, and the impingement plate is formed with a plurality of impingement cooling holes therein.

Effectiveness of a digital platform for sharing knowledge on headache management: a two-year experience.

PubMed

Raieli, Vincenzo; Correnti, E; Sandullo, A; Romano, M; Marchese, F; Loiacono, C; Brighina, Filippo

It is crucial that all headache specialists receive adequate training. Considering the unsatisfactory results obtained with standard updating courses and the growing need for continuing professional education, a digital platform was developed as a training tool. The platform has been active since 1 October 2014. It is readily accessible to doctors by free registration. Users have access to all the material available on the platform, which includes scientific articles, e-books, presentations and images. Users can share their own material and clinical cases directly. At the time of this study, the platform had 37 users. In the second year following its launch 316 files were downloaded and five discussions were started. These saw 22 contributions. Fifteen of the 37 members did not perform any action on the platform. In total, 74 files were uploaded in the second year of activity, but 90% of the contributions came from a very small group of users. There were no significant differences in use of the platform between members of the Italian Society for the Study of Headache and other specialists. Even though the platform appears to be an easily accessible, interactive and inexpensive instrument, the higher number of downloads than uploads suggests that it is used passively.

Strategies for comparing gene expression profiles from different microarray platforms: application to a case-control experiment.

PubMed

Severgnini, Marco; Bicciato, Silvio; Mangano, Eleonora; Scarlatti, Francesca; Mezzelani, Alessandra; Mattioli, Michela; Ghidoni, Riccardo; Peano, Clelia; Bonnal, Raoul; Viti, Federica; Milanesi, Luciano; De Bellis, Gianluca; Battaglia, Cristina

2006-06-01

Meta-analysis of microarray data is increasingly important, considering both the availability of multiple platforms using disparate technologies and the accumulation in public repositories of data sets from different laboratories. We addressed the issue of comparing gene expression profiles from two microarray platforms by devising a standardized investigative strategy. We tested this procedure by studying MDA-MB-231 cells, which undergo apoptosis on treatment with resveratrol. Gene expression profiles were obtained using high-density, short-oligonucleotide, single-color microarray platforms: GeneChip (Affymetrix) and CodeLink (Amersham). Interplatform analyses were carried out on 8414 common transcripts represented on both platforms, as identified by LocusLink ID, representing 70.8% and 88.6% of annotated GeneChip and CodeLink features, respectively. We identified 105 differentially expressed genes (DEGs) on CodeLink and 42 DEGs on GeneChip. Among them, only 9 DEGs were commonly identified by both platforms. Multiple analyses (BLAST alignment of probes with target sequences, gene ontology, literature mining, and quantitative real-time PCR) permitted us to investigate the factors contributing to the generation of platform-dependent results in single-color microarray experiments. An effective approach to cross-platform comparison involves microarrays of similar technologies, samples prepared by identical methods, and a standardized battery of bioinformatic and statistical analyses.

Development of an IHE MRRT-compliant open-source web-based reporting platform.

PubMed

Pinto Dos Santos, Daniel; Klos, G; Kloeckner, R; Oberle, R; Dueber, C; Mildenberger, P

2017-01-01

To develop a platform that uses structured reporting templates according to the IHE Management of Radiology Report Templates (MRRT) profile, and to implement this platform into clinical routine. The reporting platform uses standard web technologies (HTML / JavaScript and PHP / MySQL) only. Several freely available external libraries were used to simplify the programming. The platform runs on a standard web server, connects with the radiology information system (RIS) and PACS, and is easily accessible via a standard web browser. A prototype platform that allows structured reporting to be easily incorporated into the clinical routine was developed and successfully tested. To date, 797 reports were generated using IHE MRRT-compliant templates (many of them downloaded from the RSNA's radreport.org website). Reports are stored in a MySQL database and are easily accessible for further analyses. Development of an IHE MRRT-compliant platform for structured reporting is feasible using only standard web technologies. All source code will be made available upon request under a free license, and the participation of other institutions in further development is welcome. • A platform for structured reporting using IHE MRRT-compliant templates is presented. • Incorporating structured reporting into clinical routine is feasible. • Full source code will be provided upon request under a free license.

Design and Proof-of-Concept Use of a Circular PMMA Platform with 16-Well Sample Capacity for Microwave-Accelerated Bioassays.

PubMed

Mohammed, Muzaffer; Aslan, Kadir

2013-01-01

We demonstrate the design and the proof-of-concept use of a new, circular poly(methyl methacrylate)-based bioassay platform (PMMA platform), which affords for the rapid processing of 16 samples at once. The circular PMMA platform (5 cm in diameter) was coated with a silver nanoparticle film to accelerate the bioassay steps by microwave heating. A model colorimetric bioassay for biotinylated albumin (using streptavidin-labeled horse radish peroxidase) was performed on the PMMA platform coated with and without silver nanoparticles (a control experiment), and at room temperature and using microwave heating. It was shown that the simulated temperature profile of the PMMA platform during microwave heating were comparable to the real-time temperature profile during actual microwave heating of the constructed PMMA platform in a commercial microwave oven. The model colorimetric bioassay for biotinylated albumin was successfully completed in ~2 min (total assay time) using microwave heating, as compared to 90 min at room temperature (total assay time), which indicates a ~45-fold decrease in assay time. Our PMMA platform design afforded for significant reduction in non-specific interactions and low background signal as compared to non-silvered PMMA surfaces when employed in a microwave-accelerated bioassay carried out in a conventional microwave cavity.

Framework Design of Unified Cross-Authentication Based on the Fourth Platform Integrated Payment

NASA Astrophysics Data System (ADS)

Yong, Xu; Yujin, He

The essay advances a unified authentication based on the fourth integrated payment platform. The research aims at improving the compatibility of the authentication in electronic business and providing a reference for the establishment of credit system by seeking a way to carry out a standard unified authentication on a integrated payment platform. The essay introduces the concept of the forth integrated payment platform and finally put forward the whole structure and different components. The main issue of the essay is about the design of the credit system of the fourth integrated payment platform and the PKI/CA structure design.

Establish a Data Transmission Platform of the Rig Based on the Distributed Network

NASA Astrophysics Data System (ADS)

Bao, Zefu; Li, Tao

In order to control in real-time ,closed-loop feedback the information, saving the money and labor,we distribute a platform of network data. It through the establishment of the platform in the oil drilling to achieve the easiest route of each device of the rig that conveying timely. The design proposed the platform to transfer networking data by PA which allows the rig control for optimal use. Against the idea,achieving first through on-site cabling and the establishment of data transmission module in the rig monitoring system. The results of standard field application show that the platform solve the problem of rig control.

Platform C North Arrival

NASA Image and Video Library

2016-08-30

A section of the second half of the C-level platforms, C North, for NASA’s Space Launch System (SLS) rocket, arrives at the agency’s Kennedy Space Center in Florida. The platform was offloaded from a heavy lift transport truck and secured in a staging area in the west parking lot of the Vehicle Assembly Building (VAB). The Ground Systems Development and Operations Program is overseeing upgrades and modifications to VAB High Bay 3 to support processing of the SLS and Orion spacecraft. A total of 10 levels of new platforms, 20 platform halves altogether, will surround the SLS rocket and Orion spacecraft and provide access for testing and processing.

A Web Tool for Research in Nonlinear Optics

NASA Astrophysics Data System (ADS)

Prikhod'ko, Nikolay V.; Abramovsky, Viktor A.; Abramovskaya, Natalia V.; Demichev, Andrey P.; Kryukov, Alexandr P.; Polyakov, Stanislav P.

2016-02-01

This paper presents a project of developing the web platform called WebNLO for computer modeling of nonlinear optics phenomena. We discuss a general scheme of the platform and a model for interaction between the platform modules. The platform is built as a set of interacting RESTful web services (SaaS approach). Users can interact with the platform through a web browser or command line interface. Such a resource has no analogues in the field of nonlinear optics and will be created for the first time therefore allowing researchers to access high-performance computing resources that will significantly reduce the cost of the research and development process.

[Study on network architecture of a tele-medical information sharing platform].

PubMed

Pan, Lin; Yu, Lun; Chen, Jin-xiong

2006-07-01

In the article,a plan of network construction which satisfies the demand of applications for a telemedical information sharing platform is proposed. We choice network access plans in view of user actual situation, through the analysis of the service demand and many kinds of network access technologies. Hospital servers that locate in LAN link sharing platform with node servers, should separate from the broadband network of sharing platform in order to ensure the security of the internal hospital network and the administration management. We use the VPN technology to realize the safe transmission of information in the platform network. Preliminary experiments have proved the plan is practicable.

30 CFR 250.609 - Well-workover structures on fixed platforms.

Code of Federal Regulations, 2014 CFR

2014-07-01

... proposed. Prior to moving a well-workover rig or well-servicing equipment onto a platform, the lessee shall..., taking into consideration the corrosion protection, age of the platform, and previous stresses to the...

30 CFR 250.609 - Well-workover structures on fixed platforms.

Code of Federal Regulations, 2013 CFR

2013-07-01

... proposed. Prior to moving a well-workover rig or well-servicing equipment onto a platform, the lessee shall..., taking into consideration the corrosion protection, age of the platform, and previous stresses to the...

30 CFR 250.609 - Well-workover structures on fixed platforms.

Code of Federal Regulations, 2012 CFR

2012-07-01

... proposed. Prior to moving a well-workover rig or well-servicing equipment onto a platform, the lessee shall..., taking into consideration the corrosion protection, age of the platform, and previous stresses to the...

Conceptual design study Science and Applications Space Platform SASP. Volume 2: Technical report

NASA Technical Reports Server (NTRS)

Runge, F. C.

1980-01-01

The platform payload accommodations, configuration drivers, and power system are described in detail. The platform design was analyzed and is presented. Demonstration tests are described and the results are reported.

Microfluidic platform for optimization of crystallization conditions

NASA Astrophysics Data System (ADS)

Zhang, Shuheng; Gerard, Charline J. J.; Ikni, Aziza; Ferry, Gilles; Vuillard, Laurent M.; Boutin, Jean A.; Ferte, Nathalie; Grossier, Romain; Candoni, Nadine; Veesler, Stéphane

2017-08-01

We describe a universal, high-throughput droplet-based microfluidic platform for crystallization. It is suitable for a multitude of applications, due to its flexibility, ease of use, compatibility with all solvents and low cost. The platform offers four modular functions: droplet formation, on-line characterization, incubation and observation. We use it to generate droplet arrays with a concentration gradient in continuous long tubing, without using surfactant. We control droplet properties (size, frequency and spacing) in long tubing by using hydrodynamic empirical relations. We measure droplet chemical composition using both an off-line and a real-time on-line method. Applying this platform to a complicated chemical environment, membrane proteins, we successfully handle crystallization, suggesting that the platform is likely to perform well in other circumstances. We validate the platform for fine-gradient screening and optimization of crystallization conditions. Additional on-line detection methods may well be integrated into this platform in the future, for instance, an on-line diffraction technique. We believe this method could find applications in fields such as fluid interaction engineering, live cell study and enzyme kinetics.

Research on the influence of helical strakes on dynamic response of floating wind turbine platform

NASA Astrophysics Data System (ADS)

Ding, Qin-wei; Li, Chun

2017-04-01

The stability of platform structure is the paramount guarantee of the safe operation of the offshore floating wind turbine. The NREL 5MW floating wind turbine is established based on the OC3-Hywind Spar Buoy platform with the supplement of helical strakes for the purpose to analyze the impact of helical strakes on the dynamic response of the floating wind turbine Spar platform. The dynamic response of floating wind turbine Spar platform under wind, wave and current loading from the impact of number, height and pitch ratio of the helical strakes is analysed by the radiation and diffraction theory, the finite element method and orthogonal design method. The result reveals that the helical strakes can effectively inhibit the dynamic response of the platform but enlarge the wave exciting force; the best parameter combination is two pieces of helical strakes with the height of 15% D ( D is the diameter of the platform) and the pitch ratio of 5; the height of the helical strake and its pitch ratio have significant influence on pitch response.

Blade platform seal for ceramic/metal rotor assembly

DOEpatents

Wertz, John L.

1982-01-01

A combination ceramic and metal turbine rotor for use in high temperature gas turbine engines includes a metal rotor disc having a rim with a plurality of circumferentially spaced blade root retention slots therein to receive a plurality of ceramic blades, each including side platform segments thereon and a dovetail configured root slidably received in one of the slots. Adjacent ones of the platform segments including edge portions thereon closely spaced when the blades are assembled to form expansion gaps in an annular flow surface for gas passage through the blades and wherein the assembly further includes a plurality of unitary seal members on the rotor connected to its rim and each including a plurality of spaced, axially extending, flexible fingers that underlie and conform to the edge portions of the platform segments and which are operative at turbine operating temperatures and speeds to distribute loading on the platform segments as the fingers are seated against the underside of the blade platforms to seal the gaps without undesirably stressing thin web ceramic sections of the platform.

(abstract) Altimeter Calibration and Geophysical Monitoring from Collocated Measurements at the Harvest Oil Platform

NASA Technical Reports Server (NTRS)

Haines, B. J.; Christensen, E. J.; Norman, R. A.; Parke, M. E.; Born, G. H.; Gill, S. K.

1996-01-01

Prior to the launch of TOPEX/ Poseidon in August 1992, NASA established its primary in situ verification site on the Harvest oil platform located in the Pacific Ocean off the coast of central California. Data from a suite of geodetic and oceanographic instruments attached to the platform have been combined to yield a precise record of absolute sea level simce the beginning of the mission. Critical to the computation of this geocentric sea level record is the precise determination of the platform geodetic height and the vertical velocity in the global terrestrial reference frame.We compare estimates of the platform height and vertical velocity from global positioning system (GPS) data alone and from a combination of GPS and satellite laser ranging (SLR) information. Current estimates suggest the platform is subsiding at a rate of about 8 mm per year. This height information is combined with in situ tide gauge measurements of sea level relative to a platform reference mark in order to produce a continuous record of the local geocentric sea height.

Reconfigurable, Intelligently-Adaptive, Communication System, an SDR Platform

NASA Technical Reports Server (NTRS)

Roche, Rigoberto

2016-01-01

The Space Telecommunications Radio System (STRS) provides a common, consistent framework to abstract the application software from the radio platform hardware. STRS aims to reduce the cost and risk of using complex, configurable and reprogrammable radio systems across NASA missions. The Glenn Research Center (GRC) team made a software-defined radio (SDR) platform STRS compliant by adding an STRS operating environment and a field programmable gate array (FPGA) wrapper, capable of implementing each of the platforms interfaces, as well as a test waveform to exercise those interfaces. This effort serves to provide a framework toward waveform development on an STRS compliant platform to support future space communication systems for advanced exploration missions. Validated STRS compliant applications provided tested code with extensive documentation to potentially reduce risk, cost and efforts in development of space-deployable SDRs. This paper discusses the advantages of STRS, the integration of STRS onto a Reconfigurable, Intelligently-Adaptive, Communication System (RIACS) SDR platform, the sample waveform, and wrapper development efforts. The paper emphasizes the infusion of the STRS Architecture onto the RIACS platform for potential use in next generation SDRs for advance exploration missions.

Kinematics of an in-parallel actuated manipulator based on the Stewart platform mechanism

NASA Technical Reports Server (NTRS)

Williams, Robert L., II

1992-01-01

This paper presents kinematic equations and solutions for an in-parallel actuated robotic mechanism based on Stewart's platform. These equations are required for inverse position and resolved rate (inverse velocity) platform control. NASA LaRC has a Vehicle Emulator System (VES) platform designed by MIT which is based on Stewart's platform. The inverse position solution is straight-forward and computationally inexpensive. Given the desired position and orientation of the moving platform with respect to the base, the lengths of the prismatic leg actuators are calculated. The forward position solution is more complicated and theoretically has 16 solutions. The position and orientation of the moving platform with respect to the base is calculated given the leg actuator lengths. Two methods are pursued in this paper to solve this problem. The resolved rate (inverse velocity) solution is derived. Given the desired Cartesian velocity of the end-effector, the required leg actuator rates are calculated. The Newton-Raphson Jacobian matrix resulting from the second forward position kinematics solution is a modified inverse Jacobian matrix. Examples and simulations are given for the VES.

Detail view of fourth level platform winch used to lift ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Detail view of fourth level platform winch used to lift platform segments away from the Shuttle assembly during testing. - Marshall Space Flight Center, Saturn V Dynamic Test Facility, East Test Area, Huntsville, Madison County, AL

Keeping a Competitive U.S. Military Aircraft Industry Aloft: Findings from an Analysis of the Industrial Base

DTIC Science & Technology

2011-01-01

industries as credit cards , health maintenance organizations (HMOs), travel reservations, video games, container shipping, music, and (remarkably) cement... iTunes . It is a software platform that is replacing the (nonplatform) strategy of selling CDs in retail stores. In other words, a platform-mediated...boundar- ies. Brokerage, mortgage, checking, savings, and credit cards are inte- grated around a major platform. This banking platform is even pen

Gas turbine bucket with impingement cooled platform

DOEpatents

Jones, Raphael Durand

2002-01-01

In a turbine bucket having an airfoil portion and a root portion, with a substantially planar platform at an interface between the airfoil portion and root portion, a platform cooling arrangement including at least one bore in the root portion and at least one impingement cooling tube seated in the bore, the tube extending beyond the bore with an outlet in close proximity to a targeted area on an underside of the platform.

FORCEnet Net Centric Architecture - A Standards View

DTIC Science & Technology

2006-06-01

SHARED SERVICES NETWORKING/COMMUNICATIONS STORAGE COMPUTING PLATFORM DATA INTERCHANGE/INTEGRATION DATA MANAGEMENT APPLICATION...R V I C E P L A T F O R M S E R V I C E F R A M E W O R K USER-FACING SERVICES SHARED SERVICES NETWORKING/COMMUNICATIONS STORAGE COMPUTING PLATFORM...E F R A M E W O R K USER-FACING SERVICES SHARED SERVICES NETWORKING/COMMUNICATIONS STORAGE COMPUTING PLATFORM DATA INTERCHANGE/INTEGRATION

Improvement of Resilience to Disasters in Local Community Using Information Sharing Platform

NASA Astrophysics Data System (ADS)

Hayama, Toru; Suzuki, Yuji; Park, Wonho; Hayashi, Akira

This paper presents a proposal for Disaster Information Sharing Platform, which enable local government and residents to share the disaster information, and to cope with the disaster under the proper balance of Self-help, Mutual-help and Public-help. Informagic, which has been developed as a concrete example of the information sharing platform, enable us to collect information from variety of sources, such as government, local government, research institutes, private contents providers and so forth, and to transmit these information to residents through multi-media, such as internet, mobile-phone network and wireless system. An experiment was conducted under the cooperation of City of Fujisawa, to investigate the effectiveness of such platform for the disaster mitigation. Further, the platform was utilized to provide information to refugees at refuges for the Iwate-Miyagi Inland Earthquake. Through these experiments, effectiveness and issues of the platform and information sharing were investigated.

The Generation Challenge Programme Platform: Semantic Standards and Workbench for Crop Science

PubMed Central

Bruskiewich, Richard; Senger, Martin; Davenport, Guy; Ruiz, Manuel; Rouard, Mathieu; Hazekamp, Tom; Takeya, Masaru; Doi, Koji; Satoh, Kouji; Costa, Marcos; Simon, Reinhard; Balaji, Jayashree; Akintunde, Akinnola; Mauleon, Ramil; Wanchana, Samart; Shah, Trushar; Anacleto, Mylah; Portugal, Arllet; Ulat, Victor Jun; Thongjuea, Supat; Braak, Kyle; Ritter, Sebastian; Dereeper, Alexis; Skofic, Milko; Rojas, Edwin; Martins, Natalia; Pappas, Georgios; Alamban, Ryan; Almodiel, Roque; Barboza, Lord Hendrix; Detras, Jeffrey; Manansala, Kevin; Mendoza, Michael Jonathan; Morales, Jeffrey; Peralta, Barry; Valerio, Rowena; Zhang, Yi; Gregorio, Sergio; Hermocilla, Joseph; Echavez, Michael; Yap, Jan Michael; Farmer, Andrew; Schiltz, Gary; Lee, Jennifer; Casstevens, Terry; Jaiswal, Pankaj; Meintjes, Ayton; Wilkinson, Mark; Good, Benjamin; Wagner, James; Morris, Jane; Marshall, David; Collins, Anthony; Kikuchi, Shoshi; Metz, Thomas; McLaren, Graham; van Hintum, Theo

2008-01-01

The Generation Challenge programme (GCP) is a global crop research consortium directed toward crop improvement through the application of comparative biology and genetic resources characterization to plant breeding. A key consortium research activity is the development of a GCP crop bioinformatics platform to support GCP research. This platform includes the following: (i) shared, public platform-independent domain models, ontology, and data formats to enable interoperability of data and analysis flows within the platform; (ii) web service and registry technologies to identify, share, and integrate information across diverse, globally dispersed data sources, as well as to access high-performance computational (HPC) facilities for computationally intensive, high-throughput analyses of project data; (iii) platform-specific middleware reference implementations of the domain model integrating a suite of public (largely open-access/-source) databases and software tools into a workbench to facilitate biodiversity analysis, comparative analysis of crop genomic data, and plant breeding decision making. PMID:18483570

A systems approach to designing next generation vaccines: combining α-galactose modified antigens with nanoparticle platforms

NASA Astrophysics Data System (ADS)

Phanse, Yashdeep; Carrillo-Conde, Brenda R.; Ramer-Tait, Amanda E.; Broderick, Scott; Kong, Chang Sun; Rajan, Krishna; Flick, Ramon; Mandell, Robert B.; Narasimhan, Balaji; Wannemuehler, Michael J.

2014-01-01

Innovative vaccine platforms are needed to develop effective countermeasures against emerging and re-emerging diseases. These platforms should direct antigen internalization by antigen presenting cells and promote immunogenic responses. This work describes an innovative systems approach combining two novel platforms, αGalactose (αGal)-modification of antigens and amphiphilic polyanhydride nanoparticles as vaccine delivery vehicles, to rationally design vaccine formulations. Regimens comprising soluble αGal-modified antigen and nanoparticle-encapsulated unmodified antigen induced a high titer, high avidity antibody response with broader epitope recognition of antigenic peptides than other regimen. Proliferation of antigen-specific CD4+ T cells was also enhanced compared to a traditional adjuvant. Combining the technology platforms and augmenting immune response studies with peptide arrays and informatics analysis provides a new paradigm for rational, systems-based design of next generation vaccine platforms against emerging and re-emerging pathogens.

Dielectrophoresis-based microfluidic platforms for cancer diagnostics.

PubMed

Chan, Jun Yuan; Ahmad Kayani, Aminuddin Bin; Md Ali, Mohd Anuar; Kok, Chee Kuang; Yeop Majlis, Burhanuddin; Hoe, Susan Ling Ling; Marzuki, Marini; Khoo, Alan Soo-Beng; Ostrikov, Kostya Ken; Ataur Rahman, Md; Sriram, Sharath

2018-01-01

The recent advancement of dielectrophoresis (DEP)-enabled microfluidic platforms is opening new opportunities for potential use in cancer disease diagnostics. DEP is advantageous because of its specificity, low cost, small sample volume requirement, and tuneable property for microfluidic platforms. These intrinsic advantages have made it especially suitable for developing microfluidic cancer diagnostic platforms. This review focuses on a comprehensive analysis of the recent developments of DEP enabled microfluidic platforms sorted according to the target cancer cell. Each study is critically analyzed, and the features of each platform, the performance, added functionality for clinical use, and the types of samples, used are discussed. We address the novelty of the techniques, strategies, and design configuration used in improving on existing technologies or previous studies. A summary of comparing the developmental extent of each study is made, and we conclude with a treatment of future trends and a brief summary.

Abundance of Corals on Offshore Oil and Gas Platforms in the Gulf of Mexico

NASA Astrophysics Data System (ADS)

Kolian, Stephan R.; Sammarco, Paul W.; Porter, Scott A.

2017-08-01

Scleractinian, octocoral, and antipatharian corals have colonized many of the offshore oil and gas platforms in the northern Gulf of Mexico. We surveyed 25 offshore oil and gas platforms for these cnidarians. Few to no corals were detected on inshore, shallow-water structures at <25 m depth; however, the abundance of corals increased, ranging from 14 to 194/m2, on platforms in waters deeper ≥25 m. The most common coral encountered were Tubastraea coccinea (Scleractinia) and Telesto spp. (Octocorallia). The data suggest that the offshore platforms located in waters of >25-30 m in the study area are often colonized by these corals. We recommend that structures located in deeper waters should be surveyed for coral and, if the populations are substantial, consider alternate uses for the retired platforms, and leaving them in place, when feasible.

Exergames vs. traditional exercise: investigating the influencing mechanism of platform effect on subthreshold depression among older adults.

PubMed

Li, Jinhui; Theng, Yin-Leng; Foo, Schubert; Xu, Xuexin

2017-10-06

This study aimed to examine the influencing mechanism of exercise platform effect on subthreshold depression among older adults by comparing exergames and traditional exercise. One hundred and two Singaporean older adults were assigned to either playing Wii exergames or performing traditional exercise programs once a week, for six weeks. Results confirmed a direct negative platform effect on subthreshold depression and further supported the mediation role of positive emotions in the platform effect. It implied that exergames led to higher positive emotions than traditional exercise, which further reduced the subthreshold depression among older adults. Self-efficacy was not supported to be a significant mediator in the relations between exercise platform and subthreshold depression. A better understanding of the mechanisms behind the antidepressant effects of exercise platform would not only provide additional insight into a possible causal association, but also inspire the future use of exergames in the treatment of subthreshold depression.

VAB Platform K(2) Lift & Install into Highbay 3

NASA Image and Video Library

2016-03-07

Preparations are underway to lift the second half of the K-level work platforms for NASA’s Space Launch System (SLS) rocket up from High Bay 4 inside the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. The platform will be lifted up and over the transfer aisle and then lowered into High Bay 3 for installation. It will be secured about 86 feet above the VAB floor, on tower E of the high bay. The K work platforms will provide access to the SLS core stage and solid rocket boosters during processing and stacking operations on the mobile launcher. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to High Bay 3 to support processing of the SLS and Orion spacecraft. A total of 10 levels of new platforms, 20 platform halves altogether, will surround the SLS rocket and Orion spacecraft.

VAB Platform K(2) Lift & Install into Highbay 3

NASA Image and Video Library

2016-03-07

A 250-ton crane is used to lift the second half of the K-level work platforms for NASA’s Space Launch System (SLS) rocket up from High Bay 4 inside the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. The platform will be lifted up and over the transfer aisle and then lowered into High Bay 3 for installation. It will be secured about 86 feet above the VAB floor, on tower E of the high bay. The K work platforms will provide access to the SLS core stage and solid rocket boosters during processing and stacking operations on the mobile launcher. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to High Bay 3 to support processing of the SLS and Orion spacecraft. A total of 10 levels of new platforms, 20 platform halves altogether, will surround the SLS rocket and Orion spacecraft.

VAB Platform K(2) Lift & Install into Highbay 3

NASA Image and Video Library

2016-03-07

A 250-ton crane is used to lift the second half of the K-level work platforms for NASA’s Space Launch System (SLS) rocket up from High Bay 4 inside the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. The platform is being lifted up and over the transfer aisle and will be lowered into High Bay 3 for installation. It will be secured about 86 feet above the VAB floor, on tower E of the high bay. The K work platforms will provide access to the SLS core stage and solid rocket boosters during processing and stacking operations on the mobile launcher. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to High Bay 3 to support processing of the SLS and Orion spacecraft. A total of 10 levels of new platforms, 20 platform halves altogether, will surround the SLS rocket and Orion spacecraft.

Abundance of Corals on Offshore Oil and Gas Platforms in the Gulf of Mexico.

PubMed

Kolian, Stephan R; Sammarco, Paul W; Porter, Scott A

2017-08-01

Scleractinian, octocoral, and antipatharian corals have colonized many of the offshore oil and gas platforms in the northern Gulf of Mexico. We surveyed 25 offshore oil and gas platforms for these cnidarians. Few to no corals were detected on inshore, shallow-water structures at <25 m depth; however, the abundance of corals increased, ranging from 14 to 194/m 2 , on platforms in waters deeper ≥25 m. The most common coral encountered were Tubastraea coccinea (Scleractinia) and Telesto spp. (Octocorallia). The data suggest that the offshore platforms located in waters of >25-30 m in the study area are often colonized by these corals. We recommend that structures located in deeper waters should be surveyed for coral and, if the populations are substantial, consider alternate uses for the retired platforms, and leaving them in place, when feasible.

A holistic approach to SIM platform and its application to early-warning satellite system

NASA Astrophysics Data System (ADS)

Sun, Fuyu; Zhou, Jianping; Xu, Zheyao

2018-01-01

This study proposes a new simulation platform named Simulation Integrated Management (SIM) for the analysis of parallel and distributed systems. The platform eases the process of designing and testing both applications and architectures. The main characteristics of SIM are flexibility, scalability, and expandability. To improve the efficiency of project development, new models of early-warning satellite system were designed based on the SIM platform. Finally, through a series of experiments, the correctness of SIM platform and the aforementioned early-warning satellite models was validated, and the systematical analyses for the orbital determination precision of the ballistic missile during its entire flight process were presented, as well as the deviation of the launch/landing point. Furthermore, the causes of deviation and prevention methods will be fully explained. The simulation platform and the models will lay the foundations for further validations of autonomy technology in space attack-defense architecture research.

Content Management System for Developing a Virtual Platform for Association of Women's Aid with Lack of Resources

NASA Astrophysics Data System (ADS)

Sainz de Abajo, Beatriz; Flores García, Alberto; García Salcines, Enrique; Burón Fernández, F. Javier; López Coronado, Miguel; de Castro Lozano, Carlos

In this paper we show a Virtual Platform for an Association of Women's Aid called Centro Integral de Ayuda a la Mujer (CIAM). After analyzing different Content Management Systems (CMS) and the benefits that its use would contribute to the development of the Virtual Platform, taking into account the needs and requirements set by CIAM, we have opted for the use of Joomla!. This free CMS, for its characteristics, is the most benefits provided us. The virtual platform design has been developed following customer specifications, to have understood the simplicity and easy handling of the resulting platform. This platform will be integrated into the Web portal that has the Amarex Association and it will be able to be administrates from the CIAM without specific knowledge of programming languages. If new services were necessary, they would be easily implemented, adding new modules and components to perform these services.

Data-acquisition system for environmental monitoring aboard a twin-engined aircraft

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tichler, J.; Bernstein, H.; Brown, R.M.

A number of experimental platforms have been used in support of the Multistate Atmospheric Power Production Study (MAP3S) and the Coastal Meteorology programs at Brookhaven National Laboratory. These platforms include a twin-engine Britten Norman Islander aircraft, a motorized van, a variety of boats and temporary enclosures set up in the field. Each platform carried a data logger consisting of a multiplexer, an analog to digital (A/D) converter and a four track endless loop magnetic tape for data storage. In recent years it has become increasingly evident that the data loggers in use were no longer adequate. Since the aircraft providedmore » the most constraints on the data acquisition system as well as being the most important research platform, a data system was designed for that platform with the secondary goal that the system would serve as a prototype for systems to be used on other platforms.« less

Functional comparison of microarray data across multiple platforms using the method of percentage of overlapping functions.

PubMed

Li, Zhiguang; Kwekel, Joshua C; Chen, Tao

2012-01-01

Functional comparison across microarray platforms is used to assess the comparability or similarity of the biological relevance associated with the gene expression data generated by multiple microarray platforms. Comparisons at the functional level are very important considering that the ultimate purpose of microarray technology is to determine the biological meaning behind the gene expression changes under a specific condition, not just to generate a list of genes. Herein, we present a method named percentage of overlapping functions (POF) and illustrate how it is used to perform the functional comparison of microarray data generated across multiple platforms. This method facilitates the determination of functional differences or similarities in microarray data generated from multiple array platforms across all the functions that are presented on these platforms. This method can also be used to compare the functional differences or similarities between experiments, projects, or laboratories.

Analysis and experimental evaluation of a Stewart platform-based force/torque sensor

NASA Technical Reports Server (NTRS)

Nguyen, Charles C.; Antrazi, Sami S.

1992-01-01

The kinematic analysis and experimentation of a force/torque sensor whose design is based on the mechanism of the Stewart Platform are discussed. Besides being used for measurement of forces/torques, the sensor also serves as a compliant platform which provides passive compliance during a robotic assembly task. It consists of two platforms, the upper compliant platform (UCP) and the lower compliant platform (LCP), coupled together through six spring-loaded pistons whose length variations are measured by six linear voltage differential transformers (LVDT) mounted along the pistons. Solutions to the forward and inverse kinematics of the force sensor are derived. Based on the known spring constant and the piston length changes, forces/torques applied to the LCP gripper are computed using vector algebra. Results of experiments conducted to evaluate the sensing capability of the force sensor are reported and discussed.

Power in the loop real time simulation platform for renewable energy generation

NASA Astrophysics Data System (ADS)

Li, Yang; Shi, Wenhui; Zhang, Xing; He, Guoqing

2018-02-01

Nowadays, a large scale of renewable energy sources has been connecting to power system and the real time simulation platform is widely used to carry out research on integration control algorithm, power system stability etc. Compared to traditional pure digital simulation and hardware in the loop simulation, power in the loop simulation has higher accuracy and degree of reliability. In this paper, a power in the loop analog digital hybrid simulation platform has been built and it can be used not only for the single generation unit connecting to grid, but also for multiple new energy generation units connecting to grid. A wind generator inertia control experiment was carried out on the platform. The structure of the inertia control platform was researched and the results verify that the platform is up to need for renewable power in the loop real time simulation.

Modular turbine airfoil and platform assembly with independent root teeth

DOEpatents

Campbell, Christian X; Davies, Daniel O; Eng, Darryl

2013-07-30

A turbine airfoil (22E-H) extends from a shank (23E-H). A platform (30E-H) brackets or surrounds a first portion of the shank (23E-H). Opposed teeth (33, 35) extend laterally from the platform (30E-H) to engage respective slots (50) in a disk. Opposed teeth (25, 27) extend laterally from a second portion of the shank (29) that extends below the platform (30E-H) to engage other slots (52) in the disk. Thus the platform (30E-H) and the shank (23E-H) independently support their own centrifugal loads via their respective teeth. The platform may be formed in two portions (32E-H, 34E-H), that are bonded to each other at matching end-walls (37) and/or via pins (36G) passing through the shank (23E-H). Coolant channels (41, 43) may pass through the shank beside the pins (36G).

Design of self-contained sensor for monitoring of deep-sea offshore platform

NASA Astrophysics Data System (ADS)

Song, Yang; Yu, Yan; Zhang, Chunwei; Dong, Weijie; Ou, Jinping

2013-04-01

Offshore platform, which is the base of the production and living in the sea, is the most important infrastructure for developing oil and gas resources. At present, there are almost 6500 offshore platforms servicing in the 53 countries' sea areas around the world, creating great wealth for the world. In general, offshore platforms may work for 20 years, however, offshore platforms are expensive, complex, bulky, and so many of them are on extended active duty. Because of offshore platforms servicing in the harsh marine environment for a long time, the marine environment have a great impact on the offshore platforms. Besides, with the impact and erosion of seawater, and material aging, the offshore platform is possible to be in unexpected situations when a badly sudden situation happens. Therefore, it is of great significance to monitor the marine environment and offshore platforms. The self-contained sensor for deep-sea offshore platform with its unique design, can not only effectively extend the working time of the sensor with the capability of converting vibration energy to electrical energy, but also simultaneously collect the data of acceleration, inclination, temperature and humidity of the deep sea, so that we can achieve the purpose of monitoring offshore platforms through analyzing the collected data. The self-contained sensor for monitoring of deep-sea offshore platform includes sensing unit, data collecting and storage unit, the energy supply unit. The sensing unit with multi-variables, consists of an accelerometer LIS344ALH, an inclinometer SCA103T and a temperature and humidity sensor SHT11; the data collecting and storage unit includes the MSP430 low-power MCU, large capacity memory, clock circuit and the communication interface, the communication interface includes USB interface, serial ports and wireless interface; in addition, the energy supply unit, converting vibration to electrical energy to power the overall system, includes the electromagnetic generator, voltage multiplier circuit and a super capacitor which can withstand virtually unlimited number of charge-discharge cycles. When the seawater impacts on offshore platforms to produce vibration, electromagnetic generator converts vibration to electrical energy, its output(~ 1 V 50 Hz AC) is stepped up and rectified by a voltage multiplier circuit, and the energy is stored in a super capacitor. It is controlled by the MSP430 that monitors the voltage level on the super capacitor. The super capacitor charges the Li-ion battery when the voltage on the super capacitor reaches a threshold, then the whole process of energy supply is completed. The self-contained sensor for deep-sea offshore platform has good application prospects and practical value with small size, low power, being easy to install, converting vibration energy to supply power and high detection accuracy.

Evolution of Cupido and Coahuila carbonate platforms, early Cretaceous, northeastern Mexico

USGS Publications Warehouse

Lehmann, Christoph; Osleger, David A.; Montañez, Isabel P.; Sliter, William V.; Arnaud Vanneau, Annie; Banner, Jay L.

1999-01-01

The Cupido and Coahuila platforms of northeastern Mexico are part of the extensive carbonate platform system that rimmed the ancestral Gulf of Mexico during Barremian to Albian time. Exposures of Cupido and Coahuila lithofacies in several mountain ranges spanning an ∼80000 km2 area reveal information about platform morphology and composition, paleoenvironmental relations, and the chronology of platform evolution. New biostratigraphic data, integrated with carbon and strontium isotope stratigraphy, significantly improve chronostratigraphic relations across the region. These data substantially change previous age assignments of several formations and force a revision of the longstanding stratigraphy in the region. The revised stratigraphy and enhanced time control, combined with regional facies associations, allow the construction of cross sections, isopach maps, and time-slice paleogeographic maps that collectively document platform morphology and evolution.The orientation of the Cupido (Barremian-Aptian) shelf margin was controlled by the emergent Coahuila basement block to the northwest. The south-facing margin is a high-energy grainstone shoal, whereas the margin facing the ancestral Gulf of Mexico to the east is a discontinuous rudist-coral reef. A broad shelf lagoon developed in the lee of the Cupido margin, where as much as 660 m of cyclic peritidal deposits accumulated. During middle to late Aptian time, a major phase of flooding forced a retrograde backstep of the Cupido platform, shifting the locus of shallow-marine sedimentation northwestward toward the Coahuila block. This diachronous flooding event records both the demise of the Cupido shelf and the consequent initiation of the Coahuila ramp.The backstepped Coahuila ramp (Aptian-Albian) consisted of a shallow shoal margin separating an interior evaporitic lagoon from a low-energy, muddy deep ramp. More than 500 m of cyclic carbonates and evaporites accumulated in the evaporitic lagoon during early to middle Albian time. Restriction of the platform interior dissipated by middle to late Albian time with the deposition of peloidal, miliolid-rich packstones and grainstones of the Aurora Formation. The Coahuila platform was drowned during latest Albian to early Cenomanian time, and the deep-water laminites of the Cuesta del Cura Formation were deposited.This study fills in a substantial gap in the Cretaceous paleogeography of the eastern Gulf of Mexico coast, improving regional correlations with adjacent hydrocarbon-rich platforms. The enhanced temporal relations and chronology of events recorded in the Cupido and Coahuila platforms significantly improve global correlations with coeval, economically important platforms worldwide, perhaps contributing to the determination of global versus regional controls on carbonate platform evolution during middle Cretaceous time.

Establishment and Comparison of Two Different Diagnostic Platforms for Detection of DENV1 NS1 Protein

PubMed Central

Tang, Yin-Liang; Chiu, Chien-Yu; Lin, Chun-Yu; Huang, Chung-Hao; Chen, Yen-Hsu; Destura, Raul V.; Chao, Day-Yu; Wu, Han-Chung

2015-01-01

Dengue virus (DENV) infection is currently at pandemic levels, with populations in tropical and subtropical regions at greatest risk of infection. Early diagnosis and management remain the cornerstone for good clinical outcomes, thus efficient and accurate diagnostic technology in the early stage of the disease is urgently needed. Serotype-specific monoclonal antibodies (mAbs) against the DENV1 nonstructural protein 1 (NS1), DA12-4, DA13-2, and DA15-3, which were recently generated using the hybridoma technique, are suitable for use in diagnostic platforms. Immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA) and Western blot analysis further confirmed the serotype specificity of these three monoclonal antibodies. The ELISA-based diagnostic platform was established using the combination of two highly sensitive mAbs (DA15-3 and DB20-6). The same combination was also used for the flow cytometry-based diagnostic platform. We report here the detection limits of flow cytometry-based and ELISA-based diagnostic platforms using these mAbs to be 0.1 and 1 ng/mL, respectively. The collected clinical patient serum samples were also assayed by these two serotyping diagnostic platforms. The sensitivity and specificity for detecting NS1 protein of DENV1 are 90% and 96%, respectively. The accuracy of our platform for testing clinical samples is more advanced than that of the two commercial NS1 diagnostic platforms. In conclusion, our platforms are suitable for the early detection of NS1 protein in DENV1 infected patients. PMID:26610481

Contemporary engagement with social media amongst hernia surgery specialists.

PubMed

Lui, D H; McDonald, J J; de Beaux, A; Tulloh, B; Brady, R R W

2017-08-01

Healthcare professional engagement is increasing. This study aims to identify levels of adoption and engagement of several social media platforms by a large international cohort of hernia surgery specialists. Hernia specialists attending the 38th International Congress of the European Hernia Society were identified. A manual search was then performed on Twitter, ResearchGate, and LinkedIn to identify those who had named accounts. Where accounts were identified, data on markers of utilisation were assessed. 759 surgeons (88.5% male) from 57 countries were identified. 334 surgeons (44%) engaged with a social media platform. 39 (5.1%) had Twitter accounts, 189 (24.9%) had ResearchGate accounts and 265 (34.9%) had LinkedIn accounts. 137 surgeons (18.1%) had accounts on 2 or more social media platforms. There was no gender association with social media account ownership (p > 0.05). Engagement in one social media platform was associated with increased engagement and utilisation on other platforms; LinkedIn users were more likely to have Twitter accounts (p < 0.001) and ResearchGate profiles (p < 0.001). Surgeons on all three SM platforms were more likely to have high markers of engagement across all SM platforms (multiple outcomes, p < 0.05). Geographical variation was noted with UK and South American Surgeons being more likely to be present on Twitter than their counterparts (p = 0.031). The level of engagement with social media amongst Hernia surgeons is similar to other surgical specialities. Geographical variation in SM engagement is seen. Engagement with one SM platform is associated with presence on multiple platforms.

Development of jacket platform tsunami risk rating system in waters offshore North Borneo

NASA Astrophysics Data System (ADS)

Lee, H. E.; Liew, M. S.; Mardi, N. H.; Na, K. L.; Toloue, Iraj; Wong, S. K.

2016-09-01

This work details the simulation of tsunami waves generated by seaquakes in the Manila Trench and their effect on fixed oil and gas jacket platforms in waters offshore North Borneo. For this study, a four-leg living quarter jacket platform located in a water depth of 63m is modelled in SACS v5.3. Malaysia has traditionally been perceived to be safe from the hazards of earthquakes and tsunamis. Local design practices tend to neglect tsunami waves and include no such provisions. In 2004, a 9.3 M w seaquake occurred off the northwest coast of Aceh, which generated tsunami waves that caused destruction in Malaysia totalling US 25 million and 68 deaths. This event prompted an awareness of the need to study the reliability of fixed offshore platforms scattered throughout Malaysian waters. In this paper, we present a review of research on the seismicity of the Manila Trench, which is perceived to be high risk for Southeast Asia. From the tsunami numerical model TUNA-M2, we extract computer-simulated tsunami waves at prescribed grid points in the vicinity of the platforms in the region. Using wave heights as input, we simulate the tsunami using SACS v5.3 structural analysis software of offshore platforms, which is widely accepted by the industry. We employ the nonlinear solitary wave theory in our tsunami loading calculations for the platforms, and formulate a platform-specific risk quantification system. We then perform an intensive structural sensitivity analysis and derive a corresponding platform-specific risk rating model.

Influence of platform and abutment angulation on peri-implant bone. A three-dimensional finite element stress analysis.

PubMed

Martini, Ana Paula; Barros, Rosália Moreira; Júnior, Amilcar Chagas Freitas; Rocha, Eduardo Passos; de Almeida, Erika Oliveira; Ferraz, Cacilda Cunha; Pellegrin, Maria Cristina Jimenez; Anchieta, Rodolfo Bruniera

2013-12-01

The aim of this study was to evaluate stress distribution on the peri-implant bone, simulating the influence of Nobel Select implants with straight or angulated abutments on regular and switching platform in the anterior maxilla, by means of 3-dimensional finite element analysis. Four mathematical models of a central incisor supported by external hexagon implant (13 mm × 5 mm) were created varying the platform (R, regular or S, switching) and the abutments (S, straight or A, angulated 15°). The models were created by using Mimics 13 and Solid Works 2010 software programs. The numerical analysis was performed using ANSYS Workbench 10.0. Oblique forces (100 N) were applied to the palatine surface of the central incisor. The bone/implant interface was considered perfectly integrated. Maximum (σmax) and minimum (σmin) principal stress values were obtained. For the cortical bone the highest stress values (σmax) were observed in the RA (regular platform and angulated abutment, 51 MPa), followed by SA (platform switching and angulated abutment, 44.8 MPa), RS (regular platform and straight abutment, 38.6 MPa) and SS (platform switching and straight abutment, 36.5 MPa). For the trabecular bone, the highest stress values (σmax) were observed in the RA (6.55 MPa), followed by RS (5.88 MPa), SA (5.60 MPa), and SS (4.82 MPa). The regular platform generated higher stress in the cervical periimplant region on the cortical and trabecular bone than the platform switching, irrespective of the abutment used (straight or angulated).

The Role of Bed Roughness in Wave Transformation Across Sloping Rock Shore Platforms

NASA Astrophysics Data System (ADS)

Poate, Tim; Masselink, Gerd; Austin, Martin J.; Dickson, Mark; McCall, Robert

2018-01-01

We present for the first time observations and model simulations of wave transformation across sloping (Type A) rock shore platforms. Pressure measurements of the water surface elevation using up to 15 sensors across five rock platforms with contrasting roughness, gradient, and wave climate represent the most extensive collected, both in terms of the range of environmental conditions, and the temporal and spatial resolution. Platforms are shown to dissipate both incident and infragravity wave energy as skewness and asymmetry develop and, in line with previous studies, surf zone wave heights are saturated and strongly tidally modulated. Overall, the observed properties of the waves and formulations derived from sandy beaches do not highlight any systematic interplatform variation, in spite of significant differences in platform roughness, suggesting that friction can be neglected when studying short wave transformation. Optimization of a numerical wave transformation model shows that the wave breaker criterion falls between the range of values reported for flat sandy beaches and those of steep coral fore reefs. However, the optimized drag coefficient shows significant scatter for the roughest sites and an alternative empirical drag model, based on the platform roughness, does not improve model performance. Thus, model results indicate that the parameterization of frictional drag using the bottom roughness length-scale may be inappropriate for the roughest platforms. Based on these results, we examine the balance of wave breaking to frictional dissipation for rock platforms and find that friction is only significant for very rough, flat platforms during small wave conditions outside the surf zone.

Use of a platform in an automated open-field to enhance assessment of anxiety-like behaviors in mice.

PubMed

Pogorelov, Vladimir M; Lanthorn, Thomas H; Savelieva, Katerina V

2007-05-15

The present report describes a setup for simultaneously measuring anxiety-like behaviors and locomotor activity in mice. Animals are placed in a brightly lit, standard automated open-field (OF) in which a rectangular ceramic platform 8 cm high covers one quadrant of the floor. Mice preferred to stay under the platform, avoiding the area with bright illumination. Activities under and outside the platform were measured for 5 min. Chlordiazepoxide and buspirone dose-dependently increased time spent outside the platform (L-Time) and the light distance to total OF distance ratio (L:T-TD) in both genders without changing total OF distance. By contrast, amphetamine decreased L-Time and L:T-TD in males, thus displaying an anxiogenic effect. Imipramine was without selective effect on L-Time or L:T-TD, but decreased total OF distance at the highest dose indicative of a sedative effect. Drug effects were also evaluated in the OF without platform using conventional anxiety measures. Introduction of the platform into the OF apparatus strongly enhanced the sensitivity to anxiolytics. Comparison of strains differing in activity or anxiety levels showed that L-Time and L:T-TD can be used as measures of anxiety-like behavior independent of locomotor activity. Changes in motor activity are reflected in the total distance traveled under and outside the platform. Therefore, the platform test is fully automated, sensitive to both anxiolytic and anxiogenic effects of drugs and genetic phenotypes with little evidence of gender-specific responses, and can be easily utilized by most laboratories measuring behavior.